Evolutionary medicine or Darwinian medicine is the application of modern evolutionary theory

Evolution

Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...

 to understanding health and disease

Disease

A disease is an abnormal condition affecting the body of an organism. It is often construed to be a medical condition associated with specific symptoms and signs. It may be caused by external factors, such as infectious disease, or it may be caused by internal dysfunctions, such as autoimmune...

. It provides a complementary scientific approach to the present mechanistic explanations

Mechanism (biology)

In biology --and in science in general-- a mechanism is a complex object or, more generally, a process that produces a regular phenomenon. For example, natural selection is one of the mechanisms of biological evolution, other being genetic drift, biased mutation, and gene flow; competition,...

 that dominate medical science, and particularly modern medical education

Medical education

Medical education is education related to the practice of being a medical practitioner, either the initial training to become a doctor or additional training thereafter ....

. Researchers in the field of evolutionary medicine have suggested that evolutionary biology should not simply be an optional topic in medical school, but instead should be taught as one of the basic medical sciences.

Such adaptation

Adaptation

An adaptation in biology is a trait with a current functional role in the life history of an organism that is maintained and evolved by means of natural selection. An adaptation refers to both the current state of being adapted and to the dynamic evolutionary process that leads to the adaptation....

s concern:

• The evolution of pathogens in terms of their virulence
  Virulence
  Virulence is by MeSH definition the degree of pathogenicity within a group or species of parasites as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenicity of an organism - its ability to cause disease - is determined by its...
  
  , resistance to antibiotics
  Antibiotic resistance
  Antibiotic resistance is a type of drug resistance where a microorganism is able to survive exposure to an antibiotic. While a spontaneous or induced genetic mutation in bacteria may confer resistance to antimicrobial drugs, genes that confer resistance can be transferred between bacteria in a...
  
  , and subversion of an individual’s immune system
  Immune system
  An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
  
  .
• The processes, constraints and trade-off
  Trade-off
  A trade-off is a situation that involves losing one quality or aspect of something in return for gaining another quality or aspect...
  
  s of human evolution.
• The evolved responses that enable individuals to protect, heal and recuperate themselves from infections and injuries such as immunity
  Immunity (medical)
  Immunity is a biological term that describes a state of having sufficient biological defenses to avoid infection, disease, or other unwanted biological invasion. Immunity involves both specific and non-specific components. The non-specific components act either as barriers or as eliminators of wide...
  
  , fever
  Fever
  Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
  
  , and sickness behavior
  Sickness behavior
  thumb|350px|right|[[Michael Peter Ancher|Ancher, Michael]], "The Sick Girl", 1882, [[Statens Museum for Kunst]]Sickness behavior is a coordinated set of adaptive behavioral changes that develop in ill individuals during the course of an infection....
  
  , and the processes that regulate their deployment to maximize fitness.
• How past adaptation of early humans to their ancestral environment now affects contemporary humans with their different diet
  Diet (nutrition)
  In nutrition, diet is the sum of food consumed by a person or other organism. Dietary habits are the habitual decisions an individual or culture makes when choosing what foods to eat. With the word diet, it is often implied the use of specific intake of nutrition for health or weight-management...
  
  , life expectancy
  Life expectancy
  Life expectancy is the expected number of years of life remaining at a given age. It is denoted by ex, which means the average number of subsequent years of life for someone now aged x, according to a particular mortality experience...
  
  , degree of physical exercise
  Physical exercise
  Physical exercise is any bodily activity that enhances or maintains physical fitness and overall health and wellness. It is performed for various reasons including strengthening muscles and the cardiovascular system, honing athletic skills, weight loss or maintenance, as well as for the purpose of...
  
  , and hygiene
  Hygiene
  Hygiene refers to the set of practices perceived by a community to be associated with the preservation of health and healthy living. While in modern medical sciences there is a set of standards of hygiene recommended for different situations, what is considered hygienic or not can vary between...
  
  .

Important researchers in evolutionary medicine include: Randolph M. Nesse

Randolph M. Nesse

Professor Randolph M. Nesse, M.D. is an American physician and evolutionary biologist. He is notable for his research on evolutionary psychology and evolutionary medicine, as well as the evolutionary origins of emotions and how natural selection shapes the capacity for mood.Nesse is a professor...

