Why We Get Sick, The new science of Darwinian medicine (1996), Nesse & Williams

Chapter 1: The mystery of disease

• Proximate explanations answer “what?” and “how?” questions about structure and mechanism; evolutionary explanations answer “why?” questions about origins and functions
• Most medical research seeks the proximate explanations about how a body part works or how a disease disrupts function. The other half of biology, that tries to explain what things are for and how they got there, has been neglected in medicine
• One may worry that evolutionary explanations are mere speculation, however studies are showing that evolutionary hypotheses can predict what to expect in proximate mechanisms (e.g., morning sickness evolved to protect the developing fetus from toxins during its most vulnerable state)
• 6 categories of evolutionary explanations of disease:
  1. Defenses: while not actually an explanation of disease, this is listed because it is so often confused with other manifestations of disease. An example provided is that of a pneumonia patient who has blue-ish skin and a cough. The blue skin comes from a lack of oxygen in the hemoglobin which leads to darker blood. This is a problem that should be addressed, lack of oxygen is no bueno. The cough, however, is a defense, evolved to expel foreign material from the respiratory tract. Coughing is not a problem, and suppressing this defense puts the body at more risk
  2. Infection: we evolved defenses to counter viral and bacterial threats, viruses and bacteria have evolve ways to overcome our defenses and even use them to their own benefit. This evolutionary arms race explains why eradication of all infections is futile
  3. Novel environments (i.e., evolutionary mismatch)
  4. Genes: some of our genes are perpetuated even though they cause disease, as some of their effects were “quirks” that were harmless in our evolutionary environment
  5. Design compromises: walking upright gives us the ability to carry food, tools, and babies while walking, but predisposes us to back problems. To better understand diseases, we need to understand the hidden benefits of apparent mistakes in design
  6. Evolutionary legacies: evolution is an incremental process and cannot make huge jumps. As such, some designs at this point can be sub-optimal, e.g., our food passes over our windpipe. Once a system is in place, it is costly to re-engineer the evolutionary history

Chapter 2: Evolution by natural selection

• If tendencies towards anxiety, heart failure, nearsightedness, and cancer are somehow associated with reproductive success, they will be selected for and we will suffer even as we “succeed” in the purely evolutionary sense
• When Henry Ford asked, while in a junkyard of Model T’s, what particular systems never fail on those cars, he was answered with “the steering column never fails”. He instructed his chief engineer to redesign it, as if it never breaks, they must be spending too much on it
  • In a similar way, natural selection avoids overdesign
• Some genes that cause aging are not necessarily maladaptive. They may confer benefits during the early years of life, when reproduction (and thus selection) is at its highest potential. These benefits are more important to fitness than the later costs of aging and inevitable death
• When we ask these “why” questions about adaptive reasoning, we must guard against too readily believing fanciful stories. A bogus hypothesis to why our noses protrude would be that they evolved that way to hold up glasses. May seem plausible at first, but upon critical review it doesn’t hold up
• Hypotheses about evolutionary origins require testing, and due to the impossibility of rewinding time and re-running evolution, testing of evolutionary hypotheses are especially challenging. This is no reason not to pursue them, the work just becomes more challenging and interesting

  Chapter 3: Signs and symptoms of infectious disease

• Numerous studies have found that animals consistently seek to warm their body temperature to combat disease, and when this is suppressed, by a fever-lowering drug for example, they are more likely to die
• Studies have found that children with chicken pox take an average of 1 day longer to recover when fever was suppressed, similarly results were observed with colds
• Fever has its costs; it depletes energy reserves 20 percent faster and causes temporary male sterility. High fevers can cause delirium and seizures
• Iron deficiencies were found to be associated with infection, so physicians have in the past attempted to supplement iron. However, the body is actually trying to rid itself of iron such that it can’t be used by pathogens - supplementing iron enhances the pathogens and results in worsened infection. Care should be taken to respect the evolved wisdom of the body.
• The female reproductive system normally finds fluids flowing outwards, hence protecting the system from infection. The only exception to this is during sex, when sperm flow inwards, and have the potential to carry bacteria along with them
• This is a reason why mammals are thought to have menstrual cycles, and why humans have particularly profuse menstruation. Since human sexual activity is more constant, i.e., not constrained to a brief fertile window, females are presented with more opportunity of infection. Hence, the menstrual flush can help remove unwanted bacteria from the system
• A functional classification of the signs and symptoms of disease is important and useful. To choose an appropriate treatment, we need to know if the symptom benefits the host or the pathogen. We need to analyze the strategies taken by the pathogen and attempt to oppose each of them, rather than just relieving symptoms and trying ineffectively to kill the pathogen

