|Part of a series on|
Evolutionary medicine or Darwinian medicine is the application of modern evolutionary theory to understanding health and disease. The goal of evolutionary medicine is to understand why people get sick, not simply how they get sick. Modern medical research and practice has focused on the molecular and physiological mechanisms underlying health and disease, while evolutionary medicine focuses on the question of why evolution has shaped these mechanisms in ways that may leave us susceptible to disease. The evolutionary approach has driven important advances in our understanding of antibiotic resistance, cancer, autoimmune disease, and anatomy. Medical schools have been slower to integrate evolutionary approaches because of limitations on what can be added to existing medical curricula.
- 1 Key concepts
- 2 Trade-offs
- 3 Pathogens
- 4 Defenses
- 5 Human adaptations
- 6 “Diseases of civilization”
- 7 Specific explanations
- 8 Evolutionary psychiatry / Clinical evolutionary psychology
- 9 History
- 10 See also
- 11 References
- 12 Further reading
- 13 External links
- Trade-offs: changes that could make an organism less vulnerable to disease can lead to a decrease in fitness due to effects on other traits.
- Pathogens evolve rapidly and respond quickly to human intervention.
- Some symptoms are useful defenses.
- Because cultural and demographic changes are more rapid than biological evolution, humans are often mismatched to modern environments.
- Human phylogenetic history leaves a legacy of biological constraint.
- Cancer is the result of somatic evolution.
- Humans have not stopped evolving.
- All phenotypes are products of gene-environment interaction and are often shaped by developmental calibration.
A trade-off is a situation that involves losing one quality or aspect of something in return for gain of another. Trade-offs are pervasive in human physiology. The evolutionary perspective on trade-offs starts with the notion that changes in physiology that could reduce disease susceptibility might also lead to a decrease in fitness due to effects on other traits. This can be due to limited resources or simply to constraints on physiological capacities.
For instance, take the radial bone; the bone's shape and density has been shaped by natural selection for an optimal balance between strength, function, and cost of development and maintenance. It is relatively common for humans to break their distal radius from a fall. It is called a Colles' fracture. Evolutionary medicine helps us understand why people do not have a thicker bone that would be more resistant to this type of fracture. Humans' remarkable dexterity appears to come at a cost of increased risk of this type of fracture.
As another example, the capacity to repair and regenerate enables humans to respond to damage, but leave them susceptible to developing cancer. Inflammation is critical for response to injury. Chronic inflammation arises in settings of repeated damage. Chronic inflammation of the liver, also known as chronic hepatitis, is a major risk factor for hepatocellular carcinoma.
The adaptive evolution of bacteria, viruses, other microbes and parasites plays a central role in medicine since this process is needed to understand antibiotic resistance, pathogen virulence. and pathogen subversion of the immune system.
Microorganisms evolve resistance through natural selection acting upon random mutation. Once a gene conferring resistance arises to counteract an antibiotic, not only can those bacteria thrive, but that gene can spread to other types of bacteria through horizontal gene transfer of genetic information by plasmid exchange.
For more details on this topic, see antibiotic resistance
The effect of organisms upon their host can vary from being symbiotic commensals that are beneficial, to pathogens that reduce fitness. Many pathogens produce virulence factors that directly cause disease, or manipulate their host to allow them to thrive and spread. Since a pathogen’s fitness is determined by its success in transmitting viable offspring to other hosts, it was thought at one time, that virulence moderated and it evolved toward commensality. However, this view is now questioned by Ewald.
The success of any pathogen depends upon its ability to evade host immunity. Therefore, pathogens evolve methods that enable them to infect a host, and then evade detection and destruction by its immune system. These include hiding within host cells, within a protective capsule (as with M. tuberculosis), secreting compounds that misdirect the host's immune response, binding its antibodies, rapidly changing surface markers, or masking them with the host’s own molecules.
Fever, pain, nausea, vomiting, diarrhea, cough, and anxiety are among the most common reasons why people seek medical care. At the same time, all of these are also defenses against certain dangers. For instance, fever is a defense against infection, a cough can in certain cases prevent pneumonia. However, these defenses can cause morbidity by being excessive in degree and frequency.
For example, anemia of chronic disease is a defense that arises in the context of chronic inflammation, e.g. an autoimmune disease or chronic infection. A peripheral blood smear appears very similar to iron deficiency anemia, because of limited supply of iron for the stem cells synthesizing new red blood cells. The body has plenty of iron, but it is being sequestered by hepcidin, which is an acute phase protein secreted by the liver. This is adaptive during an infection because iron is required for bacterial growth. Restricting bacterial access to iron restricts growth and aids the body to clear the infection. It is imperative to not confuse this defense with a disease because critically ill patients have been harmed by blood transfusions. An evolutionary perspective enables one to make this crucial distinction.