, George C. Williams

George C. Williams

Professor George Christopher Williams was an American evolutionary biologist.Williams was a professor emeritus of biology at the State University of New York at Stony Brook. He was best known for his vigorous critique of group selection. The work of Williams in this area, along with W. D...

, Paul W. Ewald

Paul W. Ewald

Paul W. Ewald is an evolutionary biologist, specializing in the evolution of infectious disease. He received his B.Sc. in 1975 from the University of California, Irvine, in Biological Sciences and his Ph.D. in 1980 from the University of Washington, in Zoology, with specialization in Ecology and...

, James McKenna, and Rainer H. Straub.

History

Charles Darwin

Charles Darwin

Charles Robert Darwin FRS was an English naturalist. He established that all species of life have descended over time from common ancestry, and proposed the scientific theory that this branching pattern of evolution resulted from a process that he called natural selection.He published his theory...

 did not discuss the implications of his work for medicine, though biologists

Biology

Biology is a natural science concerned with the study of life and living organisms, including their structure, function, growth, origin, evolution, distribution, and taxonomy. Biology is a vast subject containing many subdivisions, topics, and disciplines...

 quickly appreciated in the germ theory of disease

Germ theory of disease

The germ theory of disease, also called the pathogenic theory of medicine, is a theory that proposes that microorganisms are the cause of many diseases...

 its implications for understanding the evolution of pathogen

Pathogen

A pathogen gignomai "I give birth to") or infectious agent — colloquially, a germ — is a microbe or microorganism such as a virus, bacterium, prion, or fungus that causes disease in its animal or plant host...

s, and 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

Mechanism (biology)

In biology --and in science in general-- a mechanism is a complex object or, more generally, a process that produces a regular phenomenon. For example, natural selection is one of the mechanisms of biological evolution, other being genetic drift, biased mutation, and gene flow; competition,...

.

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

George C. Williams

Professor George Christopher Williams was an American evolutionary biologist.Williams was a professor emeritus of biology at the State University of New York at Stony Brook. He was best known for his vigorous critique of group selection. The work of Williams in this area, along with W. D...

 was the first to apply evolutionary theory to health in the context of senescence

Senescence

Senescence or biological aging is the change in the biology of an organism as it ages after its maturity. Such changes range from those affecting its cells and their function to those affecting the whole organism...

. abstract Also in the 1950s, John Bowlby

John Bowlby

Edward John Mostyn "John" Bowlby was a British psychologist, psychiatrist and psychoanalyst, notable for his interest in child development and for his pioneering work in attachment theory.- Family background :...

 approached the problem of disturbed child development from an evolutionary perspective upon attachment.

An important theoretical development was Nikolaas Tinbergen’s

Nikolaas Tinbergen

Nikolaas "Niko" Tinbergen was a Dutch ethologist and ornithologist who shared the 1973 Nobel Prize in Physiology or Medicine with Karl von Frisch and Konrad Lorenz for their discoveries concerning organization and elicitation of individual and social behaviour patterns in animals.In the 1960s he...

 distinction made originally in ethology

Ethology

Ethology is the scientific study of animal behavior, and a sub-topic of zoology....

 between evolutionary and proximate mechanisms

Tinbergen's four questions

Tinbergen's four questions, named after Nikolaas Tinbergen, are complementary categories of explanations for behavior. It suggests that an integrative understanding of behavior must include both a proximate and ultimate analysis of behavior, as well as an understanding of both...

.

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.

Pathogens

The adaptive evolution of bacteria, viruses, other microbes and parasites plays a central role in medicine since this process is needed to understand issues such as 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 that bacteria thrive, but it can spread that gene to other types of bacteria through horizontal gene transfer

Horizontal gene transfer

Horizontal gene transfer , also lateral gene transfer , is any process in which an organism incorporates genetic material from another organism without being the offspring of that organism...

 of genetic information by plasmid exchange

Bacterial conjugation

Bacterial conjugation is the transfer of genetic material between bacterial cells by direct cell-to-cell contact or by a bridge-like connection between two cells...

.
It is unclear whether the genetic information responsible for antibiotic resistance typically arises from an actual mutation, or is already present in the gene pool of the population of the organism in question.

For more details on this topic, see antibiotic resistance

Antibiotic resistance

Antibiotic resistance is a type of drug resistance where a microorganism is able to survive exposure to an antibiotic. While a spontaneous or induced genetic mutation in bacteria may confer resistance to antimicrobial drugs, genes that confer resistance can be transferred between bacteria in a...

