“£515 . M llmllllll Ilflllllllllflll'lllllllliflll ‘ f." . , ll] 3 1293 00852 8626 -. ,.., .I .. 1 I243: -. _ ;; :9 U:;1'*;;;.;~-.c.;;ly J This is to certify that the thesis entitled FAVISM AND GfiPD DEFICIENCY IN RHODES, GREECE. THE INTERACTION OF ENVIRONMENT, INHERITANCE AND CULTURE presented by Deanna J. Trakas has been accepted towards fulfillment of the requirements for Doctorate degree in W9)! /' . ’ / ,ma /7' , , / ' . / Major professor L ' A ‘:a ‘EEZV ‘§S\ t‘ “3"33 ””1”, stall? ‘1 '7 JUll 1 I 3= ‘ .msffflp OVERDUE FINFS: 25¢ per day per item RETURNING LIBRARY MATERIALfi: M Place in book return to remove charge from circulation regz” J .‘x' ..... . . .T ..;o .I s. i .3}! ‘1‘}!er 3. N03 (-4» a Isinpfiuxl. 2.. ..... .o onn. .. 9 Ind. -. .tlt .|.. o a Oi‘no’toOQIH¢1w1v04000.111. 3.14. .nlOOO.. .‘r. .V..»0c . V: ..... v.i..... FAVISM AND GGPD DEFICIENCY IN RHODES, GREECE. THE INTERACTION OF ENVIRONMENT, INHERITANCE AND CULTURE By Deanna J. Trakas A DISSERTATION Submitted to Michigan State University in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Department of Anthropology l981 ABSTRACT FAVISM AND G6PD DEFICIENCY IN RHODES, GREECE. THE INTERACTION OF ENVIRONMENT, INHERITANCE AND CULTURE By Deanna J. Trakas Fava beans are cultivated in most areas of rural Greece even though their consumption is associated with the acute hemoly- tic crisis diagnosed as favism. This reaction occurs in some, but not all, individuals with a reduced activity level of the red blood cell enzyme, glucose—6-phosphate dehydrogenase. The inter- action between this genetic trait (Gd') and culturally influenced behavior makes favism an interesting problem in epidemiology and preventive medicine. The findings of this study, conducted on the island of Rhodes, Greece, illuminate the epidemiological charac- teristics of favism and address the interests of preventive medicine. Screening results for the Gd' trait in boys, aged seven to twelve, from seven villages revealed an average frequency (26%) compatible with earlier studies on the island. Even though this average is very high, and fava beans are grown and consumed on the island, the annual average frequency of favism (l966-l978) is only 0.16 per thousand. Differences in micro-regional Gd' frequency and consumption of fava beans, as well as other socio-economic and behavioral factors suspected to contribute to the low favism frequency were examined during ethnographic field work conducted in two villages. Both villages were similar in size; one was a mountain location, the other coastal. They differed in 6d” (43% and 27%) and favism frequencies (nine and two cases). The distribution of land-holdings, necessitating daily and seasonal movement through a variety of eco-niches, and patterns of village endogamy and residence preferences after marriage, pro— mote differences in the distribution of the Gd' trait in Rhodes which is not necessarily related to the physical environment; the inverse relationship between altitude and trait frequency, reported in the literature, was not observed in Rhodes. Health and fertility histories comparing Gd' individuals with their non- trait counterparts indicate that the trait may be selectively neutral. The regional and seasonal distribution of the l23 favism episodes reported in Rhodes during l966 to 1978 is in agreement with earlier studies. Yearly fluctuations in favism frequencies appear to be associated with the interaction between the timing of Easter and the harvest of fava beans. Village locations at the highest altitudes reported the greatest number of total favism cases, with coastal villages reporting a longer favism season each spring and an earlier period of peak cases. For every adult case of favism, nearly two (l.7) pediatric ones were reported, with the female to male ratio (l:l.4) more nearly equal than reported elsewhere. According to eighteen case histories (l0 boys : 8 girls), children under six did not report hemolytic signs any earlier than their older counterparts, and 80% of the episodes in the 0-5 age cohort presented additional symptoms other than the hemolytic signs alone. The majority of these cases were associated with fresh fava beans which had been consumed outside of the household. In popular usage, the word favism is replaced by the phrase, "poisoning from fava beans." This neatly implicates only the fava beans, associates favism with other types of food poisoning and ig- nores the stigmatizing effect of having a familial disease or a blood deficiency. The emphasis on the genetic trait involved in the bio- medical etiology of favism requires that the individual, and even the entire family line, share in the blame for the hemolytic crisis. Food sharing cements social relationships in Greek society, while the presence of fava beans in the home during the Lenten period show that the family is observing the fast. Avoiding the beans, in the name of preventive medicine, may affect the family's or indi- vidual's social relationships and community position. Dedicated to Woodaki ii ACKNOWLEDGEMENTS The field research for this study was made possible through funds from a Michigan State University Biophysical Research Grant, the National Science Foundation, and the Wenner-Gren Founda- tion for Anthropological Research. At the Institute of Child Health in Athens, Greece, Dr. Spiros Doxiadis, President, and Dr. Stephanos Pantelakis, Director, were instrumental in obtaining permission for the research project and appr0priate assistance for the hematological screenings. The hematological tests were conducted under the auspices of Dr. Aris Karaklis, Director of the Hematology Laboratory at Aghia Sophia Children's Hospital, Athens, Greece. The blood samples in the villages of Rhodes were collected with the help of the agrarian physicians serving their internship requirements and assigned to the different localities by the Minis- try of Social Services, Dodecanese Islands, Greece. Mary Basilakis, registered midwife, was among the several medical professionals who assisted in the rural areas of Rhodes by providing advice and a sympathetic ear during the many phases of the field work. Dr. Joseph Spielberg, Professor of Anthropology and Chair- nan of my Dissertation Committee, never seemed to tire as he provided continual challenges during the review and analysis of field data. Throughout the writing of this dissertation, he refused to allow me to lose sight of the goals of anthropological inquiry. Dr. John Hunter, Professor of Geography and Co-Chairman of my Dissertation iv Committee, helped me to develop the methodology (and courage) to investigate a subject which heretofore had been reserved for medical scientists, and, was ever-constant in his clear and constructive criticism. Dr. Arthur Ruble, Professor of Anthropology and Member of my Dissertation Committee, gave me insights into the merits of social epidemiology and ethnographic information, helping me to place this study in larger context. Dr. Cheryl Ritenbaugh, Assistant Professor of Anthropology, helped with the technical parts of the dissertation devoted to population genetics. Dr. Anne Millard, Assistant Professor of Anthropology, graciously reviewed these parts in the final draft. Dr. Bernard Gallin, Professor and Chairman of the Department of Anthropology, provided me with his steady and foresighted knowledge of the discipline of Anthropology. It has been a pleasure knowing and working with these people. The manuscript was prepared by Merrilyn Nenner, and David Brown attended to the graphics. They both added their expertise to the format of the completed work. My parents, John C. Trakas and Virginia Niendorf Trakas, supported me throughout all the stages of this study. They were all and more that a daughter and student could desire. If it had not been for their value of education and knowledge, I would not have completed this dissertation. My brother and sister, Charles and Victoria Trakas, allowed me the privilege of sharing my ideas with them, even though I am sure that they preferred to talk about their own interests. Finally, my son, Noodaki White, is most certainly unaware of how much he contributed. Through the trials, tribulations and travel involved in this project, he kept me going by giving me his child's-eye-view of another culture. To all these people, and the people of Rhodes, Greece . . . Thank you. TABLE OF CONTENTS INTRODUCTION .......................... l Chapter I. PREVIOUS RESEARCH ABOUT FAVISM ............. ll Etiological Models and Favism Research ........ l2 Early ideas about the etiology of favism ...... l3 The G6PD enzyme deficiency (Gd' trait) ....... l7 The hemolytic agent in vicia faba ......... 20 Research on a synergistic etiology ......... 21 Epidemiological Studies of Favism .......... 23 Epidemiology of the Gd‘ trait ........... 24 Epidemiology of fava bean consumption ....... 27 Descriptive and social epidemiology of favism . . . 28 Seasonal and distribution of favism ....... 30 Geographic distribution of favism ........ 3l Age and sex distribution of favism ........ 32 Familial predisposition and multiple cases of favism ..................... 34 Ethnographic Data and Epidemiology .......... 35 Fava bean consumption as described in the literature 35 Attitudes about favism reported in the literature . 38 Models Used in the Present Research ......... 4O Footnotes ...................... 43 II. RESEARCH METHODOLOGY AND STRATEGY ........... 44 Review of Models and Types of Data Collected ..... 44 Selection of the Research Sites ........... 49 Identification of favism episodes ......... 50 Identification of the 6d" trait .......... 52 Identification of fava beans in local environments. 57 Other considerations in site selection ....... 58 Field Techniques ................... 59 Ethnographic field methods: participant observa- tion and interviewing .............. 59 Selection of participant families ......... 62 Ethnographic questionnaires ............ 63 Food habits ................... 64 Genealogical information ............. 65 Health and fertility histories .......... 66 Collection of case histories of favism episodes . . 67 Footnotes ...................... 69 vi vii III. RHODES: THE ISLAND AND ITS VILLAGES .......... Population Movements in Historical Rhodes ....... Early invasions of Rhodes .............. Turkish occupation of Rhodes . L .......... Italian occupation of Rhodes ............ Contemporary Rhodes .................. Rural Rhodes .................... Major regions of Rhodes ............... The city of Rhodes and its suburb—villages . . . . The southern tip of the island .......... The alluvial east coast .............. The mountainous west side ............. The Villages of Massari and Kritinea ......... Massari: Environment and economic setting ..... Settlement pattern ................ Links with the outside .............. Agricultural activity ............... Kritinea: Environment and economic setting ..... Settlement pattern ................ Transportation and communication ......... Economic activity ................. Demographic characteristics of Massari and Kritinea. Summary ........................ Footnotes ....................... IV. THE 60' TRAIT ON RHODES ................. Results of Screenings for the Gd' Trait ........ Distribution of the Gd‘ trait ............ Gd' trait and altitude ............... Natural Selection and the Gd' Trait .......... Selective advantage of the Gd‘ trait ........ Coastal examples: Mandriko, Massari and Lindos. . Inland examples: Pylona and Lardos ........ Mountain example: Embona ............. Selective Neutrality and the 6d" Trait ........ Fertility patterns of Gd' trait mothers ....... Ages of first and last pregnancy ......... Number of children and spacing .......... Fetal loss and perinatal deaths .......... Neonatal jaundice in 6d” trait infants and their siblings ..................... Neonatal jaundice in Gd- trait and non-trait infants ..................... Neonatal jaundice in infants of Gd' trait and non- trait mothers .................. Neonatal jaundice in Gd' trait and non-trait siblings .................... Blood-related conditions in Gd‘ trait children and their non-trait siblings ............. Comparisons of height, weight and relative weight. . 137 I42 144 144 I46 147 lSl viii Chapter IV (Con't) Genetic Drift and the 6d" Trait ............ 156 Genetic drift and historical events ......... 158 Genetic drift and endogamous marriage practices. . . 160 A description of marriage and residence patterns in Rhodes .................... 161 Regional endogamy and the selection of marriage partners .................... 168 Summary ........................ 175 Footnotes ....................... 177 V. THE SOCIAL EPIDEMIOLOGY 0F FAVISM ............ 178 Part I: Seasonal and Regional Distribution of Favism. 183 Seasonal distribution of favism on Rhodes ...... 183 Hemolytic agents in the environment ........ 185 The production and use of fava beans ....... 187 Cultivation of fava beans ............ 188 Harvest and storage of fava beans ........ 189 General consumption patterns: How and when fava beans are eaten ................ 190 Fava bean consumption and the ritual calendar. - 192 Fasting periods and the distribution of favism episodes ................... 195 Lent and spring epiSodes of favism ....... 196 Spring favism and yearly differences in Easter . 197 Regionality and the distribution of favism episodes. 202 Altitude: Its relationship to favism frequencies. 209 Altitude and fava bean production ........ 209 Sping favism, altitude and Lent ......... 211 Bean use and distribution of favism ........ 214 Urban-rural differences ............. 214 Differences in village production ........ 216 Conclusion to Part I: Seasonality and regionality of favism. ................... 219 Part II: Age and Sex Distribution of Favism ..... 220 Age ......................... 220 Organic factors .................. 221 Presentation and severity of symptoms ...... 223 Autoimmunization ................ 227 Other organic weaknesses in children ...... 227 Environmental factors ............... 231 Exposure to fava beans and age .......... 235 Use in the home ................. 235 Protection of children from eating fava beans. . 236 Fasting behavior and age ............. 238 Participation in agriculture and age ....... 239 Summary of age distribution ............ 240 ix Chapter V (Con‘t) Sex distribution of episodes ............. 242 G6PD deficiency and sex distribution of favism. . . 244 Hemolytic signs ................. 245 Accompanying conditions ............. 245 Environmental factors ............... 246 Difference in bean exposure by sex ......... 248 Agriculture and exposure .............. 249 Social factors affecting bean exposure by sex . . . 250 Summary to Part II: Age and Sex Distribution . . . . 254 Part III: Familial Tendency and Multiple Episodes of Favism ........................ 256 Familial favism and genealogical data ........ 257 Sibling pairs and the distribution of favism. . . . 259 Parent-proband sets ................ 261 Cousin pairs and the manifestation of favism. . . . 263 Fava bean consumption in Gd' trait families ..... 265 Use and preparation of fava beans in the diet . . . 266 Fava bean preparations and favism episodes ..... 268 Genealogical information and fava bean consumption. . 273 Fava bean consumption in families without favism. . 274 Fava bean consumption in pedigrees reporting one favism episode .................. 275 Fava bean use in pedigrees with multiple cases of favism .................. 280 Summary Part III: Familial favism .......... 282 Discussion: Directions for Further Research ...... 283 VI. AN ETHNOMEDICAL DESCRIPTION OF FAVISM AND ILLNESS PREVENTION ........................ 287 Popular Conceptions and Explanations of Favism ..... 289 Two etiologies of favism: Biomedical and popular . . 290 Symptoms and their meaning .............. 293 Yiokteros and Krisi (jaundice) ........... 294 Dilitiriasi and Fagito (food poisoning) ...... 299 Reasons for Continued Consumption of Fava Beans . . . . 301 Ecological arguments for fava bean consumption. . . . 302 Nutritional advantage argument ........... 302 Economic necessity argument ............ 303 Socio-psychological reasons for continued bean consumption .................... 306 Mediterranean fatalism ............... 306 Risk taking and consumption of fava beans ..... 308 Using a cultural argument .............. 311 Time: Seasons and celebrations .......... 312 Hospitality: Taking and offering food ....... 316 Husband-wife roles: Fava bean use in households. . 317 Chapter VI (Con't) Illness Causation and Preventive Behavior ....... 319 The evil eye: Prevention and cure ......... 321 Theories of contagion ................ 323 Smells, odors and preventive behavior ........ 324 Food consumption and preventive behavior ...... 326 Protective Behaviors and Fava Bean Consumption . . . . 328 Avoidance of the beans ............... 328 Conceptions of protection .............. 331 Preventive Medicine and Favism ............ 333 Prevention from an anthropological perspective . . . 334 Blood symbolism .................. 338 Familial diseases ................. 340 Conflicts between preventive medicine and cultural norms ....................... 341 APPENDICES A. Variants of the G6PD Enzyme Deficiency ...... 346 B. Familial Favism .................. 349 BIBLIOGRAPHY ......................... 353 NNN N b cum—a 00000000 43de 4> 4> 4> 4>J>4>4> 4: 4>4> 4: 4> 4; O —-l u-J domfl Ch 01-9 (A) N _.a_a_.a com—'0 LIST OF TABLES Contrasts in Native Versus Biomedical Explanations of Illness and Disease .................. 2 Epidemiology of Known Favism Risk Factors ........ 25 Epidemiological Variables and Favism ........... 29 (A General Model for the Epidemiology of Favism). . . . 29 General Model for the Ethnomedical Investigation of Favism ......................... 42 Factors from an Epidemiological Model of the Gd' Trait. . 46 Epidemiological Model for Fava Bean Consumption ..... 47 Epidemiological Variables and Favism: A Model to Direct Research Strategy (Expansion of 1.2) .......... 48 Populations Represented in Screening for Gd' Trait. . . . 54 Major Historical Events in Rhodes ............ 73 Populations in Massari and Kritinea ........... 105 Distribution of Age Groups in Massari and Kritinea. . . . 108 Families with Elementary School Child(ren) in Massari and Kritinea ...................... 108 Distribution of GGPD Deficiency in 189 Male Children in Rhodes ......................... 116 Elevation and the Distribution of the Gd' Trait in Rhodes and Sardinia ............... z ...... 120 Range and Average of Childbearing Ages in Gd Trait and Non-Trait Mothers ................... 135 Number of Children per Mother in Massari ......... 136 Number of Pregnancies by Number of Childbearing Years in Massari and Kritinea ................ 137 Pregnancy Results in Gd Trait and Non-Trait Mothers (Massari and Kritinea) ................. 138 Childbearing Profile of Non-Trait Mothers (Massari) . . . 140 Childbearing Profile of Gd’ Trait and Non-Trait Infants . 141 Neonatal Jaundice in Gd- Trait and Non-Trait Infants. . . 144 Neonatal Jaundice in Infants from Gd' Trait and Non- Trait Mothers ............... z ..... 145 Infants with Neonatal Jaundice According to Gd Trait Status of Mother. . ._ ................. 146 Neonatal Jaundice in Gd Children and Their Non-Trait Siblings ................. z ...... 147 Blood-Related Conditions in Children from Gd Trait and Non-Trait Mothers ................. 149 xi h-b-b-h-b-b UT U1 01 01 U1 0'1 0 0 010101 01010101 \OQNOS U'IU‘I 010101 01010101 U1 0101 U1 0 O I O O I O O O O O .14 .15 .16 .17 .18 .19 «D (JON—4 Gd' Trait and Non-Trait Mothers Compared According to Reported Episodes of Blood-Related Conditions ..... 149 Children From Massari and Kritinea Compared According to Reported Episodes of Blood-Related Conditions. . . . 150 Comparisons of Relative Body Weight in Boys from Kritinea and Massari (Quetelet Index) ......... 154 Village Exoganous Marriages in Massari and Kritinea According to Birth-Place of In-Marrying Spouse ..... 170 Village-Exogamous Marriages from Massari: Current Residence in Massari .................. 171 Village-Exogamous Marriages from Kritinea: Current Residence in Kritinea ................. 171 Epidemiological Model for Favism ............. 179 Spring Episodes in Late and Early-Year Easter ...... 202 Gd' Trait and Favism Frequencies in Twelve Villages, Listed by Region .................... 203 Distribution of Gd' Trait in Twelve Villages: Projected Gd Trait Males Based on Frequency in 7-12 Year Old Boys .......................... 205 Five Rural Regions of Rhodes Comparing Gd‘ and Favism Frequencies ...................... 206 Altitude and Favism Frequencies ............. 209 Lenten and Spring Cases of Favism by Altitudinal Group. . 213 Rural/Urban Off-Season Favism Cases ........... 215 Gd Trait and Favism Frequencies in the Regions of Massari and Kritinea .................. 216 Fresh and Dry Fava Bean Consumption in Massari and Kritinea ........................ 218 Fava Bean Consumption in Agricultural and Non-Agricul- tural Families in Massari and Kritinea ......... 218 Presentation of Hemolytic Signs in Pediatric Favism: Two Age Cohorts Compared ................ 224 Cases With 0n1y Hemolytic Signs vs. Those With Other Symptoms: Two Age Cohorts Represented ......... 225 Cases Where Only Hemolytic Signs Were Reported ...... 226 Onset of Hemolysis in Cases Where Other Symptoms Were Reported ........................ 226 Hemolytic Episodes in Gd" Trait Children (Other than Favism) ........................ 230 Age Distribution and Altitude .............. 234 Presentation of Hemolytic Signs by Sex .......... 245 Presentation of Additional Symptoms by Sex ........ 246 Male to Female Episodes Shown by Urban and Rural Locations ....................... 247 Urban to Rural Ratios by Sex Distribution ........ 247 Female to Male Episodes by Altitude ........... 248 Form of Bean Associated with Favism Episodes in Males and Females ...................... 249 Sex Distribution of Favism Episodes by Age Cohorts. . . . 251 Most Frequent Favism by Age Cohort in Mountain and Coastal Areas ..................... 255 0'1 01010101 0'1 030‘ 0101 O O O xiii Sibling Pairs Divided According to Favism in Proband and Sibling ..................... Parent-Proband Pairs and Favism ............ Mother-Son Pairs and Favism .............. Cousin Pairs and Favism ................ Form (Fresh, Dry) and Preparation (Raw, Cooked) of Fava Beans in Thirty Families ............ Twelve Cases of Favism, Listed by Form and Preparation of Beans Implicated ................. Eighteen Cases of Favism Listed by Form and Prepara- tion of Beans Implicated ............... Use of Water in Cooked Fava Bean Preparations ..... Fava Bean Use in Pedigrees Without Favism ....... Native Terminology for Conditions Related to Favism . . Heavy and Light Foods ................. 260 262 263 265 269 271 271 272 274 295 327 01m (II 0101 #hhbbwwww 0101010101 01010101 UT-pr—J-DwN—J N—d LIST OF FIGURES Households with Elementary School Children in Massari and Kritinea, Showing Proportion Represented in Screening ...................... 55 Location of Historical Populations in Rhodes (Map). . . 78 Major Regions of Rhodes (Map) ............. Age Pyramid of Massari ................. 106 Age Pyramid of Kritinea ................ 107 Gd' Trait Distribution in Rhodes (Map) ......... 117 Heights of A11 Boys in the Massari and Kritinea Samples 152 Weights of A11 Boys in the Massari and Kritinea Samples 153 Quetelet Index: Boys from Massari and Kritinea . . . . 155 Village-Exogamous Marriages in Massari and Kritinea (Map) ........................ 173 Monthly Distribution of Reported Favism Episodes in Rhodes: 1966-78 ................... 184 Distribution of Spring Episodes Showing Cases Where Lenten Beans Are Implicated ............. 198 Spring Episodes of Favism by Seven-Day Periods ..... 200 Distribution of Favism Episodes by Year ........ 201 Regional Distribution of Favism (Map) ......... 207 Favism Frequencies and Altitude (Map) ......... 210 Altitude and Timing of Reported Spring Favism Episodes in Rural Rhodes ................... 212 Age Distribution of A11 Reported Favism Episodes in Rhodes. ....................... 222 Age Distribution by Rural and Urban Episodes ...... 232 Age Distribution of Rural Cases by Altitude ...... 233 Age and Sex Distribution of Favism Episodes ...... 243 Types of First Cousin Pairs with the Gd' Trait and/or Favism ........................ 264 Pedigree One: Gd’ Trait and Favism in Distant Cousins. 276 Pedigree Two: Gd' Trait and Favism in First and Second Cousins ..... _ .................. 278 Pedigree Three: Gd Trait and Favism in Two Second Cousins ....................... 279 Genealogical Links Between Pedigrees Two, Three and Four ...... z .................. 279 Pedigree Four: Gd Trait and Favism in Two First Cousins and Their Cousin, Once-Removed ........ 230 Pedigree Five: Favism in Two Female Distant Cousins. . 281 Pedigree Six: Consanguineal Relationship of Two Sets of Brother-Pairs with Favism ............. 282 xiv ' INTRODUCTION Seeking to purify their bodies and psyches, the Ancient Greek Pythagoreans developed a list of taboo foods. Among these were the large unusual-looking fava beans (Vicia faba) which have since become identified in the biomedical and biochemical etiology of acute hemolytic crises. This reaction to the fava beans, named jl_favismo by Italian physicians in the late 18005 (e.g., Mina la Grua 1856 cited by Sansone et al. 1958; Gasbarrini 1915) is characterized by Rene Dubos in the following quote: Favism, an anemia that occurs in some persons when they eat fava beans, can be regarded as a symbol of the manner in which environment and genetic endowment constantly interplay in all manifesta- tions of life. As far as is known, the only persons who suffer from favism are those who genetically have erythrocytes susceptible to the constituent of the fava bean which brings out the anemia. In this case, the culprit is a recessive gene that causes a reduced activity of glucose-6-phosphate dehydrogenase. The affected persons are essentially normal unless they consume fava beans. (DuBos 1965:1947-8) The mother of a young boy from Rhodes who had been stricken with the hemolytic crisis presents another picture: Several years ago, when my son was younger, he went to stay in the other village down the mountain. We have relatives there. Someone gave him fava beans to eat, and soon after, he started vomiting. Then he became yellow and his urine turned black. We took him to the hospital where he was given blood transfusions. We don't have anything inherited in our family that would make him become sick like that. You won't learn anything from writing down our family tree -- he simply ate bad beans. Maybe some people get sick from fava beans because they have something -— some deficiency in their blood, but not our family. The beans were spoiled, that's all there is to it. In these two statements, all the elements for a multifaceted investigation are present. This thesis is the result of field research in rural Rhodes, Greece, about favism. Why the subject of this hemolytic crisis which affects primarily Mediterranean populations would appeal to an ethnographer should be apparent in the contrasting statements, one by a medical physician, and the other from a mother of a favism victim. More than the interaction of inheritance and environment, as DuBos suggests, there are several contrasts represented in the hemolytic phenomena of favism: TABLE 0.1 CONTRASTS IN NATIVE VERSUS BIOMEDICAL EXPLANATIONS OF ILLNESS AND DISEASE fear, superstition --------------- scientific knowledge popular etiology ----------------- biomedical etiology illness, a socio- _________________ disease, a biomedical cultural concept concept preventive behaviors ------------- preventive medicine It might be noted that the column on the left in Table 0.1 lists topics of interest to anthropology (e.g., superstition, behavior) and on the right, topics of concern to medical science (e.g., scientific knowledge, biomedical etiology). It is no mistake that they are 1 listed in opposing columns. These contrasts are deliberately set forth here as a heuristic device to generate a polemic which will become increasingly apparent during the following chapters of the thesis. Many have commented on the shared interests of the medical and social sciences, and on the possibility for collaborative efforts between the two disciplines (e.g., Cassel 1964; Engle 1960; Kleinman 1973; Polgar 1962). In basic assumptions and goals of research, the social and medical sciences do not simply represent two disciplines, but two different paradigms and sets of goals. Medical science attempts to explain disease: social science, to explain behavior. These differences are not limited to the theoretical level alone; they permeate the operational levels in the development of research strategy and methodology. These differences become increasingly played out in medical anthropological studies, of which this present thesis is one. The biomedical paradigm includes at least the following parts: (1) a reliance on the scientific method, (2) a concern with the identification of pathogenic, genetic and/or possibly adaptive factors which contribute to the pathway of disease causation, and (3) the identification, control and eventual eradication of disease as the motivating force behind research. Preventive medicine as well as therapy grounded in scientific knowledge and disease etiology is included in the third dimension of the paradigm. All the points of contrast mentioned in Table 0.1 are present in this description: i.e., scientific knowledge, biomedical etiology, emphasis on disease as a deviation in the somatic norm, preventive and therapeutic medicine. Preventive medicine is distinguished from preventive behaviors; the latter may or may not be grounded in biomedical principles. In the search for causes, ecological and/or epidemiological approaches may be used. This has helped support the suggestion that social and medical sciences can and should collaborate. Describing illness behavior requires the use of a separate paradigm, one which stresses subjective experience and cultural influences on behavior (e.g., ideology, social sanctions, ecological and economic pressures). The ethnomedical paradigm developed out of these behavioral and cultural concerns, and is usually classified as a branch of ethnoscience and cognitive anthropology. In its strictest application, (e.g., Frake 1961), biomedical concepts are ignored and the native etiology, explanations, categories and descriptions of symptoms are analyzed. The analysis may stop once a single illness has been explained on these terms, or it may continue by using the illness categories, illness behaviors, and so forth, as ways of illuminating the culture. This is analogous to other anthropological analyses which may use, for example, the kinship system to explain the way people calculate kinship relationships and responsibilities, or to explain something else more basic to the entire culture. The early studies of health and disease conducted by anthropologists (before "medical anthropology" became a separate sub-discipline), approached this goal more than some of the more recent studies. For example, the studies of witchcraft, the evil eye, spirit possession, ‘ and body concepts, which reflected the social structural and ideologi- cal reality of a cultural system, were more clearly anthropological studies than they were medical. For lack of a better or more precise term, I refer to these types of studies as ethnomedical, as well as those which embrace the more narrowly defined methodological parameters of ethnoscience. In this definition, the ethnomedical approach involves two facies: (l) the use of ethnographic information to illuminate illness behavior; and (2) the use of illness behavior to illuminate ethnographic (cultural, social, economic, ideological) data. In this discussion of ethnomedicine, the word "illness" has been preferred over "disease." Medical scientists have often inter- changed the two terms, but social scientists interested in socio- medical studies have preferred to differentiate between them. Disease is a category created by biomedical diagnostic procedures; it is a product, and in fact, a necessary part of the biomedical model. Illness is a creation of the socio-cultural system; it may have meaning which is limited entirely to that sphere, or it may resemble the disease category used in the medical system. The latter is the case in Western, industrialized societies. When speaking of the biomedical model, it is more appropriate to use the term, disease. The term illness is reserved for use with ethnomedical, sociological and/or culturological studies which focus on behavior. Returning to the Table 0.1, the next question is whether or not it is possible to bridge the two columns with yet a third model which would allow medical sciences to collaborate on an inter- disciplinary basis. DuBos suggests that since both the medical and the social sciences are essentially human sciences, collaboration should be easy to achieve. During the time of Hippocrates, the interaction of the environment and the psycho-social dimensions of the human experience played an important role in the theory of good health and in the diagnosis and treatment of illness and disease. With the evolution of cosmopolitan medicine and the development of increasingly sophisticated technologies for the identification and treatment of disease, these other dimensions became overlooked if not neglected altogether. The need for the reintegration of the earlier holistic type of disease theory has been emphasized by contemporary medical and social scientists (Engle 1977). They stresss the ecological, open-model approach to disease and health (Gordon 1966; May 1960). In such a model, the interaction of environ- ment and adaptation through both genetic inheritance (e.g., Alland 1968 and 1970; Harris 1970) and culture (e.g., Fenner 1970; Hughes and Hunter 1970) would be included. Others suggest that social epidemiology as a methodological perspective can speak to the interests of both disciplines. Social epidemiology, an outgrowth of descriptive rather than analytical epidemiology, was introduced to the social sciences through the work of Cassels (1964) as a potential bridge between the two disciplines. Here, various social structural and social demographic variables such as occupation, education, family size, etc., were taken into the model of disease causation. Later, Kleinman (1973) stressed that at least two dimensions, the biophysical and the socio-psychological, were involved in disease phenomena, and therefore, the model needed expanding to include the socio- psychological. Although using behavioral and socio-cultural variables, all of these approaches focus on explaining disease. As such, they fall within the biomedical, not the ethnomedical, paradigm. An outstanding demonstration that ethnographic details could help explain disease resulted from the series of research efforts about the neurological dysfunction of the disease called Kuru in New Guinea (e.g., Fisher and Fischer 1961; Alpers and Gadjusek 1965; Zigas 1970). This success gave impetus to other anthropologists hoping to show that ethnographic data was invaluable in medical studies. This also played a role in initiating the present study about favism, and it was hoped that such a study would bridge the two paradigms. In retrospect, this is considered to be a premature and perhaps naive expectation. Even though this research is not a medical study, it is fully within the biomedical paradigm. This is, of course, not the first time that this has happened in medical anthropology, and, in fact, may be a major dilemma which faces the sub-discipline. Fabrega (1974) writes that the inability of most socio-cultural research about disease and health to leave the parameters of the biomedical paradigm is not unique to only a few studies. Even though the terms "ecological" or "socio—epidemiology" may be substituted for the term biomedical, the framework for these studies is still biomedical. He states that (1974:46) "....the ecological framework or approach has always been an inherent feature of medical epidemiology and that distinguishing between the two is somewhat arbitrary." In this model, the individual is not considered as an active agent in the epidemiological variables, but merely as a passive recipient of particular ecological forces. "... the way disease may affect the quality of social life is not explored, nor are the people's ways of responding socially to the disease considered relevant." (ibid.) The fact that epidemiological and/or ecological approaches to behavior and disease result in serving the interests of biomedical science in their goal to explain disease rather than behavior, is dramatized by Fabrega (1974:47): Particularly important is the fact that medical studies of this genre (that is, what I have termed epidemiological and ecological) tend to disregard the perspective of the actor, the rules and the values of the people, the meaning that illness has, and the way subjects orient and respond to illness or disease occurrences. The principal questions tend to be causal, and consequently the disease itself (that is, its occurrence, prevalence and incidence) is seen in the context of the (correctionistic) goals of Western medical science which are to control disease. These are the contradictions which repeat themselves throughout this thesis, particularly in the last two chapters. From what has been said of the two disciplines, the medical and the social, it does not appear that collaboration is a possibility. The two approaches, the biomedical and the ethnomedical, have been discussed here to clarify that this thesis is not an attempt to bridge the two paradigms: it uses ethnographic and ethnomedical data in the service of the biomedical model. I believe it clearly shows the strengths and weaknesses of using this type of approach, and illustrates how cul- turally influenced behaviors and beliefs contribute to the epidemiology of favism. It does not attempt to show how favism can be used to understand Greek rural culture and society, even though in the course of studying favism, certain cultural traits were emphasized. From its original conception, the research was designed to supplement and expand the biomedical and clinical findings about favism. Some of the questions posed in the early stages of the study remained in the forefront throughout all phases of the research project. For example, these questions were asked: 1. Is the G6PD deficiency (Gd' trait) adaptive, or does it appear to have neutral selection? 2. How many individuals with the Gd' trait actually report episodes of favism? 3. What are the general patterns of fava bean cultivation and use? 4. How do the standard epidemiological variables referred to in the literature (e.g., age, sex, season, region) relate to the Rhodian samples? 5. Are there any preventive behaviors, folk lore, and so forth, which relate to fava beans? Through the review of the scientific and biomedical literature about favism in Chapter One, the lack of ethnographic data from situations outside the clinical setting is exposed. Chapter Two discusses the concerns involved in developing a research strategy which can facilitate the collection of ethnographic information and which is able to meet scientific standards. The physical, histor- ical and contemporary social setting of the field work site, which is standard for all ethnographic research studies, is described in Chapter Three. Chapters Four, Five and Six present the data collected during the field work, showing the continual interaction between behavior and the epidemiological characteristics of favism. Chapter Four presents the results of the screenings for the G6PD deficiency (Gd') in Rhodes and discusses the applicability of various hypotheses to account for the distribution of the trait. Chapter Five takes the major epidemiological variables used in the literature, compares them with the distribution of favism in Rhodes, and shows where ethnographic data can be used in refining these variables. 