If the cost of not eliciting a defense response, i.e. a false negative, greatly outweighs the cost of a reaction to something that is actually non-threatening, i.e. a false alarm, then one would expect a low threshold for defense activation. This phenomenon has been described as the "smoke detector principle", or "better safe than sorry". People put up with false alarms from our smoke detectors because the cost of them failing in the face of a real fire is potentially very high, while the cost of a false alarm is minor. By a similar analogy, the "fight or flight" response has been selected to enhance survival against life-threatening situations. Because the cost of not responding could mean death, the threshold for eliciting an adrenal response is set relatively low. Panic disorder is repeated inappropriate activation of the "fight or flight" response. The smoke-detector principle promotes understanding for why humans are susceptible to this sometimes debilitating condition.
Other important examples include:
Adaptation works within constraints, makes compromises and tradeoffs, and occurs in the context of different forms of competition.
Adaptations can only occur if they are evolvable. Some adaptations which would prevent ill health are therefore not possible.
- DNA cannot be totally prevented from undergoing somatic replication corruption; this has meant that cancer, which is caused by somatic mutations, has not (so far) been completely eliminated by natural selection.
- Humans cannot biosynthesize Vitamin C, and so risk scurvy, Vitamin C deficiency disease, if dietary intake of the vitamin is insufficient.
- Retinal neurons and their axon output have evolved to be inside the layer of retinal pigment cells. This creates a constraint on the evolution of the visual system such that the optic nerve is forced to exit the retina through a point called the optic disc. This in turn creates a blind spot. More importantly, it makes vision vulnerable to increased pressure within the eye (glaucoma) since this cups and damages the optic nerve at this point, resulting in impaired vision.
Other constraints occur as the byproduct of adaptive innovations.
Trade-offs and conflicts
One constraint upon selection is that different adaptations can conflict, which requires a compromise between them to ensure an optimal cost-benefit tradeoff.
- Running efficiency in women, and birth canal size
- Encephalization, and gut size
- Skin pigmentation protection from UV, and the skin synthesis of Vitamin D
- Speech and its use of a descended larynx, and increased risk of choking
Different forms of competition exist and these can shape the processes of genetic change.
- genomic conflict between mother and fetus that results in pre-eclampsia
- Major histocompatibility complex mate choice
- Maternal-paternal genetic competition that by altering genetic imprinting might underlie autism and schizophrenia
“Diseases of civilization”
Humans evolved to live as simple hunter-gatherers in small tribal bands, a very different way of life and environment compared to that faced by contemporary humans. This change makes present humans vulnerable to a number of health problems, termed “diseases of civilization” and “diseases of affluence”. Humans were designed to live off of the land, and take advantage of the resources that were readily available to them. They were designed for the stone-age, and the environments of today bring about many disease causing ailments, that may or may not be deadly. “Modern environments may cause many diseases-for example, deficiency syndromes such as scurvy and rickets” (Williams, 1991)
In contrast to the diet of early hunter-gatherers, the modern Western diet often contains high quantities of fat, salt, and simple carbohydrates, which include refined sugars and flours. These create health problems.
- Trans fat health risks
- Dental caries
- High GI foods
- Modern diet based on "common wisdom" regarding diets in the paleolithic era
Examples of aging-associated diseases are atherosclerosis and cardiovascular disease, cancer, arthritis, cataracts, osteoporosis, type 2 diabetes, hypertension and Alzheimer's disease. The incidence of all of these diseases increases rapidly with aging (increases exponentially with age, in the case of cancer).
Of the roughly 150,000 people who die each day across the globe, about two thirds—100,000 per day—die of age-related causes. In industrialized nations, the proportion is much higher, reaching 90%.
Many contemporary humans engage in little physical exercise compared to the physically active lifestyles ancestral hunter-gatherers. It has been proposed that since prolonged periods of inactivity would have only occurred in early humans following illness or injury that it provides a cue for the body to engage in life-preserving metabolic and stress related responses such as inflammation that are now the cause of many chronic diseases.
Contemporary humans - due to medical treatment, frequent washing of clothing and the body, and improved sanitation - are mostly free of parasites, particularly intestinal ones. This causes problems in the proper development of the immune system although hygiene can be very important when it comes to maintaining good health. The hygiene hypothesis says that many modern humans are not exposed to microorganisms that have evolved in establishing the immune system as they should be. “Microorganisms and macroorganisms such as helminths from mud, animals, and feces play a critical role in driving immunoregulation” (Rook, 2012). They play a crucial role in building and training immune functions to fight off and repel some diseases, and protect against excessive inflammation which has been implicated in several diseases (such as recent evidence for Alzheimer's Disease).
This is a partial list: all links here go to a section describing or debating its evolutionary origin.