Virulence

The effect of organisms upon their host

Host (biology)

In biology, a host is an organism that harbors a parasite, or a mutual or commensal symbiont, typically providing nourishment and shelter. In botany, a host plant is one that supplies food resources and substrate for certain insects or other fauna...

 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 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

Evolution of Infectious Disease

Evolution of Infectious Disease is a 1993 book by the evolutionary biologist Paul Ewald. In this book Ewald contends the traditional view that parasites should evolve toward benign coexistence with their hosts. He draws on various studies which contradict this dogma and asserts his own theory...

.

For more details on this topic, see virulence

Virulence

Virulence is by MeSH definition the degree of pathogenicity within a group or species of parasites as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenicity of an organism - its ability to cause disease - is determined by its...

, virulence factor

Virulence factor

Virulence factors are molecules expressed and secreted by pathogens that enable them to achieve the following:* colonization of a niche in the host...

s and optimal virulence

Optimal virulence

Optimal virulence is a concept relating to the ecology of hosts and parasites. One definition of virulence is the host's parasite-induced loss of fitness. The parasite's fitness is determined by its success in transmitting offsprings to other hosts. At one time, the consensus was that over time,...

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

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

Evolvability

Evolvability is defined as the capacity of a system for adaptive evolution. Evolvability is the ability of a population of organisms to not merely generate genetic diversity, but to generate adaptive genetic diversity, and thereby evolve through natural selection.In order for a biological organism...

. Some adaptations which would prevent ill health are therefore not possible.

• DNA
  DNA
  Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...
  
   cannot be totally prevented from undergoing somatic replication corruption
  Mutation
  In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
  
  ; this means that cancer
  Cancer
  Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...
  
  , which is caused by somatic mutations, can never be completely eliminated by natural selection.
• Humans cannot biosynthesize
  Biosynthesis
  Biosynthesis is an enzyme-catalyzed process in cells of living organisms by which substrates are converted to more complex products. The biosynthesis process often consists of several enzymatic steps in which the product of one step is used as substrate in the following step...
  
   Vitamin C
  Vitamin C
  Vitamin C or L-ascorbic acid or L-ascorbate is an essential nutrient for humans and certain other animal species. In living organisms ascorbate acts as an antioxidant by protecting the body against oxidative stress...
  
  , and so risk scurvy
  Scurvy
  Scurvy is a disease resulting from a deficiency of vitamin C, which is required for the synthesis of collagen in humans. The chemical name for vitamin C, ascorbic acid, is derived from the Latin name of scurvy, scorbutus, which also provides the adjective scorbutic...
  
  , Vitamin C deficiency disease, if dietary intake of the vitamin is insufficient.
• Retinal neurons
  Ganglion cell layer
  The ganglion cell layer is a layer of the retina that consists of retinal ganglion cells.In the macula lutea, the layer forms several strata....
  
   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
  Optic nerve
  The optic nerve, also called cranial nerve 2, transmits visual information from the retina to the brain. Derived from the embryonic retinal ganglion cell, a diverticulum located in the diencephalon, the optic nerve doesn't regenerate after transection.-Anatomy:The optic nerve is the second of...
  
   is forced to exit the retina through a point called the optic disc
  Optic disc
  The optic disc or optic nerve head is the location where ganglion cell axons exit the eye to form the optic nerve. There are no light sensitive rods or cones to respond to a light stimulus at this point. This causes a break in the visual field called "the blind spot" or the "physiological blind spot"...
  
  . This in turn creates a blind spot
  Blind spot (vision)
  A blind spot, also known as a scotoma, is an obscuration of the visual field. A particular blind spot known as the blindspot, or physiological blind spot, or punctum caecum in medical literature, is the place in the visual field that corresponds to the lack of light-detecting photoreceptor cells on...
  
  . More importantly, it makes vision vulnerable to increased pressure within the eye
  Intraocular pressure
  Intraocular pressure is the fluid pressure inside the eye. Tonometry is the method eye care professionals use to determine this. IOP is an important aspect in the evaluation of patients at risk from glaucoma...
  