10 In the last chapter, the question of fava bean consumption and pre- ventive behavior is discussed. This has implications beyond the scope of the thesis, emphasizing the need for behavior oriented explanations when seeking answers to questions related to prevention. The organization of the chapters in this way enables the reader to move from the level of scientific knowledge and biomedical etiology (in Chapters One and Three) to popular etiology and preventive behaviors in Chapter Six. In this way, the bridge between the ethnomedical and the biomedical approaches is not fully constructed, but merely suggested. CHAPTER I OTHER STUDIES ABOUT FAVISM: MEDICAL ETIOLOGY This chapter reviews the scientific and medical research which has been published about favism and the models which were used in analyzing the data gathered during the present study. The existing studies about favism generally fall into two categories; (1) the etiological and (2) the epidemiological. These are not necessarily mutually exclusive, but represent an arbitrary division which serves as a heuristic device in examining the state of research about favism. In etiological studies, favism is examined in order to describe its pathology and/or its biochemical etiology. The early studies of this type attributed the disease to a principle of contagion, which also fit with the seasonal epidemics of favism which occurred during the spring. Later the disease was explained as an allergic reaction of some unknown cause. During this time, research was directd by concerns for diagnosing, prescribing therapy, giving a prognosis and identifying the "causes" of favism. With the identification of the red blood-cell enzyme, G6PD, in a deficient or partially deficient form as an etiological factor, research mushroomed with respect to the biochemical and genetic nature of the enzyme. Simultaneously, research focusing on the hemolytic action of fava bean extracts also accumulated. These identified the fava bean as a hemolytic agent, although the specific 11 12 hemolytic chemical in the bean could not be isolated. Both approaches. represent examples of the etiological model where causation is discussed in terms of principles of biochemistry of either the bean or the affected blood. Epidemiological studies have generally focused on the distribution of etiological factors, particularly the Gd- trait (the G6PD enzyme deficiency), rather than on the distribution of the disease itself. For example, the distribution of the disease is often described by using age and sex variables which are related, in turn, to the distribution of the Gd" trait. These are not examined as to how they might be related to fava bean consumption, or to other aspects of the disease such as the presentation of symptoms of ways of reporting episodes. Etiological_Models and Favism_3esearch Studies of favism which are guided by etiological concerns can be divided into three groups: (1) those which were conducted before the enzyme deficiency was identified as an important factor in the etiology of favism; (2) studies which analyze hematological characteristics of the enzyme deficiency; and (3) research which aims to identify hemolytic properties of the fava bean. The early studies about favism succeeded in standardizing the diagnosis of favism. Since jaundice can result from a variety of diseases and conditions (i.e., it is not a disease in and of itself), it was important to separate the jaundice which occurred in favism, from jaundice which was associated with any number of other diseases. The emphasis was on developing an understanding of the pathology of favism in order to define a syndrome of hemolytic anemia were 13 caused by exposure to a deleterious agent. Hematological studies of the enzyme deficiency, and biochemical research concerned with the hemolytic agents of the fava beans, accumulated after the G6PD enzyme had been definitely linked with fava bean extracts under laboratory conditions. Early Ideas about the Etiology of Favism It is not clear from the research whether or not favism, as a biomedical disease, actually existed in the ancient populations of the Mediterranean where it is now so prevalent. As stated in the Introduction, many different Mediterranean peoples had taboos, or at least exercised caution, regarding their consumption. It is not clear if these resulted from the recognition of the hemolytic properties of the beans, or from other, possibly symbolic, reasons. For example, it is not clear if the Pythagorean warnings about eating fava beans were based on the symbolic properties of the beans, a philosophy of good nutrition, or due to observed hemolytic reactions to the beans. In ancient Egypt and Rome, the beans were considered to be unfit for consumption by the upper classes. Perhaps this had to do with the association of the beans "... with a certain coarseness of habits, presumably because of their proverbial flatu- lence-inducing properties" (Donoso et a1. 1969:513). It is also said that Egyptian priests were not allowed to eat the fava beans. The reason for the taboo might have been symbolic as well as practical. These early cautions about the beans do not include reference to jaundice as a result of eating the beans; therefore, it is possible 14 that these taboos represent symbolic and/or social meanings rather than scientific observations. Only in an old Portugese proverb is the reason for avoiding the beans at all similar to the biomedical one. In the proverb, people with a weak liver were warned to avoid passing through a fava field (Flatz and DUES" 1957)- Early references to favism and/or the fava bean are difficult to isolate from a general bulk of writings which discuss several illnesses associated with beans, legumes and pulses. Hippocrates wrote about an illness, since labeled "Lathyrism," which affects the lower limbs with paralysis after the ingestion of the legume Lathyrus sativus and possibly Vicia sativa (the latter in the same genus as fava beans). In the 18505, the "vegetable disease" was said to affect Italians after the consumption of certain beans, legumes, and possibly other greens (Mina 1a Grua 1856, cited by Bottini 1973). Whether or not some of these diagnoses included instances of favism is not clear, although certainly possible. References to favism as a distinct disease are first noted in Italian sources. Montano (1895) postulated that some hereditary factor operated in cases of 11 favismo which were found in the Italian population. Later, Gasbarrini (1915) published a relatively complete description of favism, considering the time during which he wrote. Fava beans were implicated in the cases of hemolytic anemia and hemoglobinuria reported by Gasbarrini, and he also suggested that certain drugs might bring about similar reactions. He divided the progression of the illness into five different states; individuals may suffer from one or all of the states. The most grave form resulted 15 in death, while the light hemolytic reactions eventually stabilized themselves without therapeutic intervention. The grave form of favism was described by Gasbarrini to involve signs of recovery from the hemolytic crisis followed by a sudden relapse; this is a major danger of the disease today. Several years later, the term "Lederer's anemia" was applied to conditions of unexpected, spontaneous hemolytic crisis, suspected to be both contagious and associated with the diet. Some (e.g. Belsey 1973) have speculated that this condition was actually favism, but went undetected because no one inquired about the consumption of fava beans. Fear of the fava beans was still considered to be little more than a peasant superstition. In the 19405, the disease began to be characterized as related to some unidentified blood condition, similar to that which would cause allergic reactions to fava beans (Luisada 1941; Carcassi 1958; Kantor and Hoch 1961; Kantor, Pinkhas and Djaletti 1962). An allergic pathology, it is noted, was given credit for the disease for approximately twenty years. By the 19505, it was noted that the "sensitivity to fava beans" (Sansone and Segni 1957) and the hemolytic anemia which followed their consumption was strikingly similar to that occurring in American Blacks after exposure to or ingestion of certain antimalarial drugs (Beutler 1954a and b; Browne 1957; Carson et a1. 1958) Those suffering hemolytic anemia after exposure to these drugs were known to be affected by the G6PD enzyme deficiency (or the Gd-trait). The hemolytic conditions so closely resembled each other that the enzyme deficiency 16 was suggested as the blood trait for which scientists had been searching. Subsequent studies of the effect of fava bean extracts on G6PD- deficient blood cells clearly established this association.(Mela and Perona 1959). Following this discovery, earlier theories about favism as an allergic reaction were abandoned, and research emphasis became directed toward diagnosing the disease on the basis of the deficiency and fava bean consumption. Since the identification of the enzyme deficiency as the major predisposing factor in favism, research about the Gd—trait has accumulated much more rapidly than studies which suggest that other factors potentially involved in favism should be investigated. An Italian scientist, Sartori (1971) advocates a multicausal etiology of favism which gives less emphasis to the deficiency as a primary cause. He contends that the deficiency contributes only to the "... hemolytic course of the disease among individuals bearing the autosomal favic predisposition or its phenocopy" (1971:462). That is, favism has two diatheses, one hemolytic, the other not hemolytic. Individuals with a favic predisposition and the deficiency suffer from clinical hemolytic favism. Those who have only the favic pre- disposition also suffer from reactions to the fava bean, but do not present hemolytic symptoms. The diagnosis of favism which requires both the deficiency and hemolytic anemia to be present is considered to be clinically severe and a priori. This diagnosis promotes the false assumption that favism must always involve the dramatic hemolytic symptomology. Sartori proposes that a milder form of favism exists which 17 does not entail the hemolytic crisis. In Sardinia, he found that in nineteen cases of favism among male subjects, only one showed a positive identification of the enzyme deficiency; the other eighteen did not "have" the enzyme deficiency on the basis of scientific testing. 0n the basis of this study, Sartori claims that it is possible for favism to occur in the absence of the enzyme deficiency, but that severe hemolytic favism is never encountered without the deficiency. It is the latter type of favism which reaches hospitali- zation; the milder forms do not, and go unnoticed in the scientific studies of the disease. The erroneous opinion which identified G6-PD deficiency with a predisposition to favism arises from this indirect connexion between the enzyme deficiency and the number of patients admitted to hospitals. In reality, strong G6-PD deficiency only causes the hemolytic course of the disease among individuals bearing the autosomal favic pre- disposition of its phenocopy. (Sartori 1971:465) The G6PD Enzyme Deficiency (Gd- Trait) The G6PD enzyme (glucose-6-phosphate dehydrogenase) is normally active in the red blood cells of the circulatory system. A reduction or deficiency in the level of the enzyme activity is not considered pathological in itself (i.e., it is not classified as a hemoglobino- pathy), but it places the individual at risk of developing hemolytic anemia following the ingestion or contact with certain hemolytic agents. These agents include aspirin, many anti-malarial drugs, napthelene, vitamin K, sulfa derivatives, and Vicia faba. The deficiency is controlled by a sex-lined genetic trait. Males are always 18 genotypically hemizygous; they carry the trait on their one X chromo— some. Females may have the trait on both chromosomes (homozygous) or on only one (heterozygous). When only one X-chromosome is affected, phenotypic expression of the deficiency vary from definitely deficient to nearly normal in terms of enzyme activity levels. Research has explained this by demonstrating that heterozygous females have two populations of red blood cells, one normal and one deficient (Kattanis 1967; Beutler et a1. 1962). Blood mosaics from heterozygous females show different ratios of normal to deficient red blood cells. Hypothe- tically, they can show the enzyme deficiency in a screening test, but it may not be sufficient to interact with the fava beans. According to probability figures for the distribution of hemi-, homo- and heterozygotes in a given population, more females than males would be expected to suffer from severe favism. This discrepancy is accounted for by heterozygous females whose deficient red blood cell population is nearly equal to those who are genotypically fully affected by the enzyme deficiency1 (Russo et a1. 1972; Sartori 1963). Males have also been noted to show differences in the phenotypic expression of the deficiency, even though they are fully affected genotypically (Stamatoyannopoulos et a1. 1964). These problems related to the x-linked character of the enzyme deficiency, and to the variation in its phenotypic expression, have been referred to in order to explain why all individuals with the eznyme deficiency do not suffer from favism. Another explanation calls upon the variations in the enzyme itself, either with respect of its chemical composition or to levels of its activity. 19 When favism was first associated with the enzyme deficiency, two types of the deficiency had been identified: (1) the A- variant, found in American Blacks suffering hemolytic anemia from anti-malarial drugs (Beutler et al. 1954a, b; Beutler et al. 1955a, b; Gross et a1. 1958); and (2) the Mediterranean variant, so-named because those suffering from the fava bean induced hemolytic anemia were first identified in Mediterranean populations. The Mediterra- nean variant is the most severe form of the enzyme deficiency, with activitiy levels of the enzyme below 1/20 of normal (Sartori 1971). Compared with the A-variant, with activity levels of up to 25% of normal, the Mediterranean variant may show only 5% of normal enzyme activity. Degradation of these activity levels during red blood cell aging is much accelerated with the young erythrocytes being almost as deficient as the older ones (Hotulsky and Stamatoy- annopoulos 1966; Stamatoyannopoulos et a1. 1964). As a consequence, hemolysis in subjects with the Mediterranean variant is more acute and severe, with almost all erythrocytes being subject to destruction.2 Those with the Mediterranean variant are susceptable to a wider range of drugs than those with the A- variant, and have a greater tendency to show neonatal jaundice (Kirkman et al. 1964a). Those with the Mediterranean variant are not subject to chronic hemolytic disease which is observed in other Caucasians with more rare types of the deficiency. The Mediterranean variant is associated with hemolytic crisis following consumption of Vicia faba, sulfa derivatives, aspirin, and contact with napthelene. It has not been associated in the literature with anti-malarial drugs as has been 20 the A-variant.3 Since the early research about the A- and the Mediterranean variants of the enzyme deficiency, at least seventy-five other varia- tions have been identified (Beutler 1970; Yoshida et a1. 1971; Kirkman et al. 1964a and b, Marks and Gross 1959, Rattazzi et a1. 1969). These studies are briefly reviewed in Appendix A. While it is possible that one of the reasons that not all individuals with the enzyme deficiency suffer from favism is because they do not have the variant which interacts with the fava beans, this hypo- thesis has not been tested in medical research. When people are hospitalized and treated for favism, it is assumed that they have the Mediterranean variant. They are tested for the presence of the deficiency, but not for which type of the deficiency. For the purposes of this present study, it was assumed that individuals suffering from favism have the Mediterranean variant of the deficiency. Since it is the Mediterranean variant which is predominant in Greek populations, individuals identified with the deficiency (with or without reporting favism) are also assumed to have this variant. Even though variants have been discovered in the Greek population, their interaction with fava beans and other hemolytic agents has not been investigated. The Hemolytic Agent in Vicia Faba Studies which focus on the hemolytic agent in the fava beans are expected to clarify the etiology of favism by identifying which type of fava beans which cause the disease. In these studies, the appearance of favism in some enzyme deficient individuals and not 21 others is explained by the activity and/or toxicity of some unidentified hemolytic agent in the beans. Different beans, grown under different conditions perhaps, are hypothesized to possess different levels of activity of the hemolytic agent. The crucial variable is not whether one has the Gd" trait, but whether or not beans with critical levels of the hemolytic agent, have been consumed. A wide body of laboratory research using in liEEQ fava bean extracts, has been generated to support this position (e.g., Mela and Perona 1959; Bowman and Walker 1960 and 1961; Zacchello and Panizon 1964; Lin and Ling cited in Patwardham and White 1973; Kosower and Kosower 1967; Braham and Sarova-Pinhas 1971). Some of the chemicals suggested to be hemolytic agents are found in other vegetables which are not associated with hemolytic episodes. In general, these studies have yielded unconclusive results. Some studies suggest that environmental factors affect the toxicity of the fava beans, hypothesizing that growing and ripening conditions are more closely associated with the toxicity of the beans (Sartori 1971; Marcolongo 1941). Information gathered by Sartori from hemolytic cases produced by fava beans suggests that climatic differences are definitely involved. Favism is more prevalent during a sunny, dry spring, than during a wet, rainy one. It is expected that areas where arid springs are the norm would have higher favism frquencies. Research on Synergistic_§tiolggy The phrase, synergistic etiology, is used in three ways: (1) synergistic activity between the deficiency and some other blood 22 or genetic variable; (2) synergistic activity between the chemical compounds in the fava bean; and (3) synergistic activity between the chemical compounds in the fava bean; and (3) synergistic activity between both the deficiency and the bean. The details of these proposals are too numerous to be dealt with here. Other blood factors or genetic traits which may interact with the deficiency have been suggested to include non-corpuscular factors (e.g., Panizon and Vullo 1961), the thalassemia allele (Carcassi 1974; Siniscalco et a1. 1961; Bottini 1973), an autosomal gene (Stamatoyannopoulos et a1. 1966) or "favic sera" (Nathan et al., 1974) which favor hemolytic episodes, and the functioning of other red blood cell enzymes (Bottini 1973; Beutler 1970; Palmurino et a1. 1978). The deficiency and the fava beans are also suggested to interact twith the general status of individual health and immunity. Favism does not confer immunity against future episodes. It may occur in individuals who had consumed fava beans on earlier occasions without hemolytic crisis, or it may follow the first time the beans are consumed (Kattamis et al. 1969b; Belsey 1973). Sartori (1971) has repeatedly suggested that immunity to the beans may be accumulated through exposure in small, non-dangerous doses. More recent information indicates that cases of favism following the first consumption of the beans do not actually occur and that some sort of cumulative effect of the beans must be involved. This is in contradiction to Sartori's hypothesis. Those with a history of favism during infancy and subsequently exposed to the beans may not develop the disease a second time (Motulsky and 23 Stamatoyannopoulos 1966); however, one episode of favism does not provide immunity against a second or even a third. Of 120 patients with favism in Greece ten had already experienced at least one previous episode; four had it two previous times and one had reported several attacks (Kattamis et al. 1969b). It has also been suggested that favism in enzyme deficient individuals is often precipitated by infection (Beutler 1970), particularly of viral origin, which may in itself produce acute hemolysis in these individuals without the intervention of fava beans (Kattamis and Tjortjatou 1970). This has not been followed up in the collection of case histories in the literature, but provides a provocative epidemiological suggestion. These studies which focus on the etiological factors in favism are concerned with describing and analyzing differences in either the enzyme deficiency or the fava bean, or both, which can then be associated with the disease. The questions of why there are differences in the toxicity of the bean, or why there are variants in the deficiency, or why the deficiency is distributed the way that it is, are not central to these studies. These questions are taken up in studies which are structured by ecological paradigms. Epidemiological Studies of Favism Medical ecology, like all ecological paradigms, accepts that adaptation is a basic concept in explaining the distribution of disease. Adaptive processes may act directly on disease, or in- directly by selecting for or against certain disease "causes" or risk factors. With infectious or parasitic diseases, the adaptation 24 of invading organisms is considered in competition with human adapta- tion. In diseases which are related to diet, adaptive processes are considered with respect to the use of various animal and vegetable materials in a population. Medical ecology therefore invites the interest of many sub-disciplines of both the biomedical and social sciences. The concept of an open-systems model, expanding the links of disease causation, becomes a provocative subject for the various research interests of these human sciences. Using an ecological model, epidemiological studies may examine how causes and risk factors of disease are distributed in populations and how these are influenced by the physical environment, society, psychological characteristics, and so forth. This type of model has been most often used in studies of favism and is summarized in Table 1.1. Epidemiological studies also examine certain of these environmental, societal, psychological, cultural factors in direct association with the distribution of a disease. That is, these factors will be considered independently, not as they contribute to the distribution of risk factors, but as they contribute to the disease itself. Previous epidemiological studies of favism examine primarily the environmental factors which contribute to the distribu- tion of the enzyme deficiency. Social and/or behavioral factors which may contribute to the risk factors or to the disease itself, but have not systematically described or analyzed them. Epidemiology of the 6d” Trait Since the enzyme deficiency was first associated with favism, a large body of research has been conducted to locate the predominant 25 cmcoFaxm yo: pan .umwxm meow>mnma m>wuumu -oca was“ empmmmmzm .mczumcmuwp mcwumwxm cm umcopaxm yo: “cowgg53mcou coma m>wm mocmapwcw “saws xmm ucm mam pmgu umummmmzm mcwzogm co mvauwupm new musuwpmp czocxca czocxca czocxca czocxcs mo mucm:_$cH mammm m>mm amwcwocauc yo: mam mgOpumw aucmwuwmmu mgu mo Aocmwu mvzpwu_< cowuznwcpm_o mucmapccc -wcme 8;“ new; mpa__a mccmpumq mmmwccms “any weapon» ovpmcma we mcauo: umummmmzm “an .czocxc: mo cowpumcmacw cmxcw_ux :zocxca cowuompmm Facsumz uwmchuuo Pmczupzouowuom xocmvcm» Pm?_wsmd xmm mm< acmscocw>cm mcouumm xmwm mornmwcm> mcwucwzpmcH mm0huw040H2uoHam F.P m4mmm pwnwgoca co woos -oca mmmwpwn cwmpcmu PmowmopomuH .mmmzpmam can mmpoc Law—mEmw .xmm .mmm mo m_mma mg» co umuwo>m Lo umuos -ocq was mcowpmcmamca mo mmaxu acocmmmwo .co_uaE:mcou com umcmamca mcwmn 0cm xmcu cows: mcmmn m>mw saw: pumacou cmummcm c? cmeoz mumpa cu vmuomaxm m? xmm >5 Loam? we comw>wo Pecapozcum-owuom .mPQMBm a ma mammn m>mm mposoca gown; mmpaumgom mcwzocm m>mc meow“ -muo_ Fags; pcmcmwmwo FeynmEcocw>cm onkmzzmzou zwpom cowum -cmamca cw wcamoaxm compm>wHF=o use mcwzocm cw mczmoaxm mcopomu mczmoaxm 448 .cosue as» e» xpwsew wee secw gmwwwu was mcumn use useee mwewpee “memes e>ew we ouceewe>e ecu meeneu pew—wand .uceugeesw on e» neuoee -xe ecu meme; we was ten cewuoeeece u>—e>=w ;e_g: emcee »_ca_=uwe -cee .mepec xom ecu ea< .ccmuuee acmsepuumm ecu ecameexm new: uoecoucw cewmmc mwucecmwwwe o>wuoeeege owseceue uegu voummooem .ePUAu peceu_=e_cme saw: muuecoucw mpuxo acwamew weceuwsu-eweem .emuemwumm>cw uez emucmwumo>cw uez .eouemwamm>cw uez .acameexe saw: mueecmucw me—mww we :ewueoe_ ecu cceauoa usage—uuem .mceen e>ew we mcwcoewc uuewwe ea execs meeuwup< acoscocw>cm .mcewuueec owux—eEm; mzu we mwmen uwuecea osu saw: uuecmuew was meson e>ew we on: pew—wsow :— mmwuwce—wewm .ecauecouw— cw emuemwumu>cw ac: can .xmm we cowwwv ea eoummmmam ecumeaxm use :ewuesamceu .emu we cewwwe was ocemeexe cmgae use :ewue23mceu .eeuemwume>cw ma ea ewe: :ewuasemceo ecu cewuoaeeca cw moocucewwwu .ecowmec uegu teamemoam .xuw—ecemewm cw m—oc e xe—e cewuossmceu ecu newaoaeeca cw moocecewwwe .ucemoem «ecu emummuaem mczmeqxu came .~._ esmumw awuaoue uppowuceueu sous—ac on eu exec; uez awash lea xeceecew pawpwsew xem mm< .acewomm wecemeom 49 presence of out-migration. Fasting practices associated with religious events, expected behavior by age, sex roles, and ideas about favism and the fava bean were included under the variable of ideology. This last topic, ideology, was particularly important in developing the ethnomedical model for favism. From restrospective case histories, native etiological explanations were extracted and analyzed without respect to the biomedical model. Near the end of the field work period, families known to be at high risk of developing favism (i.e., they had the Gd' trait in one or more child) were visited and presented with the biomedical explanation of favism. Their reactions and subsequent behavior and/or plans to change behavior were collected. This was then analyzed from two perspectives: First from the goals of preventive medicine and second from the perspective of the goals of the rest of the rural Greek culture. Ultimately this analysis was used to further illuminate the epidemiology of favism, rather than in the pursuit of the essence of Greek culture. In this same sense, the study leans toward the biomedical rather than the anthropological model. Selection of thg_Research Sites Since the G6PD deficiency is so strongly implicated in episodes of favism, it was essential that the research take place in an area of the world already noted for the presence of the deficiency as well as the disease.1 This narrowed possible research sites to the cirum- Mediterranean.2 Aside from the Kurdish Jews which were found to have as high as 58% of the males tested identified with the Gd- trait 50 (Szeinberg and Sheba 1958; Szeinberg et a1. 1961), Sicily (Russo 1967) and Sardinia (Carcassi and Pitzus 1957), and Greece (Choremis et al. 1963a; Kirmlides et a1. 1965) were also reported with very high frequencies of the trait (i.e., 25-35% of those tested showed the trait). Two major pices of research (Kattamis et a1. 1969; Allison et a1. 1963) documented that the Greek island of Rhodes showed "... remarkably high frequencies of the enzyme deficiency" (Allison et a1. 1963:239). The research which had been conducted on the island provided a data base of seven village locations, and the City of Rhodes, which had been screened for the deficiency in the early 19605. In the present research, two of these villages were rescreened for the deficiency and five other locations added. Cases of favism which had been reported to the only hospital on the island were collected for the years 1966 to 1978.3 The results of the screening for the Gd' trait, and the distribution of favism cases, aided in the selection of the two villages which were used for the collection of ethnographic data. The two villages which were ultimately selected presented contrasts in the frequency of favism and the Gd- trait frequency. They occupied two different types of econiches, one coastal and the other mountainous, which was expected to have certain effects on the social organization of each. The coastal-mountain dichotomy was used to help select the villages because altitude is involved in both the distribution of the enzyme deficiency and in the production of fava beans. Both of the villages had similar demographic features; they had approximately the same number of children screened for the deficiency, 51 and the approximately the same percentage of the population was represented in the screening. Identification of Favism Episodes Episodes of favism which occurred during the years 1966 to 1976, and which were clinically diagnosed, were identified and collected from the hospital records of the Queen Olga Hospital in the City of Rhodes. These figures were used in the statistical survey of the frequency of favism, and were useful in delimiting areas to be screened for the enzyme deficiency. In latter stages of the research, the hospital cases of favism were used in follow- up studies in the village locations. In the course of the field work, other episodes were reported from the local inhabitants. These had occurred before 1966 and did not appear in the survey of the number of favism cases. Many of these episodes could not be verified in hospital records since they were either not hospitalized or they occurred before favism was the type of disease to be reported to medical professionals. While these cases reported by word-of- mouth were not used in the survey of favism on the island, they were used in the collection of ethnographic information. Since the diagnosis of a disease/illness can represent a cultural as well as a medical phenomena, several non-clinical cases of favism were recorded. These cases, and the individuals reporting them, were subjected to the same research protocol, questionnaires and inter- views, as were those who had been identified from hospital records. This has two rationales: (1) This study was designed to uncover 52 sub-clinical cases of favism as well as medically diagnosed ones, and (2) reactions to fava beans in some individuals may not include the presentation of all the symptoms necessary to diagnose hemolytic favism. These latter cases may represent valid claims which are cul- turally relevant, even though they do not meet medical diagnostic criteria. Identification of the Gd- Trait The Gd' trait can be identified through the use of a variety of laboratory tests, but the constraints of the field situation, transportation difficulties, and time, indicated that methods used in other screening studies would be most appropriate. Since the defi- ciency is a sex-linked trait, it is most easily identified in males when rapid and simple screen procedures are called for. Most of these methods do not detect female heterozygotes in sufficient numbers to justify their use among female members of the population. It was desirable that as many members of the designated age group of males be screened, therefore, elementary school boys of the selected villages were chosen as the most easily accessible participants. These boys were from 7 to 12 years of age. This approach is compatible with other screenings for the enzyme deficiency which, to date, have taken place under similar circumstances and constraints.4 In all the samples, none of the boys were known to be enzyme deficient prior to being selected for screening. They were chosen by their age, without prior knowledge of having suffered from favism. The goal of 100% participation from each village for the designated age cohort was nearly met in all but one of the locales screened. 53 The high proportion of participation, and therefore the reliability of projections based on the samples, is shown in Table 2.4. The samples taken from the school boys represented from 4.5 to 14% of the male population in each locale. This is compatible with other studies where similar screening rationale was used. Actual numbers of subjects screened for the deficiency in Rhodes are lower than those from other screenings,5 but this is a function of the low population densities found in these locations rather than from the omission of a large number of children in each age cohort. The present study was designed to be an in-depth examina- tion of favism rather than a statistical survey of the Gd' trait. Figure 2.1 shows the type of representation which was achieved on a familial basis in the two villages selected for in-depth study. All families with at least one elementary school child are contrasted with those who provided at least one child for screening. In Massari, 33 of 51 families (65%) with elementary school children were represented by at least one child in the screening. In Kritinea, the representation was even better with all but nine of 38 families (76%) having at least one Chlld screened. Laboratory facilities and services for the analysis of blood samples for the enzyme deficiency were obtained through affiliation with the Institute of Child Health, Aghia Sophia Children's Hospital in Athens, Greece. The hospital hematological laboratory and the Institute have been involved in research efforts related not only 6 to the enzyme deficiency but to other blood problems which are 8 represented in the Greek population.7 The physicians at the hospital 54 TABLE 2.4 POPULATIONS REPRESENTED IN SCREENING FOR GD TRAIT Villa e ;:;;:d / Age gohort Efisggd/Males in gopulation Lardos 14/14 100.0 14/237 5.9 Lindos 32/35 91.4 32.354 9.0 Massari 37/38 97.5 37/266* 13.9 Malona 28/30 93.3 28/460 6.0 Pylona ll/ll 100.0 11/88 12.5 Kritinea 37/38 97.5 37/293* 12.6 Embona 29/58 50.0 29/636* 4.5 Sources for Population Figures: Asterisk (*) indicates author census. All other figures are estimated on the basis of population given in the National Statistics Yearbook, 1971. 55 mcwceecem cw newcomeceem mcewuceeece mcwzecm ewcwuwcx ecm wcemmez cw cmcewwnu weecom xgeucmswwm new: mewegmmeez w.~ .mww nee: use: .6 39.52 3-o~e§3 «.9 on v N e «v o mo. ~12 e. 2888 41441119N111\,\\14444111-414 w 176¢FAA ,vw/zm/wx/zwu _ u M _ t«\\\\t\\\,\ki .1 .\ 91.me K N _ m m volt M .a p 3.5» 9:6 “20 .53.. a 8 NM 6 m 3.5 W 48.8 Efizuzflm 28 m .543 wk 3.52 nugxfi D (array E435». 56 and at the Institute discussed with me the various aspects of drawing, handling and transporting the specimens to insure that they would meet the requirements of the laboratory personnel and standard pro- cedures. The samples were drawn from the finger and stored in hematocrit tubes (Heparinized). These were kept under refrigeration until they were transported by air to the hospital in ice-filled, insulated containers. Air times between Rhodes and Athens is approxi- mately one hour. To guard against any possible problems with time or equipment, the thermoses were placed under refrigeration when they arrived at the Athens airport until they were received by a representative from the hematology laboratory. Testing for the defi- ciency began the day after the specimens had been received in the laboratory. The local agrarian physician serving in regions of Rhodes through the Ministry of Social Services, assisted in drawing blood samples.9 Samples were taken during four-day periods, stored under refrigeration, and on the fifth day they were packed in an ice- containing thermos and transported to Athens. A total of 189 specimens were collected from elementary school boys (ages 7-12) in seven villages of Rhodes. It was intended that all the samples be subject to the same analysis for the deficiency and that all results be read by the same laboratory technician. Neither of these was possible. Five villages were screened during 1975-76 and all five were subjected to the discolorization brilliant cresyl blue (858) method of analysis, using procedures outlined by Motulsky and Campbell-Kraut (1962).10 57 Two villages were screened at a later time, in 1977, and a different laboratory technician conducted the analysis and the reading of the results.H Further, the reagent necessary for the BCB method of analysis was not longer available in 1977. The Beutler fluorescence test was used. Both the BCB and the Beutler test have the same reliability, according to the standards of the laboratory personnel, and both can be used for capillary blood from hematocrit tubes. Identification of Fava Beans in Local Environments The distribution of favism episodes in the different locations on the island of Rhodes, and the results of the analysis of the blood samples, were important in selecting specific village sites for in- depth investigation. Equally important, was the second risk factor in favism, the fava bean. ‘While villages were screened for the enzyme deficiency, it was possible to survey the local setting for the presence of the fava beans in the environment. In some villages, they were not observed except in local groceries in the dry form. It was impor- tant that the villages where the field research would take place had the beans grown in the agricultural cycle. This did not turn out to be the most crucial variable in the selection of village locali- ties for the field work because the beans were grown throughout the island, with the exception of only a few areas. There were no areas which were visited which appeared to have large tracts of land devoted to the cultivation, however, some villages had plots of fava beans within the village, while others had them mainly outside the village, mixed with other plots of land. This was a difference which 58 was noted, and which contributed to the selection of the two villages in the study. One village showed the garden-lot growing pattern of the beans, and the other did not. The actual exposure to the beans, and their consumption in these localities, could not be surveyed. It was assumed that the presence and location of plots of land devoted to fava bean cultivation would be reflected in general consumption patterns. Other Considerations in Site Selection The villages screened for the enzyme deficiency were selected because other villages in their regions had been screened in earlier surveys, they were accessible to the major transportation lines which would facilitate the handling of the blood samples, and they represented a variety of econiches, some being mountainous and others coastal. The selection of the two villages which participated in the ethno- graphic field work was based on the survey of general environmental features and settlement patterns. These variables were considered along with the results of the screening, the distribution of favism episodes, and the appearance of fava beans in the natural environment. Agricultural production was particularly noted in the environmental survey, and as it turned out, the villages which were selected for the ethnographic research showed distinctly different patterns of agriculture. This was a difference which was selected for in making decisions about which villages would be involved in the ethnographic study. 59 Field Techniques Social institutions which most directly affect genetic inheritance and food habits were most closely examined during the field work. These included marriage patterns, food sharing, feasting and fasting observations, and food preparations related to fava bean consumption. Informal interviews, open-ended questionnaires, and participant observation were the basic techniques used in the research protocol. While techniques which involved my active partici- pation in eliciting data provided a standard base of information, this base was further explored through observations where I was not directing the exchange of information. Ethnographic Field Methods: Participant Observation and Interviewing The classical anthropological works begin with solid ethno- graphic description. This, in turn, relies on the use of participant observation and ethnographic interviewing (as described by Spradley 1979). These are utilized on a daily basis by those able to live among the people in the area where they are carrying out research. Cultivated as methodical tools of field investigation, participant observation and ethnographic interviewing allow the anthropologist to supplement and clarify the information which was gained through laboratory tests, questionnaires, demographic figures, and so forth. While there are many formal tools of recording and gauging human behavior, most of which must bear up under statistical analysis, there are many aspects of human behavior which do not easily allow 60 such analysis. Information gained through methodical observation may become extremely valuable when statistical measures fail to describe, explain, analyze or predict human behavior. The anthro- pological method which emphasizes the development of skills of obser- vation and which strives to describe human behavior before analysis is pursued contributes to the methods used in other social and human sciences. Instruments such as structured and standardized question- naires, interview protocals, and health histories are important because they give an indication of what people think they are doing, and what they believe they have experienced. Actually observing behavior, participating in daily life, shows how the people carry out these ideas and beliefs. Participant observation cannot verify, for example, the results of the clinical analysis for the enzyme deficiency. 