- Arthritis and other chronic inflammatory diseases
- Cystic fibrosis
- Dental occlusion
- Diabetes Type II
- Essential hypertension
- Gestational hypertension
- Iron deficiency (paradoxical benefits)
- Red blood cell polymorphism disorders
- Sickle cell anemia
- Sickness behavior
- Women’s reproductive cancers
Evolutionary psychiatry / Clinical evolutionary psychology
As noted in the table below, adaptationist hypotheses regarding the etiology of psychological disorders are often based on analogies with evolutionary perspectives on medicine and physiological dysfunctions (see in particular, Randy Nesse and George C. Williams' book Why We Get Sick). Evolutionary psychiatrists and psychologists suggest that some mental disorders likely have multiple causes.
|Possible Causes of Psychological 'Abnormalities' from an Adaptationist Perspective
|Possible cause||Physiological Dysfunction||Psychological Dysfunction|
|Fever / Vomiting
(functional responses to infection or ingestion of toxins)
|Mild depression or anxiety
(functional responses to mild loss or stress)
|By-product of an adaptation(s)||Intestinal gas
(byproduct of digestion of fiber)
|Sexual fetishes (?)
(possible byproduct of normal sexual arousal adaptations that have 'imprinted' on unusual objects or situations)
|Adaptations with multiple effects||Gene for malaria resistance, in homozygous form, causes sickle cell anemia||Adaptation(s) for high levels of creativity may also predispose schizophrenia or bi-polar disorder
(adaptations with both positive and negative effects, perhaps dependent on alternate developmental trajectories)
(over-reactive immunological responses)
(possible malfunctioning of theory of mind module)
|Frequency-dependent morphs||The two sexes / Different blood and immune system types||Personality traits and personality disorders
(may represent alternative behavioral strategies dependent on the frequency of the strategy in the population)
|Mismatch between ancestral & current environments||Modern diet-related Type 2 Diabetes||More frequent modern interaction with strangers (compared to family and close friends) may predispose greater incidence of depression & anxiety|
|Tails of normal (bell shaped) curve||Very short or tall height||Tails of the distribution of personality traits (e.g., extremely introverted or extroverted)|
See several topic areas, and the associated references, below.
Charles Darwin did not discuss the implications of his work for medicine, though biologists quickly appreciated the germ theory of disease and its implications for understanding the evolution of pathogens, as well as an organism’s need to defend against them.
medicine has modelled itself after a mechanical physics, deriving from Galileo, Newton, and Descartes.... As a result of assuming this model, medicine is mechanistic, materialistic, reductionistic, linear-causal, and deterministic (capable of precise predictions) in its concepts. It seeks explanations for diseases, or their symptoms, signs, and cause in single, materialistic— i.e., anatomical or structural (e.g., in genes and their products)— changes within the body, wrought directly (linearly), for example, by infectious, toxic, or traumatic agents. p. 510
George C. Williams was the first to apply evolutionary theory to health in the context of senescence. Also in the 1950s, John Bowlby approached the problem of disturbed child development from an evolutionary perspective upon attachment.
Randolph Nesse summarizes its relevance to medicine:
all biological traits need two kinds of explanation, both proximate and evolutionary. The proximate explanation for a disease describes what is wrong in the bodily mechanism of individuals affected by it. An evolutionary explanation is completely different. Instead of explaining why people are different, it explains why we are all the same in ways that leave us vulnerable to disease. Why do we all have wisdom teeth, an appendix, and cells that can divide out of control?
The paper of Paul Ewald in 1980, “Evolutionary Biology and the Treatment of Signs and Symptoms of Infectious Disease”, and that of Williams and Nesse in 1991, “The Dawn of Darwinian Medicine” were key developments. The latter paper “draw a favorable reception”,page x and led to a book, Why We Get Sick (published as Evolution and healing in the UK). In 2008, an online journal started: Evolution and Medicine Review.
Current activity in the field
Evolutionary medicine as a field began in the early 1990s, but has grown dramatically in recent years. These developments include the creation of the online publication, The Evolution & Medicine Review, which has served as a clearinghouse for important information in the field, two peer-reviewed journals (Evolution, Medicine and Public Health and Journal of Evolutionary Medicine), the founding of two evolution and cancer centers (The Center for Evolution and Cancer at UCSF and The Darwinian Evolution of Cancer Consortium in Montpellier) and The Center for Infectious Disease Dynamics at Penn State. There is now a national working group on evolutionary medicine education at the NSF sponsored National Evolutionary Synthesis Center, Infusing Medical Education with Evolutionary Thinking. Evolutionary Medicine programs have been established at a growing number of Universities, including UCLA, Arizona State University and Durham University in the UK.
- Evolutionary physiology
- Evolutionary psychology
- Evolutionary developmental psychopathology
- Evolutionary approaches to depression
- Paleolithic lifestyle
- Universal Darwinism
- Bergstrom, Carl; et al. (2004). "[Antigens in the blood serum in pancreatic cancer]". PNAS 25 (11): 28–31. PMID 516561.
- Merlo, LMF; et al. (2006). "Cancer as an evolutionary and ecological process". Nature Reviews Cancer 6 (12): 924–35. doi:10.1038/nrc2013. PMID 17109012.
- Elliott, DE; JV Weinstock (2012). "Helminth-host immunological interactions: prevention and control of immune-mediated diseases". Annals of the New York Academy of Sciences 1247: 83–96. doi:10.1111/j.1749-6632.2011.06292.x. PMID 22239614.
