I will investigate 2 cultural behaviors and 3 physiological responses as potential mechanisms of protection from chemical and microbial dangers in foods. <P> 1. Spice Use. I will test 3 critical predictions of the antimicrobial hypothesis: (1) quantities of spices used in recipes should kill foodborne bacteria and heat should not destroy the effects, (2) recipes from low altitudes and latitudes should be spicier, because such areas have warmer, more humid climates and higher microbial diversity and growth rates than high latitudes and altitudes, and (3) spices most often used in preparing beef, fowl, fish, and pork should be specifically effective against microbes found in each type of meat. <P> 2. Geophagy. I will investigate the alternative toxin binding and calcium provisioning hypotheses by determining when geophagy occurs. The former hypothesis predicts that ingesting toxins triggers the behavior whereas the latter predicts that calcium deficiency is the stimulus. I also will determine if geophagy clays are especially rich sources of calcium or instead are likely to bind toxins (i.e., extremely finely divided). Finally I will take a comparative approach, and see if the primates, rodents, and birds that practice geophagy do so after ingesting toxins or when they are calcium deprived. <P> 3. NVP (Morning Sickness). I will further test the critical prediction of the maternal and embryo protection hypothesis that symptoms should depend on diet. In areas where diets include few meat products or pungent vegetables NVP frequencies should be lower than in countries whose staples consist of meats and strong-tasting plants. Across the modern world diets and frequencies of NVP vary widely (i.e., from 84% of women in Japan to 35% in India), providing the information and variability necessary for my analyses. <P> 4. Lactose Intolerance. I will investigate the alternative parasite-pathogen and dairying barrier hypotheses. The former predicts that in certain geographic areas both livestock and (unpasteurized) milk are sources of dangerous communicable diseases, which makes raising cattle and drinking milk hazardous. The dairying barrier hypothesis predicts that in certain areas extreme climatic conditions (e.g., heat, high altitudes) and deadly livestock diseases make it impossible to maintain dairy herds. Data to test both hypotheses are available, but currently they are widely scattered in the veterinary and microbiological literature; I will synthesize them. <P> 5. Allergy. I will investigate whether the worm and toxin hypotheses are complementary. Perhaps parasitic worms and their by-products are proximate (immediate) triggers of IgE responses whose ultimate (evolutionary) function is protection from carcinogens. To find out I will see if helminths (e.g., schistomes) indeed cause cancer and whether atopy protects against helminths. I also will investigate whether allergies to particular foods (e.g., peanuts) trigger atopic responses that protect from carcinogenic chemicals in those foods (mycotoxins). If so, foods frequently associated with allergies should contain bacterial or fungal toxins and other carcinogens.
NON-TECHNICAL SUMMARY: Darwinian medicine investigates whether symptoms and behaviors are functional or pathological. This research focuses on mechanisms that may protect us from foodborne diseases and toxins: spice use, geophagy, morning sickness, lactose intolerance, and allergies. It will explore ecological factors underlying variations in culture and physiology, and contribute to healthy, well-nourished populations.
APPROACH: The five objectives will be addressed as follows: 1. Spice Use. To see if spices, as used in recipes, are effective as antimicrobials, I will prepare >5 beef, pork, fowl, and fish dishes with and without each spice called for, incubate the prepared dishes at two temperatures, sample the broth at regular intervals, plate the samples on nutrient media, and enumerate bacterial colonies. The prediction that traditional recipes from lower latitudes and altitudes should use spices more liberally than high latitude and altitude recipes will be tested by locating region-specific cookbooks and enumerating spices used. The predicted specificity of spice use will be investigated by gathering information on the microbial fauna of beef, pork, poultry, and fish, and then comparatively analyzing recipes for each meat (in ca. 7,000 recipes), looking for a match between spices called for and their effectiveness against meat-specific microbes. 2. Geophagy. The toxin binding hypothesis predicts that geophagy will be associated with diets high in toxins whereas the calcium provisioning hypothesis predicts that geophagy will be associated with low-calcium diets. I also will investigate whether clays that are ingested are especially rich in calcium or effective at binding and preventing absorbtion of toxins. Finally, I will determine if wild mammals and birds practice geophagy in response to toxins or calcium deprivation. 3. NVP (Morning Sickness). To examine the relationship between NVP and diet I will synthesize information on frequencies of NVP and dietary staples worldwide. A growing database now contains >60 studies of NVP and >40 studies of staple foods. I predict that NVP frequencies will be highest in countries that most often eat meat products. 4. Lactose Intolerance. I will compile information on the geographic distribution of lactose malabsorbtion from >250 different populations worldwide. Testing the parasite-pathogen and dairying barrier hypotheses will involve analyzing distributions and severity of livestock and human diseases, transmissability from cattle to humans, environmental factors (climate, altitude) that may affect livestock, and safety of consuming unpasteurized milk in each area. Populations with anomalously high or low frequencies of lactose malabsorption for their geographical location (e.g., lactose absorbing populations in central Africa) may be illuminating. 5. Allergy. I will investigate 5 predictions in a chain of causality to link the toxin and worm hypotheses: (1) atopy is associated with increased IgE titers, (2) as IgE increases helminthic infections decrease, (3) as atopy increases helminthic infections decrease, (4) helminths are associated with increased cancer (e.g., of the bladder) and, (5) atopy is associated with reduced cancer incidence. Food allergies also may provide cancer protection. I will enumerate common food allergies in different areas and investigate the carcinogenicity of those foods to test the prediction that allergies are triggered by carcinogenic foods.