0n the other hand, rumors that an individual has suffered from favism without clinical evidence that anyone in the family has the deficiency can challenge both the medical scientist and the anthropologist. While the former would order more tests, the latter might search for social and cultural explanations. It might be asked, what does the rumor mean in terms of the individual's relationships with others in the society. A decision to treat the rumor in biomedical terms alone may result in ignoring other important dimensions of the society. Ethnographic interviewing as the second major tool of the anthropological field experience is grounded in two assumptions: (1) that people hold an ideal model of what their behavior should be like, vis-a-vis their culture, and (2) that a member of a culture 61 cannot give direct answers as to why_they do the things they do, or why their culture works the way it does. Ideal, rather than real behavior, is often stated as responses to standardized questionnaires and even open-ended questionnaires tend to provide empty categories for the participant to fill-up, whether or not they reflect cultural reality. Through participant observation, coupled if one wishes with questionnaires, some of the ideal vs. real behavior can be clarified. Through ethnographic interviewing, the problem of forcing the informant to respond or provide meaning for terms, ideals, models, etc., which run contrary to his/her notion of reality, is avoided. Ideally, ethnographic interviewing elicits categories from the infor- mant rather than providing them on behalf of the interviewer. One can see that this approach is most suitable for collecting the informant's view of favism, outside the strictures of the biomedical model. In this approach, even the disease category should be avoided in initial interviewing sessions. It is notable that the word informant is used here rather than other similar terms used in other branches of the social sciences; e.g., "subject," "participant," "respondent." The difference is more than semantic even though the word, informant, conveys an active component while the terms, subject and respondent, do not. The informant gjxg§_the information, he does not simply respond to questions or participate in tests. Unfortunately, the structure of the ethnographic interview and the fact that not every participant in a study is a good informant, does not lend itself to all aspects of an epidemiological study. Therefore, ethnographic 62 interviewing was not used intensively with all in the study; it was used selectively with certain participants who also happened to be good informants. Selection of Participant Families Families which had reported episodes of favism in their members, or which showed children with the enzyme deficiency from the screening, were encouraged to participate in the research by allowing themselves to be observed and interviewed in their homes. Other families which did not show the Gd' trait and did not report episodes of favism were asked to participate. Thirty-nine families formed the core of the research. Twenty-four families were from one village and fourteen from the second. The twenty-four families from the first village were divided into two groups, ten having at least one child affected by the Gd' trait and fourteen not showing the trait. Ideally, the samples might have been balanced, but not enough children with the Gd' trait and/or favism could be identified. In the second village, all fourteen were identified by the trait and/or favism episodes. From this village, several families were identified which did not have the Gd' trait or any known cases of favism. Time did not permit their inclusion in the study. The term, family unit, refers to units of residence and biological kinship, which contain only the nuclear family. This conforms with the ethnographic reality for Rhodes. Those familiar with the ethnography of the Aegean and Dodecanese Islands (Rhodes being a member of the latter group of islands) know that there is 63 an emphasis on the ability to establish a family which is separate from the family of birth (Dubish 1976; Hoffman 1976). Unlike other areas of mainland Greece where the extended family, in some form or another prevails, the islands show the nuclear family residential pattern. A house as the major item in a dowry is almost always provided for daughters, and tends to reinforce the idea of separate house- holds between generations. It is almost unheard of for newlyweds to occupy the home of one or the other set of parents. If parents are unable to provide a daughter with a home of her own, they will move out of their own home, giving it to the newlyweds, and move into other quarters, rather than share a home with the new couple. Even though there is an emphasis on the nuclear family, child care is not restricted to its boundaries. This is an important consideration when calculating the possibilities for children to be exposed to fava beans. Even though certain nuclear units may not grow or consume the beans, a child may have plenty of other oppor- tunities to come into contact with the beans while in the care of other family members. It is reasonable to assume that in villages which grow fava beans, all members of the community are at risk of fava bean exposure, whether or not they are cultivated and consumed within the nuclear family unit. Ethnographic Questionnaires Ethnographic questionnaires is used here to refer to standard and open-ended questionnaires which elicited ethnographic data, but did not follow the protocol of ethnographic interviewing techniques 64 as described above. Certain data of a quantifiable nature was desired, and this required some form of standardized system of ques- tioning. Aside from the identification of the enzyme deficiency and/or favism cases in a family, familial information was collected through three other devices: (1) Recording of ethnographic food habits and culinary behaviors; (2) Collection of genealogical infor- mation; and (3) Description of family health and fertility patterns. These are discussed below. Food habits A short questionnaire regarding food habits and observation of food preparation activities and consumption, elicited information about the general and individual patterns of food behaviors. This necessitated gaining access to cooking areas in the households, participating in food preparation activities, sharing recipes and eating with families. Having been persuaded on many occasions prior to the field work to join families during meal times and to discuss foods and recipes, I considered that this information would be rela- tively impersonal (e.g., compared to asking about fertility patterns). This promoted the scheduling of this part of the field work early, during the first months of my residence in the village. Additional information specifically related to fava beans was collected through interviewing. All participating families were questioned as to whether or not they grew fava beans, where they grew them, if they ate fava beans, in what form, and which preparations of fava beans predominated in the household. These data were checked by observations. These families were also questioned about their understandings about the 65 beans, for example, if they understood that the beans might have deleterious effects on certain people, which people were affected, what happens to people when they are affected by the beans, and how these effects might be avoided. Other food-related questions involved asking about attitudes toward nutrition, ideas about foods considered to be good for the health or the blood, foods which some members of the family refused to eat, food allergies in the family, and pre- ferred diet of different family members. Genealogical information Genealogies of four generations in depth (when possible to recall) were collected for all individuals identified with at least one Gd" trait child and from those having reported cases of favism. At least half of each of the two villages was represented in these genealogies. These genealogies were used to supplement other demographic data on full-time village residents, out-migration and marriage patterns. Genealogical materials such as these have the advantage of serving both medical as well as anthropological interests. While the geneticist may be primarily interested in examining the distribu- tion of a trait through the generations, or to examine the pheno- typic expression of the trait in different members of the pedigree, the anthropologists are more interested to see the trait in familial settings which are influenced by society and culture. Through gaining genealogical information, the anthropologist collects data which can emphasize the cultural environment surrounding those individuals 66 who have a genetic trait, or a disease associated with a genetic trait. Genealogies are also useful for collecting chronological information such as when deaths and births occurred, intermarriages between villages and families, migration out of the village. Health and fertility histories From each of the thirty-nine families in the study, informa- tion about the family's general health, the children's health history, and the mother's pregnancy history was collected. In the health history, participants were questioned about childhood illnesses, jaundice, hepatitis, allergies, the last visit to the physician and the use of vitamins and pharmaceuticals. This series of questions included those which related specifically to favism and other blood conditions; e.g., knowledge of one's blood group, recognition of jaundice, understandings about anemia, and the association of fava beans with jaundice. Fertility and pregnancy histories included questions regarding the number of children conceived and the results of each pregnancy, birth order of the children and their spacing. Information about the attitudes of the women toward health care during pregnancy, precautions taken to promote safe delivery of the infants, methods of birth control, and diet during pregnancy was also elicited. This information was often difficult to bring out since many did not remember or recognize spontaneous abortions which happened early in a pregnancy. Others did not want to admit that they had consumed fava beans while pregnant or lactating, stating that they did not 67 eat the beans during these periods, and then later changing their answers. While there is no particular prohibition about eating fava beans at this time, some remembered having been cautioned about them. Others showed they had strong feelings about abor- tions, making it difficult for women to admit having sought them. Still others had difficulty explaining why they had not sought medical advice during pregnancies. Collection of Case Histories of Favism Episodes Eighteen case histories of favism episodes were collected. With the exception of two which occurred before medical diagnosis and treatment of the disease was used, all were verified through standard medical diagnosis and hospital records. Aside from providing standard information such as, how old the person was at the time of the episode, and the form of the bean eaten, informants were reques- ted to recount the episode in their own words (without being provided with biomedical categories). Following this, each was asked if anyone else in the family had ever experienced any "problem" from eating the beans, and, how the individual came to recognize the episode as associated with the fava bean. They were asked if they had recog- nized the episode because it had occurred in another family member, or if the attending medical professional had explained the relation- ship of the bean to the hemolytic crisis. Several possible cases of favism (i.e., showing sub-clinical symptoms, those which never reached hospitalization, and/or where Gd' trait was not tested for) were reported during the field work, 68 sometimes in the course of taking family genealogies or in recording a clinical episode. These were not used in the case histories since the individual involved in the episode was not available; some had moved away from the island, while others had died. These cases were indicated as "probable" in family genealogies, and used in analyzing familial tendencies to show favism. The goals of the present research project directed a protocol which could be of use to medical as well as social scientists. The actual feasibility of this goal was not thoroughly considered before going into the field. The problems of one person, trained as an ethnographer, to attend to all the medical and technical aspects of the identification of risk and favism episodes were not overwhelming, but time consuming. As a solo attempt, the project represents a divergence from other research which examines favism, and was successful in gaining considerable information which had not been treated in earlier studies about the disease. Footnotes Chapter Two Motulsky (1960; 1962; 1965) and Livingstone (1967) have compiled figures which show that the Gd- trait is nearly absent in Northern and Western European populations, in northern Asia, and in North America. Individuals affected with the deficiency and/or favism in these regions are usually from an ancestry which was initially located in these areas of the world where the deficiency is present. Some have reported unusual varients in non-Mediterranean popula- tions; (e.g. Vuopio et a1. 1975) their varients may go unnoticed since they are not often involved in severe hemolytic crises. Populations located in various regions of Africa, Indian, south- east and south Asia, and the circum—Mediterranean have a tendency to be affected with the deficiency. As indicated in the review of the literature, the deficiency is not uniformly distributed in these areas. In Spain, a screening of 2520 males (Flatz and Duran 1967) showed the G6PD deficiency to be limited to the coastal areas of Valencia and the Balearic Islands. A later screening (Pellicer and Casado 1970) found the trait to be fairly evenly distributed although low in frequency, throughout five provinces in Spain. The deficiency is also found on the Italian mainland (Livingstone 1967) but its most significant populations affected are found in Sardinia, with frequencies of up to 35% of those tested (Siniscalco et a1. 1961) with overall average of 12.5% (Carcassi 1958 . Iran (Belsey 1973; Donoso et al. 1969; Daneshbod 1975) , Bulgaria, Cyprus (Joannides 1952), have been noted to have high rates of the deficiency and favism, along with being noted in Yugoslavia (Fraser et a1. 1966). African populations have also been noted to show the deficiency, but these are not known to be the same varient of the enzyme deficiency trait as the Mediterranean, e.g., in Nigeria (Gilles and Taylor 1961) and Sudan (Hassan 1971). Statistics for favism were originally collected for the years 1966-76; these figures were updated during subsequent visits to Rhodes during 1977 and 1979, the latter visit not related to further field work. 69 7O Particularly when working with time and geographic limitations, previous screenings for the enzyme deficiency involved school aged boys from elementary and secondary schools (e.g., Choremis et al. 1963a; Stamatoyannopoulos and Fessas 1964; Siniscalco et a1. 1961). When Rhodes is contrasted with other regions of Greece and the Mediterranean where screening for the deficiency has taken place, it is clear that we are dealing with a much smaller population in Rhodes. Choremis et a1. (1962 and 1963a and b) screened the population of Arta, Greece, by sampling 532 males in a population of 82,630. This represented less than 0.6% of the total population of the region. It should also be noted that the entire population of Rhodes is less than 70,000 inhabi- tants. Pellicer and Casado (1970) screened five areas of Spain, resul- ting in the collection of 320 blood samples from 48 villages, and 6,610 samples from the city of Madrid. Five provinces in represented in the screening of Spain conducted by Flatz and Duran (1967). Samples from these provinces range from 93 to 504. All of these areas are larger than the regions screened in Rhodes, on the basis of overall population, and consequently the size of the samples are larger. The G6PD deficiency and favism have been investigated at Aghia Sophia Children's Hospital by numerous pediatricians, including, but not limited to, the following: In 1961 by Zannos-Mariolea and Kattamis; In 1963 by Valaes et al. In 1964 by Stamatoyannopoulos and Fessas; and Stamatoyan- nopoulos et al. In 1965 by Kirkman et al.; Kirmlides S. et al. In 1966 by Stamatoyannopoulos et al.; In 1967 by Kattamis; and Pantelakis and Doxiades In 1969 by Kattamis et al.; In 1970 by Kattamis and Tjortjatou; In 1971 by Kattamis et al.; and Pantelakis and Doxiadis. Neonatal jaundice has been investigated at the Children's Hospital by Doxiadis et a1. (1961, 1962, 1964) and Valaes et a1. (1964). Sickle-cell anemia has been researched by Choremis et a1. 1963, and Stamatoyannopoulos and Fessas 1964. Thalassemia studied by Kattamis and Lehmann (1970); Kattamis et a1. (1972), and Matsoniotis and Kattamis (1969). 71 The two physicians which were instrumental in helping me select the research site, design the strategy for testing for the deficiency, and assuring me that the blood samples would be correctly handled in the laboratory were Dr. Stephanos Pantelakis, Director of the Institute of Child Health, and Dr. Aris Karaklis, Director of the Hematological Laboratory at Aghia Sophia Children's Hospital. Agrarian physicians stationed in the rural areas of Greece immediately after finishing medical school participated in the screening. Dr. T. Latifis and Dr. Stelios Valsamakis helped in taking blood samples from school children in five villages in 1975 and 1976. Dr. Georgios Sisamatos helping in drawing blood samples from children in two villages in 1977. . This method utilizes a dye indicator, brilliant cresyl blue, which is mixed with the blood sample. If the blood sample is normal (non-Gd‘ trait) it is reduced to a colorless state within an hour. Readings of the reaction are made every five to ten minutes, starting at forty minutes after the indicator has been introduced into the sample. Samples that are normal usually discolor within the first 65 minutes, while those which take over 100 to 150 minutes are considered to be deficient and those which take over 100 to 150 minutes are considered to be deficient and those over 180 minutes are believed to be the Mediterranean variant. Only the USA National Aniline prepara- tion of BCB can be used in this test. This reagent was not available after the first five villages had been screened. . For these two villages a fluorescence test described by Beutler was used to indicate the presence of the deficiency. Prepared blood is spotted onto a paper every five minutes for 25 minutes (five drops, that is). The spots are allowed to dry, then read by the use of a fluorescent lamp. Those with the deficiency appear different under these conditions. This test can be used effectively with blood samples which have been stored under refrigeration, for up to 2; weeks after the blood was collected. CHAPTER THREE RHODES: THE ISLAND AND ITS VILLAGES According to Greek myth and the poetry of Pindar (writing in 464 B.C.), it is told that... When Zeus was dividing the islands of the Mediter- ranean and Aegean Seas among the gods and goddesses of Mt. Olympus, he forgot to allot one to the sun god, Helios. Suddenly, a new island arose off the coast of Anatolia in the Aegean. Zeus gave this island to Helios who named it for his wife, Rhoda. The children of Rhoda and Helios, the Heliades, populated the island, and the genera- tions that followed became referred to as the "descendants of the Heliades." (Paraphrased from Rhodes, 1977) Although Rhodes has been covered by water at different times in its geological history, it is unlikely that it arose suddenly from the sea. The appearance of Rhodes just off the western coast of Turkey had nothing to do with either catastrophic or volcanic events, although it averages about two major earth quakes every century with minor tremors each year. Periodic oscillations in the sea level have given the island a dissected rather than truly mountainous character. Rhodes is not a particularly large island and one might assume that its population and history must be homogeneous. This is not the case. While it has experienced certain historical events in common throughout the island, these events have not affected all of the regions in the same way. These historical events are listed in Table 3.1, and since they can be found in almost any tourist guide 72 2500 B.C. 1550 1450 1200-1000 700 - 500 480 305 316 227 332 42 A.D. 70 155 263 344 515 620 653 807 1082 1097 1248 1309 1444 1453 1480 1522 1912 1947 73 TABLE 3.1 MAJOR HISTORICAL EVENTS IN RHODES Charian and Phonecian trade contacts Minoean settlement of west coast of Rhodes Occupation of the west coast (Ialyssos) by Mycenaeans Arrival of the Dorians: establishment of three city- states (Ialyssos, Lindos and Kamieros) Extension of Rhodian naval influence to the Balearic Islands, Sicily and Asia Minor Joins the Athenian League The Great Siege of Rhodes (after which Rhodes becomes independent for limited time) Part of population of Rhodes City lost in flood Rhodes City partially destroyed by major earthquake with part of population lost. Rhodes sends troups to take part in the siege of Tyros (Tyre) on behalf of Alexander the Great Resieged by Rome Incorporated in the Roman Empire Major earthquake drives out most foreigners from Rhodes Raided by Goths Major earthquake Major earthquake partially destroys the City of Rhodes Sieged and occupied by Persians Arab Saracens sack Rhodes City Seljuk Turks siege the City Trade contacts established with Venice Rhodian harbors used during the Crusades Temporary occupation by the Genoans Rhodes ruled by the Knights of St. John Siege by the Sultan of Egypt (Marmeluks) First siege by the Turks Second siege by the Turks (Mohamed II) Third Siege by the Turks (Suleiman the Magnificent) Italians take Rhodes from Turkey Rhodes is annexed to mainland Greece Sources: Compiled from Dicks 1974; Nixon 1968; Taylour 1964; Rhodes (Clio Edition) 1977. 74 to the island, it is not necessary to describe each one. Certain events in history which influenced population size and composition are extremely important to questions which will be raised in Chapter Four regarding the dynamics of the Gd' trait distribution. These events and population movements are described in this present chapter, along with others which have a bearing on regional divisions in contemporary Rhodes. For example, the two villages which formed the comparative base of the study represent two different historical and geographical aspects of the island. Kritinea on the western part of the island, located in the mountains, claims to trace the ancestry of its inhabitants to the earliest settlements. Massari, on the coastal, alluvial eastern part of the island has no similar claims to an uncontinued line of habitation. These divisions will be referred to again in subsequent chapters, related to the distribution of the Gd- trait and favism episodes. Finally, certain historical (or mythological) events are included which give color to the present- day socio-cultural life in Rhodes. Population Movements in Historical Rhodes At some point in time, mythical or real, the descendents of the Heliades became the modern Rhodians who now populate the island. Those who inhabit the western part of the island trace their origins to the nearby island of Crete, the center of the Minoean culture in ancient history. Their foundation myth states that at one time the Cretan prince Althaemenes (grandson of Minos, the legendary king of Crete) was warned by a seer that he would someday kill his own 75 father, Katreas. To avoid this, he fled from Crete and settled in the mountainous western part of Rhodes. By standing on the highest mountain, he could see his home island.1 The archaeological record confirms that the west coast of Rhodes was in fact inhabited first by the Minoeans from Crete. With the exception of earlier trading outposts, established by the Carians, Phonecians and other Asia Minor groups, the Minoeans were the first to establish actual settlements on Rhodes with a neolithic site dating to about 1550 B.C. This same region was eventually occupied by another group of people, this time, from the mainland, the Mycenaeans.2 They eventually replaced Minoean influence in Rhodes by 14503 (Dicks 1974; Rhodes-Clio Edition 1977). 4 arrived The Dorians, another group from mainland Greece, on the island and established city-states as they had done in the other areas of the Mediterranean which they conquered.5 Two were founded on the northwest and west side of the island: Ialyssos, nearly on the same site as the original Minoean settlement, and Kaimeros, near the present-day mountain villages of Embona and Kritinea which were screened in the present research. A third city-state of Lindos was established on the east side of the island. The present-day village of Lindos occupies this ancient site, and was screened in this research, as well as the surrounding coastal areas which were probably encompassed by the power of this city state. Lindos, from its geographic position and natural harbor was able to extend maritime power over areas outside of Rhodes and contrasts with the other side of the island which remained agricultural. 76 Early Invasions of Rhodes In spite of repeated invasions by the Romans, the Egyptians, the Turks, the Persians and even the Goths, the Rhodians always tried to maintain their island as a politically independent unit. From the 12th to the 5th century B.C., Rhodes exercised independence and fostered overseas communities which reached Sardinia, Sicily and the Balearic Islands. In 480 B.C., Rhodes became officially a subject of Athens by joining the Athenian League, which further solidified its ties with mainland Greece. Turkey beseiged the island three times after the 5th century B.C., and took control of the island by 42 B.C. for the following 110 years. The Turkish control of the island ended when Rhodes was incorporated into the Roman Empire. Throughout this period, the island had maintained its Greek (Doric) culture, and the population which numbered about 500,000 at the time was still regarded as Dorian and not Turkish. Following the subdivision of the Roman Empire (395 A.D.) Rhodes was again subject to repeated attacks and sackings by popula- tions from the Anatolian mainland. The Persians attacked in 620 A.D., the Arab Saracens in 653 A.D., followed by the Seljuk Turks, who besieged the island and disrupted trade relations between Rhodes and other ports, for a major historical period. The Knights of St. John, a military order created during the crusades, besieged Rhodes, taking it by force, and slaughtering the majority of the Turkish population. They formally gained control of Rhodes in 1309, and under their control, the island reestablished its important trade links. In spite of the relative peace and economic prosperity, the 77 population of the island was half of what it had been when it belonged to the Roman Empire. The drop from 500,000 to 250,000 may have resulted from the mass slaughter which preceded the take-over by the Knights. Turkish Occupation of Rhodes In 1522, Suleiman the Magnificent laid siege to Rhodes, took the island from the Knights, and 390 years of Turkish domination began. Initially the Turkish policy towards Rhodes was one of autonomy. The only intrusion of the Turks on the island seems to have been in the City of Rhodes where taxes were collected from the countryside once a year. After 1826, the autonomous policy towards Rhodes gave way to one directed by harsh assimilation measures. This was apparently precipitated by a series of rebellions against the Turks through the Aegean. Following this change in policy, wholesale emigration from the islands in the Aegean occurred, Rhodes taking part along with the other islands. From a total population of 250,000 during the era of the Knights, the population of Rhodes fell to 35,000 (Myres 1953) in the mid-18005. The Turkish population was located primarily in the urban area (as was their usual practice in conquered lands) and in villages especially created for them. These are shown in Figure 3.1. Italian Occupation 1912—1947 Immediately following the Turkish occupation of Rhodes, the Italians took the island. During the years of the Italian occupa- tion, the Turks gradually moved out of the countryside into the City of Rhodes, and away from the villages which had been created by them. Fig. 3.1 78 ”23;. .T . m ..... 7+ 1- O o - . . T :flt '1' 0T 0 To ’ T m . Dorean City States Major Turkish Areas Minor Turkish Areas Villages with over 300 Italians Villages with about 100 Italians Villages of <75 (10-50) Italians mmnoean and Mycenaen Settlements l‘ oo-i-ia Location of Historical Populations in Rhodes 79 Population figures during this period reflect a drop in the Turkish population and a rise in the overall population. Meanwhile, the Italians moved into the countryside, imposing new rules and regula- tions on the rural inhabitants. They required the registration of surnames (until this time, village registers were not kept by local inhabitants), and made Italian the official language, and Roman Catholicism the official religion of the island. During this period, intermarriages between Italians and Greeks occurred, but the contempo- rary villagers contend that none of these unions or the results of them can be found in the countryside. Couples where one spouse was Italian, left the island, and went to Italy after 1947. Areas where the Italians settled during 1912-1947 are shown on Figure 3.1. Administrative duties and attempts to assimilate the island into an Italian colony devoted primarily to tourism required that at least a handful of Italians were present in every major village, or, more often, on the outskirts of the village on separate farm compounds. In 1947, Rhodes became part of Greece politically. Residents of Rhodes still consider themselves as distinct from mainland Greece, even though they maintained the Greek language, religion, and customs in the face of so many repeated foreign invasions. They still refer to a trip to Athens as ".... going to Greece." Contemporary Rhodes The climate and certain geographic features contribute to the agricultural potential of Rhodes, and aid in attracting tourism to the island, an economic venture which was initiated by the Italians. 80 Often called the "Island of Sun," the maritime climate of the island is marked by periodically high winds and humidity. Although it rarely rains after May and before October each year, it has an ever-present humidity, particularly along the coastal lines. The mountain areas on the west side of the island receive the major portion of the rain- fall, with the eastern areas taking advantage of the watershed. Among these mountains are the two highest elevations on the island, Mt. Attavyros (1356 meters) and Prophet Elias @3900 meters). The massive core of hard rocks, particularly limestone beds which are poor both in marble and ore, retain moisture and help to make Rhodes more agriculturally productive and greener than other islands of the Aegean Sea. It possesses a significant degree of ground cover, with irrigation being possible in selected coastal areas in the northern half of the island and along the alluvial west coast. Rural Rhodes All the villages are economically linked to the City of Rhodes, located at the northern-most point of the island, through their agricultural production for the main wholesale market in the city. This applies more to the northern villages than to the ones located in the southern most regions of the island. Vegetables and fruits are taken daily from the villages. They are trucked to the wholesale market where they are sold to middlemen who in turn sell the produce to grocers, restaurant owners, and to the retailers who open the other open-air city markets. In the northern part of the 81 island, there are no rotating markets which operate in one village during one day of the week and another village on the following day. These open air markets (laiki agora) which operate on a rotating basis and help link villages on a regional basis on other parts of Greece, do not operate in Rhodes. Small trucks or carts may travel from village to village with produce, however, this occurs under individual direction. Villages of Rhodes, therefore, are not economi- cally interdependent on each other through regional distribution of agricultural produce. While certain villages specialize in their productive efforts, it is in the service of the city market, not regional ones. The agricultural cycle on the island is divided into two periods; the summer, dry season, and the winter, rainy one. There are climatic indications of transitional periods which might be called spring and autumn, but they are short in duration and subsumed by the major seasons. The summer, dry period from May to October represents the time of the most intensive agricultural activity, beginning with the clearing of fields in preparation for sowing. Villages cultivating a variety of cr0ps must schedule their exploita- tion of the land according to the growing requirements of the culti- gens which include tomatoes, cucumbers, zuccini squash, black-eyed peas, peppers, egg plants, green onions, melons, non-citrus and citrus fruits, and grapes. All villages have olive trees, which produce enough olive oil to last throughout the year. For villages which rely on irrigation, such as those on the north-west and east coast, April marks the time during which irrigation ditches must be cleared 82 in order to receive the stored water from under- and above-ground wells and cisterns. Irrigating the fields particularly the orchards, consumes a good deal of time in the summer dry months. Grapes, 4 melons, and fig and olive trees do not require irrigation, in fact, it is said that the sun, not water, makes their fruit sweet, but citrus crops cannot be produced without lots of water. The end of the summer (August, September), is marked by the grape harvest, an extremely intensive period for all areas which cultivate grapes as a major product. Grapes are trucked to the city wine factories, but some keep at least half of the produce in order to make their own local wine. Even though Rhodes is not known for its olives and olive oil, as are other areas of Greece where they are produced as cash crops, but each village has its own trees. It is highly likely that the fava bean was among the cultigens during the neolithic period in Rhodes, where it may have been cultivated for both human and animal consumption. In contemporary Rhodes, fava beans are cultivated primarily for human consumption. While some of the villages have stopped or cut back on its production since the end of the Second World War, the fresh bean is still seasonally available throughout all regions of the island. The beans are planted during the rainy winter, and become ripe and fit for consumption from March to May. The dry form is sold in groceries during the winter months, at which time the dry fava beans are used in a variety of preparations, as are other dry beans and pulses. 83 Major Regions of Rhodes Contemporary Rhodes is so influenced by the presence of tourism that it is sometimes difficult to comprehend at first glance that a rural, agricultural life exists side-by-side with a cosmopoli- tan, fast-paced, international tourist economy. Once the tourist centers are left behind, one of the most striking features of the island which emerges is its regionality. Traveling through the country- side, different settlement patterns and house styles are noted in the different villages; it is possible to hear a variety of expres- sions and words not used in standard Greek conversation, and which differ by village; some areas display traditional dress even in every- day 1ife; and some villages show that they have slowly abandoned agricultural production in order to attract tourism which small shops and locally produced handicrafts. Geographically, the island is divided into four regions as shown in Figure 3.2. These divisions are complemented by histori- cal, demographic and economic characteristics which are further accentuated by differences in cultural content (e.g., dialect, dress, celebrations, social ties between villages). It is important to have an appreciation of these differences as they will again be referred to in subsequent chapters. The mountainous spine culminating in the central peaks forms a natural division separating the east and west coasts of Rhodes. This divide is cross-cut by the northern tip of the island and the southern half. The northern tip of the island, which includes the contemporary City of Rhodes, shows the longest period of human occupation for the island. Reviewing 84 16 villages 7749 total 484 average 9 villages 2910 total pop. 323 av. pop. Southern Tip Source: Author Survey Population Figures: National Statistics of Greece 1971 Fig. 3.2 Major Regions of Rhodes 85 Figure 3.1, it is clear that this area has been most subject to various populations, beginning with the Minoean, the Mycenean, the Dorean civilizations, and later with large numbers of Turkish and Italian settlements. The southern tip has the least record of in- truding populations and today consists of very small settlements. These are not easily brought into the rest of the island's influence nor do they participate in the major economic pursuit of the island's tourism. The east and west coastal areas and the inland locations influenced by them are so different in physical environment that their resulting and economic differences are expected. These points of differences are discussed according to the four regional divisions: (l) The City of Rhodes and its suburb-villages; (2) the southern tip; (3) the eastern alluvial plain; and (4) the mountainous Western flank. The City of Rhodes and its suburb-villages The eleven villages immediately surrounding the City of Rhodes have come to serve as suburbs to the city as well as maintain their rural character. Tourists pass regularly through them on their way to the beaches and/or hotels which have been built on the out- skirts of these villages within the last few years. Agriculture is irrigated in these areas, with the cultivation of a variety of crops. 'The villages here have retained much of their agricultural origins and it is possible to see villagers on their way to the fields side-by-side with tourists in open-topped cars on their way to the beaches. Year by year, even since the time of the beginning of this 86 research, an increasing number of fields are being left fallow, and windmills left unused. Ironically, the windmills which were built during the Italian occupation of the island for irrigation agricul- ture, have become a symbol associated with the island of Rhodes. One of the first things noted upon arriving at the airport in Rhodes is the row of windmills lining the runway, and a most characteristic spot in the city is a pier lined with three windmills which were once used to grind grain. Because these villages are close enough to the city for its inhabitants to choose from a variety of occupations ranging from full-time agriculture to full-time tourist related economic pursuits, they have been successful in holding on to their populations. This is the area of densest population with these villages being the largest on the island. With their total population of 16,260 inhabitants, they average 1478 to a locale. Some range to over 2500 inhabitants. The southern tip of the island The southern, triangular portion of the island is characterized by nine small villages of around 325 inhabitants each (total population is only 2910). Transportation links are not regular, which may relate to their being left-out of the mainstream of tourism. Bus service does not connect the villages with the city on a daily basis which would facilitate commuting to the city to work during the tourist season. Even if it did, the condition of the roads and the distance involved would make the connection take over two and a half hours. Some of the settlements in the area were established during 87 the Italian occupation when an air strip was constructed to aid in the war effort. In ancient history, this part of the island was of little interest to those traveling the Aegean trade route to Anatolia, no city-states were established here, no evidence of early settlement has yet been uncovered, and it is generally treated as an area of marginal interest on the island. None of the villages were screened for the Gd- trait primarily due to transportation difficulties which would have impeded correct handling of the samples. Few of the villages reported cases of favism to the hopital. It would be worthwhile to look at this area at some time in the future simply because it has been so neglected in previous studies of the island, as well as in the present one. The alluvial east coast Although strongly pulled into the tourists interests of the city and to those of Lindos to the south, the alluvial expanse on the east coast of Rhodes has been able to enjoy a fruitful economic base through the extensive cultivation of citrus and vine products. The villages in this area are easily accessible to each other and to the city. Settlement patterns are not restricted by sharp altitudinal increases, with village centers occupying flat areas which radiate out from a central square. Agriculture is heavily dependent on the cash cropping of citrus and vine, with some production of varieties of vegetables. Olives are produced only for village consumption and for their oil. Historically, these areas were under the domination of the 88 ancient city-state of Lindos, which has become the second most important tourist attraction on the island (in fact one of the highest ranking tourist attractions for all of Greece), drawing heavily upon these villages for personnel to provide the necessary commodities and services to maintain the tourist trade. Many fields have been abandoned in favor of the seemingly more lucrative and easy life of tourist related work. Economic alternatives and access to the cash market is considerable. Next to the northern tip of the island, this area is the most densely populated. A total of 6848 inhabitants occupy its eight villages, for an average of 856 per village. The mountainous west side As described in the history of the island, this area of the island was probably associated with Kamieros, the ancient city state. Today it is not densely populated. A total of 7749 inhabitants are scattered among sixteen villages (about 484 per village). The coastal villages of this side of the island have a strong connection to the city, while the village slightly to the south in the mountains have maintained a more traditional agricultural and herding economy. Five villages on the island can be considered as truly mountain villages, in geographic location, settlement pattern, and ecological situation. These five, plus adjacent villages in the foothills of these mountains form what is referred to here as the mountainous western flank of Rhodes. Agriculture and herding dominate these villages. The valleys 89 are expoited for fruit trees and vegetables, middle levels for grape and olive production, and the higher altitudes for grazing flocks. The small strip of arable land on the coast of the west side is used for the cultivation of the earliest spring crops. The use of "hot- houses" constructed from vinyl plastic and wooden frames, and set next to the sea to take full advantage of the sun's reflection, produce early tomatoes and other vegetables which are not usually available until later in the summer. Instead of abandoning plots of land in this area, new fields are continually being prepared and cleared. Some of these will be given to sons and daughters when they marry, and one has the sense of agricultural continuity which does not exist either in the suburban-villages around the city, or in the alluvial east coast villages. Participation in the high-paced tourist trade is lacking with the exception of the village of Embona, which imports tourists on a daily basis to tour the village, eat at the local tavernas where cutlets of goat and sheep are the local specialty along with the locally produced wine, and learn folk dances from the villagers. Land is heavily exploited by intensive labor, and the land is terraced to accomodate the vineyards located on the sloped of the mountains. Settlement patterns in these villages conform to topographic contours of the mountains. The Villages of Massari and Kritinea Based primarily on the results of testing for the enzyme deficiency, the survey of favism cases reported in different areas of Rhodes, survey of fava beans in the rural locations, and knowledge 90 of the regional characteristics of the island, two villages were selected for the collection of ethnographic data. One of these villages, Massari, is