Evolutionary medicine



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.

Key concepts

 * 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.

Important researchers in evolutionary medicine include: Randolph M. Nesse, George C. Williams, Paul W. Ewald, Stephen C. Stearns.

Trade-offs
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.

Pathogens
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.

Antibiotic resistance
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

Virulence
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.

For more details on this topic, see virulence, virulence factors and optimal virulence

Immune evasion
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.

For more details on this topic, see ''manipulation of the immune system by pathogens, and evasion of the innate immune system

Defenses
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:
 * Low mood
 * Morning sickness
 * Diarrhea
 * Fever

Human adaptations
Adaptation works within constraints, makes compromises and tradeoffs, and occurs in the context of different forms of competition.

Constraints
Adaptations can only occur if they are evolvable. Some adaptations which would prevent ill health are therefore not possible. Other constraints occur as the byproduct of adaptive innovations.
 * 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.

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

Competition effects
Different forms of competition exist and these can shape the processes of genetic change.
 * mate choice and disease susceptibility


 * 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 )

Diet
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

Life expectancy
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%.

Exercise
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.

Cleanliness
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).

Specific explanations
This is a partial list: all links here go to a section describing or debating its evolutionary origin.

Life stage related

 * Adipose tissue in human infants
 * Arthritis and other chronic inflammatory diseases
 * Ageing
 * Alzheimer disease
 * Childhood
 * Menarche
 * Menopause
 * Menstruation
 * Morning sickness

Other

 * Atherosclerosis
 * Arthritis and other chronic inflammatory diseases
 * Cough
 * Cystic fibrosis
 * Dental occlusion
 * Diabetes Type II
 * Diarrhea
 * Essential hypertension
 * Fever
 * Gestational hypertension
 * Gout
 * Hemochromatosis
 * Iron deficiency (paradoxical benefits)
 * Obesity
 * Phenylketonuria
 * Placebos
 * Osteoporosis
 * 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.

See several topic areas, and the associated references, below.


 * Agoraphobia
 * Anxiety
 * Depression
 * Drug abuse
 * Schizophrenia
 * Unhappiness

History
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, in turn, ignored evolution, and instead focused (as done in the hard sciences) upon proximate mechanical causes. "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.

An important theoretical development was Nikolaas Tinbergen’s distinction made originally in ethology between evolutionary and proximate mechanisms.

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.