- Shubin, Neil (2008). Your inner fish : a journey into the 3.5-billion-year history of the human body (1st ed.). New York: Pantheon Books. ISBN 9780375424472.
- Nesse, RM et al. (2009). "Making evolutionary biology a basic science for medicine". Proceedings of the National Academy of Sciences of the United States of America. 107 (PNAS). Suppl 1 (suppl_1): 1800–7. doi:10.1073/pnas.0906224106. PMC 2868284. PMID 19918069.
- Beasley, R.Palmer; Lin, Chia-Chin; Hwang, Lu-Yu; Chien, Chia-Siang (1 November 1981). "HEPATOCELLULAR CARCINOMA AND HEPATITIS B VIRUS". The Lancet 318 (8256): 1129–1133. doi:10.1016/S0140-6736(81)90585-7. PMID 6118576.
- Stearns SC, Ebert D (December 2001). "Evolution in health and disease: work in progress". Q Rev Biol 76 (4): 417–32. doi:10.1086/420539. PMID 11783396.
- Wickham ME, Brown NF, Boyle EC, Coombes BK, Finlay BB (May 2007). "Virulence is positively selected by transmission success between mammalian hosts". Curr. Biol. 17 (9): 783–8. doi:10.1016/j.cub.2007.03.067. PMID 17442572.
- Finlay BB, McFadden G (February 2006). "Anti-immunology: evasion of the host immune system by bacterial and viral pathogens". Cell 124 (4): 767–82. doi:10.1016/j.cell.2006.01.034. PMID 16497587.
- Nesse, RM (May 2001). "The smoke detector principle. Natural selection and the regulation of defensive responses". Annals of the New York Academy of Sciences 935: 75–85. doi:10.1111/j.1749-6632.2001.tb03472.x. PMID 11411177.
- Wessling-Resnick, M. (23 July 2008). "The irony of host defense". Blood 112 (3): 460–460. doi:10.1182/blood-2008-05-150417.
- Zarychanski, R.; Houston, D. S. (12 August 2008). "Anemia of chronic disease: A harmful disorder or an adaptive, beneficial response?". Canadian Medical Association Journal 179 (4): 333–337. doi:10.1503/cmaj.071131. PMC 2492976. PMID 18695181.
- "Social Evolution Exam 2". Quizlet. Retrieved 30 June 2013.
- Nesse, Randolph M. (1 January 2000). "Is Depression an Adaptation?". Archives of General Psychiatry 57 (1): 14–20. doi:10.1001/archpsyc.57.1.14. PMID 10632228.
- Keller, MC; Nesse, RM (May 2005). "Is low mood an adaptation? Evidence for subtypes with symptoms that match precipitants". Journal of Affective Disorders 86 (1): 27–35. doi:10.1016/j.jad.2004.12.005. PMID 15820268.
- Flaxman, SM; Sherman, PW (June 2000). "Morning sickness: a mechanism for protecting mother and embryo". The Quarterly review of biology 75 (2): 113–48. doi:10.1086/393377. PMID 10858967.
- Hecht, G (September 1999). "Innate mechanisms of epithelial host defense: spotlight on intestine". The American journal of physiology 277 (3 Pt 1): C351–8. PMID 10484321.
- Kluger, MJ; Kozak, W; Conn, CA; Leon, LR; Soszynski, D (March 1996). "The adaptive value of fever". Infectious disease clinics of North America 10 (1): 1–20. doi:10.1016/S0891-5520(05)70282-8. PMID 8698984.
- Stearns SC (2005). "Issues in evolutionary medicine". Am. J. Hum. Biol. 17 (2): 131–40. doi:10.1002/ajhb.20105. PMID 15736177.
- Sagan, Dorion; Skoyles, John R. (2002). Up from dragons: the evolution of human intelligence. New York: McGraw-Hill. pp. 240–1. ISBN 0-07-137825-1.
- Aiello LC, Wheeler P (1995). "The Expensive-Tissue Hypothesis: The Brain and the Digestive System in Human and Primate Evolution". Current Anthropology 36 (2): 199–221. doi:10.1086/204350.
- Lieberman P (2007). "The Evolution of Human Speech: Its Anatomical and Neural Bases" (PDF). Current Anthropology 48 (1): 39–66. doi:10.1086/509092.
- Howard RS, Lively CM (November 2004). "Good vs complementary genes for parasite resistance and the evolution of mate choice". BMC Evol Biol. 4: 48. doi:10.1186/1471-2148-4-48. PMC 543473. PMID 15555062.
- Haig D (December 1993). "Genetic conflicts in human pregnancy". Q Rev Biol 68 (4): 495–532. doi:10.1086/418300. PMID 8115596.
- Schuiling GA (September 2000). "Pre-eclampsia: a parent-offspring conflict". J Psychosom Obstet Gynaecol 21 (3): 179–82. doi:10.3109/01674820009075626. PMID 11076340.
- Wedekind C, Seebeck T, Bettens F, Paepke AJ (June 1995). "MHC-dependent mate preferences in humans". Proc Biol Sci. 260 (1359): 245–9. doi:10.1098/rspb.1995.0087. PMID 7630893.