located in the eastern alluvial coastal region, the second, Kritinea, is in the mountainous western flank of the island. Both villages showed high frequencies of the enzyme deficiency, with Massari being closer to the average for the island with Kritinea being considerably higher (27 and 40% respectively). A substantial number of favism cases were reported in Kritinea, while Massari had very few. Possible reasons for differences in the frequencies of the deficiency and favism will be discussed in subsequent chapters. For the present these villages will be described and placed in their regional context. Massari and Kritinea are located at two opposite ends of the widest part of the island of Rhodes. Since the island is twenty- two miles across at its widest portion, they represent the two villages located at the most extreme part of the island's width. The spine of mountains which runs the length of Rhodes separates these two villages, with travel between them almost impossible. If one wants to go from Kritinea to Massari, the mountains must be circumvented. Travel by bus requires a trip all the way into the City, one and a half hours away, where a connection is made to go to the opposite side of the island, again one and a half hours outside the City. Massari: Environment and Economic Setting A little over two kilometers from the sea, Massari occupies the alluvial coastal plain on the east side of the island. Access 91 to the sea is direct by foot a thirty minute walk along a dirt road that slopes gradually to the sea. The village itself is barely twenty-five meters above sea level, and the intermediate plain which is full of olive trees, fig trees, and grape vineyards shows signs of underexploitation. This area of the island, it is presumed, has not been subject to the invading populations which characterize the history of the other half of the island. Evidence of early occupa- tion of the area between contemporary Massari and the sea is found in the remnants of house foundations which are scattered among the vineyards. Since an old fortress (Késppo) perches on a nearby hill, it is thought that the inhabitants of these old structures used the fortress for storage of agricultural produce and protection. The inhabitants of Massari say that the old village of Massari was leveled by an earthquake some 160 years before (around 1810), during the last stage of the Turkish occupation of the island. The survivors were forced to go to nearby villages, to Malona in particular, for refuge. Slowly the village of Massari was rebuilt, closer to Malona and farther from the sea. Even though traditional enemies, the people of Massari consider themselves linked to Malona by biological ties, marriage and ritual kin. Settlement pattern The flat plain of Massari allows for the settlement pattern of the village to show a simple grid pattern. The village has one major plateia (square) onto which all the major public institutions I open. The center of the plateia was once dominated by an open 92 well surrounded by benches and trees, but this has been rebuilt and is now little more than a ceramic structure with several spigots which are used only occasionally. Three cafeneia (coffee houses or cafes), three small grocery shops, the school, the church, and the equipment shed for the local football team surround the plateia. Almost all inhabitants pass by or through the plateia at least once a day, on the way to shop, on the way to the fields, to collect mail from the passing mailman who arrives on motorcycle, or to meet the children at school. The plateia also makes a convenient stopping off point for tourists on their way to visit Lindos, twenty minutes away by automobile, who are out of earshot of the comments being passed around about them at the cafeneia which enjoy a clear vantage of all events transpiring around the platefa. The houses in Massari are connected to each other in block form, sharing courtyards which are separated by walls and gates. In most cases, the wall seems to be purely a matter of style, as one can easily see directly into the neighbor's courtyard by simply peering over the low wall. Even so, the courtyard is defined as part of the house, not the outside or the street. Rarely does any- one pass through the gate of the courtyard without first shouting to ask permission to enter. The oldest homes in Massari date to 1870, the first ones rebuilt after the earthquake. These were one-room structures built in a row, attached and not separated at that time by a courtyard. Some had a small shed attached perpendicular to the main one-roomed house. Because they were attached on either side, the only place 93 for a window was on the side of the door. Inside, the ceiling was made of cane and held up by major wooden strips transcrossing the cane. The large room was superficially divided and supported by an archway. Space in these one-room homes is used economically. The "first room" the one before the arch, is usually left open, but the second room is again subdivided with the use of a raised platform or loft at about 5 feet above the ground. Underneath, the area is used for sleeping. This style is noted throughout the islands. Even in homes built in the 19405, the loft was retained, or modified for sleeping areas. Sanitary facilities (e.g., running water, toilet and bath facilities) in the oldest homes were non- existent as people used the fields and carted water from central wells. The oldest members of Massari's population still live quietly in these homes, all of which have at least one electric fixture, although many do not have running water either inside or in the court- yard. Sometime between 1870 and 1950, houses were enclosed with courtyards, a second room added (or even a third) perpendicular to the main room, and some outdoor plumbing installed in the way of a cabinét, that is a small outhouse with a hole in the ground and/or a sink in the courtyard with running water. This likely happened to most homes during the Italian occupation. The houses then assumed and L-shaped enclosed court with all rooms Opening onto the court, the cabinet being unattached. Some even had a special cooking hut, set next to the cabinet where water was supplied to both. These houses still stand; in fact, I occupied one such house during 94 field work. Until the last ten years, this form dominated, being elaborated upon with improved sanitation facilities, a kitchen or cooking shed or extra room. Lately, entirely new homes are being built, all enclosed, surrounded by a courtyard. These are made with all the rooms opening onto the hall, each being able to be shut off. Many, although enclosed, have an additional room which is roofless and has a storage closet in it for all the things which were at one time stored under the loft in the traditional house. Friedl (1967) has argued that due to the agonistic character of the Greeks, households are placed so that windows and doors do not face each other so that no one can look directly into another's home. This does not hold true for Massari: houses are laid out quite symmetrically, and it is not uncommon to be able to see into a neighbor's home from one's own courtyard. The flat environment surrounding Massari, plus the fact that all the structures were built within the same period following the earthquake, promote a predictable regularity in the placement of the hoses. Gates to the courtyards, more often than not, open directly across from each other. In Kritinea, where the houses are built on terraces cut into the mountain, it is difficult to have rows of structures which face each other at the same level. Entrances to houses are made according to the conven- ience allowed by the immediate surroundings. If houses happen to have doors which face each other, it is by chance just as is the reverse . 95 Links with the outside The presence of tourism on the island, and particularly the link necessary to transport tourists from the City for one or two day visits to the Acropolis of Lindos puts Massari in greater contact with the outside world than is possible in Kritinea. Trans- portation is direct, with several daily bus lines running through the village. These are increased in number during the tourist season to accommodate not only tourists, but those from Massari and surrounding villages to travel to their tourist-related jobs. Although Massari is on a much traveled bus line, it has limited facilities for communication with the City and neighboring villages. There is only one telephone in the village, located in a small grocery store where everything said becomes public knowledge. Telephone connections are often not reliable, and if one wants to send a telegram and/or make a reliable phone connection, travel to another better equipped village is advised. Mail arrives usually on a daily basis in both villages, brought by a postman on motor- cycle to Massari where all converge on the central square to hear if they have received anything. In Kritinea, the central post office for the village and surrounding areas receives and sorts all incoming mail. Agricultural activity Agricultural efforts in Massari are directed toward the production of citrus fruits for the wholesale city market and of grapes which are processed into wine in the city wine factories. 96 Most of the inhabitants of Massari who have been born into the village hold plots of land exploited for vine production. Others with more extensive holdings have citrus orchards in addition to their vine- yards. None of the land around Massari is intensively exploited; in fact, it is common to see large vineyards left untended. The orchards, located immediately surrounding the village center, are very well tended. During the summer, beginning in late April, most of the agricultural activity is centered around grape production: e.g., weeding, cutting back the vines, dusting the leaves with pesticides. The vines are not staked up and therefore require careful attention that they do not become too heavy and spread out before they reach their peak of production. Because as many as eight varieties of grapes may be cultivated, the harvest is separated into distinct periods. Scheduling for their harvest and sale must be arranged so that virtually everyone in the village is concentrating on the harvest of a particular variety at the same time. Each variety is scheduled to be weighed during specific time periods lasting about two weeks each. This is handled by the agricultural union with dupli- cate records kept by both the individual producer and the village secretary. Grapes are brought to the central weighing station where they are weighed, recorded, and taken to trucks for their transport into the City of Rhodes. It may take up to three months after the final harvest for the producers to receive their cash from the union, which means that from the beginning of the time when the vineyards are first attended to in November, to the time when 97 cash is received for the harvest, more than ten months may have passed. During this time, pesticides and fertilizer may be purchased from the agricultural bank on credit. While it is forbidden to harvest certain varieties of grapes during the period of time other than those specified by the wine factory, additional harvesting may take place in order to send grapes to the open market in the City of Rhodes, or for personal family consumption. Many families with large vine holdings have a difficult time harvesting all their grapes in order to meet the wine factory deadlines, and may employ others in the village to help. Members of the village who do not have large vineyards may supplement their income and family diet by fishing. Access to the sea is direct from Massari, and as such promotes fishing as an economic activity, although few inhabitants state their occupation as fisher- men. During the summer months, the sea on this side of the island is tranquil enough so that small boats can be used for fishing. The larger boats, adapted to the requirements of open-sea fishing are not required. Portions of the catch may or may not be sold within the village. Although tourists often pass through Massari, stop and take snapshots, or have a drink at one of the cafes, the village does not have any small business enterprises which cater specifically to tourists (e.g., handicraft shops, small restaurants). In spite of the lack of visible tourist enterprise, Massari's participation in the tourist business is essential to its economy. A substantial number of the village's men, particularly those under thirty years 98 of age, leave the village for the entire summer to work as hotel night clerks, servitores, janitors in hotels and restaurants, and so forth, in the City of Rhodes and in Lindos. Others confine their supplemental economic activities where they are able to commute on a daily basis. Many of the women sew, crochet or embroider items for the tourist shops in Lindos (at the rate of 25 drachma a dress, which will sell for 350 drachma in some Lindian tourist shop: 1975 figure). Within the last generation, many of the younger women of Massari have been traveling on a daily basis to the City of Rhodes to offer their services as chambermaids at hotels; others prepare food or wash dishes at the seaside restaurants in Lindos. Kritinea: Environment and Economic Setting Although the west side of the island has exhibited the longest continual habitation, it is probable that Kritinea developed somewhat later than the original settlements slightly to the north (e.g., Embona, Aghios Isideros). Located in the mountains, 350 meters above sea level, Kritinea probably arose in response to the needs of the ancient city-state of Kamieros, located to the northeast of the present day village. Descending to the sea, the ancient ruins of Kamieros Scala (steps of Kamieros) can be found, which indicates that original habitation in the area included all the area from the acropolis of the city-state, Kamieros, to the sea. Kamieros Scala was at one time the harbor for the west coast of the island. This is evidenced by the still-standing custom's house for which there is no longer enough business flowing in from the outside to warrant a staff. 99 It might be assumed by the remains of an ancient period, that this harbor also serviced ancient Kaimeros. The inhabitants of Kritinea trace their ancestry to the Cretans, maintaining Cretan surnames which all end with ":pgigf. Local inhabitants say they descended more recently from a pair of shepherds and their wives who came to inhabit the region. They even- tually quarreled, with one of the two families moving higher up the mountain to found the present-day village of Embona. Even though they trace common ancestry with Embona, little attempt is made to maintain transportation and communication links between the two villages, nor are intermarriages common between them. Close to Kritinea, slightly north along the sea coast from Kamieros Scala, is a small village which is a direct offshoot from Embona. Although Kritinea is closer to Mandriko geographically, ties between Embona and Mandriko usually exclude Kritinea. Settlement pattern Kritinea is a nucleated mountain village, not unlike the majority of Mediterranean villages in similar environments. ‘The mountainous topography promotes the placement of structures on terraces which were cut into the mountainside. The village has only two major roads running through it, although it is connected together by a series of winding small roads and pathways, from level to another. These are laid such that from the road or path, one is able to step onto the roof of the houses at the immediately lower level. Assent to the road behind a row of houses requires that one climb at an 100 angle of approximately 45 degrees. The important public institu- tions such as the coffee houses, the central square, the church, the school, the village hall and the post office are all located at different levels throughout the village. There is virtually no central plateia, such as is found in Massari, where the majority of the members of the village converge at some time during the day. With the school located at the edge of the village, even mothers taking children to and from school do not pass at all through the central parts of the village. Houses are laid out according to the contours of the land, which does not allow them to be connected in a block pattern. Only at the lower levels of Kritinea are the houses likely to be connected in groups of three or four households. Traditional homes have one or two rooms, the second room servicing as a store room where food preparation may also take place, such as sifting flour for bread, sorting dried beans, cleaning vegetables. These homes have outside plumbing in the form of one spigot emptying into an outdoor sink fixture. Here, dishes are washed throughout the year, even in the winter when it is likely to be raining, and chilly. Water for personal hygiene is drawn from this central faucet as well as the water for flushing the toilet facility in the outdoor cabinet, and water for the small gardens which often surround the house. In the summer, water shortages result in a lack of piped-in water to the homes. During these periods, water is drawn from the central village well, on the lower level of the village. This well was renovated by the Italians. 101 Unlike Massari, the houses of Kritinea do not have an enclosed courtyard. Houses are usually rectangle and composed of two rooms, or L-shaped with three rooms. The majority have plumbing located outside these two or three rooms; toilet facilities are enclosed in a cabinet, and the sink for washing dishes may or may not be enclosed in a cooking hut. Often steps may go up to the house or down to the house area. Some houses have courtyards, not enclosed by walls or fences. As with Massari, the newer houses are all enclosed, with all facilities inside, but again, rarely having courtyard space. Instead of a courtyard, however, many homes have small gardens in their immediate environment, some of these include fava beans. Newer houses are often built on two levels, the upper for living, the lower for parking machinery, storing foods and holding animals. Even though there is the tendency to make newer style homes, therefore, the necessity exists to have an area set aside for storage. In the older houses this was handled by a second or third room of the house where animals and fodder and stored commodities were all housed. Transportation and communication Transportation facilities to and from Kritinea are less accessible than to any of the neighboring villages at the same eleva- tion. There is one bus which leaves the village early in the morning and returns the same day in the mid-afternoon. The bus is primarily to service young people going to the public high school a half an hour away from the village. The roads to neighboring villages are not being well-kept, and often the road through Kritinea is avoided 102 when descending from villages higher up the mountain. Individuals from these other villages do not pass through Kritinea on their way to the City of Rhodes. Kritinea is actually no farther from the City of Rhodes than is Massari on the opposite side of the island, yet Kritinea manages to be more isolated. What Kritinea lacks in roads and transportation, it makes up for in communication facilities. It houses the regional post office, telephone and telegraph office, as well as the regional police station. The major pieces of infor- mation then are usually funneled through Kritinea. The postman from Kritinea services five other villages in the region; telegram messages from other villages are sent out and received in Kritinea; telephoning to areas of Greece outside of Rhodes may often require a trip to Kritinea. Economic activity Kritinea is primarily an agricultural village, with a few families engaging in fishing activities at nearby Kaimeros Scala. This handful of families, who are winter residents in the village of Kritinea, take up summer residence at the small hamlet of Kameros Scala. These families do not have extensive land holdings, if any at all, and their sole livelihood during the summer is based on fishing. Their catch goes to one of the restaurants in Kameiros Scala. The sea on this side of the island is more exposed than on the east side. There are fewer protective harbors here, with the consequence that fishing requires larger boats and more elaborate equipment. There is no possibility that agriculturalists can supplement their income 103 with daily fishing excursions since they cannot afford the capital investment which would be necessary to support both economic activities. Aside from these few families involved in fishing, the rest of the population in Kritinea relies on agricultural production, the major crops being grapes, olives, and a variety of fruits and vegetables. The more successful farmers produce a variety of crops which are regularly taken to the city market. Although the village has several cafeneia, small groceries and one restaurant, these estab- lishments are run by individuals who also engage in agricultural activities. Kritinea is not among the several villages of Rhodes which participate in the tourist economy. Except as producer of certain vegetables for the City which may eventually be consumed by tourists, Kritinea does not participate in the tourist trade. This was not always the case. During the Italian occupation of the island, Kritinea and its neighboring village of Embona, would stage folk dancing competitions for the benefit of visiting tourists (and for the benefit of the local economy). Embona has continued this tradition to the present day, and expanded it to the point that tourists arrive daily by bus to watch folk dancing, dine at the local restaurants and buy traditional Rhodian commodities from small tourist shops. Since the departure of the Italians, Kritinea has not continued with this practice. Many felt that it was doing more harm than good to the village. Kritinea does not, today, draw tourists into the village, and it does not export personnel or products out of the village to directly serve tourist interests. 104 Demographic Comparison of Massari and Kritinea In terms of settlement patterns, general environment, economic pursuits, Massari and Kritinea represent two different types of villages found in contemporary Rhodes. Kritinea, in the mountains, shows the typical nuclear settlement pattern, an economy based on agriculture and herding which take place in a variety of altitudinal ranges. Massari, in the alluvial west coast region, shows a different settle— ment pattern, agriculture centered on the production of two crops, and with economic alternatives such as fishing and services related to the tourist trade. Both have frequent transportation links with the City of Rhodes. What Massari lacks in communication facilities is compensated for by transportation links with the city. Kritinea, better equipped in communication networks, lacks transportation facilities which are as good as those surrounding Massari. In spite of the reasonable transportation and communication links between the villages and the City of Rhodes, neither village has its own resident physician, mid-wife or nurse, its own pharmacy or clinic. Villagers must rely on the agrarian physician who visits the village on a weekly basis, bringing with him (or her) an assortment of pharmaceuticals, limited diagnostic equipment, and therapeutic advice. Emergencies must be treated on the spot by local people, or taken to the nearest village with a full-time physician, or taken into the City of Rhodes. The demographic features of Massari and Kritinea are more similar than are their respective ecological settings and economic 105 adaptations. Fifty-two percent (52%) of Kritinea's 516 inhabitants are male, forty-eight percent (48%) are female. This compares favorably with Massari's population of 540, with fifty-four percent (54%) males and forty-six percent (46%) females. Table 3.2 shows these figures. TABLE 3.2 POPULATION IN MASSARI AND KRITINEA Massari Kritinea Males 292 (54%) 266 (51.5%) Females 248 (46%) 244 (48%) Total 540 516 Age pyramids for each village are presented in Figures 3.3 (Massari) and 3.4 (Kritinea). Each step in the pyramids represents a ten year period. Table 3.3 distributes the population in each village by twenty-year age cohorts, showing that even though the pyramids have some major dissimilarities, the populations compared by twenty-year cohorts are quite similar. Massari's population dis- tribution (Figure 3.3) more clearly approximates the classical pyramid form than does Kritinea's. No explanation can be given for the lack of females born between 1916 to 1925 in Kritinea, shown by the obvious space during that time period in Figure 3.4. Women who were 52 to 61 years of age at the time of the present study would be included in this age cohort. No similar drop in Massari's popula- tion is noted at that time period. The composition of the actual samples used in the study were described in Chapter Two. The number of households with young 106 wcemmez we ewsecxm em< m.m .mwu 0% on ON or o or ON on 0v On 8 mu . comp - me . ommp mm . cem— - me . emmw - mm . ema— mm . mwmw - . comp comp meceuem wcemmez we mmewww> "eugeem mmwesem mewez 107 amewewcx co e_5ac»a wee e.m .e_a Ow mm mm mm me mm mm mp mo mmwesew Ow comp ommw meow omm— mum— mpmp oomw camp as on 0% on Oh mmmp mmwez meceeem eecwuwcx we emewww> ”euceem 108 TABLE 3.3 DISTRIBUTION OF AGE GROUPS IN MASSARI AND KRITINEA Massari Kritinea Under age 21 34.5% 38.1% 21 to 40 28.3 25.2 41 to 60 22.5 18.0 61 to 80 13.7 17.2 81 and over 0.9 1.4 children (aged 7-12) in Massari comprised 37% of the total number of households, and in Kritinea 23% of the total number of households. While Massari and Kritinea had nearly the same total number of house- holds, Kritinea had fewer with school aged children. The number of children per household was slightly more in Kritinea which helps to account for the difference in the number with school-aged children. Table 3.4 summarizes these differences. TABLE 3.4 FAMILIES WITH ELEMENTARY SCHOOL CHILDREN (AGES 7-12) IN MASSARI AND KRITINEA Massari Kritinea Total households 163 159 One or more elemen- tary aged child 52(37%) 37(25%) §EEEELX The selection of Massari and Kritinea for ethnographic inves- tigation in this study was related to the factors outlined in the 109 methodology. I wanted to find two areas which were representative of two different types of physical environment, and which showed differences in both the rates of the enzyme deficiency and in the numbers of favism cases reported. The earlier studies of Kattamis et al. (1969a) and Allison et a1. (1963) gave an idea of where these villages were most likely to be found. The screening for the defi- ciency and the identification of the numbers of favism episodes from different areas on the island supported the selection of Massari and Kritinea on the basis of their environmental differences and other impressionistic observations. FOOTNOTES CHAPTER THREE Local legend in Kritinea says that one of the sons of a Minoan noble came to the area of Kritinea selected in order to avoid an oracle's prediction that he would kill his own father. The son settled in Kritinea with his family and entourage. Years later, a ship arrived from Crete (Kriti), and the son mistook his own father's ship for that of an invader. He fired on the ship and killed his father. The remainder of the crew then stayed on in Kritinea. Another local legend says that two brothers came to Kritinea with their wives and families. They quarrelled, and separated, with the one brother staying in Kritinea and the other settling higher up the mountain. Surnames in Crete are noted to end in -akis, which, in Greek usually indicates a diminuative form of the noun. Some scholars follow the theory that the ending was imposed during Turkish rule in Crete (and in Greece) to indicate the subjugated posi- tion of the Greeks with respect to their Turkish rulers. Others, however, believe that the -akis indicates the equiva- lent of the English "son of" in surnames. Villagers in Kritinea, with very few exceptions, use the ending, akis, in their surnames. This ending is found in other surnames throughout the island of Rhodes, but only in limited number. Certainly no other village which was visited during the course of the field work in Rhodes exhibits surnames with this ending to the extent that Kritinea does. Massari sur- names do not have this ending. Evidence of the Mycenaen settlement in Rhodes comes from two sources: (1) the presence of Linear 8 writing, and (2) the distribution of pottery styles. The Mycenaen Linear B was distinctly different from the Minoan system of notation: Linear B "... was in fact an early form of Greek virtually identical with the Achaen (or Arcado-Cyprian) dialect which survived in Cyprus and Arcadia into historical times." (Nixon l968:3) The Minoan system, in contrast, was written in hieroglyphics similar to that which the Egyptians used. The change from Cretan to Mycenaean activity in Mediterranean commerce is signaled by the nature of pottery finds at Trianda, in the northern part of the island. At first, only Minoan wares were brought to Rhodes, but as time went on, Minoan and Mycenaean pottery was intermixed, with Mycenaean styles eventually domina- ting. (Samuel 1966:111) 110 111 Nixon (1968:102) contends that the Mycenaeans and Dorians held the same ancestry; the Mycenaeans representing the southern branch, the Dorians, the northern branch. The link between the two groups is considered to be the Minyans, which had appeared in Macedonia about 2500 B.C., spreading to Chalkidiki and Thessaly (all regions in northern mainland Greece). He states, “It appears, therefore that we can regard the Minyans as the cement which held the Greek peoples together. They must have played much the same role in the Aegean as the Normans did in forming the English people. The Greeks, whether Mycenaean, Dorian or the later classicial Greeks, must in just the same way be looked upon as a blend of the various people who came into the land at various periods. Thus the Greeks ultimately became an ethnical composite of at least the early Neolithic settlers, who probably came from Asia Minor or Syria, with the Early and Middle Bronze Age (or Minyan) peoples from the north, together with other intrusive elements.“ The Minyans, Nixon contends. intermingled with the people already in the Mediterranean area of contemporary Greece. Skulls from graves of the period (2500 BC) show a blending of broad-headed and long- headed peoples, indicating that the "Nordic" invaders and their "Mediterranean" forerunners had settled down side by side. Archaeological evidence from the mainland shows that at the time of the Dorian invasion, "... the culture of the greater part of the areas from which they came (Thessaly and Macedonia) was primarily Mycenaean. It is therefore not surprising that the culture of the areas overrun by the Dorians should remain Mycenaean." (Nixon 1968:59) Nixon reiterates this point: "The Dorians from the north and the Mycenaeans from the south therefore must have had a common nationality varying only in the predominance of one ethnic group or the other. We can therefore describe the Dorians as being Mycenaeans, or at least "fringe" Mycenaeans, because by this we understand primarily the culture corresponding to the people known as "Mycenaeans," and the archaeological evidence makes it clear that by the time of the Dorian migrations, the Mycenaean culture had spread over Thessaly and into parts of Macedonia." 102 CHAPTER FOUR THE GO. TRAIT ON RHODES In the medical diagnosis of favism and scientific research about the disease, the G6PD enzyme deficiency (Gd') is always given prime importance. It is listed as a critical but not sufficient factor in the etiology of favism; as such, it assumes the role of risk factor in the epidemiology of favism. The distribution of this risk factor in a given population is not always directly related to the frequency of favism, therefore it has limited predictive value; however, it is convenient to begin with the distribution of this central risk factor in our discussion. The dynamics of the genetic inheritance of the Gd' trait are not necessary in order to gain understanding of its distribution in a population. Rather, it is more important to appreciate that certain environmental and socio-cultural factors, as well as random events, may influence the distribution of the trait. The screening in the present and previous studies in Rhodes show that the Gd' trait fluctuates in its distribution. Although the average figure for Rhodes is one of the highest in the world, the fluctuations may be from 18.8% to 46.6% of the males in the village sample showing the trait. The trait has been shown to be inversely related to altitude, where different altitudinal locations have been screened and compared 112 113 (e.g., Siniscalco et a1. 1966; Stamatoyannopoulos and Fessas 1964). The results from Rhodes show that while this is the general rule, some locations fall outside the predictable range if altitude alone is considered, with some of the highest elevations on the island showing the highest frequencies. Malarial endemicity, known to be a function of altitude and known to be related to the sickle cell trait, has been suggested as a selective factor in the environ- ment which helps regulate the Gd" trait/altitude relationship. Possible selective and/or neutral features of the Gd" allele are discussed in this chapter with respect to the data for Rhodes. Among certain endogamous, ethnically closed groups, the frequency of the allele is higher than in surrounding populations. For example the Kurdish Jews have a very high frequency, while the adjacent Arab populations have much lower frequencies (Allison et a1. 1963; Szeinberg and Sheba 1958). This leads to speculation that the factor of isolation, either by geography (e.g., island community) or by social sanction (e.g., marriage customs) may exacer- bate the extreme-end frequencies found in areas where surrounding populations have much different, more uniform average frequencies. This hypothesis will be discussed with respect to the Rhodian data. Finally, the chance factors from history and others operating in present populations are suggested to have contributed to the higher average frequency of the trait in Rhodes and to the unexpected fluctuations from specific locations. Based on historical events in Rhodes, the principle of genetic drift explains the high average frequency of the Gd" trait on the island. This same principle, 114 emphasizing the breeding population size as a factor influencing randomness in gene frequency, aids in explaining the Gd" trait dis- tribution by altitudinal location. Five hypotheses are offered to explain the distribution of the Gd" trait in Rhodes: 1. Altitude is expected to be inversely related to the Gd" trait frequency; Malarial endemicity, past or present, is expected to promote higher frequencies of the trait through the process of natural selection; The trait appears randomly as a result of neutral selectivity; Marriage customs promote village-endogamous unions, thereby exacerbating extreme-end differences in Gd" trait frequencies; Chance events in history as well as in present-day differences in size of breeding populations have acted to promote both the high average and the fluc- tuations in village-by-village frequencies. The first hypothesis is discussed in the first major section of this chapter which gives the results of the screenings. Points two and three are treated in the section on national selection and points four and five are included in the last section about genetic drift. 115 Results of Screenings for the Gd" Trait The results of the screening among 189 male school children, ages 7-12, showed a high average frequency (26.5%) for the Gd" trait on Rhodes. This is in keeping with the earlier literature for the island which reported an average of 25% (Kattamis et al. 1969a) to 31.8% (Allison et a1. 1963) for locations screened. The results of the present screening are compared with these earlier studies in Table 4.1 which shows all the locations in Rhodes which have been screened to date. In the Allison study, three villages were screened: Aghios Isideros, Laerma, and Massari. Four other villages were screened by Kattamis: Kremasti, Siana, Pylona, and Archangelos. The present study screened for the trait in a total of seven villages, five of which had not been previously screened. Embona, Kritinea, Lindos, Lardos, and Malona. Two villages were re-screened from earlier studies: Pylona and Massari. For these latter two villages, frequencies for the Gd" trait will be given as they were calculated in the present study unless otherwise indicated. Distribution of the Gd" Trait The results of the present screening along with earlier studies showed that the range of the Gd" trait among those tested is from 18.7% in Lindos (present study) to 46.6% in Laerma (Allison et a1. 1963). This latter figure may be high, but even in the present study similarly high figures were found; for example, 43.2% in Kritinea. These findings are shown in Figure 4.1 and Table 4.1. As discussed in Chapter Two (Research Strategy), the numbers 116 .ecmcw -ee ago see; eaomao ee.mm co socazemcc new: weep .owmcw -ee age new: emommo eo.mm co xoemaeacw gee: meme .we we cemwww< an emceecem emw mmoozm 2H >uzmHuHumo name no zoahzmmmkao _.v m4m400 m oAGHIOS ISIDEROS 1.3 8%’ . LSIANA LAERMA o Archangelos 21.2% 0 Malona 21. 4% . Massari 26. 3% PYLONA 36.2% C EQRBQS . LINDOS ' 18.7% Average Frequencies of Gd" Trait 0 >36% 0 25-34% 0 <24% Source: Screenings for present research with these exceptions: l. Kremasti, Archangelos, Siana and Ag. Isideros by Kattamis et a1. 1969 2. Laerma by Allison et a1. 1963 Fig. 4.1 Gd" Trait Distribution in Rhodes 118 screened for the Gd" trait in each location are to be considered representative. The size of the samples used from each village are in keeping with other screenings which have been conducted at the village level in terms of the proportion of the entire male popula- tion represented by the sample. These figures are expected to give at least as good an indication of the Gd" frequency for the genera- tion involved in the present study as for earlier studies. Repre- sentation in the seven to twelve year old cohort was 91.5 to 100% in all the villages screened in the present study, with the excep- tion of Embona. In both Massari and Kritinea, 37 school boys, aged 7-12 were screened. This represents 97.5% of all the boys in the cohort for each location, with 12.6% and 14.2% of all the males in these village poulations represented. Twenty-eight nuclear families are represented from Kritinea, and thirty nuclear families represented from Massari. Kritinea had five additional families with children from 7 to 12 years of age at the time of the screening, but none were males, and therefore were not represented in the screen- ing. Massari had 22 families with young children not appearing in the screening for the same reason. That is, there was no male representative of the family in the age cohort. Gd" Trait and Altitude Studies of the relationship between altitude and frequencies of the enzyme deficiency in Greece and Sardinia show that there is an inverse relationship between elevation above sea level and 119 the frequency of the enzyme deficiency, that is, the Gd" allele (Siniscalco et a1. 1961; Carcassi 1957; Allison et a1. 1963; Stamatoyannopoulos and Fessas 1964). In fifteen Sardinian villages, Carcassi reported a general drop in the enzyme deficiency frequency as altitude increased. At altitudes of under 100 meters the frequency was given at 17.5% while at over 501 meters the frequency dropped to 4.9%. The work of Siniscalco et a1. (1961 and 1966) supports this material by adding 37 more Sardinian villages to the ones which Carcassi had screened. From these 52 total villages, those under 100 meters show an average of 19.3% affected with the Gd" trait. In the intermediate altitudes (101-400 meters) the average remains nearly the same at 19.8%, while in the higher altitudes of over 401 meters, the average drops dramatically to 7.3%. These data were compared with those from Rhodes, excluding eight Sardinian villages at elevations of over 525 meters above sea level. Rhodian villages are not located at higher altitudes than 525 meters, and for this reason the eight Sardinian villages were excluded. The comparison is shown in Table 4.2. All the RhOdian . villages show higher frequencies in comparison with the Sardinian ones. In each altitudinal grouping the average and range are higher than those for Sardinia. No inverse relationship between altitude and Gd" trait frequency can be observed in the Rhodian locations, and, in fact, no real systematic distribution of the trait is shown. Possible reasons for the lack of agreement with previous altitude/ trait relationship involve the nature of the samples in Rhodes as compared to those in Sardinia. The Sardinian samples involved much 120 ES EEEE EEEEE omm owe one omm mp .wwmw .eummco we meew>cem mewpmwpeum Fecewuez Aeemwv .Pa om oowmomw:_m .ewme .e< eeewm eceesu magma; emcwuwcx .mcegec< meow»; ecewez wcemmez wpmeeecx menace meecee esez am w.ww m.mm N.ww o.o¢ N.mv N.PN N.mm ¢._N m.m~ w.mm w.ww N.om mamm__w> eaweoem .F.e ownmw mom m.__ i o.w m.mm . N.N_ e.m¢ . N.—N w.mm . w.m w.mm . w.m— o.mm u o.m meeegm ewcwecem emcem hwepu mmeegm Lew newcwecem Lew m.w F.mm m.N m.em w.mw m.em m.m_ maeogm a_ceecam emece>< m4m N.