  Chapter 4: An arms race without end

• Bacteria have two substantial advantages over humans:
  • High reproductive frequency: bacteria can evolve as much in a day as we can in a thousand years. Thus, we cannot evolve fast enough to escape from microorganisms
  • High numbers: due to their small size, bacteria’s enormous numbers in our body means that improbable mutations occur more frequently
• Some of the most effective antibiotics come from molds. Antibiotics are chemical warfare agents that evolved in fungi and bacteria to protect them from pathogens and other biological competitors
• Early in their discovery, antibiotics were extremely effective. However, over time the bacteria that antibiotics fended off evolved to evade their defence, and since the antibiotics are removed from their natural environment and thus less capable of adapting, they saw they their effectiveness dwindle.
• New antibiotics are churned out, and bacteria evolve resistance to those antibiotics, and the cycle continues
• Long term exposure to antibiotics, and increasing the dosage of antibiotics when they aren’t sufficiently effective, puts a selective pressure on bacteria to develop resistance to the antibiotics, enhancing them and decreasing the effectiveness of the antibiotics
• The use of antibiotics in farm animals can also end up harming the animals and the humans that eat them, this problem needs to be carefully measured against the economic gains that may be claimed from their use
• It is critical that the pharmaceutical not promote inappropriate use of antibiotics for animals and humans, as the selective pressure that ensues enhances the bacteria that they fight. It is unlikely this advice be heeded, as moral exhortations for the good of the group are often welcomed but rarely acted upon. This would require costly government intervention and a sacrifice in profits
• Within-host selection favours increased virulence (i.e., increases the diverting of resources from the host to the pathogen), while between-host selection acts to decrease it
  • Pathogens compete with one another for resources within the host, but will not be able to proliferate if their host dies before transmitting them to another host
• Diseases from vector borne pathogens (e.g., insects) tend to be more severe than those spread by personal contact. This is likely because between-host selection of person to person transmission would favour a less virulent pathogen that allows its host to go infect others; whereas, if for example a mosquito is the vector of transmission, the hosts health is of little interest to the pathogen as it will be transmitted by the insect anyways—the more vulnerable it makes the human, the easier it is for more mosquitos to suck their blood. In this case, it is in the viruses’ interest to have a mild effect on the mosquito, whilst feasting on the subsequently infected humans
• Increased transmission can lead to increased virulence, if the pathogen doesn’t have to worry much about between-host transmission, it can afford to be greedy as it is likely to be transmitted in a shorter amount of time. AIDS was thought to be particularly virulent because of high sexual activity frequency and frequent use of drug users’ unsanitized needles. Safe sex and the use of clean needles can thus cause the evolution of lowered virulence

  Chapter 5: Injury

• Risk of melanoma is related more closely to number of sunburns than to total amount of time spent in the sun. People who are outdoors often adapt to their amount of usual exposure and are unlikely to get sunburnt; people who go out infrequently do not adapt and are at increased risk of sunburn
• Sunglasses without UV protection reduce the total amount of visible light, leading pupils to dilate and admit more UV light that then damages the eye more than had the user not worn the glasses
• Why don’t our fingers regenerate when cut off? The repair machinery would have to conform to an optimal trade-off between the advantages of rapid and reliable repair, the costs of the needed machinery, and the dangers of cancer (associated with mechanisms of cell replication)

  Chapter 6: Toxins: New, old, and everywhere

• Tall fescue grass is popular because it grows fast and resists pests. A symbiosis between a fungus and the grass exists, where the fungus creates toxins that are transported to the tips of the blades of grass to discourage hungry herbivores
• If a fruit is eaten before the seeds are ready for dispersal, the whole investment of the plant is wasted. Ripeness of a fruit corresponds to the peak fertility of the seeds within
• A diverse diet helps to minimize the damage caused by dietary toxins (the evolved defenses of plants), whereas a non diverse diet may lead to a toxin overload
• Concerns over pesticides have led to attempts to breed plants that are naturally resistant to insects. This involves increasing the level of natural toxins, which tend to make humans sick as well. We are re-introducing the same natural toxins that farmers first bred out of plants generations ago. Natural toxins and artificial pesticides need be treated with the same amount of caution
• In the context of alleviating morning sickness during pregnancy: “Unfortunately, making people feel better does not always improve their health or secure other long-term interests.”
• Children avoidance of vegetables could also be adaptive. Strong-tasting vegetables contain more toxins, and during their development they would best stick to low-toxin vegetables. As such, certain vegetables repulse children, and this repulsion tends to fade as they age