- Chaix R, Cao C, Donnelly P (2008). Przeworski, Molly, ed. "Is Mate Choice in Humans MHC-Dependent?". PLoS Genet. 4 (9): e1000184. doi:10.1371/journal.pgen.1000184. PMC 2519788. PMID 18787687.
- Crespi B, Badcock C (June 2008). "Psychosis and autism as diametrical disorders of the social brain". Behav Brain Sci 31 (3): 241–61; discussion 261–320. doi:10.1017/S0140525X08004214. PMID 18578904.
- Eaton, S. Boyd; Konner, M; Shostak, M (April 1988). "Stone agers in the fast lane: chronic degenerative diseases in evolutionary perspective". American Journal of Medicine 84 (4): 739–749. doi:10.1016/0002-9343(88)90113-1. PMID 3135745. Retrieved 2010-06-18.
- William, Knowler; Peter Bennett, Richard Hamman and Max Miller (1978). "Diabetes incidence and prevalence in Pima Indians: a 19-fold greater incidence than in Rochester, Minnesota". American Journal of Epidemiology 108 (6): 497–505. PMID 736028. Retrieved 2010-06-18.
- Williams, G. C. (1991). The dawn of darwinian medicine.Europe PubMed Central, 66(1), 1-22. doi:10.1086/417048
- Eaton SB, Strassman BI, Nesse RM, Neel JV, Ewald PW, Williams GC, Weder AB, Eaton SB 3rd, Lindeberg S, Konner MJ, Mysterud I, Cordain L (2002). "Evolutionary health promotion" (PDF). Prev Med 34 (2): 109–18. doi:10.1006/pmed.2001.0876. PMID 11817903.
- Eaton SB (2006). "The ancestral human diet: what was it and should it be a paradigm for contemporary nutrition?". Proc Nutr Soc. 65 (1): 1–6. doi:10.1079/PNS2005471. PMID 16441938.
- Milton K (2003). "Micronutrient intakes of non-human primates: are humans different?" (PDF). Comparative Biochemistry and Physiology Part A 136 (1): 47–59. doi:10.1016/S1095-6433(03)00084-9. PMID 14527629.
- Aubrey D.N.J, de Grey (2007). "Life Span Extension Research and Public Debate: Societal Considerations" (PDF). Studies in Ethics, Law, and Technology 1 (1, Article 5). doi:10.2202/1941-6008.1011. Retrieved August 7, 2011.
- Abuissa H, O’Keefe JH, Cordain, L (2005). "Realigning our 21st century diet and lifestyle with our hunter-gatherer genetic identity" (PDF). Directions Psych 25: SR1–SR10.
- Eaton, S. Boyd; Cordain, Loren; Sebastian, Anthony (2007). "The Ancestral Biomedical Environment". In Aird, William C. Endothelial Biomedicine. Cambridge University Press. pp. 129–34. ISBN 0-521-85376-1.
- Eaton SB, Eaton SB (Sep 2003). "An evolutionary perspective on human physical activity: implications for health". Comp Biochem Physiol a Mol Integr Physiol. 136 (1): 153–9. doi:10.1016/S1095-6433(03)00208-3. PMID 14527637.
- Cordain, L., Gotshall, R.W. and Eaton, S.B. (Jul 1998). "Physical activity, energy expenditure and fitness: an evolutionary perspective" (PDF). Int J Sports Med 19 (5): 328–35. doi:10.1055/s-2007-971926. PMID 9721056.
- Cordain, L., Gotshall, R.W., Eaton, S.B. (1997). "Evolutionary aspects of exercise" (PDF). World Rev Nutr Diet. World Review of Nutrition and Dietetics (Vol. 81 + 82) 81: 49–60. doi:10.1159/000059601. ISBN 3-8055-6452-X. PMID 9287503.
- Charansonney, O. L.; Després, J. P. (2010). "Disease prevention—should we target obesity or sedentary lifestyle?". Nature Reviews Cardiology 7 (8): 468–472. doi:10.1038/nrcardio.2010.68. PMID 20498671.
- http://www.microbemagazine.org/index.php? option=com_content&view=article&id=4700:a-darwinian-view-of-the-hygiene-or-old-friends- hypothesis&catid=950&Itemid=1301
- Fox, Molly; Leslie A. Knapp, Paul W. Andrews, Corey L. Fincher, (August 11, 2013). "Hygiene and the world distribution of Alzheimer’s disease". Evolution, Medicine, and Public Health 2013 (1): 173–186. doi:10.1093/emph/eot015.
- Kuzawa CW (1998). "Adipose tissue in human infancy and childhood: an evolutionary perspective". Am. J. Phys. Anthropol. Suppl 27: 177–209. doi:10.1002/(SICI)1096-8644(1998)107:27+<177::AID-AJPA7>3.0.CO;2-B. PMID 9881526.