¢ meme_m 121 greater representation of locations at each altitude, both in number of villages and in population. While the eight Sardinian villages found at altitudes of over 525 meters were excluded, the sample still included 22 villages at locations of under 100 meters, 17 villages from 101 to 400 meters, and 5 at the highest locations. For these three altitudinal groups, the number of villages from Rhodes were five, four and three, respectively, as Table 4.2 shows. In addition, the frequency of the Gd" trait in Rhodes is so much higher on the average than for Sardinia, that it may not be subject to the same type of processes as it is in Sardinia in general, let alone at the different altitudinal locations. The range of 18.7 to 35.7% of the Gd" trait frequencies for most of the locations screened in Rhodes is included in each of the three altitudinal ranges. While this range is expected in the lower elevations, the high frequencies found at the higher eleva- tions is not. When unexpectedly high frequencies of a genetic trait are found in populations, two different hypotheses can be offered to explain them: (1) natural selection, and (2) genetic drift. On the basis of research in other geographic areas, the high fre- quency of the trait in the high Rhodian elevations provides an example of what is meant by "unexpected", and offers a challenge to utilize environmental and ethnographic information in checking these hypotheses. Natural Selection and the Gd" Trait Natural selection favoring a genetic trait results from the trait's adaptive advantage. This is demonstrated in populations 122 where that portion of the population with the adaptive trait has the advantage and is able to survive in order to reproduce the follow- ing generation, where in many more of whom will have the trait. Some alleles are selectively neutral, while other potentially lethal ones manage to continue to circulate in the gene pool from one genera- tion to the next by mechanisms associated with (l) inherent character- istics of the allele (e.g., attached to another adaptive trait, recessiveness, sex linkage), (2) through the interruption of natural selection by human intervention (e.g., treating congenital inherited defects, sexual selection), or (3) as a balanced polymorphism. According to the theory of natural selection, the Gd" trait has --~~-- been maintained in certain populations because it aids in the adaptive process in favor of humans in a particular environment. Even though selection may be working against the trait in the homozygous and hemizygous condition by provoking hemolytic crises, the trait is perpetuated by the heterozygous female and this state, may have some advantage (e.g., Doxiadis et a1. 1961; Allison et a1. 1963). In order for traits to be perpetuated they do not need to always be adaptive: some are perpetuated because they are not strongly maladaptive or they form a balanced polymorphism. A 1967 report by a World Health Organization research team assigned to investigate the distribution of the enzyme deficiency summarizes the need for further research on the topic of the selective aspects of the deficiency: Further information is required regardin the positive and negative effects that G6PD (variants? may exert upon the biological fitness of affected individuals. In particular, the possible contribution of G6PD deficiency to mortality and its interaction with 123 malaria and possible other disorders require study. (p. 26) The arguments generated by the theory of natural selection have at least three subparts: l. The Gd" allele and/or fully expressed has adaptive advantage. 2. The Gd" trait has negative features (e.g., hemolytic crisis), which are overshadowed by its Selective advantage; 3. The factors which led to the perpetuation of the allele have ceased to exist in the environment but the negative effects are still limited or even neutral and the trait persists by virtue of its genetic composition. The first and the third points are treated in the following sections. Selective Advantage of the 6d“ Trait The demonstration that the allele for sickle-cell anemia in the heterozygous state offers protection against malaria (Living- stone 1971; Wiesenfeld 1967) has led to the hypothesis that the allele for other hemoglobinopathies (e.g., thalassemia) and abnormal hemoglobins (e.g., G6PD deficiency) may also confer some protection against the disease. Considering that altitude often delineated malarial regions, and that the Rhodian data show little association between the deficiency and altitude, it might be projected at the start that the malaria hypothesis will not aid significantly in 124 clarifying the problem of the distribution of the deficiency in different altitudes. The argument must be considered on the basis of established knowledge about red blood cell chemistry and malaria. Malarial organisms depend on the integrity of red blood cells; they need some of the enzymes and metabolites of the erythrocyte, therefore, one would expect "...suboptimal growth of malarial para- sites in red blood cells which deviate from the norm" (Motulsky 1960:44). Theoretically the trait or allele is suspected of offering —~«~ some protection against malaria, and even in the presence of selective forces against it (e.g. favism), the G6PD deficiency continues to appear as a balanced polymorphism. The evidence which has been reported in the Mediterranean areas more clearly than not supports the malarial hypothesis. Siniscalco et a1. (1961) find that variations in the gene frequency for the deficiency in nineteen Sardinian villages where malaria has been endemic until about 1950 are directly related to variations in the prevalence of malaria in these locations. The study did find, however, some areas of very high incidence of the enzyme deficiency without malaria having been significantly present in the population. Flatz and Duran (1967) also found the same associa- tion in Spain between the deficiency and malarial endemicity. Malarial areas tended to be associated with those where the enzyme deficiency was present, although the deficiency is reported in much lower fre- quencies in Spain than in either Greece or Sardinia. Further, from their data in five Spanish provinces, Pellicer and Casado (1970) 125 were unable to support the hypothesis that high malarial endemicity is associated with high frequencies of the enzyme deficiency. In Greece, five areas examined by Stamatoyannopoulos and Fessas (1964) showed a good degree of correlation between areas of high enzyme deficiencies and those areas which had been endemic with malaria prior to 1945. The deficiency in highly malarious areas was six times more frequent than in non-malarious ones. Chore- mis et a1. (1963) also found the same association between malaria and enzyme deficiency frequencies. Archival research in the City of Rhodes, Public Health Depart- ment (which holds records for the entire twelve-island group of which Rhodes is the administrative center) indicated that malarial records before 1954 are not available for specific village locations on the island. Cases before then were reported by island in the twelve-island group (Dodecanese). Cases occurring after 1954 are minimal. Village records are in greater disarray due to the various administrative upheavals which occurred in recent history. A careful search of statistics for the island, through the collaboration with officials of the Department of Public Health both in Athens and in the City of Rhodes revealed that since 1955, the majority of malaria cases reported were from two sources: (1) relapses of old cases which cannot show endemicity; and (2) new cases which first appeared outside of Greece and were returned to Rhodes for medical care and recuperation. These often occurred in people who had migra- ted to Africa, or in sailors who were exposed to malarial conditions in other countries and then had to be returned to Greece for treatment. 126 Actual figures, by village or micro-region, then, are not available to trace areas of malarial endemicity on the island. By interviewing health officials located on the island for the last thirty years, information was gained on the regional distribution of malaria within Rhodes. This information which cannot be statis- tically verified, is presented descriptively below. Coastal examples: Mandriko, Massari, and Lindos Malarial breeding grounds are not necessarily associated with coastal areas since it is standing and stagnant fresh water as opposed to salty sea water which facilitates the propagation of the anopheles mosquito. In some areas of Rhodes, particularly on the eastern alluvial flank, water tends to collect more than it does in the raised elevations along the central mountain spine. Further the human settlements in these areas have shifted around during at least the last 400 years such that the actual malarial conditions in these areas must be reconstructed. Mandriko and Massari, both coastal villages, were noted V for their continued persistence of malaria even after the advent of DDT. Both of these villages fell within the epidemiological and ethnographic focus of the present research. Massari, as discussed in Chapter Three, participated in this present study and Mandriko is the coastal village closest to Kritinea. Both Massari and Kritinea were researched for factors other than the enzyme deficiency, therefore both these environments are quite familiar in the study. 127 In both cases, the ecological situation is not grossly different from any number of coastal villages in Rhodes; they are located two kilometers from the sea shore, on land that slopes toward the sea. In both areas it is likely that the sea level was at one time lower, judging from remains of old structures in the strata along the coast. It is interesting that, while screening did not take place in Mandriko, the closest village to it is Kritinea. Kritinea is located about 350 meters above Mandriko but shows unexpectedly high frequencies for the deficiency. Plots of land belonging to villagers in both Mandriko and Kritinea extend to the sea, even though Kritinea is at a higher elevation than Mandriko. Therefore, in order to work their land, individuals form Kritinea must travel regularly to the area of Mandriko, and are assumed to have been subject to the same malarial exposure as those in Mandriko, and consequently subject to the same selective pressures. Perhaps this is a plausible hypothesis which explains the unexpectedly high frequency of the deficiency in Kritinea. It is not only where villages are located in terms of altitude and malarial endemicity, but where villagers work and which altitudes and areas they exploit in agriculture which may be important. High altitudes which are not intermixed or close to malarial areas may be expected to show the expected enzyme deficiency frequency. Areas which are close to malarial centers, even though these areas may be high in altitude, are expected to share essentially the same environmental factors as those in the malarial areas. 128 Lindos represents a different case. Traditionally it has not been involved to a great degree in agricultural pursuits. His- torically it is the site of the ancient city-state of Lindos, taking in the surrounding agricultural territory as well as the natural harbor. Its inhabitants are not expected to have devoted time to agricultural emphasis since Lindos had become a powerful maritime center. It is unusual in the contemporary village of Lindos to find the occupation of field worker or farmer given (children in Lindos were questioned about father's profession during screening). It is more common to find those who are descendents and wives of sailors and merchants, or who are involved in touriSt related activities. Present-day inhabitants of Lindos are almost always involved in tourist related occupations: photographers, keepers of donkeys to take tourists around the village and the Acropolis of Lindos; waiters, bartenders, bus drivers, tour guides. Wives may tend tourist shops and wash dishes in small restaurants and taverns. Grandmothers often cook at restaurants, or crochet and embroider fabrics for table cloths and dresses for sale to touriSts. The area around Lindos is not noted as a region of past malaria endemicity. Among the villages screened, Lindos has the lowest Gd" frequency. Inland examples: Pylona and Lardos There are many examples which illustrate the exchange of populations or the movement of populations, in altitudinal locations on a seasonal or daily basis. Villages located in middle range 129 altitudes are most likely to exhibit population changes. Pylona and Lardos, both middle-altitude villages, show 36.3 and 21.4% for the Gd" trait. Lardos is noted to have been among the first villages on Rhodes where malaria was reported according to the information of the Public Health officials in Rhodes. It is located at a slightly lower elevation than is Pylona, however, plots of land belonging to the inhabitants of the two villages overlap. Even though the two villages occupy different altitudes, the populations in both should be considered as participants in the same interdependent econiche. Both villages then should have similar frequencies of the trait since they exploit the same range of altitudes and environments. The more than 15% difference does not follow this hypothesis. It might be explained by reasons: (1) The size of the samples influenced the results of the screening, both being too small to give an adequate picture of the frequency of the trait; and (2) Differences may have been smaller, even fifteen years ago. With respect to the last point, Pylona was reported to have a fre- quency of 25% in the Allison study which took place fifteen years before the present one. Mountain example: Embona The village of Embona represents another situation. The frequency of the deficiency is lower here than in the seaside areas on the west coast of the island surrounding the village of Embona. This is consistent with what would be predicted according to the altitudinal location of the village. Embona has been traditionally 130 a herding and agricultural village. Plots of land and grazing areas take the inhabitants of Embona down to the lower elevations less frequently than in villages of the intermediate altitudinal range. In spite of the high altitude of the village itself, one can see the plots of land and the pasture areas for goats and sheep even higher up the mountain. These examples from the different altitudinal and historically different areas of Rhodes illustrate that more than statistical correlations between malaria and the Gd" trait are necessary in order to unravel the nature of their relationship to each other. Some preliminary conclusions may be drawn from the present data: 1. The intermixture of land holdings at different altitudes such that exploitation of land at these altitudes at different times of the year places people in varying degrees of exposure to malaria. This tends to even out the malarial factor at the intermediate altitudes of under 400 meters. 2. In altitudes of over 400 or 500 meters, the limits of the physical environment or the adaptation to higher altitudes in economic exploitation, promote less exchange of populations with lower altitudes. This does not seem to be the case for any of the villages in Rhodes, but may hold true for Sardinia where many villages of over 500 meters above sea level were screened in earlier studies. Certainly, the problem of ascertaining the relationship of the Gd" frequencies to altitude and malaria has so far given inconclusive results. The trait may in fact have been a protective 131 feature against malaria, but to map out the areas which were endemic without taking into consideration the economic and physical adaptations in the different altitudes results in the inconclusive data. According to the most recent research on the subject: The hypothesis that G6PD deficiency protects in some way against malaria derives solely from the associa- tion between the high frequency of G6PD deficiency and endemic malaria and should be considered unproven until other evidence becomes available. (Martin et a1. 1979: 562) Selective Neutrality and the Gd" Trait The interaction of the enzyme deficiency with hemolytic agents is known: acute hemolytic anemia, hyperbilirubinemia, and urine discolorization. The effects of the Gd" trait in the absence of these agents are not known. It is possible that there are none that can be attributed to the allele or to the fully expressed G6PD deficient phenotype. That is, the deficiency in and of itself is not a pathological hemoglobin type. It is possible that the enzyme deficiency allele or fully expressed phenotype is selectively neutral. Evidence supporting the malarial hypothesis is not con- clusive, especially when dealing with small village populations where agricultural practices and land tenure patterns require mobility between several areas, often quite distant and occupying different altitudes and econiches. Malarial conditions which existed for Rhodes in general may have promoted the deficiency in the gene pool, but in contemporary Rhodes, malaria is not an important selective factor. The allele may be neutral. During the research, information was gathered which may 132 aid in assessing the possible natural effect of the Gd" trait. These data are discussed in the four following sections: (1) fertility patterns of Gd" trait mothers; (2) neonatal jaundice in Gd" trait infants and their siblings, (3) childhood episodes of blood-related conditions (such as jaundice and hepititis) in Gd" trait children and their siblings, and (4) height, weight and relative weight (Quetelet Index) distribution of children with the Gd" trait compared to those without the trait. Fertility Patterns of Gd" Trait Mothers Biological adaptation is often assessed by measuring fertility. With human populations, where a variety of choices about number of children in a family may be exercised, indicators related to fertility may have limited use. (For example, the figures may be unreliable due to family planning, induced abortions, neglect of perinatal health care, etc.) By using small samples some of the choice related problems may be compensated for since, among the families of the small samples in this study, methods of family planning and birth control were nearly identical. In the course of gathering information related to other topics, many of the women themselves broached the subject of birth control. Their questions, as opposed to those which I constructed for fertility patterns, are considered as a much more accurate gauge of childbearing and perinatal concerns. Women in the villages often try to hide the number of spontaneous abortions which they have experienced since women who have difficulty bearing children are not thought to be 133 fully fulfilling their sexual role. The use of solicited abortion as a form of birth control is an even more seriously guarded secret. While morally objectionable it is nevertheless practiced. The major methods of limiting families are not particularly reliable. They include periodic abstinence (modified rhythm method), interrupted sexual coitus, and prophylactic use among men. Abortion is the major form of controlling births in Rhodes as well as in all of Greece. It is not performed in rural Rhodes at present, although at one time, the practical midwife was credited for knowing the appropriate measures to end an unwanted pregnancy. The procedure is usually handled by going into the City of Rhodes to a private gynecologist's office where the abortion is performed and the woman is able to leave the office in a matter of two to three hours. Hospitalization is not required, and if desperate enough the woman might go by herself to the physician in order to maintain her secret. Women do not go to physicians alone as a rule, but this situation may prompt them to go without a relative in order to avoid gossip. In spite of precautions, women usually fear that their abortion will be learned of in the village, or that they will become sterile from the abortion. This relates to the question of barrenness, again, since women who are unable to conceive after marriage may be the object of gossip which claims they became barren from having an abortion. Thus, seeking and going through with abortion may not affect the decision of a woman who has already had as many children as she desires, but is a consideration for a young woman who has not yet married and started her family. 134 From Massari, seven mothers affected with the Gd" allele were compared to fourteen non-trait mothers for differences in their fertility patterns, e.g., number of children, number of pregnancies, childbearing histories, spacking of offspring, etc. These mothers were selected through their sons who had been identified with the trait. Three additional mothers had daughters with the trait (identified by favism episodes). They were not included in the fertility history analysis since they were either not tested or they showed normal enzyme activity (which is not necessarily an indication that they do not possess at least one Gd" allele). The fourteen other mothers from Massari had sons who had been screened and did not show the trait and did not have any genealogical links to anyone with either the trait or favism. Fourteen mothers from Kritinea were identified by having at least one son affected with the trait, or by having had a clinical episode of favism herself. These fourteen Gd" trait mothers were compared to the seven mothers with the allele from Massari. Ages at first and last pregnancies In Massari, the average for the first pregnancy of Gd" trait mothers was 22.6 years; for non-trait mothers, 22.2 years. Among Gd" trait mothers in Kritinea, the average first pregnancy was at 23.7 years, slightly older than either of the averages for Massari. The range of last pregnancies for Gd" trait Massari mothers were given at 23 to 36 years. Non-affected mothers in Massari reported last pregnancy at 35-40 years. Affected mothers from Kritinea reported 135 last pregnancy at 35-40 years. Affected mothers from Kritinea reported last pregnancy at 24-43 years. These figures are shown on Table 4.3 Mothers in Kritinea begin child-bearing a year later than both Gd" trait and non-trait mothers from Massari (for this sample). These same mothers from Kritinea reported their last preg- nancy at least three years later than the mothers from Massari, independent of the enzyme deficiency. Child-bearing years cover a longer period of time for Kritinean mothers than in Massariani mothers. Half of the mothers in the sample from Kritinea had preg- nancies after thirty years of age, while in Massari, only five of twenty-three mothers had pregnancies after this age. TABLE 4.3 RANGE AND AVERAGE OF CHILDBEARING AGES IN GD" TRAIT AND NON-TRAIT MOTHERS Massari Kritinea Gd" Trait Average 22.6 23.7 Range 15 - 32 18 - 27 Non-Trait Average 20.7 unknown Range 19 - 31 Number of children and spacing Seven Gd" trait mothers from Massari reported a total of eighteen live births, an average of 2.6 births per mother. The fourteen non-trait mothers from Kritinea had forty live births, for an average of 2.8 live births/mother. These figures are shown 136 in Table 4.4. They are consistent with what might be expected on the basis of the demographic characteristics of the two villages, rather than from differences in fertility related to the enzyme deficiency. Kritinea has larger families than does Massari, inde- pendent of the Gd" trait. It may be that cultural pressures have more influence on the number of pregnancies a woman will experience than does the enzyme deficiency. TABLE 4.4 NUMBER OF CHILDREN PER MOTHER IN MASSARI Number of Children Mother's Status 4+ bwlw 2 Gd" Trait 5 Non-trait 10 Even though Kritinea mothers have more children, they begin reproduction a year later than those in Massari, on the average. Mothers from both villages tend to go through full-term pregnancies at about the same rate, i.e., they have approximately the same number of live births in the same period of time. Mothers in Kritinea con- tinue reproduction into later years, while mothers in Massari usually stop after two children. Table 4.5 shows that there is little differ- ence between the three groups of mothers according to the number of live births compared to the number of years in which they occurred. For example, women with three live births showed a range approxi- mately four to seventeen years during which they occurred regardless of village or the Gd" trait. More mothers in Kritinea had three 137 live births than did those in Massari. TABLE 4.5 NUMBER OF PREGNANCIES BY NUMBER OF CHILDBEARING YEARS IN MASSARI AND KRITINEA - RANGES IN Number of Childbearing Years Number of Massari Massari Kritinea Children Non-Trait Gd Trait Gd Trait 2 2 - ll 3 - ll 2 - 5 3 4 - 9 4 - l7 3 - l7 4 --- 4 --- 7 - l7 Fetal loss and perinatal deaths Pregnancy results for twenty-one Gd' trait and fourteen non- trait mothers are summarized in Table 4.6. The figures are given in raw numbers and in % (rather than o/oo). The 21 Gd" trait mothers shared a total of 58 live births from 65 pregnancies; 89.2% of their pregnancies resulted in live births, with the rate being only slightly more successful in Massari than in Kritinea. Non-trait mothers had 89.l% of their pregnancies end in successful births. The category of abortions and miscarriages includes only abortions which were non-solicited (i.e., spontaneous), miscarriages up to the 5th month of pregnancy, and still births in the last trimester. These figures were slightly higher for the Gd' trait mothers (l0.7%) than for the non-trait ones (8.1%). The sample is too small to conclude that the Gd- trait in mothers contributes to lower fertility (and hence suggests less adaptability). l38 .xvzpm ucmmmca sogw mmwcoumw: xuwpwugmm "mugzom .swgwa FFPHm .mmmwgcmumws Amsomcmucoamv cowpgoa< u mmo_ _mumm ¥ N.N Am\_ _.m Nm\m _.mm “m\mm Aepv Penman: mgmcpoz pwmgh-coz o m m.mm m¢\o¢ Ae_v wacwpwcx o.m mm\mv N.o_ mc\- N N c.om om\mp ARV Penman: & c x c x : mcwgpoz “Lack -uw mcummo Fmpmcwcma «mummog Foam; mmwocmcmwga can mzucwm m>w4 AozN ummg meNN pcmNcH w>N4 No mm< cmaszz saw: mm< 5pm; mm< mNADmNm >uzP4 No mm< mmnuzN conga: me pm mm Nm om am pm mm mm mm em mm mm mm mm mm mm mm mm mm mm “was sup: ma< mmnuzmv a ucmccmpm . 1 N9 3: :28: .33 N.<~_._..wu 202 N m.o_ m.op com: me oN c -uu :oz -uo mzom _N< .0. 1m. NTdO'llHD JO d38Mf1N 156 and non-trait mothers of these children, no substantial differences could be found to indicate that the Gd" trait is maladaptive. While malarial conditions may have played a role in selecting for the trait at one time, in the absence of contemporary malarial conditions, the trait may be perpetuated because it does not carry particularly strongly maladaptive aspects. Even considering that favism may occur in individuals with the trait, frequencies of the illness are always significantly lower than would be expected on the basis of Gd" trait frequencies, while mortality figures for favism are even lower. Genetic Drift and the Gd‘ Trait From the information for contemporary Rhodes, selection does not appear to have an influence on the distribution of the Gd" trait frequency or geographical range. In the introductory section of this chapter, five hypotheses were advanced to account for the trait distribution. Three have been discussed (relation- ship to altitude, selection for the trait by protection from malaria, and neutral selectivity). Two hypotheses remain:( (l) Endogamous marriage customs contribute to the perpetuation of the trait in high frequencies in some isolated areas, and (2) Random factors contribute to the high frequency and fluctuations in Gd" trait distribution. These latter two are taken up in this section. Given the situation in the micro-regions of Rhodes, there is a reasonable indication that genetic drift contributes to the rather significant differences in Gd" frequencies which are found 157 in the different localities on the island. Genetic drift acts independently of natural selection, and can promote a predominance of alleles that actually oppose adaptation. Genetic drift is a random fluctuation in the gene frequency from one generation to the next (Cavalle-Sforza 1969). As an example, two villages which had been screened in earlier studies of the Rhodian population showed differences from one period to the next which might be explained by genetic drift. In one of these villages (Massari), Allison et a1. (1963) found 34.4% of the males tested to be enzyme deficient. Approximately fifteen years later, the screening for this study shows 27% of those tested with the trait. In another village (Pylona), Kattamis et al. (1969a) found 25% of those tested with the Gd" trait. Nearly ten years later, the present study found 36.3% of those tested with the trait. In one area, the percentage was lower and in the other, it was higher, than those reported by the earlier studies. These differences are probably not related to environmental factors but are most likely random. Genetic drift is influenced by a variety of non-genetic factors, particularly those related to demographic dynamics (popula- tion size, breeding population size and random out-migration). Random historical events and natural or man-made catastrophes which severely reduce population size without preference for any particular geneti- cally determined trait, play an important role in promoting genetic drift. When considering genetic drift, population size does not refer to the actual number of individuals residing in a locale, but to the possible parameters of the breeding population. Therefore, 158 cultural practices which relate to the selection of marriage partners must also be taken into account. Genetic drift has a strong influ- ence in small populations where a slight change in the actual number of people with a trait causes a large change in the proportion of the population affected by it. For example, Cavalli-Sforze (1969) found in a study of Italian villages, that genetic variation between villages declined as population size increased, but that, under the influence of drift, village populations will tend to become more different, even if at the beginning they were homo eneous in the compo- sition of hereditary types. (p. 334) In this section it is suggested that random historical events which occurred in Rhodes aided in promoting high over-all frequencies of the Gd" trait. Contemporary marriage and residence patterns in certain villages act to make genetic drift a more important variable in explaining Gd" distribution (than other environ- mental causes). Genetic Drift and Historical Events Temptations are strong to search for historical causes to explain the high average frequency and range of frequencies of the deficiency on Rhodes. Given the island's tumultous history (inva- sions, sieges, sackings and rapes) and lack about the origins and interrelationships between the early peoples on the island, these temptations may only result in interesting but unscientific specula- tions.1 Siniscalco (1966:372) had to come to the same conclusions for the questions of the deficiency and its presence on the island of Sardinia, where, in spite of being an island and historically 159 "intact," it must be accepted that "... a few sets of 'external' genes must have entered the genetic pool from time to time." The history of Rhodes is replete with events both man-made and natural which contributed to the random and fairly rapid popula- tion declines. During the Dorian period in Rhodes, the population of the island grew to 500,000 inhabitants, a figure which has not since been equalled. Following this population zenith, the island suffered two distinct periods of drastic and rapid decline (Kolodny 1974). When Rhodes began its alliance with the Roman Empire in 395 A.D., the population was nearly 500,000, the same that it had been during the Dorian period. Six hundred fourteen years later, when the Knights of St. John began their occupation of the island in 1309, the population had halved to 250,000. There are no indica- tions that the drop in the number of inhabitants was related to selective features promoting or inhibiting the perpetuation of particu- lar genotypes. No epidemics are recorded during this historical period of the isalnd which would have tended to wipe out certain sectors of the population which may have shared a genetic weakness toward the disease. Rather, the population decline is attributed to random factors, such as those which resulted from repeated sackings and seiges of the island, and natural catastrophes such as earthquakes. Again, the population fell to the figure of 35,000 recorded after the Turkish occupation began harsh assimilation tactics in 1826. It is not clear if the depopulation from 250,000 (in 1309) 160 to 35,000 occurred during the entire 517 years of the Turkish occupation of Rhodes, or if it happened suddenly around 1826. During a period of no more than 517 years, the population declined by 214,000 inhabitants. This drop is attributed to extremely high rates of out-migration and mass slaughter. Both of these factors are random with respect to particular genetic characteris- tics shared by those eliminated in the drastic reduction of the population. These two significant periods of depopulation, each occurring within about a 600 year time span, give plausibility to the theory that genetic drift may have been at work in the Rhodian population. It is possible that the random forces of history and geology, the enzyme deficiency became predominant throughout the island, at higher frequencies than would have been promoted by natural selection. Further, these frequencies then became associated with particular localities by chance, and cultural factors reinforced them. In particular, cultural practices related to the selection of marriage partners acted on these distributions. Genetic Drift and Endogamous Marriage Practices Certain groups with very high Gd" trait distribution are noted to be ethnically endogamous, possibly perpetuating the trait in spite of pressures of natural selection. The Greek Islanders have been noted to stress the practices of insular endogamy, if not village endogamy. As with the falacious idea that island communi- ties can be treated as genetic isolates, the same applies for villages. 161 The cultural ideal of village endogamy, while promoted by economic constraints as well as ideological sanctions, does not hold true throughout the island of Rhodes. It is not only marriage, but resi- dence after marriage which must be considered. The latter gives an estimate of possible breeding population which is importance in calculating the potential for genetic drift to be an active factor in influencing trait frequencies. Some villages may allow fully exogamous marriages, both on and off the island. In this case the potential breeding population is larger than the population of the village, and genetic drift less likely to be a factor in affecting frequency fluctuations. Other villages enforce only endogamous marriages and/or expell the couple who have married outside the village. In this case the breeding population is limited to the size of the village, and drift is expected to be a more sig- nificant factor in explaining fluctuations in gene frequency. A description of marriage and residence practices in Rhodes The practice of provisioning marriageable young Greek women with a dowry (Erika) has been noted in the ethnographic literature (e.g., Friedl 1963; Dubish 1975; Hoffman 1975), however the form and content of the dowry differ by region. While the intent of the dowry is to provide the new couple with an economic basis with which to begin their life together, it also promotes female premarital chastity and emphasizes the arrangement of an honorable and economically profitable union. Even though the dowry is now 162 illegal in Greece, it is no secret that young men and women consider more than romantic attraction when selecting their marriage partner. In Athens, Salonika and other large towns of the Greek mainland, the dowry may consist of money or a promised position in the father of the bride's business. In the rural areas of the mainland, the dowry may involve little more than a trousseau, house- hold linens, and other household items, and land. In the Greek islands, in general, the dowry reaches its most elaborated form where it included not only all the aforementioned goods and promises, but a house as well. This tends to promtoe the selection of marriage partners from one's own island if not village. It is not uncommon to find a mother who will completely ostracise a son or daughter (more often a son) who has married someone from another island. Even if the entire family has migrated to an urban center on the mainland, it may be expected that their children will marry someone from their native island. Some young men have purposely concealed a financee for several years simply because she is not from the island of their birth. In Rhodes, the dowry consists of a house, its furnishings, and land holdings. Men also have an inheritance in the form of land, if they marry outside the region, they must leave their share of the family inheritance behind. If they make a marriage with a woman from their own region, they can maintain their own land- holdings, and combine them with those in the wife's dowry. Since these are basically unmovable holdings, it is economically wise for both sexes to marry within one's own village or region. 163 Pressure is exerted for village endogamy, not only from the economic position, but from the moral one as well. Ideally, young men and women should behave so as not to damage the honor of the family, and thus lessen their marriagability. Informants during the research expressed the opinion that the selection of marriage partners within the village was the ideal situation. This insured that the family knew where the intended spouse came from in terms of family background, honorability, honesty, and potential. In both Kritinea and Massari, there was the explicitly stated preference that the young people in one's family select to marry another person from the same village. Mothers would say that if the daughter was good and proper, that she need not look elsewhere for a husband. If the young man is honorable, then he does not need to go to another village to search for a good wife. Although arranged marriages are uncommon, the fact that the spouse is from the same village helps to insure the family position is clearly known, and behavior patterns of the intended are known from child- hood. The pressure to marry and the emphasis on family honor result in the situation where there is virtually no institution for social relationships between unrelated young men and women, except through the institution of engagement and eventual marriage. Engagement, although no longer marked by a large public ceremony in Rhodian villages, represents a serious and singular step toward marriage. It is, at the same time, the only way in which a young man and woman may keep company together away from the other members of the family. 