   (glaucoma
  Glaucoma
  Glaucoma is an eye disorder in which the optic nerve suffers damage, permanently damaging vision in the affected eye and progressing to complete blindness if untreated. It is often, but not always, associated with increased pressure of the fluid in the eye...
  
  ) since this cups
  Cup-to-disc ratio
  The cup-to-disc ratio is a measurement used in ophthalmology and optometry to assess the progression of glaucoma. The optic disc is the anatomical location of the eye's "blind spot", the area where the optic nerve and blood vessels enter the retina. The optic disc can be flat or it can have a...
  
   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
  Encephalization
  Encephalization is defined as the amount of brain mass exceeding that related to an animal's total body mass. Quantifying an animal's encephalization has been argued to be directly related to that animal's level of intelligence. Aristotle wrote in 335 B.C...
  
  , and gut size
• Skin pigmentation protection from UV, and the skin synthesis of Vitamin D
  Vitamin D
  Vitamin D is a group of fat-soluble secosteroids. In humans, vitamin D is unique both because it functions as a prohormone and because the body can synthesize it when sun exposure is adequate ....
  
  
• Speech
  Origin of language
  The origin of language is the emergence of language in the human species. This is a highly controversial topic. Empirical evidence is so limited that many regard it as unsuitable for serious scholars. In 1866, the Linguistic Society of Paris went so far as to ban debates on the subject...
  
   and its use of a descended larynx, and increased risk of choking
  Choking
  Choking is the mechanical obstruction of the flow of air from the environment into the lungs. Choking prevents breathing, and can be partial or complete, with partial choking allowing some, although inadequate, flow of air into the lungs. Prolonged or complete choking results in asphyxia which...
  
  

Competition effects

Different forms of competition exist and these can shape the processes of genetic change.

• mate choice
  Sexual selection
  Sexual selection, a concept introduced by Charles Darwin in his 1859 book On the Origin of Species, is a significant element of his theory of natural selection...
  
   and disease susceptibility

• genomic conflict
  Parent-offspring conflict
  Parent–offspring conflict is a term coined in 1974 by Robert Trivers. It is used to signify the evolutionary conflict arising from differences in optimal parental investment to an offspring from the standpoint of the parent and the offspring...
  
   between mother and fetus that results in pre-eclampsia
  Pre-eclampsia
  Pre-eclampsia or preeclampsia is a medical condition in which hypertension arises in pregnancy in association with significant amounts of protein in the urine....
  
  
• Major histocompatibility complex
  Major histocompatibility complex
  Major histocompatibility complex is a cell surface molecule encoded by a large gene family in all vertebrates. MHC molecules mediate interactions of leukocytes, also called white blood cells , which are immune cells, with other leukocytes or body cells...
  
   mate choice‎
• Maternal-paternal genetic competition that by altering genetic imprinting might underlie autism
  Autism
  Autism is a disorder of neural development characterized by impaired social interaction and communication, and by restricted and repetitive behavior. These signs all begin before a child is three years old. Autism affects information processing in the brain by altering how nerve cells and their...
  
   and schizophrenia
  Schizophrenia
  Schizophrenia is a mental disorder characterized by a disintegration of thought processes and of emotional responsiveness. It most commonly manifests itself as auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking, and it is accompanied by significant social...
  
  

Evolved defense mechanisms

Evolution has selected defense mechanisms that protect against injuries and infections. These include

• Sickness behavior
  Sickness behavior
  thumb|350px|right|[[Michael Peter Ancher|Ancher, Michael]], "The Sick Girl", 1882, [[Statens Museum for Kunst]]Sickness behavior is a coordinated set of adaptive behavioral changes that develop in ill individuals during the course of an infection....
  
   (Lethargy, Depression
  Depression (mood)
  Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...
  
  , Anorexia
  Anorexia (symptom)
  Anorexia is the decreased sensation of appetite...
  
  , Sleepiness, reduction in grooming, and failure to concentrate
  Attention
  Attention is the cognitive process of paying attention to one aspect of the environment while ignoring others. Attention is one of the most intensely studied topics within psychology and cognitive neuroscience....
  
  )
• Expulsions: Sneezing, Vomiting
  Vomiting
  Vomiting is the forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose...
  
  , Coughing, Diarrhea
  Diarrhea
  Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...
  
