BIO228_ZF.pdf

BIO228: Evolutionary Medicine EvoMed L01: Introduction Evolution in medicine By studying evolution of e.g., viruses & bacteria -> one could predict to an extent future evolution - Mutations in the genome of viruses have large effects on the success of the virus -> if a mutation occur...

BIO228: Evolutionary Medicine EvoMed L01: Introduction Evolution in medicine By studying evolution of e.g., viruses & bacteria -> one could predict to an extent future evolution - Mutations in the genome of viruses have large effects on the success of the virus -> if a mutation occurs in a conserved region of the genome, it could be detrimental for the virus - A virus has to balance transmissibility & mortality/virulence - Virulence/transmission tradeoffs affect viral evolution! - Our public health interventions, like vaccines, social distancing etc. affect to a large extent viral evolution too “Always finish the full 10-day course of antibiotics” poses an important question, also for evolutionary medicine -> it has an effect on bacterial evolution - During bacterial evolution -> an antibiotic resistance can develop - Bacterial evolution is unbelievably fast (generational time of 20 minutes in E. coli) - Most antibiotics (particularly the early ones) are actually naturally from other (micro-) organisms -> antibiotic selection pressure was already existing - Antibiotic resistance: happens every time a new antibiotic is invented - Aggressive treatment selects for resistance -> especially if already present - Alternatives -> leverage the competition, drug cocktails, better use in hospitals (alternate the treatment with antibiotics), phage therapy (evolution proof? Viruses are even faster evolving and therefore can compete with bacterial evolution) Cancer is another example on how evolution plays an important role in medicine - Tumor cells are evolving, competing for resources (like nutrients, oxygen) - Chemotherapy could select for resistance (-> low chemo) - Alternatively an adaptive chemotherapy is better, as it controls growth, rather than wanting to eliminate the tumor -> this keeps up the competition between the evolving tumor cells Our bodies have evolved too, which brings implications for medicine and/or public health History of EvoMed The first time evolution was introduced into medicine was in 1969 by Bowlby -> Psychiatry: Childcare in evolutionary perspective -> back then psychiatry was still based on behaviorism In 1985 in the NEJM -> our nutrition was looked at from an evolutionary perspective (what nutrients/diets are we adapted to eat -> “paleolithic diet vs modern western diets” In 1980 more biomarkers were introduced into medicine -> reproductive physiology was examined in hunter gatherer & modern societies -> constant breastfeeding -> keeps estrogen levels low. Consequently in 1994 a connection between differences in lifetime estrogen exposure and reproductive cancer was drawn. Paleopathology -> at origins of agriculture our health worsened (counterintuitively) -> 1st epidemiological transition (the first farmers in history were malnourished and shorter and generally less healthy), furthermore, there were more zoonotic diseases as animal domestication started During 2nd epidemiological transition -> where we changed from an agricultural society to an industrial society -> change from acute (infections etc.) to more chronic disease -> “stone agers in the fast lane” In the early 90s -> first synthesis of the field (called it Darwinian medicine) [Nesse & Williams] -> today international society, journal, several centers, IEM established What does Evolutionary Medicine add? Proximate -> how does it work? Ultimate -> Where does it come from? What is it good for? How does it evolve? EvoMed -> takes an ultimate level/perspective of disease Tinbergen’s 4 questions -> originally to answer behavioral questions, like “Why does animal do X?” Nothing in biology/medicine makes sense except in the light of evolution – Dobzhansky (1973) Why we get sick -> Evolutionary reasons for vulnerability to disease Mismatch Hypolactasia -> lactose intolerance -> not actually a disease, but normal for most people. In societies where dairy farming was introduced early on and drinking milk was an important evolutionary advantage -> lactase persistence prevalence is high Myopia (nearsightedness) -> heritable -> prevalence is >80% in some East Asian countries Is the fact that it still exists evidence for the weak natural selection in humans? (Myopia risk alleles don’t produce myopia in ancestral conditions -> Gene x Environment is most probable (artificial light, indoors, reading) Bolivian hunter gatherer society [Tsimane’] -> no heart disease, diabetes etc. -> don’t seem to be affected by diseases thought to be caused by mismatches (CVD, IBD etc.) Defenses Fever is part of the innate immune system -> raising the temperature above normal range -> against bacterial/viral infections (slows pathogen reproduction, more efficient immune system) - Is the standard of care -> Antipyretics (fever lowering medicine) a problem? - Desert Iguana (cold blooded) experiment -> to fight infection they seek heat lamps to raise body temperature -> Iguanas treated with antipyretics or were unable to get to a lamp were more likely to die -> similar results were found in rabbit - Why not maintain a constant temperature of 40° C -> high energy expenditure & selection pressure on pathogens would result in fast adaption by pathogens anyway - HEAT trial (NEJM 2015) -> 700 ICU patients with fever (outcomes: # of days ICU free, dead by day 28, dead by day 90) -> no differences between treatment and placebo Defenses: the “smoke detector principle” Error 1: false alarm – smoke detector goes off without fire Error 2: fail to alarm – smoke detector does not go off despite fire  Cost of error 2 >>> error 1 -> rather go off once too much -> less costly to organism Defenses are designed to be overreactive -> reduction/treatment of fever (or coughing, sneezing) often not that harmful -> also applies to mental health e.g., anxiety, panic attacks It’s all about reproductive success and NOT survival (or health, or well-being) Example of the praying mantis -> female eats male after fertilization! This means the male mantis was highly successful in passing on its genes to future generations (even supplying nutrients to the female ensuring better chances of survival for her, at least until offspring is “born”) Similar behavior can also be observed in humans (particularly young males) -> high risk behavior to establish them in the adult male world or impress females (e.g. smoking) Trade offs Reproduction vs maintenance = ageing - Why not live forever? - Force of selection declines with age, once we started reproducing - Eternal live would require much more investment into maintenance (immune functions, cellular repair, etc.) at the cost of reproduction - Natural selection favors a limited life span! - Antagonistic pleiotropy [Pleiotropy -> one gene can have several functions in an organism, antagonistic -> a gene can have negative effect on an organism] -> alleles that are beneficial early in life will spread even if detrimental late in life (e.g. many oncogenes)