164 Being engaged means that arm-in-arm walks together may be taken, that the young man may take some of his meals at the home of the intended bride, that the couple may attend summer festivals together, and spend extended periods of time in each other's home. The act of engagement breaks all the barriers formerly standing between the young man and woman, and, in the eyes of the community, they are as good as married. There are exceptions to this rule. Engagements may follow family pressure when continual company kept between a young man and woman becomes noticed by others in the community and family honor is threatened. This may result in a marriage which was not really the choice of the couple involved. Pregnancy may suddenly become evident and an engagement forced to be announced before actually intended. In this way, the pregnancy is considered as legitimate as one which occurs within the marriage, since, they rationalize, the couple had publically announced the engagement. The actual wedding ceremony is not as important as the fact that it followed an engagement which was formally recognized. Often, illegitimate births are excused by this as well. An unmarried mother will say that her fiance was killed before they could marry; or is involved with the army and will come shortly to marry her. These women, if the fiance does not show up, are usually barred from ever marrying. The seriousness with which engagement is considered helps to explain why the breaking of one causes public shame. Engagements are, nevertheless, broken, with the result that the young woman 165 becomes morally marked, and may find it difficult to contract a marriage within the village. This is another reason why marriages with outsiders are often thought to be only for young women whose virtue is flawed. The engagement is marked by two objects: the wearing of a gold band on the left ring finger (later changed to the right ring finger upon marriage), and the beginning of the construction of the dowry house by the bride's family (if construction had not already begun). If, during the time of the engagement, a pregnancy does occur, but the house is not ready for occupancy, it is considered that the marriage ceremony is bound to take place sooner or later, and the young couple simply miscalculated the time at which the house would be ready. The families of the bride and groom begin to call each other by the appropriate kinship terms following the engagement. The young woman refers to her finace as "my husband" (9_andras mou), and her family calls him "our son-in-law" (9_gambr65 I mas). Equivalent terms are used for the bride to be, (1 gynaika you; y_nifi mas) "my wife", and "our daughter-in-law". In-laws also call each other by apprOpriate terms (sympether6s - masculine; sympethera - feminine), and the young couple address the in-law relations by correct terminology. Even the best-man (koumbaros - masculine) will also be addressed by his ritual kinship term even before the wedding has taken place. The accumulation of household goods begins long before the house construction is under way. Young girls begin to learn to sew, crochet, embroider and weave during their elementary school 166 years. By the time they have finished the elementary school, they begin these chores on a more regular basis, as many still do not attend school after the age of twelve. Often, they are engaged by the age of fourteen, and married by seventeen. Women who marry outside of their village usually bring their husband into their dowry home, but when the woman leaves her own village to go to that of her husband, she is at a disadvantage. Not only does she leave her dowry land behind, but also her dowry home. Even though the plots of land may be near to the village which she has married into, her husband must provide a home for them. Men who do this are often thought to be a little stupid by others in his village; even worse, is the husband who is willing to contribute the building of their home. Sometimes it is virtually impossible for the bride's family to provide her with a house, and she and her husband may build their own. Even though the resulting home and its furnishings might be more luxurious and modern than either would have been able to afford separately, the husband is referred to as stupid (vlacas) when he undertakes such a venture. The importance of the dowry house, both practically and symbolically is most in evidence immediately preceding the wedding ceremony. During the week prior to the ceremony, the house and all its furnishings is open to the public eye, with the bride and groom receiving guests in the home. Gémgs, the word for both the wedding ceremony and the marriage itself, is also used to refer to the actual house where the new couple will live. People will often use the expression, "... go to see the gamos..." when they 167 mean to visit the house of the bride and groom. They may say in passing the new house, "There is the place of the gémgs," The bride and her best girl friends will stay in the house the night before the wedding ceremony takes place. The day of the ceremony, as well as earlier, relatives of the bride gather at the house to cook, to prepare the bride for the ceremony and to dance local folk dances. If a family cannot provide a new home for the daughter, she is given the home of her parents who then move into another, older and smaller dwelling, which is usually from a grandparent of the male side of the family. It is uncommon for parents to share a dwelling with a married offspring of either sex. The occupation of a parental home by a married daughter happens when the family is unable to provide a full dowry, or when the daughter is the last in the family to marry. There is no particular social stigma attached to this; the important thing is the daughter has her own place which has been given to her by her parents, and will not be shared as a dwelling unit by her parents. When land holdings as part of the dowry tend to promote regional marriages, the house as part of the dowry promotes a pattern of residence in the bride's village. This encourages the selection of marriage partners within one's own village. In villages with a population of little more than 600, such as in Massari and Kritinea, it is difficult to find anyone not distantly related. Marriages with first cousins are said to be avoided, but do in fact happen. Second cousin marriages are not necessarily avoided, occur sporadi- cally, along with marriages between affinal relatives. Since there 168 are no mechanisms for courtship outside of engagement, certain courtship behaviors are played out within the context of the family. Small flirtations and gift bringing takes place between cousins and affinal relatives of the opposite sex, with the result that some of these lead to rather inescapable commitments for marriage between second and third cousins. Further, it often happens that two sisters will marry two brothers, or two men who are related to each other as cousins. Again, once a daughter has married, the groom's entire family becomes included in family gatherings, and contact the unmarried brothers and sisters of the bride and groom become regular. In general, Kritinea and Massari follow the same patterns for marriage, with the majority of unions taking place between indi- viduals from the same village. One major difference is observed which will be considered here with respect to genetic drift. Regional endogamy and the selection of marriage partners Neither Massari nor Kritinea follow the ideal marriage behavior for selecting mates from within the same village. Both have nearly the same rates of Out-marriage from the village. In Massari, a total of 222 marital unions were counted from village records and genealogies. Of these, 31.9% were village exogamous. In Kritinea, 251 unions were counted, with 32.2% of them being village exgamous. Considering the place of residence after marriage, over half of the village exogamous unions in Massari continue to live in the same village (52%) while only 8.6% of the village-exogamous unons 169 from Kritinea continue to live in the same village. This is a sig— nificant factor in terms of the implicatons for genetic drift. All but a few of the individuals who marry outsiders to the village of Kritinea continue to live in the village. Residence after marriage effects the representation of genetic factors in small local units such as Massari and Kritinea. The breeding population represented in Kritinea is smaller than that shown in Massari; in Kritinea, the pattern of residence after exoga- mous marriages tends to limit the introduction of outside genetic material into the village. In Massari, where there is an equal tendency for those marrying out of the village to either remain in the village or to leave, it can be expected that there are more opportunities for genetic mixture from outside the village. In reviewing the localities from which new alleles and genetic material might come, in the case of Massari, it is evident that the introduction of new genetic material is not random but comes regularly from the region immediately surrounding the village. These locations are shown in Tables 4.17, 4.18, and 4.19, and summarized in Figure 4.5. As Table 4.17 shows, the greatest number of marriage partners from outside the village of Massari were chosen from the region on the east coast. This region to which Massari belongs, shares many of the economic and geographic as well as cultural patterns which are found in Massari itself. Considering the nature of Massari's dependence on the City of Rhodes (as described in Chapter Three), the daily interchange of people on their way to the city would make 170 relationships outside the village a likely outcome. TABLE 4.17 VILLAGE-EXOGAMOUS MARRIAGES IN MASSARI AND KRITINEA ACCORDING TO RESIDENCE OF SPOUSE Number of Exogamous Marriages Birth-Place of In-Marrying Spouse Massari Kritinea Island of Rhodes (total) (45) (25) City 6 5 East coast 28 0 West coast 3 16 Southern 1 Unknown village 7 3 Other Islands 4 18 Mainland and Other _g§__ ._§Z_ Total 72 80 Table 4.18 illustrates the overwhelming difference between Massari and Kritinea when the number of village-exogamous, but in- resident marriages are totaled. In-resident marriages are those where one or both spouses and their unmarried chidren claim residence in the village and were in fact in residence during the time of the study. Exceptions to this might include children who were momentarily in the army or attending a higher education institution outside of the village. Of the seventy-two exogamous marriages from Massari (see Table 4.17), thirty-seven still reside in the village, while only six of the eighty village-exogamous unions from Kritinea still reside in the village. There is a much greater tendency for villagers 171 of Massari to remain in the village after they have married an outside than was observed in Kritinea. TABLE 4.18 EXOGAMOUS MARRIAGES STILL RESIDING IN THE VILLAGE In-Marrying Spouse's Birthplace Massari Kritinea Rural Rhodes, 1-6 km radius 11 0 Rural Rhodes, 6+ km radius 13 O Rhodes City 2 1 Other Islands 3 5 Mainland Greece 3 0 Unknown _jL_ __£L_ Totals 37 6 0f the thirty-seven unions between villagers from Massari and spouse from elsewhere in Rhodes, twenty-six remained in Massari. 0f the twenty-four in Kritinea (with spouse from elsewhere in Rhodes), only one stayed in the village after marriage. The unions from Massari in this category are shown in Table 4.19. TABLEA4.19 VILLAGE-EXOGAMOUS MARITAL UNIONS FROM MASSARI COMPARING RESIDENCE AFTER MARRIAGE Birthplace of Spouse, Total In-Resident km Distance Unions Unions 1 - 6 20* ll 6 - 20 l9 13 20+ 6 2 *Fourteen of these twenty were exchanges between Massari and Malona 172 Massari acts not only as a donor population to other areas of Rhodes, it is also a recipient of new genetic material. Kritinea is primarily a donor population, receiving little new genetic material from the rest of the island. Compared to the 45 marital unions in Massari where one of the spouses came from outside of the village, Kritinea had only six such unions. All of the other village-exogamous marriages from Kritinea are now found outside of the village. Figure 4.5 illustrates these differences between village-exogamous marriages and subsequent residence in Massari and Kritinea. Only one of the six village-exogamous unions which was residing in Kritinea at the time of the study involved a spouse from Rhodes. The other five village-exogamous unions consisted of one member from Kritinea and the other from another island of the Aegean. That is, when and if the people of Kritinea marry outside of the village they do not usually continue to live in Kritinea. Those who did maintain residence in Kritinea, had spouses from areas of Greece other than Rhodes. This has ramifications for the size of the breeding popula- tion in each village. In Kritinea, the breeding population is nearly equal to the number of inhabitants. In Massari, with the exogamous parameters extending to a radius of more than twenty kilometers, with the greatest concentration within a six kilometer radius. The most modest estimate of the increased breeding population would include at least the population of the adjacent village to Massari, Malona. This more than doubles the breeding population of Massari when compared to that of Kritinea. 173 ~ Rhodes City o 1 2 3 4 5 IIEJIIZZII KIA Other Islands Mainl\ if"... 5.9:...Kri t i nea 53" Other fig 55 Other ’"I; Y islands 3:. ’0': )1 Mainland/ other Relative Expression of # of Marriages ........m 1-3 l----- 4-8 >8-20 — 21-30 >31 Direction of arrow indicates direction of marriage and residence Fig. 4.5 Village-Exogamous Marriages in Massari and Kritinea 174 While the populations of Massari and Kritinea are nearly equal, Massari has many more genes entering its gene pool on a con- tinuous basis from areas outside of the village boundaries. Kritinea's gene pool, in contrast, remains closed. Its smaller breeding popu- lation means that less genetic material enters from the outside, and therefore, is more likely (than Massari) to be subject to genetic drift. If an equivalent number of elementary school boys were to be tested in another ten to fifteen years, one would expect to find that the frequency of the trait fluctuating more than it would in Massari, on the basis of genetic drift alone. The unusually high frequency of the Gd" trait in Kritinea, located 300 meters higher than Massari, and probably not as subject to malarial endemicity as Massari, is explained by two factors. First, the altitudinal location of Kritinea is not sufficiently high enough to inhibit its livestock herders and agriculturalists from moving through intermediate and even sea level eco-niches, some of these potentially malarious. The location of agricultural lands and the arrangement of these holdings necessitates travel to these different eco-niches on a daily, weekly and seasonal basis. Calculating the possibility for malarial infection by taking into consideration only the altitudinal location of the villages does not consider the pattern of movement through these other regions. Secondly, populations of villages which tend to maintain endogamous marriage and rather exclusive residence patterns after marriage, have a smaller breeding population than can be calculated for popu- lations which follow more open marriage and particularly residence 175 patterns. Marx In the scientific literature, conclusions about the nature of the relationship between altitude, malarial endemicity and the possible protective advantage of the Gd" allele are not yet unequivo- cably established. Statistically, the direct correlations between malarial endemicity and Gd" trait frequencies are supported in the literature. The problem arises when the exceptions to the standard correlation of high malarial endemicity and high Gd" frequency are noted. Considering the types of land holding patterns, modes of agricultural and horticultural exploitation, and population move- ments (either related to land holdings or to livestock patterns) on a daily to seasonal basis through different eco-niches, may help to explain some of the exceptions. The inverse relationship between altitude and the frequency of the Gd" trait, most clearly supported by the literature from Sardinia, does not hold true for Rhodes. The inverse relationship may not be observed in Rhodes because the Gd" trait frequencies are uniformly higher and altitudinal ranges less diverse than those represented in Sardinia. From a historical perspective, the principle of genetic drift may help to explain the high frequencies for the entire island, Rhodes having suffered severe and random depopulation at various periods of time. This principle may also be at work on a regional or village-level where differences in marriage and residence practices encourage great differences in the size of breeding 176 populations and allow genetic drift to operate to a greater degree in some areas (e.g., Kritinea) than in others (e.g., Massari). This, in turn, gives at least one indication of why the frequency of the Gd" trait is higher than would be expected, both on the basis of past malarial exposure and altitude. FOOTNOTES CHAPTER FOUR Hypothetically, one might insist that the Dorians brought the GGPD deficiency allele with them and spread it throughout the island of Rhodes. It was the Dorians who were responsible for populating the island, although other settlements had been on the island, they were confined to the sea coasts. The Dorians were responsible for constructing the three city-states of Kamieros, Ialysos and Lindos. The latter became a powerful maritime center with trade outposts established in Sardinia and the Balaeric Islands. Both of these have much higher frequencies of the deficiency than do their respective mainland areas (Italy and Spain). The areas on mainland Greece from which the Dorians originated (Macedonia, Thessaly and Thrace) also happen to show higher frequencies of the enzyme deficiency than any other areas of the mainland thus far screened. Some of these regions, in fact, show even higher frequencies than the average found in Rhodes. 177 CHAPTER FIVE THE SOCIAL EPIDEMIOLOGY OF FAVISM The results of the survey of reported favism episodes in Rhodes for 1966-78 show that the distribution is in general agreement with that which is described in the literature. The epidemiological pattern of favism includes these five characteristics: 1. Seasonality: It is a seasonal disease, usually occurring in the spring. 2. Regionality: Certain geographic areas often show high frequencies of favism, with these frequencies not always related to the distribution of the major risk factors (the Gd' frequency and/or the level of fava bean exposure). 3. Age-Related: Favism is most often reported in children under the age of ten. 4. Sex-Related: More males than females report episodes of favism. 5. Familial: Certain families with the Gd" trait will more often report episodes than other families, equally affected with the trait. At least four major types of variables, other than the Gd" trait itself, are suggested to relate to the distributional patterns of favism: (l) fava bean exposure, (2) environment, (3) socio-economic factors, and (4) ideological influences. These are shown in Table 5.1 which reintroduces the epidemiological model shown in Chapter One. Using the categories shown in this Table, a set of hypotheses was formed for each of the known distributional traits of favism (seasonality, regionality, etc.). The investigation of these 178 179 .xmps cgozou mmu:u_uum acmgmumpu ecu .Em_>mm No acmsuomgu acogmNNFu muosoca pppx .mooaou coom —ag=u_:u mg» Eogm twang—mm mm .mconou pmNNNEuu .mmo m_>-u-mw> :owucp iaaon asp No mgmasme No :o_uumuoga powucmcmwwwu muoeoga ——N: mmpoc xmm .mcamn mzu wszmcou o» moms Loun— aa soumch zoppo ___3 go .. :o_uasam:ou o>mw xo—_m —__3 nope; ua< .cmumo «cos mamas mg» own new apmaogom_c mgos m:_ummN zoppow cu cmuumaxm use mmuw—mcaz .Emw>mm cw mxown cu m:_u:n_cu:ou .coNuqsamcou coma a>mm muoeoga muopgma acmumou pagaupzuuo_uom .xmpc gmummgm an me —~.3 magma mg» cuN: mv_m_u :36 so mcmon u>om :»_3 mcwvgom czo g.o;a m>ug gown: mo___smu .mm—as macaw mgamcqu guuawgm :op—c ——_3 conu— NucaupauNLmo No :o_m_>_u mg» c, mmucocoNNpu xmm .smw>mu No mm_uco=cch :p venom ma cu umuumaxm mgc acmNuoga —oc:c-:oac= can zowaauop mom—__> cu mcwvgouua moucmcmmw_u mm< .mw_u:o=aogN Emw>aw :_ veaow mg a» umuumaxm mg» mmucagmNN_u smog: -—~g=g can pa:_uzu_u—< .umm>co; use =o_au:uOLa came m>ow No mccwuuoa gmupu moucocwmm_u —~:_u:u_u—< geeseos_>cu .xm_g Loummca an on ___3 mcmmn on» No mgoe m=_m: mm_—Nsmu .cmm: mcopuogoaoca camn u>uN No max» vcm >u_u=m:a o» a:_ugouua toxcmc N—ucm -meuwc as _p_3 mw_—_sou .mcumn agu EOLN coauouoca «so on: cage—_gu opus m:o&m cwzop me o» vouuwaxo mgzmoaxm coma m>mm .omu Na LoNN_u cu umuuwaxo m, mgamoaxm coma o>ou .omo——_> an om—u LmNNPu Nae "maven pugs; :. cmuuo mcos won: an cu vmuumaxo ago mecca a>au .=omoom o>Nuuau -oga Noon c, momma uses m:_¥ae “mmuomwam Emp>aw No Nawpc:Omawm o» amen—mg o—zcmzum =o_uu:uoga comm mgamoaxu came zm~>uN acoamg o» vmuumaxm ago mm—ue «has "smNL um mmpasom coca mm—me «cos magma ”_ugu -uu No «Laue: noxcwpux .uwuapmg me o» exec; uoz .Ngaou Louauguv umuupmg on o» :zocx .vmuupmg on an execs uoz awash inc Nucuucop _oNppsau xom mm< Nocopmwm .mcomamm 180 hypotheses is presented in this chapter. Factors which were suspected to influence the seasonality of favism were: 1. The schedule of fava bean production; 2. Micro-environmental differences such as altitude which might affect availability of fava beans; 3. Seasonal dietary differences regulated by the agricul- tural and ritual calendar. The fluctuation of the Gd" trait by season was not believed to play a role in the seasonal differences in the number of reported episodes of favism. While the scientific literature indicates that the trait does not change according to season, it was not possible to check for this during the present research. In the literature, regional differences in favism frequencies are usually related to the distribution of the Gd" trait, even though some areas do not fit the pattern expected if only the Gd" trait is considered to be involved. Differences in fava bean exposure by region is suggested to influence the distribution of favism, but is not usually investigated in the research. Hypothetically, villages in different kinds of physical and social settings are expected to exhibit variations in the cultivation and quantitative use of the beans. This is aside from the influences that environ- ment might have on the Gd" trait. In the present study, the following aspects of region were explored: 1. Regional and village variations in the cultivation and use of fava beans; 181 2. Comparison of features of the physical environment; such as altitude, settlement patterns, distance from urban centers; 3. Economic pursuits of village members which might tend to influence the level of bean exposure; 4. Regional economic integration (or lack of it) and interdependence of villages in a given region. As Table 5.1 shows, age is not known to be related to fluc- tuations in the Gd" trait, which would then help to explain why favism is not reported in older members of populations with the trait. A variety of other factors might operate to influence the age distribution, some of these related to fava bean exposure, others to organic characteristics of the individuals involved. In addition to organic and environmental factors, it is suggested that fava bean exposure and age might be regulated by: 1. Use of fava beans within the household, e.g., as a weaning food; 2. Protection from fava bean exposure, of certain age groups, e.g., very young children; following an episode; 3. Settlement in areas where fresh, ripe fava beans are available and where certain age groups participate in agricultural activities which bring them into close contact with the beans. Potentially, organic factors might be involved in the age distribu- tion of favism, with the older children and adults having acquired 182 some form of resistence. Roles prescribed by age may also inter- vene to influence the reporting of symptoms and episodes to health authorities. These same factors were looked at regarding the sex-distribu- tion of favism. The x-linked nature of the Gd" trait is expected to influence the ratio of males to females suffering from favism. Beyond the trait, additional environmental, social and ideological factors are expected to influence fava bean exposure, reporting of episodes, and perhaps organic resistence. The study checked to see if there were any variations in: 1. Expression of symptoms by sex, such that reporting of episodes might be affected; 2. Distribution of cases by rural-urban and altitudinal locations according to sex; 3. Exposure to fava beans by sex, either through sexual division of agricultural labor or sex role differences. The familial tendency to report multiple favism episodes (in different members of the same familial pedigree), is related to the Gd" trait being an inherited characteristic. More than genetic inheritance is shared by families. Of interest to the present study were familial differences in fava bean use, in economic activities and the interrelationships of the nuclear units of the Gd" pedigrees to each other. This chapter has three major parts. The first deals with the seasonal and regional distribution of favism cases, these being most closely tied to the physical environment. Part 11 presents 183 the age and sex distributions and investigates different hypotheses which might help explain them. Part III presents the familial data on favism, comparing pedigree materials with other characteristics of the family. PART I Seasonal and Regional Distribution of Favism The seasonal and regional distribution of favism episodes are closely related to the agricultural practices and cycles in Rhodes; for this reason they are treated together in this part. Ideologically influenced behaviors also have an effect on the seasonal distribution of the disease. Seasonal Distribution of Favism on Rhodes Consistent with the reports from the literature, the figures for favism from Rhodes show it to be a spring disease, with 111 of 123 total cases reported during the months of March, April and May each year. A second period of increase in the number of favism episodes occurs in late November and December as shown in Figure 5.1. This has not been noted in the favism literature for Greece. In fact,there may be many more unreported or undiagnosed cases of favism during these months since both the public and the physicians tend to be more alert in recording fava consumption during the spring "epidemics" of hemolytic anemia. Cases of hemolytic anemia happening in the winter may not be diagnosed as favism because during the collection of case information the patient is not asked about fava Number of Cases 10 J F Fig. 5.1 184 Source: Records from Queen Olga - Hospital, Rhodes, Greece. In A. In J .1 Al .8 <3 II I) Months Monthly Distribution of Reported Favism Episodes in Rhodes: l966-78 185 consumption prior to the attack. The Spring months in Rhodes coincide with the period during which fava beans are ripe as well as with the pre-Easter fasting period of Lent. The December cases also happen to coincide with another period of ritual fasting which precedes the Christmas feast. These periods of fasting as coincident with at least one major season of favism have not been referred to in the literature. The fact that fasting periods coincide with peaks in favism episodes is a new finding, and represents an additional approach to studying the seasonality of favism. Hemolytic agents in the environment Hemolytic anemia and jaundice in enzyme deficient individuals is known to occur from a variety of substances; the most common of these which circulate widely in Greek rural society are aspirin and napthelene. Episodes of hemolytic crisis associated with aspirin and napthelene have been diagnosed only recently and sporadically. The records from Rhodes in 1966-78 show only three cases from aspirin and two from napthelene. The vast majority of hemolytic episodes in enzyme deficient people are associated with the fava beans. It is the cases of favism associated with the beans which are the major concern here; however, the use of other hemolytic agents, or the circulation of these agents in the environment, may be involved in episodes of favism because these agents interact with the hemoly- tic agent in fava beans. The overwhelming peak of favism episodes in the spring coincides with not only the ripe fava bean season, 186 but also with the widespread use of napthelene at this same time. The slight rise of episodes in the winter, again, coincides with the use of napthelene. In village homes, all clothing and bedding, regardless of fabric, are stored in napthelene moth balls when they are not in use. Items which are included in the bride's trousseau, dowry, and wedding gifts are often too numerous to be displayed in the house at all times. Pillow cases which were embroidered for the marriage, table covers, crocheted items, and so forth, are usually reserved for display during particular times of the year, especially during the spring celebration of Easter, the summer feast of the Virgin Mary on August 15th, and the winter Christmas celebration. The celebration of these holidays is preceded by intensive house- hold cleaning, the opening of closets and trunks which contain the specially stored linens and other items and bringing them out for display in the central room of the house. In April and May, as the weather becomes warm, the family's wardrobe is changed from the heavy woolen clothes of the winter to the summer cotton clothes. Again, closets and trunks containing the summer clothes are opened, summer items taken out and aired to remove the smell of the moth balls, while winter clothes are washed and stored in the trunks with moth balls. This same wardrobe change takes place again in late October when the weather change requires the use of woolen attire and heavy bedclothes. Individuals come into direct contact with napthelene when they wear these items for the first time. 187 This variable was not examined as systematically as it could have been. It is mentioned here to draw attention to the fact that the fava beans are not the only hemolytic agents circulating in the villages during the spring months when favism is so prevalent. The production and use of fava beans The cultivation of fava beans.and their harvest covers a period of approximately six months, with the greatest period of exposure to the fresh bean occurring in the three months when it is ripe and becomes fit for consumption. In Rhodes, the summer months are devoted to the daily harvest of a variety of vegetables such as tomatoes, cucumbers, zucchini squash, eggplants, and to the tending of citrus orchards and vineyards. It is a period marked by several different kinds of agricultural activities in all areas of the island without involving daily, and intensive labor. The participation in agricultural labor is not characterized, for example, by the family leaving before sun-up and returning after sun-down as it is during the grape or the olive harvest. In August, Septem- ber, and October, a period of intense activity is noted in areas which produce grapes as cash crops. Most of the villages on the island have some of their own grapes, but not all are intensively involved in their cultivation. Beginning in November, the citrus crops and olives are harvested, along with a variety of greens, both wild and cultivated. This is a period of intense agricultural activity, but due to the rain, not all days are suitable for harvesting activities. Spring brings the continuation of the citrus harvest, 188 the continuation of using available greens, and introduces early garden vegetables such as artichokes. The fava bean is the first bean available in the spring months; other beans do not become avail- able until late summer. Cultivation of fava beans. Fava beans are planted during the rainy winter months of November and December, using the dry beans which had been saved from the previous year's harvest. The beans themselves are large, flattened rather than rounded, and with a distinct black mark at the one end of the bean. They are found in well-padded pods which are five to seven inches in length. Families which plant the beans save a few dozen each year which will be used to start the new crop. Those which are said to be best suited for planting have an extra mark which distinguishes them from those for consumption. This extra mark results from the way in which the beans are aligned in the pod. Beans for planting and beans for consumption are not grown on separate stalks. Those for planting are referred to as paligéri; those for eating, thilik6. The former term is the same as the word used to refer to a young, tough and courageous boy; the latter is a gender term for female. The beans are put in small plots of land, or in the corners of citrus orchards, olive tree fields, or vineyards. They are not intercropped with other vegetables within a plot, but may be placed among olive trees which have been long-standing on the plot of land. Their placement among citrus trees is more difficult since the or- chards are covered with clover around each tree; however, they may appear at the edges of these citrus orchards. Those which are put 189 in vineyards are again placed in the corners or edges of these plots, so as not to interfere with the expanding root system of the vine. The bean plants are not staked up, even though they will reach a height of over a meter at maturity. The stalks are quite sturdy, and the plant does not tend to branch out or develop large leaves which would require tying them to stakes. Once the plants blossom in early February (depending on altitude), the bean pods appear and mature rapidly, leaving the beans available for consumption in some areas by March. Fava beans are most often grown for household use and very limited market exchange; the latter are sent to the City of Rhodes, but they are not exported from the island. They are usually found in small plots and household gardens, rather than in large fields which would be associated with their production as a cash crop. Villages close to the city supply its inhabitants with a limited amount of fresh beans every spring. Harvest and storage of fava beans. Because the beans- are not a basic cash crop, large-scale harvesting of both the fresh and the dry form of the bean does not occur. In many areas of Greece where beans are grown as cash crops, the entire stalk of the bean will be cut or uprooted, and the beans sorted out within the confines of the villages. At the end of their growing cycle, beans will be left on their stalks, and harvested in that form. Such activities require that the stalks, pods and beans, are all loaded onto carts (or trucks, depending on the area), taken back 190 into the village, laid out in the street where the individual beans are separated from the rest of the plant bulk, and again separated by desirability for consumption. Such gross exposure to both the fresh and dry plant does not occur in Rhodes. Rather, the fresh beans are gathered by handfuls from their stalks while the plant is still green. Many times, a handful of pods will be gathered as pe0ple pass by on their way to work in an adjacent field. The pod will be cleaned away, and the raw beans eaten during a work break. Those which are gathered for home use are picked by the pod, and put into sacks to be taken back to households in the village. Often they may be picked while other fresh greens are gathered, and placed in the same sack or basket. By the time the plant begins to dry out, most of the beans have already been picked. At this time, the remaining pods are picked and taken to the households where they are left to dry out completely in the courtyard or outside work area. Beans which will be used to plant the following years crop are separated from the others which may be used during the winter. These are stored in separate sacks in the household storage area. These usually do not fill very large sacks. General consumption patterns: how and when fava beans are eaten;_ The fava beans and their pods become fit for consumption when the plant is nearly a meter high. At this time, the pod is about three to four inches in length (early March). Only the beans and occasionally their pods are consumed; no other parts are consumed. The plant greens may be fed to other livestock, such as the goats 191 and sheep. The period during which the beans begin to be available starts in March, representing one of the early spring cultigens and coinciding with the last months of the citrus harvest and the gathering of wild, edible greens. These early fresh beans are often eaten raw or cooked with the pod along with other wild greens. The combination is served as a luke-warm or cold salad, with chopped onions or garlic sauce, or with olive oil and lemon juice. By middle April, depending on the location in Rhodes, the pod becomes too tough to be consumed; therefore, the beans are shelled and eaten either raw or in the boiled salad form. Others are simply boiled in water without the addition of other ingredients and served plain or with a small amount of oil and lemon juice. .As the beans grow larger, on stalks of over a meter and with the pods reaching seven inches in length, they continue to be available through the month of April. They are stripped of their cuticle which has become fibrous and not very tasty (or easy to swallow), eaten raw, boiled in salads, or boiled and mashed into a puree called 1332, This is served with chopped fresh onions and olive oil spread over the top of the puree. By May, the stalks begin to droop downward from their weight, the pods begin to dry and open, dropping some of the beans onto the soil. This easy self-seeding means that not all fava bean patches are cultivated, and some may perpetuate themselves from year to year without human intervention. Usually by late May, fava bean consumption has dropped off and the diet replaced by other vegetables which have become available. The people still find them in the 192 fields while working and may eat them raw, stripping them of both the pod and the cuticle. Care is exercised in eating the raw beans at this time since they may contain small larva or worms. The same care is exercised in sorting out dry beans for cooking. These are carefully inspected for the presence of worms before being stored or cooked, while beans which rise to the top of boiling water are often picked out of the water and discarded as they are believed to be spoiled. The fava bean, therefore, represents a crop which is seasonally available in the fresh form, consumed raw or with other greens which are ripe at this time. The greatest levels of fresh fava bean consumption occur during the months of March, April and May. The beans are consumed during other times of the year after the ripe period has passed, particularly during the winter when other dry bean preparations are widely used. As shown in Figure 5.1, the majority of favism episodes coincide with the spring months when the bean is widely consumed and handled, and abundant oppor- tunities exist for its raw consumption even though it may not be brought into certain households. Fava bean consumption and the ritual calendar With a few exceptions, the villagers on the island of Rhodes are Greek Orthodox in religion, and as such, they observe days of fasting and days of feasting as designated in the ritual calendar. These complement the agricultural cycle in terms of available foods which are reserved for fasting and others which are used in feasting. 193 Aside from one-day fast periods, there are three major and lengthy fasting periods in the ritual calendar: (1) the pre-Easter Lenten season which spans more than forty days in the spring; (2) the pre-Christmas Advent period which also spans forty days; and (3) the fifteen—day period from August lst to the 15th before the Feast of the Virgin Mary (Panagh{a) which falls on August 15th. Aside from breaking the year into special periods of time related to a variety of agricultural, household, and social activities, these fasting and feasting days promote the consumption of certain foods which are considered appropriate during these days. Many of the feast days emphasize the consumption of special foods, such as lamb at Easter, egg-lemon soup following the midnight church services on the Saturday night preceding Easter Sunday, pork on Christmas and freshly slaughtered lamb on August 15th. Fasting involves the avoidance of animal products such as meats of all types, fish, cheese, eggs, yoghurt and butter. Olive oil, a non-animal product is also included on the list of forbidden foods during fasting, but it is avoided only for a limited period of time. The reason for this is unclear, except that the oil is so central to the diet that its denial represents austerity in the diet. It is not only the foods which are avoided, but the use of other foods which may be conspicuously present in the household, often more for social than religious reasons. The use of these foods in the home attest to the fact that the family is observing the fast. The importance of these additional fasting-foods in the diet is emphasized by the I use of a semantic category for these foods (nistisima). Such foods 194 include boiled potatoes, pickled vegetables such as cauliflower and peppers, octopus and squid (not classified as fish), fresh fruits and vegetables, nutmeats, and halyés (sesame and honey past cake), and boiled beans. All individuals claiming the Orthodox faith do not maintain strict fasting rules, especially when the period is a long one such as the three mentioned above. Generally, the elderly women of the villages observe the strictest rules of fasting. Men do not consciously adhere to fasting rules except as they are promoted by their mothers and wives within the context of household cooking. Children and pregnant women are exempt from fasting. Many women presently of child bearing age claim that they do tend to observe fasting because they are ashamed to go to the market to buy meat, or to slaughter their own household chickens and rabbits. The village, as a body, promotes the abstinence of meat by not slaughtering the large animals such as lamb, goat and pig. Social pressure therefore tends to reduce the consumption of the various foods forbidden during fasting periods. More than any other part of the fasting cycle, Lent is set apart from the normal diet. Even though strict fasting may not be observed throughout, the period introduces a different set of food into the diet. It is not only the foods which are avoided during this time period which are important to note, but those which are considered as appropriate and are therefore conspicuous in the households. The nist5sima foods which are consumed during this time, are not symbolic or ritual foods in and of themselves, but 195 their consumption exaggerates that the Lenten period is symbolically set apart from the rest of the year. During this time, whether or not the entire family is fasting, the women attend to the display of particular Lenten foods in the home. When visitors come to the house during Lent, the usual sweet, cooking and liqueurs are not usually offered to them. Since hospitality dictates something be offered, no matter how simple, the nist5sima foods may be used. While Christmas and the August 15th Feast of the Virgin Mary do not change from year to year, the celebration of Easter does. Consequently, the former two fasting periods are fixed from one year to the next, while the fasting period preceding Easter is not set to cover the same days every year. Easter may occur anytime from the first week in April to the first week in May. Lent begins with "Clean Monday" (Katharé Deftéra) forty-eight days before the Easter celebration. Lenten fasting may begin very early in February and end very late in April, or it may begin late February early March, and end in the first week of May, depending upon the year. Fasting periods and the distribution of favism episodes. Of the 123 favism episodes which occurred in Rhodes during 1966-68, 111 occurred in the spring months of March, April, and May, which are potentially covered by the Lenten fasting period. Of the twelve remaining cases, eight occurred during the pre-Christmas fasting period, and one occurred during the August fasting period. Only three episodes were reported during periods other than these periods. All the spring cases of favism cannot automatically be considered 196 as ones which followed the consumption of fava beans from the Lenten fasting period, because Lent changes each year. Lent and spring episodes of favism. In order to determine the spring cases which have pdtentially followed beans consumed during Lent, the dates that the episodes were reported to the hospi- tal were considered to be a week later than the dates at which fava beans had been consumed. Seven days were subtracted from each date that favism was reported to the hospital and, according to the year, each episode was then determined to have occurred from beans which had been potentially consumed during Lent. This is actually a large figure which was used to calculate on which day the "faulty" beans might have been consumed. Most cases of favism show signs of hemolytic anemia within 24 hours after eating the beans, according to both the medical opinion and to the reports of informants in this present study. Some, however, have been noted (e.g., Kattamis) to show hemolysis at a later time. Even if hemolysis is noticed to occur within 24 hours following bean consumption, it may take another three to four days before the affected individual reaches hospitaliza- tion. Therefore, a period of time from four to seven days before the episode reaches the hospital should be calculated to show the earliest time at which the fava beans were eaten. I selected to use the figure of seven days. Using the larger figure has the advan- tage of covering the possible cases which resulted from Lenten fava beans; on the other hand, during a period of seven days, the beans may have been eaten two or three times, and the actual date of the beans which "caused" the onset of hemolysis is obscured. Some feel 197 that the disease actually occurs after the beans have been eaten several times during a period of a few days, and that the effects are cumulative; therefore, the actual date is not as important as are the dates. This type of information was not available for the 111 spring episodes of favism, and for this reason, the potential consumption of the beans was calculated as a rough estimate of whether or not they had been consumed during the Lenten period. Figure 5.2 shows the distribution of spring episodes of favism in Rhodes for 1966-78. The shaded portion indicates the episodes which are calculated to have occurred following beans consumed during Lent. Lenten fasting (expected to promote fava bean use) and the easy availability of the ripe, fresh beans are believed to act in conjunction with each other to promote a greater number of episodes during this time of the year. This is demonstrated by the yearly fluctuations in episodes of favism, and in the time of Easter. Spring favism and yearly differences in Easter. While it might be suggested that the yearly fluctuations in the number of favism episodes is related to differences in climatic condition which affect the ripening and toxicity of the beans, the present study shows that the episodes in Rhodes tend to fluctuate in accord with the time of Easter. During 1966 to 1978, the date of Easter ranged from April 9 to May 4, which means the period of Lent differed by as much as 26 days. Because the beans ripen quickly and are most desirable for fresh consumption for approximately a month, these 26 days can make a difference in the coincidence of the ripe 198 Lenten Beans Implicated 88838818 '0 0| Number of Cases M O March April Fig. 5.2 Distribution of Spring Episodes Showing Cases Where Lenten Beans Are Implicated 199 period and the use of the beans in fasting. As Figure 5.3 shows, more than half (65) of the 111 cases of spring favism occurred during a l4-day span from April 25th to May 9th. No spring cases were reported before March 7th or after May 23rd. When Easter falls late, for example on May 4th as it did in 1975, almost all of Lent has spanned the time of the ripe beans, offering sufficient opportunities for their consumption. When Easter falls as early as April 9th, as it did in 1972, the fresh beans have been available for only half of the Lenten fasting period. Hypothetically, it might be expected that the timing of Easter would have an effect on the number of Lenten cases of favism, and perhaps on the total number of annual cases, with the more numerous cases reported when Easter occurs late. A "late" Easter is defined as one which falls after April 25th, the date shown to be the latest one at which spring cases peak. In the thirteen years included in the present survey, Easter fell after April 25th in six years: 1967, 1970, 1973, 1975, 1976 and 1978. Figure 5.4 shows that in these years, there is a definite tendency for spring favism to be higher than in the other years when Easter fell early. This tendency is further supported by totalling all the spring episodes for these six years when Easter fell late, and comparing this sum to that for the seven years where Easter was early. The difference of nearly 20 episodes, not striking perhaps, but the late Easter years include one less year than the early ones. 200 muovcmm awoncm>mm an Emw>mm No mmuommam mcwgqm m.m .mmm ><: w l ._ :34 1 l zumNo>:H cmmm :mucmd mFanoca mommu mcpgam —_< I'll‘ I or up VP ow up «N 201 ALL CASES '- SPRING CASES LENTEN CASES '1 2L, //‘ fi 4 f \ ‘ "l {“1 §\\\\\\s\\\\* ‘1 - 1"” r I 1 no 3 / /// / 5% .6 Z// "// I“ I I l O l A A l l A 1 0 15- 53510 :10 3381/4011 0 m C 1978 1977 19% 1975 117119.72 1972 1969 1970 ' 1971 1968 1967 1966 Fig. 5.4 Distribution of Favism Episodes by Year 202 Calculating an average for each group gives a figure of 10.8 cases in years where Easter was late, and only 6.6 cases in years where Easter was early. TABLE 5.2 SPRING EPISODES IN LATE AND EARLY-EASTER YEARS Number of Number of Average Episodes Years Spring Episodes per Year Late Easter 6 65 10.8 Early Easter 7 46 6.6 To summarize, while only 54 of the 111 spring episodes of favism could be accounted for by beans consumed during Lent, the yearly totals indicate the Lenten period plays a role in promoting higher numbers of favism cases in the years when it ends late in the fresh fava bean season. This is supported by the individual yearly fluctua- tions as well as combined totals for those years where Lent ends late compared to years where it ends early. Regionality and the Distribution of Favism Episodes Ten regions of Rhodes were designated according to their geographical characteristics, agricultural similarities, and social interrelationships within the region such as dialect and sharing the celebration of religious events. These divisions were not made on the basis of either the known distribution of the Gd" trait or the frequency of favism. The regions are depicted in Figure 5.4 and in Table 5.3. 