  

Management
Evolved defense mechanisms can be costly, due to increased energy use (fever increases BMR by 10-15% for each degree rise in body temperature), and due to the risk of damaging the body (vomiting can risk aspiration). A fitness advantage therefore exists in deploying defense mechanisms selectively only when the potential benefits outweigh such costs. Their deployment is controlled at several levels, including through biomolecular pathways using factors such as proinflammatory cytokine

Proinflammatory cytokine

A proinflammatory cytokine is a cytokine which promotes systemic inflammation.Examples include IL-1 and TNF alpha....

s, and through higher neural top down

Neural top down control of physiology

Neural top down control of physiology concerns the direct regulation by the brain of physiological functions...

 processes in cerebral cortex areas such as the insular cortex

Insular cortex

In each hemisphere of the mammalian brain the insular cortex is a portion of the cerebral cortex folded deep within the lateral sulcus between the temporal lobe and the frontal lobe. The cortical area overlying it towards the lateral surface of the brain is the operculum...

. Neural control provides advantages in that deployment can be based on tradeoffs between costs and benefits that take into account relevant health circumstances. This evolved regulation functions as a health management system

Health management system

The health management system is an evolutionary medicine regulative process proposed by Nicholas Humphrey in which actuarial assessment of fitness and economic-type cost-benefit analysis determines the body’s regulation of its physiology and health...

.

“Diseases of civilization”

Humans evolved to live as simple hunter-gatherers in small tribal bands, a very different way of life and environment than that faced by contemporary humans. This change makes present humans vulnerable to a number of health problems, termed “diseases of civilization

Lifestyle diseases

Lifestyle diseases are diseases that appear to increase in frequency as countries become more industrialized and people live longer...

” and “diseases of affluence

Diseases of affluence

Diseases of affluence is a term sometimes given to selected diseases and other health conditions which are commonly thought to be a result of increasing wealth in a society...

”.

Diet

In contrast to the diet of early hunter-gatherers, the modern one contains high quantities of fat, salt, and refined sugars. 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
  Paleolithic diet
  The modern dietary regimen known as the Paleolithic diet , also popularly referred to as the caveman diet, Stone Age diet and hunter-gatherer diet, is a nutritional plan based on the presumed ancient diet of wild plants and animals that various hominid species habitually consumed during the...
  
  

Exercise

Contemporary humans engage in little physical exercise

Physical exercise

Physical exercise is any bodily activity that enhances or maintains physical fitness and overall health and wellness. It is performed for various reasons including strengthening muscles and the cardiovascular system, honing athletic skills, weight loss or maintenance, as well as for the purpose of...

 compared to the physically active lifestyle engaged in by ancestral hunter-gatherer

Hunter-gatherer

A hunter-gatherer or forage society is one in which most or all food is obtained from wild plants and animals, in contrast to agricultural societies which rely mainly on domesticated species. Hunting and gathering was the ancestral subsistence mode of Homo, and all modern humans were...

s. It has been proposed that since prolonged periods of sedentariness 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

Inflammation

Inflammation is part of the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. Inflammation is a protective attempt by the organism to remove the injurious stimuli and to initiate the healing process...

 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

Intestinal parasite

Intestinal parasites are parasites that populate the gastro-intestinal tract in humans and other animals. They can live throughout the body, but most prefer the intestinal wall. Means of exposure include: ingestion of undercooked meat, drinking infected water, and skin absorption...

. This causes problems in the proper development of the immune system.

• autoimmune disease
  Autoimmune disease
  Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...
  
  s
• Allergies
• hygiene hypothesis
  Hygiene hypothesis
  In medicine, the Hygiene Hypothesis states that a lack of early childhood exposure to infectious agents, symbiotic microorganisms , and parasites increases susceptibility to allergic diseases by suppressing natural development of the immune system...
  
  
• Helminthic therapy
  Helminthic therapy
  Helminthic therapy, a type of immunotherapy, is the treatment of autoimmune diseases and immune disorders by means of deliberate infestation with a helminth or with the ova of a helminth. Helminths are parasitic worms such as hookworms and whipworms....
  
  

Specific explanations

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

Life stage related

• Alzheimer disease
• Childhood
• Menarche
  Menarche
  Menarche is the first menstrual cycle, or first menstrual bleeding, in female human beings. From both social and medical perspectives it is often considered the central event of female puberty, as it signals the possibility of fertility....
  
  
• Menopause
• Menstruation
• Morning sickness