- Straub RH, Besedovsky HO (December 2003). "Integrated evolutionary, immunological, and neuroendocrine framework for the pathogenesis of chronic disabling inflammatory diseases". FASEB J. 17 (15): 2176–83. doi:10.1096/fj.03-0433hyp. PMID 14656978.
- Straub, R. H., del Rey, A., Besedovsky, H. O. (2007) "Emerging concepts for the pathogenesis of chronic disabling inflammatory diseases: neuroendocrine-immune interactions and evolutionary biology" In: Ader, R. (2007) "Psychoneuroimmunology", Volume 1, Academic Press, San Diego, pp.217-232
- Straub RH, Besedovsky HO, Del Rey A (2007). "[Why are there analogous disease mechanisms in chronic inflammatory diseases?]". Wien. Klin. Wochenschr. (in German) 119 (15–16): 444–54. doi:10.1007/s00508-007-0834-z. PMID 17721763.
- Williams GC (1957). "Pleiotropy, Natural Selection, and the Evolution of Senescence" (PDF). Evolution (Society for the Study of Evolution) 11 (4): 398–411. doi:10.2307/2406060. JSTOR 2406060. abstract
- Wick G, Berger P, Jansen-Dürr P, Grubeck-Loebenstein B (2003). "A Darwinian-evolutionary concept of age-related diseases". Exp. Gerontol. 38 (1–2): 13–25. doi:10.1016/S0531-5565(02)00161-4. PMID 12543257.
- Bogin , B. (1997) "Evolutionary hypotheses for human childhood". Yearbook of Physical Anthropology. 104: 63-89 abstract
- Gluckman PD, Hanson MA (2006). "Evolution, development and timing of puberty". Trends Endocrinol. Metab. 17 (1): 7–12. doi:10.1016/j.tem.2005.11.006. PMID 16311040.
- Kuhle BX (August 2007). "An evolutionary perspective on the origin and ontogeny of menopause". Maturitas 57 (4): 329–37. doi:10.1016/j.maturitas.2007.04.004. PMID 17544235.
- Profet M (September 1993). "Menstruation as a defense against pathogens transported by sperm". Q Rev Biol 68 (3): 335–86. doi:10.1086/418170. PMID 8210311.
- Strassmann BI (June 1996). "The evolution of endometrial cycles and menstruation". Q Rev Biol 71 (2): 181–220. doi:10.1086/419369. PMID 8693059.
- Finn, C. A. (1998). "Menstruation: A nonadaptive consequence of uterine evolution". The Quarterly review of biology 73 (2): 163–173. doi:10.1086/420183. PMID 9618925.
- Flaxman SM, Sherman PW (June 2000). "Morning sickness: a mechanism for protecting mother and embryo". Q Rev Biol 75 (2): 113–48. doi:10.1086/393377. PMID 10858967.
- Flaxman SM, Sherman PW (July 2008). "Morning sickness: adaptive cause or nonadaptive consequence of embryo viability?". Am. Nat. 172 (1): 54–62. doi:10.1086/588081. PMID 18500939.
- Wick G, Perschinka H, Millonig G (December 2001). "Atherosclerosis as an autoimmune disease: an update". Trends Immunol. 22 (12): 665–9. doi:10.1016/S1471-4906(01)02089-0. PMID 11738996.
- Rotter JI, Diamond JM (1987). "What maintains the frequencies of human genetic diseases?". Nature 329 (6137): 289–90. doi:10.1038/329289a0. PMID 3114647.
- Kaifu, Y.; Kasai, K.; Townsend, G. C.; Richards, L. C. (2003). "Tooth wear and the ?design? Of the human dentition: A perspective from evolutionary medicine". American Journal of Physical Anthropology 122: 47–61. doi:10.1002/ajpa.10329. PMID 14666533.
- NEEL JV (December 1962). "Diabetes Mellitus: A "Thrifty" Genotype Rendered Detrimental by "Progress"?". American Journal of Human Genetics 14 (4): 353–62. PMC 1932342. PMID 13937884.
- Neel JV, Weder AB, Julius S (1998). "Type II diabetes, essential hypertension, and obesity as "syndromes of impaired genetic homeostasis": the "thrifty genotype" hypothesis enters the 21st century". Perspect. Biol. Med. 42 (1): 44–74. PMID 9894356.
- Williams, George; Nesse, Randolph M. (1996). "Evolution and healing". Why We Get Sick: the new science of Darwinian medicine. New York: Vintage Books. pp. 37–8. ISBN 0-679-74674-9.
- Wick G, Jansen-Dürr P, Berger P, Blasko I, Grubeck-Loebenstein B (February 2000). "Diseases of aging". Vaccine 18 (16): 1567–83. doi:10.1016/S0264-410X(99)00489-2. PMID 10689131.
- Kluger MJ, Ringler DH, Anver MR (April 1975). "Fever and survival". Science 188 (4184): 166–8. doi:10.1126/science.1114347. PMID 1114347.
- Kluger MJ, Rothenburg BA (January 1979). "Fever and reduced iron: their interaction as a host defense response to bacterial infection". Science 203 (4378): 374–6. doi:10.1126/science.760197. PMID 760197.