203 TABLE 5.3 GD" TRAIT AND FAVISM FREQUENCIES IN TWELVE VILLAGES, LISTED BY REGION Village Gd" Frequency (%) By Village Kremasti 35.7* 1.3 Archangelos 20.2* 1.3 Malona 21.4 4.4 Massari 27.0 4.7 Kritinea 43.2 13.5 Embona 17.2 5.5 Isidoros 18.8* 11.4 Siana 33.3* 19.0 Pylona 36.3 11.4 Lindos 18.7 4.2 Lardos 21.4 3.6 Laerma 46.6** 1.3 Source for Favism Frequency: Records, Queen Olga Hospital, Rhodes 1966-1978. Source for Gd" Trait: Favism Frequency (O/OO) By Region 1.6 (A) 1.7 (F) 1.7 (F) 1.7 (F) 7.0 (D) 7.0 (D) 11.5 (G) 11.5 (G) 3.5 (H) 3.5 (H) 3.5 (H) 3.5 (H) Screening by Kattamis et al. l969(*); by Allison et al. l963(**) and present study. 204 Population totals for each of the ten regions were calculated on the basis of the latest census from the National Statistics Ser- vices of Greece. These totals were used in estimating the (1) frequency quency of favism, and (2) the actual number of males expected to be at risk, projected on the basis of the results of the Gd" screenings in previous studies as well as the present one. As suggested earlier in this chapter, factors other than the general growing and consumption patterns of fava beans must be considered in explaining the regional distribution of favism episodes. Figure 5.4 shows the regional distribution of favism on Rhodes, indicating that the frequencies range from 0.8 to 8.2 per thousand inhabitants in any given region. These frequencies are also listed in Table 5.3. The projected number of males expec- ted to be at risk, on the basis of the Gd" trait frequencies, and male population size are shown in Table 5.4. The actual number of males projected to be at risk is then standardized on the basis of 1000 in order to compare with the favism frequencies in each location. At least three categories of information are suggested to be useful in examining the distribution of favism in Rhodes: 1. Distribution of the enzyme deficiency; 2. Altitude and frequency of favism episodes; 3. Regional differences in exposure to fava beans. According to epidemiological principles, certain correlations are expected on the basis of the distribution of risk factors and the appearance of the actual disease. In Rhodes, the average ENDS ooap .Pa “a m_e~uaax mm. ma mac m.mp accou_m_ .a< mamcmu mmoppp> umuuaucou Logua< _N_ mop on» N.N— accosu mmmp .Na um mpsouuox mmm mm oN— «.mm new.» mmm— .Nm um ccmvpp< mme we. mpm o.o¢ magma; mamcmu ma~NPN> vmuuzocou casua< mme NNN mmN N.n¢ omcpuvsx moap ._a u» n.5aauag NPN mm_ one N._~ mo_au=~;uc< A—Nmpv wummgw no mmuv>gwm mupum—Hmum po:o_umz eon Nm mm m.om ace—am Nme—v mummco No mmu_>gmm mu.um_uoum pogoNHoz oNN mm mmN ¢.NN agape: mamcmo mooppw> umuuaccou Lozua< _NN NN ooN c.NN Nsmmmu: Nmop .Nm um mPEmuuax mmN NmN moo N.mm .umueogx APNN_. auaacu to mmu.>cmm movemvuuum pm:o_uaz cap mo omm N.mp macaw; APNa_v voyage co mmup>gom muvumvuaum pmcovuoz NNN mN Nmp o.pN mecca; cowum—aqoa Lou mugaom oooNquom Lucas: cowuapaaoa new a mun—p.> mm—mz -uo nouumaxu ups: m>om ado m N— N z— >uzu=onm zo omm m>4m3h z— N~<¢h no no zc~h=m~¢hm_a v.m u4m10 0/00 . 5-9 0/00 . <5 0/00 Source: Queen Olga Hospital, Rhodes Fig. 5.6 Favism Frequencies and Altitude 211 In Rhodes, the village in the mountainous chain on the west side of the island received the greatest amount of rainfall during the winter months. The rainy season coincides with the time that the beans are planted and reach maximum growth. The higher the altitude at which the beans are planted, the later in the spring months during which they are ready for con- sumption. The distribution of spring favism episodes, considered by seven-day intervals reflects these altitudinal variations. Figure 5.7 shows that mountain cases peak from the 9th to the 16th of May, while coastal ones “peaked by April 25th. The fluctuation in inland and foothill episodes which peak twice, once before April 25th and again by May 16th, may result from the variety of eco-niches which the intermediate level villages occupy. The inhabitants of the intermediate-range villages exploit a variety of levels which inhabi- tants of coastal villages do not. Spring favism, altitude and Lent. Fifty-four of 111 spring episodes could be attributed to beans eaten during Lent. This is the figure for the entire island (48.6% of all the cases in the spring were associated with Lenten beans). Taking the cases reported only from the rural areas, forty-one of eighty-five rural cases were attributed to beans eaten during Lent (48.2%). The distribution of these Lenten and spring cases according to altitude is shown in Table 5.7. From these data, altitude is shown to have an inverse relationship to the proportion of spring-Lenten cases, even though the higher elevations have a higher favism frequency (Refer to Table 5.6). Given the previous discussion about altitude, this is 212 mmuozm cham :_ mmuomwam Emw>mm mcwcam umugoqmm No mcwewk ucm muzuwup< N.m .mwu , m o. o m m m. : «N .w 2 ENZDQI III. , n:241:4_ J42 1 Jan? 1_1 . +951 . I; .v N; saw: :10 2138mm 213 TABLE 5.7 LENTEN AND SPRING EPISODES 0F ALTITUDE Lenten Spring Beans* Beans Lenten/Spring Cases (%) Mountain 11 28 39.3 Inland 8 21 38.0 Coast 22 36 61.1 *Beans which are calculated to have been consumed during Lent. to be expected, as the beans ripen slightly later in the higher altitudes than they do in the lower ones. As shown, greater numbers of spring cases tend to occur slightly later in the higher altitudes than the lower ones. Aside from these factors, three other explanations might be offered: 1. In the coastal areas, fava bean consumption stops with the end of Lent; therefore, fewer cases of favism are observed in this area following Easter; 2. In the mountains, fava bean consumption continues after Lent has passed; 3. The availability of the fresh beans cases earlier in the lower elevations and are therefore not consumed after this time. With the available data, it is not possible to determine which of these might be the more accurate suggestion. 214 Bean use and distribution of favism The potential for exposure to fava beans differs by region, altitude, and particular practices in different villages. These factors of exposure can be expected to relate to the distribution of favism episodes. Urban-rural differences. It has been suggested in other studies on the distribution of favism episodes in Greece that only a fraction of the rural episodes are reported due to problems in understanding the need for hospitalization or in transportation difficulties from remote areas. Further, those in rural areas are known to tend to many of their health and medical needs without the intervention of health professionals. Based on these factors, one might expect that statistics for favism would show more urban than rural cases. This is not the situation for Rhodes. From a total of 123 cases, 95 were from villages and only 28 from the City of Rhodes. Kattamis et al. (1969) found that 8% of the males tested in the City of Rhodes had the enzyme deficiency. The present study and earlier ones find that the enzyme deficiency was over 10% in each of the rural locations screened. While these figures make it difficult to deny that the deficiency is implicated in the urban- rural distribution of favism, it must be stressed that those in the urban areas have little access to the fava plant. While they have many opportunities to buy the fresh bean from local markets, those in the urban center are not likely to have opportunities 215 to eat the fresh, raw fava beans while working in agricultural fields, or to handle the bean as it is picked from the field, or to gather the fresh beans from the fields. To emphasize this, regions immedia- tely outside the City of Rhodes show relatively more favism episodes reported. In the City, the frequency is only 0.8/1000 while in the regions surrounding the City (the village-suburbs), it ranges from 1.18 to 2.42. Certainly the greater participation in the pro- duction of fava beans in these village-suburbs effects possible exposure to the beans. Depending on location, the rural consumption of fava beans is spread throughout the entire year and not confined only to the spring. Nonspring episodes of favism were more predomi- nant in the rural locations than in the urban ones. From twelve off-season (non-spring) cases, ten were from villages. Considering that half of the island's inhabitants are located in the City of Rhodes, the figure of 2/32,517 is lower than 10/33,86l. Table 5.8 shows this rural to urban distributional pattern. TABLE 5.8 RURAL/URBAN OFF-SEASON FAVISM CASES Off-Season All % Off-Season to Total Episodes Episodes All Episodes Population Villages 10 95 10.5 10/33,861 City 2 28 7.1 2/32,517 In the villages, 10.5% of all episodes were accounted for by off- season favism, while in the City, only 5.2% of all the urban episodes were accounted for by the off-season ones. 216 Differences in village production of fava beans. Using data from Massari and Kritinea demonstrates that all the villages in Rhodes do not produce relatively the same amount of fava beans. Massari and Kritinea serve as representative villages of the two regions described earlier in this section (regions F and 0). They also represent two altitudinal differences, Massari being a coastal village, and Kritinea a mountain location. In the Massari region the frequency of favism was calculated to be 1.7 with the frequency for Massari itself at 4.7/1000. As a member-village of a mountainous region where the average favism frequency was calculated at 7.0/1000 the frequency for Kritinea was 13.4/1000 Again, it is tempting to attribute these differences to the enzyme deficiency frequencies which are 27.0% in Massari and 43.0% in Kritinea; however, the concern here is with the differences in fava bean production and consumption. The two villages are compared in Table 5.9. TABLE 5.9 GD" TRAIT AND FAVISM FREQUENCIES IN THE REGIONS OF MASSARI AND KRITINEA Gd" Trait Favism Favism Frequency in the Frequency Frequency Region Represented Massari 27.0% 4.7/1000 1.7/1000 (Region F) Kritinea 43.2% 13.4/1000 7.0/1000 (Region 0) In these two villages, 36 families were questioned about their production of fava beans. Twenty families were from Massari, and sixteen from Kritinea. In Massari, only three of the twenty families grow their own beans. In Kritinea, fourteen of the sixteen 217 families interviewed produce their own beans. The fewer families from Massari who produce their own fava beans tend to lower the population at risk. In Kritinea, the greater number of families producing their own beans complements the high Gd" frequency. In both locations, the fava bean exposure risk factor at the Gd" frequency are directly related. Two annual periods of fava bean consumption patterns were designated in the analysis of regional variations in fava bean expo- sure: the first coincides with the fresh beans season in the spring, and the second covers the remainder of the year. While the majority of cases occur in the spring, it should not be assumed that all of these resulted from fresh beans, or that it is only the fresh bean which is associated with episodes. Fava bean consumption tends to be higher in the spring; if the same level of fava consump- tion continued throughout the year, it is likely that more episodes would be reported. Nutritional information from thirty-nine families in Massari and Kritinea shows that the families from Kritinea tend to eat fava beans more often throughout the year and in greater variety. This information was collected from families which all had school-aged children so that the differences between them with respect to using the beans cannot be attributed to having only infants of pre-schoolers in the family (a factor which might tend to influence their use). In Massari, six families did not consume the beans at all, thirteen ate them only in the fresh form, and one family ate the beans in both fresh and dry forms. In Kritinea, two families did not eat 218 the beans at all, seven ate them only fresh, and ten ate them in a variety of fresh and dry preparations. These characteristics are summarized in Table 5.10 TABLE 5.10 FRESH AND DRY FAVA BEAN CONSUMPTION IN MASSARI AND KRITINEA Massari Kritinea Don't eat 6 2 Fresh only 13 7 Both Fr/Dr l 10 In Massari fourteen families used the fava beans. While in Kritinea seventeen families used them, the majority of these latter used them in both fresh and dry preparations. It is possible that using the beans throughout the year in a variety of preparations is related to growing them in greater abundance. Earlier, it was shown that sample families in Massari usually do not grow their own beans. Considering only those families involved in agricultural pursuits from both villages, those from Kritinea eat the bean more often than those from Massari. Table 5.11 Summarizes these data. TABLE 5.11 FAVA BEAN CONSUMPTION IN AGRICULTURAL AND NON-AGRICULTURAL FAMILIES IN MASSARI AND KRITINEA Massari Kritinea Agriculture Other Agriculture Other Don't eat 5 l l 1 Only fresh 5 8 7 0 Both forms 0 l 9 l 219 Those in Kritinea not only grow more of the beans, but eat them more often throughout the year in a variety of forms. Con- sumption of the beans may be related to features of the environment (such as altitude) or other cultural traditions which are not inves- tigated here. Conclusion to Part I: Seasonality and Regionality of Favism In Rhodes, the rural locations which have the highest altitude happen to be those with the highest frequencies of the enzyme defi- ciency and the greatest amount of exposure to the fava beans. In these areas, the beans become ripe later in the spring than they do in the coastal areas, and show more cases of favism occurring later in the spring when compared to coastal villages. Almost all the coastal cases in the spring are accounted for by fava beans consumed during ritual fasting associated with Lent. Following this period, the use of the fava beans drops considerably in the coastal areas, while their use continues in the higher elevations. Even though the Gd" frequencies are high for certain villages at high altitudes (e.g., 33.3% in Siana, and 42.3% in Kritinea) the average for the mountainous regions is not any higher than it is in the coastal areas around Massari (See Table 5.3 for review). Although the other villages around Kritinea were not examined for bean consumption patterns in families, it can be assumed that they follow similar patterns to those found in Kritinea. Therefore, high risk for favism in Rhodes is associated with living in high 220 altitudes, regardless of particular enzyme deficiency frequencies. PART II Age and Sex Distribution of Favism Favism is primarily a pediatric disease most often affecting male children under the age of ten. The epidemiological attributes of favism, known in scientific research, are reflected in popular belief as well. The statistics gathered in this study show the age distribution to be in conformity with the literature. The females to males ratios in Rhodes for 1966-78 are more nearly equal than has been reported in the literature (from 1:2 to 1:22 female to male). Reasons for the age and sex distribution of favism are suggested to relate to organic and/or exposure (to the fava bean) factors. Organic factors may directly affect the level of the G6PD enzyme activity or indirectly related to the general resistence of the individual when exposed to hemolytic agents. Behavioral and cultural variables are suggested to affect these distributions of favism. The present study was able to elicit some of this infor- mation which is used to discuss the age and sex distribution of favism on Rhodes. Age Distribution As reported in the literature, favism occurs most often in children under the age of ten, at which point, the numbers of episodes drop drastically. In at least one major series of studies in Greece (Kattamis et al. 1969, 1971) the research team had difficulty 221 in finding adult cases, however, as Figure 5.8 shows, adult cases do indeed occur in Rhodes. From 123 cases of favism, 79 occurred among children (64.2%) under the age of fifteen. For every one adult case of favism, 1.7 cases of pediatric favism were reported. Reasons for this age distribution are often examined in terms of organic factors. Other variables related to environment, exposure to fava beans, and socially influenced practices such as changes in consumption patterns by age which may be implicated are not ex- plored in the literature one considered in this section. Organic factors It is usually suggested that children have a greater "vul- nerability" than do adults, to the effects of the fava beans. This lack of resistence may result from at least two organic factors: (1) changes in the levels of the enzyme deficiency in terms of the number of red blood cells affected with the deficiency; and (2) some unknown factors related to acquired immunity or autoimmuniza- tion which act either on the red blood cell itself or in other fea- tures of blood biochemistry. Childhood illnesses, bacterial or viral infections, may also interact with the Gd" trait so that children show more hemolytic episodes than do adults with the trait. These episodes are attributed to the beans in the diagnoses rather than the viral infection. It is generally accepted that the enzyme deficiency genotype does not alter with time; individuals carrying the trait on one or more x-chromosome are recognized as bearing the trait and capable 222 mmuogm cw maGOmwam Em_>aa cmutoamm PP< to =o_u=awtumwo mm< m.m .a_a mcmw> cm mm< no oaw mN _oN mo .09 mm _om me oe. mm on ma" ow up mN-momp mmuosm .Nmpwamoz capo cmmao .mucoumm "mugzom or VP Np or a Q C 9! $3 53593 go aaqwnN V P or up 223 of passing it on to the next generation. It is not clear if the population of enzyme deficient red blood cells changes through time, as a consequence of age, or acquired immunity through low levels of fava bean exposure. It is also possible that the ratio of affected to unaffected blood cells may be altered by unspecified dietary and environmental factors. Virtually no research has examined if, or how, populations of enzyme deficient red blood cells change. Since screening has usually taken place using school-aged popula- tions, no comparison can be made with individuals of ages over, say, twenty to sixty with respect to the level of enzyme activity. Recently, regular screening of newborns has been instituted in various areas of Greece (Institute of Child Health, Athens, Greece). This will provide a basis for rescreening at later dates if research can be promoted in this area. Therefore, at the present, potential changes in either the blood or immunological factors present must be examined indirectly. If changes involving the blood chemistry of deficient cells actually take place through aging, either in the population of the red blood cells or in the acquisition of immunity, it should be expected that children in the younger age groups will have more serious episodes of favism. Further, if autoimmunization is invol- ved, which is predicted to occur by low and long-range exposure to fava beans, those families which consume the beans throughout the year in a variety of preparations, would be expected to report fewer children showing episodes of favism. Presentation and Severity of Symptoms. Sixteen episodes 224 of favism were reviewed according to their case histories collected through interviews and the severity of symptoms. All the cases which occurred when the affected individual was from 0-13 years of age, were divided into two groups: 0-5 (ten cases) and 6-13 (six cases). The method of calculating the severity of the episodes involved the following: (1) the onset of signs of hemolysis in number of hours after fava bean consumption (jaundice and discolored urine), and (2) the manifestation of other symptoms such as dizzy- ness, headache, and temperature, along with the hemolytic signs. As Table 5.12 shows, the children in the 0-5 year old cohort did not show any tendency to present hemolytic signs earlier than their older counterparts. Four of the children in the young age cohort presented hemolytic signs within 24 hours after eating the suspected fava beans, and six showed these signs after 24 hours. Among the eight older children, five showed hemolytic signs within 24 hours, and three showed them after 24 hours. TABLE 5.12 PRESENTATION OF HEMOLYTIC SIGNS IN PEDIATRIC FAVISM: TWO AGE COHORTS COMPARED Hemolytic Signs w/in 24 hrs. after 24 hrs. Age '0-5 6 - l3 5 Of seven cases where only the hemolytic signs were reported, two were in the 0-5 year old cohort, and five in the 6-13 cohort. 225 Regardless of age, the majority of these seven cases which showed only the hemolytic signs, were reported to have occurred within 24 hours after the beans were eaten. Table 5.13 shows a comparison of the manifestation of only the hemolytic signs with cases where other symptoms were also present (such as dizzyness, palor, fever, vomiting). In all cases these symptoms preceded or occurred simultaneously the hemolytic signs of jaundice and/or discolored urine. Of the ten episodes in the younger age cohort, eight involved additional symptoms. The distribution of the hemolytic compared to additional symptoms in the older age cohort was evenly distributed. TABLE 5.13 CASES WITH ONLY HEMOLYTIC SIGNS V.S. THOSE WITH OTHER SYMPTOMS: TWO AGE COHORTS COMPARED Only Hemolytic Additional Signs Symptoms Age 0 - 5 6 - 13 3 5 Episodes which involved only the hemolytic signs usually showed these signs within 24 hours of eating the suspected fava beans, as Table 5.14 shows. In eleven cases, additional symptoms as well as the hemolytic signs were reported. Eight of these were in the O - 5 cohort, and only three in the 6 l 13 cohort. All but two of these eleven cases were associated with hemolytic symptoms which appeared within 24 226 hours, and both were in the younger cohort. Regardless of age, when additional symptoms are reported the hemolytic signs appeared after 24 hours. All additional symptoms preceded the hemolytic signs. It appears that when the hemolytic crisis became evident within 24 hours after consuming fava beans, additional symptoms were not experienced (or, in any case, reported). TABLE 5.14 CASES WHERE ONLY HEMOLYTIC SIGNS WERE REPORTED Hemolytic Signs Presented Within After 24 hours 24 hours .Age 0 - 5 2 6 - l3 3 2 TABLE 5.15 ONSET OF HEMOLYSIS IN CASES WHERE OTHER SYMPTOMS ARE REPORTED Hemolytic Signs Reported Within After Age 24 hours 24 hours 0 - 5 2 6 6 - 13 O 3 In summary, the children in the younger age cohort did not report hemolytic signs any faster than did their older counterparts, however, they did show a variety of accompanying symptoms which preceded the manifestation of jaundice and anemia. Therefore, it 227 is not possible to say that hemolysis occurs more rapidly in younger children. From the data, younger children suffer a complex of symptoms more often than do their older counterparts. The greater number of symptoms in younger children may be related to a number of factors not dependent on the Gd" trait. Some of these might include the closer observation of symptoms by adults or the lack of reporting early symptoms by the older children. Autoimmunization. If acquired immunity is a factor not only in the age distribution of favism, but in the etiology of the disease as well, at least two variables would be expected to play a role: (1) the ability of one episode to confer immunity, and (2) immunity acquire by the low grade, continuous exposure to fava beans. It is well documented that same person recorded. Indeed, one of the dangers of favism is that after remission of hemolytic signs, a relapse may occur without subsequent consumption of fava beans. Nutritional information collected from the families in Massari and Kritinea indicates that favism is suffered more often in families consuming the beans throughout the year and in a variety of forms. In many instances, the episode followed the consumption of fresh beans, even though the family consumed the beans in a variety of preparations, both dry and fresh, at other times of the year. Other organic weaknesses in children. Individuals with the enzyme deficiency have been known to exhibit hemolytic episodes unassociated with any known hemolytic agent. These episodes are generally attributed to organic stress, particularly viral infections. Children between the ages of two to twelve are subject to a variety 228 of viruses and microbes for the first time, passing through a number of infectious diseases to which they are rendered immune. This is more the case for the children of Greece than for the children of the United States because many children are not routinely immunized for the diseases that U.S. children are, in particular, mumps and rubeola. Immunization for rubella and polio is a relatively new feature of the public health program. These childhood diseases may possibly play a role in provoking favism episodes, which are in diagnosis attributed to fava beans, but which in reality have multiple causes associated with childhood diseases and infections. Of the eighteen cases for which histories were taken, two had been preceded by infectious diseases. The one followed a prolonged episode of tonsilitis, where the symptoms of favism were at first mistaken for a continuation of the tonsilitis. The other occurred following measles. In many childhood diseases and common colds, various drugs are administered, some of which are known hemolytic agents for the enzyme deficient individual. Therefore, it is not certain if hemolytic episodes following infections and infectious diseases might not be attributed to the use of aspirin, Novalgin (a popular pain reliever), and sulfa derived antibiotics. In Greece, many of the drugs which are regulated through prescriptions in northern Europe and Canada and the U.S., are available without signed prescriptions. This allows the circulation and use of drugs for infections and diseases for which they might not be prescribed by a physician. For viral infections, many people use antibiotics, which in turn might affect 229 the appearance of a hemolytic episode. One of the eighteen cases in the present study followed the use of aspirin (for a toothache) as well as the consumption of fava beans. Therefore, it is not clear which of these hemolytic agents was the "cause" of the hemolytic crisis. These cases which were attributed to the fava bean, but which might have involved viral infection and/or the use of hemolytic drugs indicate that more information is needed on this subject. This type of information could be routinely collected during the admittance and treatment of favism episodes, which has not been the practice in the past. This should aid in gaining a clearer picture of the association of favism, childhood diseases, and the use of antibiotics and other hemolytic drugs. Other than the episodes of favism which followed viral or bacterial infections, and the use of hemolytic agents, other hemolytic episodes were noted in children with the deficiency, some of whom suffered also from favism. If some unknown organic factor promoted hemolytic episodes from fava beans in the young children, it might be expected that cases of such episodes would also be more prominent in these children. To explore this hypothesis, two groups of enzyme deficient children were examined: (1) those with favism plus at least one previous case of hemolytic crises suffered under other conditions, and (2) those without favism, but which reported one case of hemolytic crisis not associated with fava beans. Of thirty-four children identified with the deficiency, and for which case histories of diseases and conditions related to health were available, seven had experienced hemolysis or jaundice 230 for reasons other than those associated with the fava bean as the hemolytic agent: (1) Three were jaundiced shortly after birth; (2) One had unexplained, severe anemia at age two; ( One had hepatitis at age four; ( Two had spontaneous, unexplained jaundice at the ages of eight and ten. These episodes of non-fava bean episodes of hemolytic crisis are shown in Table 5.16. TABLE 5.16 HEMOLYTIC EPISODES IN GD" TRAIT CHILDREN (OTHER THAN FAVISM) Hemolytic Episodes Not Total Related to Favism Favism 12 3 (25% No Favism 22 4 (18%) Total 34 7 (20.6%) Three of twelve Gd" trait children who suffered from favism also reported earlier episodes of hemolytic anemia (25%), while four of twenty-two children not reporting favism had suffered previous episodes of hemolytic anemia (18%). Children with favism had a higher percentage of earlier hemolytic episodes than did those with the deficiency but without favism. From the sample, those having had hemolytic anemia from non-fava bean related agents at earlier ages were more likely to report favism later in life. This does not mean that children with the deficiency have a greater tendency 231 toward favism at earlier ages, but have a tendency toward hemolytic episodes in general. 0f the thirty-four children, sixteen suffered from at least one hemolytic episode from fava beans or from some other cause (twelve cases of favism and four cases of hemolytic not related to favism). Analyzing the age distribution of favism episodes from health histories has not been considered in the literature. The cases in the present study which had other physical factors preceding the onset of favism episodes are too few to make any conclusions about the relationship between the health status at the time of the episode and the favism case itself. This needs further investi- gation, along with the role which previous hemolytic episodes play in individual cases of favism. Environmental factors The distribution of favism episodes among the different age groups is now shown to vary according to either urban-rural or altitudinal locations. Figure 5.9 shows the age distribution by urban-rural cases. The upper line, showing the total cases, is nearly parallel to the line showing the urban and the line showing the rural cases by age. That is, there is no appreciable difference by age in these distributions. Figure 5.10 shows the age distribution of rural cases by altitude. In the children under six years of age, the mountain cases account for 44% of all the rural episodes. In the coastal areas, the 6-10 year old cohort accounts for 57% of all rural cases 35 3O 8 1?- Number of Cases 232 ----0 Rural o———o Urban <6 6-10 11-15 1.6-20 21-55 >56 Age in Years Fig. 5.9 Age Distribution by Rural and Urban Episodes wup=5w5_< Na mamau _at=m to coauaawt5m_o am< o,.m .a_a Wu Z. m0< 0n A mm¢N ON-@. m7: 079 P P 233 2.528: _U 0252. § ._ <15 (ow . E . N A A \ . \ QGQ 0 $39)!) :10 HQSHflN N $29! 92. 234 in this cohort. For this sample, the youngest children in the moun- tain regions and the six to ten year olds in the coastal regions show the greatest number of episodes. TABLE 5.17 AGE DISTRIBUTION AND ALTITUDE Age Coast Inland Mountain Total 0-5 12 10 17 39 6-10 8 3 3 14 11-15 2 4 4 10 16-20 1 O 0 1 21-55 4 2 7 13 56+ 11 3 4 18 Total 38 22 35 95 While all cases drop after age five to six, according to the Rhodes figures, the drop in cases in the mountain areas is larger than would be expected based on (1) the previous representation in the 0-5 age cohort, and (2) the fact that the greatest frequencies are from the mountain areas, and these would be expected to influence the characteristic pattern for all total episodes. More information is needed about the age composition in the localities in order to account for this drop by demographic factors. (The distribution of the population among the different age groups in Massari and Kritinea is nearly the same.) While changes in consumption patterns are expected to vary by age and by region, separately, they are not expected to vary by age between regions. That is, it is not expected that 6-10 year olds in the mountains would abruptly stop 235 eating fava beans, while their inland and coastal counterparts would continue. This requires further investigation to rule out that purposeful changes take place in fava consumption from ages six to ten; it is more likely that the drop in mountain cases in this age group is a chance event. Exposure to fava beans and age Exposure to fava beans is expected to include that which takes place both in and outside of the household unit. These were listed in the introduction to be (1) use in home, (2) protection of young children; (3) protection after lst episode; and (4) partici- pation in agriculture. While families may not use the beans or offer them to children, other potential exposure to the beans may exist outside of the home. Use in the home. Fava beans are often used as a weaning food for infants in many parts of the Mediterranean because they can be mashed up easily into a puree, and perhaps because they have been long-recognized for their nutritious value. This is not the case for Rhodes where they are not usually given to children under the age of two. The age distribution shows very few cases occurring before the age of two, which is probably a reflection of this practice. Italian observers, in the early history of the medical recording of favism episodes, wrote that Italian mothers have been known to feed their children small amounts of fava puree or soup to protect them from the effects of larger doses. This behavior was not observed in Rhodes. Depending on the particular caution exercised 236 in different families, fava beans may or may not be given to young children under the age of six. Some of the episodes in this age group occurred from fava beans given to the child by neighbors, relatives, or from beans which were taken from a plate of beans left unguarded during their preparation. Protection of children from eating fava beans. Throughout Rhodes, the idea is expressed that fava beans should not be given to children; however, the conviction that children must eat, and eat a lot, in order to grow interferes with this idea of protection. When families are asked what foods are good for children, they almost always respond, "all foods". If asked specifically about fava beans, they will, on the other hand, say that they should not be given to younger children. Therefore, if a child who is viewed as a difficult eater, which most infants and toddlers are considered to be, any food that they show interest in will be given to them. One dramatic episode of favism occurred in a two-year old child who had seen the family eating cooked fava beans in a tomato soup mixture. The infant cried and carried on so, insisting that he wanted a portiOn of the beans, that he was finally given a piece of bread soaked in the soup by his resigned mother to stop his crying. Shortly thereafter, hemolytic signs appeared, the child was taken belatedly to the hospital, but the hemolytic crisis was sufficiencly severe to result in death. This was the only death recorded among the child- ren in Rhodes during the twelve year survey. It was well known to the inhabitants of the region, who supplied the details of the 237 episode. The emphasis on food consumption among young children involves the idea that chubby and even obese children and infants are most healthy. The most common complaint from parents in interviews and in the local agrarian physician's office is that one or more of their children "refuse to eat". This phrase must be considered in relation to the proportion of food which children are given on a plate and expected to consume entirely. The portion is usually adult-size, and when they do not consume all of it during the meal- time, it may be left out for several hours, during which time the mother, grandmother, or older sister will try to give the young child a spoonful of the serving every so often. Many children before the age of eight become passive eaters; that is, they never sit down to eat a meal, but circulate while the family is eating, and are given portions of food off the table by different family members. While fava bean preparations may not be cooked with the idea of serving the child a portion, it is common to find a child being given a spoonful or even taking a few beans from the table. This holds true when children visit other homes in the village. If they happen to visit a neighbor's home with other family members or children, they will be offered whatever happens to be on the family table, or whatever the housewife has cooked for her family. Again, fava bean may be among these preparations, and children may be given a serving, perhaps on the assumption that well-cooked beans cannot harm them. As an example from the present study, one favism episode occurred following fava beans which were 238 offered to the child from the neighbor's kitchen. The child wandered into the kitchen while playing with the neighbor's children, and was given the beans. The bean had not reached the family's meal table. Even though many adults and parents adamantly claim that fava beans should not be given to children to the point of arguing with grocers who have left the beans outside of the store, the emphasis on food consumption for children overrides this concern for fava beans to be avoided by them. Further, the majority of the eighteen children who suffered from favism stopped eating the beans there- after but the rest of their families continued to consume them. Fasting behavior and age Lenten fasting coincides with the ripe fava bean season, but not all spring cases are associated with beans consumed during Lent. Figure 5.10 shows the