PROGRESS: 2001/10 TO 2007/09<BR>
I investigated the adaptive significance of (1) lactose malabsorption, (2) gestational hypertension, (3) morning sickness, and (4) allergies. Regarding (1), 70-90 percent of African, Asian, Native American, and Hispanic people are lactose intolerant. Only individuals descended from areas where dairying is practiced (northern Europe) produce the enzyme lactase in adulthood. What determines where dairying occurs? To find out, I synthesized studies of adult lactose malabsorption in 270 indigenous populations. Partial correlation analyses revealed that malabsorption is associated with extreme climates (high and low latitudes) and with the pre-1900 geographical occurrence of 9 deadly cattle diseases. Today's lactose malabsorbers descended from geographical areas where dairy herding was precluded by lethal pathogens and harsh climates. The different physiological trajectories of Africans, Asians, and Europeans stem from differences in their ecological environments. Regarding (2), gestational hypertension occurs in 10 percent of pregnancies. I studied a cohort of 698 small-for-gestational age (SGA) infants born to hypertensive mothers in Canada. Among them, maternal hypertension was associated with higher neonatal survival and greater odds of a healthier neonate (based on Apgar and SNAP-II scores). Thus, pregnancy-induced hypertension can serve an adaptive role for a small fetus, by enabling it to obtain better nourishment and oxygenation. Regarding (3) I tested two hypotheses for morning sickness (NVP): "maternal and embryonic protection," which suggests that NVP serves to expel and cause temporary aversions to foods that may contain harmful toxins and microorganisms, and "byproduct," which suggests that NVP is a nonfunctional side-effect of conflict between the mother and embryo over resource allocation. The timing of NVP, its association with reduced miscarriages, its variation among societies differing in diets, and patterns of food cravings and aversions are consistent only with the prophylaxis hypothesis. Regarding (4), I evaluated three alternative hypotheses for how allergies and cancers are related: antigenic stimulation, which predicts positive associations (i.e., allergy sufferers are more likely to get cancer), and immunosurveillance and prophylaxis, which predict inverse associations. Total evidence analyses of 646 studies of patients' histories of 11 specific allergies and cancers of 19 tissues or organ systems (in 148 papers, 1955-2006) revealed that more than twice as many studies reported inverse allergy-cancer associations as reported positive or null associations, and that inverse associations with allergies were twice as common for cancers of 9 tissues or organ systems that interface with the external environment compared to cancers of 9 tissues or organ systems that do not interface with the external environment. These results are most consistent with the prophylaxis hypothesis. Allergy symptoms rapidly expel carcinogenic toxins, pathogens, and other antigens before they can trigger malignant neoplasia in exposed tissues.
IMPACT: 2001/10 TO 2007/09<BR>
My studies contribute strongly to the development of Darwinian Medicine, an exciting, emergent interdisciplinary field that takes an evolutionary approach to human health and disease. Investigations focus on determining which symptoms and behaviors serve useful purposes (adaptations) and which do not (pathologies). Whereas medical researchers traditionally study how symptoms are brought about (their underlying mechanisms) and attempt to design more effective ways to eliminate them, from a Darwinian perspective the questions are why particular symptoms occur (their reproductive consequences) and whether it is advisable to eliminate them. Decisions about whether or not to suppress allergies, gestational hypertension, or morning sickness must take into account whether or not they are functional (whether they evolved to aid the individual) or are impairing health and hindering recovery. These two approaches are complementary, not alternative. The promise of Darwinian Medicine is that it will lead to better informed medical practices throughout the world. Before trying to "fix" something it is imperative to know why it is there in the first place. For example, our finding that allergies can help protect against certain types of cancers calls into question the commonly held belief that allergies are simply immune system disorders. In turn, this raises the issue of whether allergies should be routinely suppressed chemically. Our results thus have important practical implications, and point the way to epidemiological research programs that involve new kinds of cost/benefit analyses.