- Ames BN, Cathcart R, Schwiers E, Hochstein P (November 1981). "Uric acid provides an antioxidant defense in humans against oxidant- and radical-caused aging and cancer: a hypothesis". Proc. Natl. Acad. Sci. U.S.A. 78 (11): 6858–62. doi:10.1073/pnas.78.11.6858. PMC 349151. PMID 6947260.
- Naugler C (2008). "Hemochromatosis: a Neolithic adaptation to cereal grain diets". Med. Hypotheses 70 (3): 691–2. doi:10.1016/j.mehy.2007.06.020. PMID 17689879.
- Moalem S, Percy ME, Kruck TP, Gelbart RR (September 2002). "Epidemic pathogenic selection: an explanation for hereditary hemochromatosis?". Med. Hypotheses 59 (3): 325–9. doi:10.1016/S0306-9877(02)00179-2. PMID 12208162.
- Wander K, Shell-Duncan B, McDade TW (October 2008). "Evaluation of iron deficiency as a nutritional adaptation to infectious disease: An evolutionary medicine perspective". Am. J. Hum. Biol. 21 (2): 172–9. doi:10.1002/ajhb.20839. PMID 18949769.
- Eaton SB, Eaton SB, Konner MJ (April 1997). "Paleolithic nutrition revisited: a twelve-year retrospective on its nature and implications". Eur J Clin Nutr 51 (4): 207–16. doi:10.1038/sj.ejcn.1600389. PMID 9104571.
- Eaton SB, Konner M (January 1985). "Paleolithic nutrition. A consideration of its nature and current implications". N. Engl. J. Med. 312 (5): 283–9. doi:10.1056/NEJM198501313120505. PMID 2981409.
- Woolf LI, McBean MS, Woolf FM, Cahalane SF (May 1975). "Phenylketonuria as a balanced polymorphism: the nature of the heterozygote advantage". Annals of Human Genetics 38 (4): 461–9. doi:10.1111/j.1469-1809.1975.tb00635.x. PMID 1190737.
- Humphrey, Nicholas (2002). "19. Great Expectations: The Evolutionary Psychology of Faith-Healing and the Placebo Effect". The mind made flesh: essays from the frontiers of psychology and evolution. Oxford [Oxfordshire]: Oxford University Press. pp. 255–85. ISBN 0-19-280227-5.
- Karasik, D. (Nov 2008). "Osteoporosis: an evolutionary perspective". Human Genetics 124 (4): 349–356. doi:10.1007/s00439-008-0559-8. ISSN 0340-6717. PMID 18781328.
- Williams TN (August 2006). "Human red blood cell polymorphisms and malaria". Current Opinion in Microbiology 9 (4): 388–94. doi:10.1016/j.mib.2006.06.009. PMID 16815736.
- Ayi K, Turrini F, Piga A, Arese P (November 2004). "Enhanced phagocytosis of ring-parasitized mutant erythrocytes: a common mechanism that may explain protection against falciparum malaria in sickle trait and beta-thalassemia trait". Blood 104 (10): 3364–71. doi:10.1182/blood-2003-11-3820. PMID 15280204.
- Williams TN, Mwangi TW, Wambua S et al. (July 2005). "Sickle cell trait and the risk of Plasmodium falciparum malaria and other childhood diseases". J. Infect. Dis. 192 (1): 178–86. doi:10.1086/430744. PMC 3545189. PMID 15942909.
- Hart BL (1988). "Biological basis of the behavior of sick animals". Neurosci Biobehav Rev 12 (2): 123–37. doi:10.1016/S0149-7634(88)80004-6. PMID 3050629.
- Eaton SB, Pike MC, Short RV et al. (September 1994). "Women's reproductive cancers in evolutionary context". Q Rev Biol 69 (3): 353–67. doi:10.1086/418650. PMID 7972680.
- Nesse, R., & Williams, G. (1996) Why We Get Sick. NY: Vintage.
- Gaulin, Steven J. C. and Donald H. McBurney. Evolutionary psychology. Prentice Hall. 2003. ISBN 978-0-13-111529-3, Chapter 1, p 1-24.
- Buss, D.M. (2011). Evolutionary Psychology.
- Gaulin & McBurney (2004), Evolutionary Psychology
- Workman & Reader (2004), Evolutionary Psychology
- Nesse R (1997). "An evolutionary perspective on panic disorder and agoraphobia". In Baron-Cohen S. The maladapted mind: classic readings in evolutionary psychopathology. East Sussex: Psychology Press. pp. 73–84. ISBN 0-86377-460-1. Retrieved 21 January 2011.
- Grinde B (June 2005). "An approach to the prevention of anxiety-related disorders based on evolutionary medicine". Prev Med 40 (6): 904–9. doi:10.1016/j.ypmed.2004.08.001. PMID 15850894.
- Nesse RM (January 2000). "Is depression an adaptation?". Arch. Gen. Psychiatry 57 (1): 14–20. doi:10.1001/archpsyc.57.1.14. PMID 10632228.