distribution of all the favism episodes by age compared to both the spring and the Lenten episodes. It would be expected that all age groups would show relatively fewer cases from beans consumed during Lent, however, the marked difference in the total cases compared with Lenten cases in the 0-5 age group indicates that children may be protected from fava bean consumption most strictly during this period. Of all the seasons during the year, the fava beans (fresh or dry) are most likely to be in the households during the Lenten fasting period. Due to the coincidence of Lent with the ripe period, the majority of these beans are likely to be ripe which means that 239 they can be easily picked up and eaten by the children while left laying around in the home or the outside area adjacent to the home. From the case histories of eighteen favism episodes, none of the Lenten cases followed the consumption of beans which were given to the child within the home. Some followed the consumption of beans which had been taken from the kitchen, unknown to the family; others were given to the child by friends or neighbors, and others were taken from the field. While the use of case history information from a small sample of cases cannot verify that fava beans used during Lent are even more cautiously not served to children than during the rest of the year, they indicate that the interplay of general food habits in children, protection from fava beans and Lent might be looked at closer in other epidemiological studies. For the present data, the protection of children from fava beans operates to lower the number of expected episodes. Even though entire families, aside from the children under five, may consume the beans during Lenten fasting, the children appear to be quite protected from exposure. As soon as Lent ends each year, a drop in the cases is observed, suggesting that the self-will of the children overrides protective precautions. Participation in agricultural and age Children after the age of six begin to be more mobile outside the household. Often they will be taken into the fields surrounding the village. At this time, they have cone into greater contact 240 with the growing beans and those which are seasonally present outside of grocery stores. Because the bean pods are easily visible on the plant, they may be picked by the children, and held in the hand or saved in a pocket. Their large size makes them a likely target to be picked up by young children, whether or not they are actually given to the children by older adults. By the age of twelve, young people are left to go into the fields and participate in harvesting activities. They may be sent to gather grape leaves for other food preparations (especially young girls),to gather greens, to check olive trees, and so forth. Again, they come into direct contact with the beans as they are growing, and abundant opportunities exist for picking and eating the beans while other agricultural activities are pursued. By the time young pe0ple reach the age of fifteen, they are participating in most of the agricultural chores that adults do, and have equal Opportunity to eat the fresh beans at will, as do the adults. By this time, however, the number of reported cases of favism has dropped drastically from the earlier years. Adults over the age of fifty eat the beans by habit, since they grew up with the beans being a much more conspicuous feature of the annual diet. These are those adults who were born before the Second World War, when the beans were widely eaten, and meat was rarely available. Summary of age distribution By the age distribution of the 1966-78 reported episodes of favism in Rhodes, the highest risk group was found in children 241 from one to five years of age living in mountain villages. The ratio of pediatric to adult cases was 1.7:1, more nearly equal than has been noted in the literature. The sample of eighteen favism cases showed that hemolysis did not appear earlier in the youngest children (0-5) than in older cohorts, but that additionally symptoms occurred more often in the former group. Data is inconclusive on whether or not viral and bacterial infections and/or exposure to other known hemolytic agents immediately prior to the episode is an important variable. Gd" trait children who suffered previous hemolytic anemia had slightly greater tendency to develop a second hemolytic crisis (favism) later. Childrensunder 5 in the mountains are almost two times more likely to have favism than inland and coastal children in the same cohort. After this, their risk drops. Coastal children are at their greatest risk until ten years of age. Families with beans in the home have more episodes, even though most occur from unsupervised bean consumption outside of the home. This suggests that autoimmunity is not a factor in protecting against favism, and a complex interplay between familial habits and physical environment. In Rhodes, the individual most likely to suffer from favism would be expected to be under age six, regardless of altitude. Those in the coastal areas over fifty-five years old are also at a higher risk of favism than other age groups. A previous hemolytic crisis was not a particularly reliable indicator of whether or not an individual would later suffer from favism. In children, eating fava beans after Lent and/or in an unsupervised manner was more 242 often associated with favism than not. The consideration of the age distribution of favism is complimented by looking at factors which interact with the sex distribution. Some of these have already been mentioned; for example, the participation in bean production activities by age also relates to the sexual division of agricultural labor where women are more often involved in gathering and food preparation activities than men. Sex Distribution of Episodes Medical investigators who have noted the sex distribution of favism, which shows more males than females represented, have often remarked that it is yet another enigmatic aspect of the disease. As with the explanations offered to examine the age distribution, the focus in previous research has been on characteristics of the enzyme deficiency or other organic factors which might interact with the deficiency. Environmental factors, differences in fava bean exposure and other social or ideological variables have not been investigated. In Rhodes, the male to female ratio of favism episodes is more nearly equal than in any of the reports from other areas. Of 123 total cases, 52 were reported in females, 71 in males for a ratio of 1:1.36. Figure 5.11 shows that age does not appear to act on this nearly balanced ratio. In all age cohorts, more than as many females as males report favism. Aside from the x- linked nature of the Gd" trait, three other factors listed in the introduction will be discussed in this section. (1) differences in expression of symptoms; (2) environmental differences; (3) 1:1 MALES @ FEMALES 243 rL/////////.//// //////¢/Q i v . 7////// _ _V///////// 7///7//////////////////////// —bb|bip b.8642 21-55 >56 4 6°20 11-16 QVWO <6 AGE IN‘YEARS Fig. 5.11 Age and Sex Distribution of Favism Episodes 244 exposure factors. G6PD deficiency and sex distribution of favism Because the enzyme deficiency is an x-linked trait, it is tempting to explain the sex distribution of favism episodes on this basis,lnrtthis temptation is best avoided. As discussed in Chapter One, genotypes and phenotypic expression may have little to do with each other. Males who are expected to be fully enzyme- deficient according to their genotype show a wide range of enzyme activity on the basis of phenotypes. Female heterozygotes compli- cate the picture even further as their phenotypic expression may show cases as nearly deficient as male hemizygotes while others are nearly normal. Episodes of favism which are used in the present study were not tested as to quantifiable levels of enzyme activity preceding the hemolytic crisis. Further, while such information would have been valuable, it is not the object of this present study to make these distinctions. It is possible that the differences noted in the sex ratios of favism are due to differences in the symptoms and progress of the disease as experienced by males on the one hand and females on the other. These differences may be due to organic and/or socio- psychological factors. It is not the object here to establish one or the other: certainly social constraints on sex-role behaviors have an impact on the presentation of symptoms just as much as purely physiological sex-related differences. Using the case histories from 18 cases from Massari and Kritinea, this possibility is discussed 245 in two parts: (1) the timing of hemolytic signs; and (2) the mani- festation of accompanying symptoms or conditions. Hemolytic signs. Table 5.18 shows that females tend to manifest hemolytic signs sooner than do males among the 18 cases. Hemolytic signs of jaundice and/or discolored urine usually appeared more often after 24 hours following bean ingestion (10 of 18 cases) with the largest number of these showing hemolytic signs after 24 hours being males (7 of 10 cases). Those assumed to hemolyze slower were, in the majority males. TABLE 5.18 PRESENTATION OF HEMOLYTIC SIGNS BY SEX Presentation of Hemolytic Signs w/in 24 hours after 24 hours (total) males 3 7 (10) females 5 3 ( 3) (total) (8) (10) From eight female cases of favism, three showed hemolysis after 24 hours (37.5%), while seven of ten males (70%) showed hemolytic signs after this same time. Females did not tend to show hemolytic signs any sooner than did their male counterparts, and in fact, the opposite trend was observed. The idea that males hemolyze faster following bean consumption, perhaps due to some characteristics of the level of enzyme activity, is not supported by this data. It is not possible to state if this is applicable to all the 123 cases which were reported in Rhodes during 1966-78. Accompanying conditions. In both sexes, the majority of 246 all cases showed other accompanying conditions such as dizzyness, palor, vomiting and elevated temperature. Where one or more of these accompanying symptoms were noted, they first appeared before or in conjunction with the hemolytic signs, never after. Six of ten males showed additional conditions, while seven of the eight females were in this group. These results are shown in Table 5.19. TABLE 5.19 PRESENTATION OF ADDITIONAL SYMPTOMS BY SEX Additional Only Hemo- Symptoms lytic Signs (Total) Males 6 4 (10) Females 7 l ( 8) Considering both hemolytic signs and additional conditions together, all males which reported hemolytic signs within 24 hours did not have any other signs, while all males which hemolyzed after 24 hours had other accompanying conditions. Among males in this sample, early hemolytic signs did not carry other conditions with them, while later hemolysis did. Females in contrast, showed accompany- ing conditions even when the hemolytic signs were reported early. It might be concluded that female episodes of favism are perceived to be more severe in that they present hemolytic signs sooner as well as involve accompanying conditions. Environmental factors As with age distribution, urban and rural ratios of the sex distribution in Rhodes show little difference. The rural female 247 to male ratio was 1:1.3 and the urban female to male ratio was 1:1.5, as shown in Table 5.20. TABLE 5.20 MALE TO FEMALE EPISODES SHOWN BY URBAN AND RURAL LOCALITIES Female to Male Episodes Number of Episodes Ratio Urban ll : 17 1:1.5 Rural 41 : 54 1:1.3 Total 52 : 71 1:1.4 Both female and male rural episodes were higher than female and male episodes when compared within the same sex. For all male episodes, the rural to urban ratio was 1:3.2, while for all female episodes, the rural to urban ratio was 1:3.7. These figures are given in Table 5.21. Since the urban and rural population in Rhodes is nearly equal, these ratios are not a result of demographic factors (such as the largest proportion of the population being located in the rural areas). TABLE 5.21 URBAN TO RURAL RATIOS BY SEX DISTRIBUTION Urban: Rural Episodes Raw Ratio Males l7 : 54 l : 3.2 Females ll : 41 l : 3.7 Total 28 : 95 l : 3.4 In the 95 rural cases of favism, the 41:54 female to male 248 ratio (l:l.4) is distributed according to the altitude in which the village cases are found. Using the mountain, inland and coastal divisions introduced earlier, slight differences in each altitudinal group appear. These are shown in Table 5.21. The most striking point is that the female to male ratio is equal in the coastal areas. This is the first time that as many female as male cases of favism have been reported. In fact, the average ratio of 1:1.4 for Rhodes is the most equally balanced ratio for a population. TABLE 5.22 FEMALE TO MALE EPISODES BY ALTITUDE Female to Male Episodes Raw Number Ratio Mountain 13/22 1:1.7 Inland 8/14 1:1.8 Coast 19/19 1:1.0 Reasons for this distribution may have to do with the way in which the altitudinal groups were subdivided, however, it should be emphasized that the population in the coastal area includes the major centers of population on the island, which gives greater importance to the equal female to male ratio. Differences in fava bean exposure by sex From the 18 cases of favism, 11 were found to have been associated with fresh raw fava beans. Seven of these (eleven) episodes from raw beans occurred in female children aged five to fifteen. None of these involved beans which were given to these young girls, 249 but were from beans eaten during food preparation or gathering activi- ties. Only one episode in female children followed the consumption of dry beans. These figures are shown in Table 5.23. TABLE 5.23 FORM OF BEANS ASSOCIATED WITH FAVISM EPISODES IN MALES AND FEMALES Form of Bean Cases causedppy Fresh : Dry Fresh : Dry Male 6 4 1.3 : 1 Female 7 1 7.0 : 1 This table also shows that six of ten males had eaten the fresh bean before the episodes, while four of ten had eaten it in the dry form. Male cases from fresh beans compared to dry were 1.3 cases from fresh for every case from dry beans. Female cases were 7 to 1, fresh to dry. That is, females suffering from favism from the fresh form were 5.4 times more numerous than the male form (7.0/1.3). Even though males are allowed greater access to the fields, their cases of favism do not occur following beans consumed from this location as often as they do among the young girls. Male cases occur often from beans consumed in the home or from prepared beans given to them by other relatives or neighbors. Agriculture and exposure As mentioned earlier, age differences in fava bean exposure are also influenced by age. Young children of both sexes usually have contact with the bean only in the household or neighborhood setting, however, as the children become older, different amounts 250 of freedom are influenced by being male or female. Boys at a younger age than girls have greater chances of going to the close-in fields (vis-a-vis the village center) to play. Here they are likely to come into contact with the fresh, ripe bean as it grows. Girls, on the other hand, begin to take part in duties related to food gathering and preparation, beginning around age eight. They too, have opportunities to eat the bean in the process of preparing them for a family meal. Males after the age of eighteen begin to frequent the local cafeneia (coffee houses) on a daily basis. Here they drink coffee in the early morning before going to the fields, and again, sit there in the afternoon to play cards and drink coffee or a whiskey or ouzo. In the evenings, they may drink beer, ouzo or wine together. Alcoholic beverages are never served alone in Greece (outside of tourist restaurants or bars), but are always accompanied by mgze or mezedakia. These are small food items such as bread, a small portion of fried potatoes, sliced cucumber or tomatoes, and often, fava beans. This places males after the age of twenty at greater risk of coming into contact with fava beans, however, they have already passed the age at which the majority of cases occur. Social factors affecting exposure by sex The ethnographic studies of Greece and the Mediterranean area almost always include an examination of sex roles, and in particu- lar, the place of female and male children in the Mediterranean family. Female children are depicted as a burden, both economically 251 and morally, on their families. Fathers are perpetually concerned about the loss of a young daughter's virginity as well as the accumu- lation of her dowry; however, in observing the treatment of young female children under the age of six in rural Rhodes, it is ho less affectionate than the treatment extended to male children of equiva- lent age. It is only at puberty or pre-puberty that the parental affection changes from open display to concern for the future for the young girl. Her circulation on the village is suddenly restricted; she is allowed out of the household area or neighborhood only for agricultural duties or errands which can take place before early afternoon. It is worth noting that only two of the total eighteen cases occurred in female children from the age of 0-5, while six more were reported after that age. That is, the majority of the 18 cases were reported in male children in this age group. This does not support the thought that female children are neglected and male ones protected. These figures are presented in Table 5.24. TABLE 5.24 SEX DISTRIBUTION OF FAVISM EPISODES BY AGE COHORTS (0-5 AND 6-15) Ages Males 8 2 Females 2 6 The fact that more cases among males in the present sample followed beans which were consumed in a cooked form (either dry or fresh), indicates that they may have been given these bean preparations by a relative or neighbor. This is consistent with 252 what has been observed in the villages. While young girls are not "neglected“ in their disease and presentation of symptoms, they are not pressured to eat the amount of food that young boys are. In order to explore the idea that male children are protected more than females, the reporting of episodes to medical personnel was examined. The results show that male episodes reach medical personnel before female ones do on the bases of the time of hemolytic signs. Only hemolytic signs were used as indicators that the disease represented a condition more serious than usual colds and influenza, since many of the preceding and accompanying symptoms could be con- tributed to "non-serious" disease. For example, vomiting might not be immediately reported to a physician, while jaundice and dis- colored urine were expected to be more rapidly reported following their manifestation. Using case history material from 18 cases it was found that all ten males represented were reported to the hospital within 24 hours after hemolytic signs were first noted, while only three of the eight female cases were reported in this time. Three additional female episodes were not reported at all, but two of these occurred in the late 1940s when favism was not generally recognized as treatable in hospitals and, in all fairness, they should not be considered in the figures. Even discarding these two female cases, it is still evident that female cases in this sample reached the notice of medical personnel later than did the male ones. This must also be considered with respect to the severity of symptoms. Female episodes tended to show more additional symptoms and to present hemolytic signs 253 earlier than did male cases. Based on this data, there appears that some preferential treatment of males may influence the sex ratios of favism. Males may not be protected from fava bean consumption any more than females, in fact, many of the male cases resulted from beans which had been offered to them rather than taken from fields. This is consistent with the emphasis on children's eating patterns where they are con- tinually being offered something to eat during and after meal times. Further, this is more likely to be the case with male children as males are believed to need more food than females. The cases of favism among young boys reach hospitalization sooner than do female ones, which may be a result of greater precaution taken about the signs of illness in males, or a result of the role model for young boys which promotes greater activity levels. If the young boys are not as active as expected to be by the model, they are considered to be affected by illness much more often than young girls. The latter may sit quietly for longer periods of time, and go unnoticed. These are suggested because the severeity of symptoms did not relate to the time of hospitalization in the sample. Age and sex role expectations may interact with the presen- tation of non-hemolytic symptoms such that the reporting of episodes is affected even if equal protection of both sexes is exercised. For example, six of eight children affected by favism and reporting vomiting as a symptom were females. Two of these reported dizzyness as an accompanying symptom, while none of the male children men- tioned this consistent with illness behavior in the villages of 254 Massari and Kritinea. Women almost daily complained of dizzyness (ggléga), while men rarely complained of feeling off balance or dizzy. Women are more likely to mention vomiting either in relation to a specific disease, or alone, while men conceal it or ignore it as important. Summary, Part II: Age and Sex Distribution of Favism The cases of favism reported in Rhodes show a more nearly equal distribution by sex than any earlier studies. It cannot be stated conclusively if the distribution is a result of preferential treatment of male children of the nature of the disease which allows more females to be reported than they are in other areas. Both males and females in rural areas are more likely to suffer from favism than their urban counterparts. The greatest number of rural favism episodes are accounted for by the 0-5 age cohort, with almost half of these being reported from mountain locales. This suggests that either high elevation in and of itself (as physicalenvironment) or some aspect of it adaptative process demanded by the higher elevations, may be a factor in promoting more cases in this youngest age cohort. After six years of age, the number of episodes in all areas drops, except for the coastal area where 58% of the cases in this cohort are accounted for by the coastal. Further, in the 0-5 mountain cohort, four of the seventeen cases were male (23.5%), while in the 6-10 coastal cohort, six of eight (75%) were male. Table 5.25 shows this inverse relationship of sex ratios in the two age cohorts in 255 the two altitude groups. The reasons for this distribution are not known but may relate to agricultural participation of women. In Massari, a coastal village fewer women participate in agricultural activities to the extent that they do in Kritinea, a mountain village. TABLE 5.25 MOST FREQUENT FAVISM BY AGE COHORTS IN MOUNTAIN AND COASTAL VILLAGES Mountain Coast Age cohort under 6 6 - 10 Female: male (4:14) (6:2) Ratio 1:35 3:1 Males who suffered from favism were more often from the inland and mountain locations, under the age of six, and had not eaten fava beans from the fields prior to favism. Female children were most often from the coast, over the age of six, and had eaten beans from the fields prior to their episodes. This is the opposite of what would be projected on the basis of sex roles. Obviously, a more complex process is going on. This may have something to do with the role of the young boy who is conditioned to having more freedom in the home and allowed to break rules more often than the young girls. The latter, trained to uphold the household rules, have a chance to be on their own more often when they are with other young girls, outside in the fields and away from the home. 256 PART III Familial Favism Many medical investigators contend that one episode of favism should be expected to promote changes in familial habits with respect to fava bean production and consumption. The tendency for cases of favism to be reported along familial lines shows that this is probably not the case. The familial tendency for favism cases to repeatedly appear was noted before the enzyme deficiency and its genetic pattern of inheritance could be used as a reason for these familial episodes. This tendency was initially explained by the theory of contagion; that family members spread the disease among themselves. Later, an inherited allergic weakness was suspected which led some families to show the disease. Members of families known to have reported favism who did not themselves develop favism were suspected of having developed an immunity to the beans. Since the deficiency was discovered, this factor was thought to explain the familial distribution of favism; however, it was soon found that not all individuals and familial lines with the deficiency in many members all reacted in the same way to the fava beans. This led to the hypotheses that some unidentified characteristic, also gene- tically inherited, was involved. This trait was hypothesized to act separately from the enzyme deficiency but to interact with it in certain families. Families might have only the enzyme deficiency and not the other, unidentified, genetic trait, and therefore did not report favism in any members. Families having both the defi- ciency and the genetic factor, were expected to show multiple episodes 257 of favism. This hypothesis was studied by Stamatoyannopoulos and Motulsky (1969), whose work shows that favism does indeed have a tendency to appear in familial lines and that certain familial lines show multiple episodes of favism.‘ The fact that a multitude of other variables which are not inherited genetically, but shared by virtue of location, tradition, fava bean consumption, etc., was not considered in their study. Familial Favism and Genealogical Data The Stamatoyannopoulos and Motulsky study is one of the few existing works on the subject of favism which utilized genealogi- cal information (and extrapolating pedigrees). This research showed that certain family lines with the Gd" trait tended to report favism more often among their members than did other pedigrees also affected with the trait. These data were taken from the Greek islands of Lemnos and Corfu, and the north-western mainland area of Karditsa. The Rhodian pedigrees collected during the present study showed "the same type of familial tendency that Stamatoyannopoulos found for his data. The comparison of these pedigrees appears in Appendix 8. Aside from comparing pedigrees where multiple favism cases had been noted, the Stamatoyannopoulos study did not compare families with the Gd" trait who did not ever report favism to those who reported one or multiple cases. It does not include any information about the consumption of or exposure to fava beans in these different pedigrees. Even though they are from three different regions of 258 Greece, the basic assumption was that all families are likely to be exposed to the beans in nearly the same manner and amounts. The present study did not begin from this assumption, and while collecting genealogical information, other data regarding familial differences in fava bean use and exposure were also elicited. Thirty nuclear family units with the Gd" trait and/or favism in one or more number from Massari and Kritinea were used for the analysis familial favism. While twenty of these did not report favism in the nuclear unit, eight of them reported favism in a consanguineal relative. Ten others reported favism in the nuclear unit with sex of these ten also reporting the disease in other con- sanguineal kin (either sibling or cousin-related). Two units reported single cases of favism in both the nuclear unit and in consanguineal kin, and three reported favism in a parent but not in Gd" son. Genalogical information was taken from all thirty nuclear families, even though some were included in the genealogical information from other nuclear representatives. The information was then worked into simplified pedigreed based on the circulation of the Gd" trait in a pedigree and in the presentation of favism episodes. Pedigrees differ from genealogies in that the latter is an ego—centered reporting of biological kinship as perceived by the person giving the genealogy. It has social and cultural meaning as well as biologically related kin for reasons known or unknown to the individual reporting the genealogy (e.g., family feuds, absent members, unrecognized marriages). Pedigrees are schematic represen- tations of actual biological descent which are gathered through 259 reported genealogies, village records, double-checking information given in the ego-centered reckoning of kinship. In the pedigree, certain individuals are identified with particular genetic traits or diseases; in this case, they were identified with the Gd" trait and/or reported favism episodes. The term proband is used in pedigrees instead of the term, egg, which is reserved for genealogies, to refer to the focal point of the schematic representation of biologi- cal kinship. In addition to the thirty families in the study, two others were added from a nearby village of Kritinea. These were included because they added to the analysis of sibling pairs, and were used only for this portion of the study. The probands were first analyzed by biological relationships, describing the different types of pairs which were found. These were considered in three categories: (1) Sibling pairs: (2) Parent-offspring pairs: and (3) Cousin pairs. In each set of pairs, the status of each member was known, either through screening or through the identification of a favism episode. Sibling pairs and the distribution of favism Nine sibling pairs where the status of both was known, appeared in the data from Rhodes. Seven of these were from Massari and Kritinea, and two more were added from a village adjacent to Kritinea. In three of these, both siblings showed favism; in five, neither sibling showed favism; and in one pair, only one of the siblings was affected by the disease. In this case, both boys had eaten the fava beans on the same day, in the same form, and the one was affected by favism, 260 while the other was not. Table 5.26 shows the comparison of these sibling pairs. TABLE 5.26 SIBLING PAIRS DIVIDED ACCORDING TO FAVISM IN PROBANO AND SIBLING Status of Sibling Favism No Favism Status of Proband Favism 3 1 No Favism O 5 Eight pairs had the same reaction to the fava beans; that is, they either reacted with hemolytic crisis or they did not. Only one pair showed different reactions to the fava beans, the one suffer- ing from hemolysis and the other not. In four no-favism pairs, three pairs included one sibling who was still under seven years of age at the time of the study (i.e., the sibling was still within the high risk category by age alone). Two of these pairs with one sibling still under the age of seven were both males, the other pair was composed of a male and female child (the female child con- sidered to be at less risk than her brother). The three sibling pairs with favism in both members involved cases where both were over seven years of age at the time of the study. Because the sibling sets where neither child suffered from favism are composed of younger children, it is possible that the distribution of these pairs will change within five years after the study (i.e., that some of these children will suffer from favism during that time). 261 Parent-proband sets All but six probands were identified by the Gd" trait and/or clinical favism in a male child. Therefore, the Gd" trait status of the mother in all but six cases was automatically known to be at least heterozygous. This section is divided into the considera- tion of all parent-child pairs, and only the mother-son pairs (where the status of the son is known, and the status of the mother is extrapolated from that of the son). Children with the Gd' trait and/or favism were compared with their parents of both sexes. The Gd" trait/favism status of the child or children was considered as one variable in the set, and the status of both of the parents as another variable. None of the nuclear units showed favism in both parents, although in all cases where a child had the trait, at least one of the parents was considered to have at least one allele for the trait. In the cases where two siblings were both Gd" trait, they were considered as a unit of one in the set. Favism in one of the two is treated as the presence of favism in the set of siblings (i.e., whether it occurs in one of the two or in both is not relevant in this compari- son). As Table 5.27 shows, except for the instance of favism in both generations, favism in the parent is the least reliable indicator in potential favism in the Child(ren). Only three cases of parental favism were found, and in all instances, favism has not yet been reported among the Child(ren). Favism was more likely to occur in the Child(ren) than either parent. Eight of thirty pairs shown 262 favism in the child(ren) and not the parent; i.e., a quarter of the cases were found here. Over 63% of the cases showed favism in none of the Gd" trait children or their parents. No cases of favism in both parent and child(ren) were reported from Massari or Kritinea, but one case from another Rhodian village, found during field research, is worth mentioning. A mother had suffered from favism two times during her childhood and adolescence. She continued to use the beans in food preparations for her family after she married, and only when her son suffered from favism did she stop using the beans. This was the only triple instance of favism in one nuclear family unit found during the research. TABLE 5.27 PARENT-PROBAND PAIRS AND FAVISM Status of Parent Favism No Favism Status of Proband Favism 0 No Favism 3 l9 Twenty-three males were identified with favism or the Gd" trait, which automatically makes their mothers at least heterozygous for the trait. These pairs were compared with the results that none of them showed favism in both mother and son (with the exception of the above case). One pair showed favism in the mother and not the son, four showed the disease in the son and not the mother, and the remaining eighteen showed favism in neither. These are shown in Table 5.28. 263 TABLE 5.28 MOTHER-SON PAIRS AND FAVISM Status of Mother Favism No Favism Status of Son Favism O 4 No Favism l 18 These data from all parent-child pairs (both mother-son and mother daughter pairs show that favism in a parent cannot be used as a reliable indicator of expected favism in an offspring, regardless of the sex of the child. Cousin pairs and the manifes- tation of favism Six first-cousin pairs, both affected by the enzyme deficiency and/or favism were found in the present study. These are represented by four types as are summarized in Figure 5.12. Two of these four types were parallel cousins related through their mothers, the other two were cross-cousins. One cousin pair both suffered from favism, in fact, this pair was composed of four members rather than two, all suffering from favism. Four pairs showed one favic member and the other non-favic, while the last pair showed neither member with favism. Table 5.29 shows this information. Out of curiosity and in the interest of preserving certain data for further comparisons in later studies, second cousin pairs were extracted from the Rhodes data. From a total of eight pairs, three showed the same reaction to fava beans, and in five pairs, 264 Parallel Cousin Pairs This configuration shows at least one favic male and a male first parallel cousin who was deficient but non-favic. Three cases were found with the type of configuration. male first parallel cousins shows both members to be favic. ]) if: :i: 2) i f A second configuration of two One case was found in this type of configuration. Cross Cousin Pairs 3) 5a 4) i This shows two favic sibs with their first cross-cousin with the deficiency but without favism. One case was found with the type of configuration. " A final configuration was found with two cross-cousin males both deficient but neither affected with favism. This configuration included one pair. Non-Gd" trait male Non-Gd" trait female _ Male with 1 allele for the Gd trait (hemizygote) Female with at least 1 allele for the Gd“ trait (either hetero- or homozygote) Male with the Gd- trait and favism . Female with the Gd‘ trait and favism Figure 5.12: Types of First Cousin Pairs with the Gd" Trait and/or Favism. 265 one showed favism, the other did not. These data are shown in Appendix B. TABLE 5.29 COUSIN PAIRS AND FAVISM Status of Cousin Favism No Favism Status of Proband Favism l 4 No Favism O The analysis of data by pairs of sibs, parent-proband, and cousins, shows that while favism may occur along familial lines, the lapk of favism cases also follows familial lines. Further, the closer in relation to each other two enzyme deficient individuals are, the more likely they will experience the same reaction to the beans. Eight of nine sibling pairs showed the same reaction to the beans, eighteen of twenty nine parents-probands showed the same reaction, and two of six cousin pairs showed the same reaction (88%, 62% and 33% respectively). Fava Bean Consumption in Gd- Trait Families While the study of Stamatoyannopulous and Motulsky represents the first use of genealogical data to study favism, the examination of fava bean consumption patterns was largely neglected. It was assumed that in all areas, the exposure to the beans was relatively the same; that means that all individuals with the Gd" trait were considered equally at risk of developing favism. The present study 266 in Rhodes shows that not all individuals at risk consume the beans in the same quantity or type of preparation. Families with the enzyme deficiency identified in one or more child were questioned about their use of fava beans in the family diet. Some claimed that they did not use them at all, and observations from other members of their neighborhoods proved these claims to be correct. Others used the beans in different forms, ranging from fresh and raw, fresh and cooked and dry boiled or soaked beans. Use and preparation of fava beans in the diet While fava beans can be eaten both raw (only the fresh beans) and cooked (both fresh and dry beans), several families claimed that they ate them only in the raw form. Some of these had originally stated that they did not eat the beans at all, but later revealed that they might eat them from the growing plant while they were in the fields, or along with a glass of ouzo. Others may bring a small amount of the fresh raw beans into their home, but not use them in any specific food preparation. Instead, they are cleaned of their pod and outside covering, as they are in the fields, and eaten this way. If the beans are young, newly ripe, they may not be cleaned of the outer cuticle before being eaten. This is pri- marily a matter of taste. Where the beans are grown, it is probably safe to say that "all'I individuals have eaten at least one raw fava bean. The fresh beans may be boiled separately or with other greens, with or without the pod, depending upon how young the beans are. 267 When the fresh beans are used in their pods, they are treated as any other green fresh bean (e.g., string beans). They are cleaned, the ends of the pod cut away, stringy portions of the pod removed, and then they are boiled until tender. When the individual fresh beans are boiled, the first batch of water in which they are boiled may be discarded, the beans rinsed, and fresh water used to replace the other for boiling to continue. The fresh beans are rarely boiled alone, they are usually combined with fresh greens (wild or cultivated), served with olive oil and lemon or with garlic or onions. A garlic sauce skordalig is usually made to top the fresh boiled beans and their pods (as with other green beans and pods). Skordali; is made from crushing garlic, adding moistened bread and mashing it with the garlic, and adding oil and lemon. The dry beans are used in a variety of prepara- tions, perhaps even more than the fresh ones. The fresh, raw beans are edible alone, while the dry ones require soaking and boiling and usually additional ingredients. The dry beans may be boiled or soaked over night to provide meze mentioned earlier, as an addition to alcoholic beverages. They may be boiled with other winter greens, served with oil, lemon, fresh onions, or skordalié sauce. They may also be boiled with other ingredients such as a combination of tomatoes, onions, and olive oil, or they may be boiled with lentils. One of the most tasty preparations for dry beans if in faya, where the beans are parboiled, stripped of their cuticle, and reboiled until they form a puree. Olive oil and freshly chopped onions are poured over the top of the puree. The term fava is taken from the 268 Greek word for the preparation, which refers to both this mixture made from fava beans and another puree made from small dry yellow lentils. Another popular preparation from the dry beans uses tomatoes, onions and olive oil which are boiled along with the beans in a preparation called yioknié. This is a term used for tomato sauce preparations using other types of dried beans as well. Fava bean preparations and favism episodes Earlier, fava bean consumption patterns in Massari and Kritinea were compared to see how village levels of exposure differ in order to help account for the more numerous in Kritinea than Massari. Here, these patterns are re-examined with respect to only families with the deficiency, comparing those who report favism to those who do not. Table 5.30 reviews this distribution for Massari and Kritinea. The total column shows that favism affects more often families which eat a variety of fava beans than those who eat them only in one type of preparation (or only fresh and raw). Eight of the eleven families eating both fresh and dry fava beans reported favism in one or more member. Two of these families had reported favism in more than one child such that eight cases of favism are accounted for by those eleven families eating fava beans in both fbrms. Two other cases were accounted for by families eating only the fresh fava beans. 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