- Nesse RM, Berridge KC (October 1997). "Psychoactive drug use in evolutionary perspective". Science 278 (5335): 63–6. doi:10.1126/science.278.5335.63. PMID 9311928.
- Crow TJ (July 1995). "A Darwinian approach to the origins of psychosis". Br J Psychiatry 167 (1): 12–25. doi:10.1192/bjp.167.1.12. PMID 7551604.
- Brüne M (March 2004). "Schizophrenia-an evolutionary enigma?". Neurosci Biobehav Rev 28 (1): 41–53. doi:10.1016/j.neubiorev.2003.10.002. PMID 15036932.
- Nesse RM (September 2004). "Natural selection and the elusiveness of happiness". Philosophical Transactions of the Royal Society B 359 (1449): 1333–47. doi:10.1098/rstb.2004.1511. PMC 1693419. PMID 15347525.
- Weiner H (1 July 1998). "Notes on an evolutionary medicine". Psychosom Med 60 (4): 510–20. PMID 9710299.
- Tinbergen N (1963). "On Aims and Methods in Ethology" (PDF). Zeitschrift für Tierpsychologie 20 (4): 410–433. doi:10.1111/j.1439-0310.1963.tb01161.x.
- Nesse RM (December 2008). "Evolution: medicine's most basic science". Lancet 372 (Suppl 1): S21–7. doi:10.1016/S0140-6736(08)61877-2.
- Ewald PW (September 1980). "Evolutionary biology and the treatment of signs and symptoms of infectious disease". J. Theor. Biol. 86 (1): 169–76. doi:10.1016/0022-5193(80)90073-9. PMID 7464170.
- Williams GC, Nesse RM (March 1991). "The dawn of Darwinian medicine". Q Rev Biol 66 (1): 1–22. doi:10.1086/417048. PMID 2052670.
- Williams, George; Nesse, Randolph M. (1996). Why We Get Sick: the new science of Darwinian medicine. New York: Vintage Books. ISBN 0-679-74674-9.
- Stearns SC, Koella JK (2008). Evolution in health and disease (2nd ed.). Oxford [Oxfordshire]: Oxford University Press. ISBN 0-19-920745-3.
- McKenna, James J.; Trevathan, Wenda; Smith, Euclid O. (2008). Evolutionary medicine and health: new perspectives (2nd ed.). Oxford [Oxfordshire]: Oxford University Press. ISBN 0-19-530706-2.
- O'Higgins, Paul; Sarah Elton (2008). Medicine and Evolution: Current Applications, Future Prospects (Society for the Study of Human Biology Symposium Series (Sshb). Boca Raton: CRC. ISBN 1-4200-5134-2.
- Ewald, P. W. (1996). Evolution of Infectious Disease. Oxford: Oxford University Press. ISBN 0-19-511139-7.
- Moalem, S.; Prince, J. (2007). Survival of the Sickest. New York: HarperLuxe. ISBN 978-0-06-088965-4.
- Straub, RH.; Besedovsky, HO. (2003). "Integrated evolutionary, immunological, and neuroendocrine framework for the pathogenesis of chronic disabling inflammatory diseases". FASEB J 17 (15): 2176–2183. doi:10.1096/fj.03-0433hyp. PMID 14656978.
- Straub, RH. (2012). "Evolutionary medicine and chronic inflammatory state--known and new concepts in pathophysiology". Journal of Molecular medicine 90 (5): 523–534. doi:10.1007/s00109-012-0861-8. PMID 22271169.
- LeGrand, E. K.; Brown C. C. (1 July 2002). "Darwinian medicine: Applications of evolutionary biology for veterinarians". Canadian Veterinary Journal 43 (7): 556–9. ISSN 0008-5286. PMC 341948. PMID 12125190.
- Randolph M. Nesse, Stephen C. Stearns (2008). "The great opportunity: Evolutionary applications to medicine and public health" (PDF). Evolutionary Applications 1 (1): 28–48. doi:10.1111/j.1752-4571.2007.00006.x.
- Naugler, Christopher T. (1 September 2008). "Evolutionary medicine: Update on the relevance to family practice". Canadian Family Physician 54 (9): 1265–9. PMC 2553465. PMID 18791103.
- Childs, B.; Wiener, C.; Valle, D. (2005). "A science of the individual: Implications for a medical school curriculum". Annual Review of Genomics and Human Genetics 6 (1): 313–330. doi:10.1146/annurev.genom.6.080604.162345. PMID 16124864.
- Stiehm ER (2006). "Disease versus disease: how one disease may ameliorate another". Pediatrics 117 (1): 184–91. doi:10.1542/peds.2004-2773. PMID 16396876.
- The Evolution and Medicine Review
- Evolution and Medicine Network
- Randolph M. Nesse Website
- Steve Lewis's new Evolutionary Medicine site
- Special Issue of Evolutionary Applications on Evolutionary Medicine
- Publications in evolutionary medicine and further aspects of human evolution