  Chapter 7: Genes and disease: defects, quirks, and compromises

• Many genetic conditions that ail us now may have caused no trouble in our ancestral environment (and may have conferred some benefits), and only become a problem due to an evolutionary mismatch. For example, a craving and motivation for fatty foods might have been adaptive when foods were scarce
• “We should rebel against the tyranny of the selfish replicators.” - Dawkins

  Chapter 8: Aging as the fountain of youth

• Over the past few hundred years, the average length of life in modern societies has steadily increased, the maximum duration of life has not.
• Senescence: the process of bodily deterioration that occurs at older ages. Increased susceptibility to disease and decreased ability to repair damage
• Those with a genetic predisposition to get peptic ulcers, and die from these ulcers at old age, may benefit the individual by providing more protection throughout life from gastrointestinal infection via higher levels of stomach acid
• The whole immune system is age biased, releasing damaging chemicals that protect from infection, but also lead to accumulated tissue damage
• Genes with benefits in early age tend to contribute to senescence (trade off between effectiveness during fertile years at the expense of deteriorated function in infertile years)
• Studies showed that beetles better able to reproduce early in life reproduced more and generate more offspring, but age and die earlier. Genes will generally select for whatever maximizes reproduction.
• Any genes whose deleterious effects occur earlier than that of other genes will be selected against most strongly, thus selection acts on genes to delay deleterious effects until they are all in synchrony - hence the effect of the body’s functions decaying in seeming unison
• Postulates of impotence - pessimistic assessments of what science can accomplish can have utility (investigate this further)
• The preoccupation of living forever is likely to be supplanted by a desire to live as fully as possible, while it’s possible

  Chapter 9: Legacies of evolutionary history

• We have inherited systems that were not optimized for our bodies, they are historical legacies from our ancestors
• Examples include:
  • our air and food passages intersecting (making us vulnerable to choking),
  • a retina in front of the interior of the eyeball instead of behind (causing optic nerves and vessels to obstruct the view),
  • the appendix (used to help process low nutritional value food, rabbits still use it for example)
  • Our spine was originally designed to withstand loads from back to belly, not head to bum. Same with the joints in our leg

    Chapter 10: Diseases of civilization

• “What are the long-term consequences of such meager challenge to our body’s built-in temperature controls?”
  • In reference to our environments being constantly temperature controlled for maximum comfort (A/C, heating)
• Diseases brought about by civilization include obesity (energy excess, sedentariness), cavities (sugar excess), crooked teeth (lack of jaw development due to soft foods in diet), substance abuse/addiction (concentrations/availability of alcohol, opium, etc. would have been lower pre-agriculture, specialization led to increased potency of substances)
• Rickets was a frequent malady due to vitamin D deficiencies. When humans started occupying regions with more cloud cover, forest cover, and cold areas requiring cave dwelling and clothing, they received less sun exposure. Heavily pigmented skins admit less light for vitamin D synthesis and yield more malady in sun-starved skin, thus less pigmented skins were gradually selected for
• When faced with a problem of medical importance ask: What is its evolutionary significance?
  • If it’s an adaptive mechanism, it generally means it was adaptive in the Stone Age. Some aren’t adaptive, but represent costs to other adaptations (e.g., senescence)

    Chapter 11: Allergy

    Chapter 12: Cancer

• A common man marvels at uncommon things; a wise man marvels at the commonplace
• Multicellular organisms arose from some group of protozoa, in which each cell was a functionally independent individual. Most reproduction was asexual, with one cell dividing into two new ones.
• In some modern protozoan species, the two new individuals do not break completely apart but stick together in pairs, or the offspring of pairs stick together in filaments or sheets called colonies.
• In some colonies, cells may have differentiated into germ cells and somatic cells, meaning that some previously independent cells gave up reproduction to become genealogical dead ends. They would supply nutrients and protection to the few germ cells that sexually reproduce
• All cells within these colonies had the same genes, so if sacrificing reproduction improved the genetic progress of the colony the cells would do so
• For large colonies of cells, we may expect a mutant cell to appear that behaves in ways other than what maximally benefits the colony. Such large colonies thus need adaptations for maintaining discipline among the many component cells
• In the human body, among our ten trillion cells there exists a small chance (say, 0.01%) that a cell reproduces when it shouldn’t. This leaves a billion of such faulty cells. Given the amount of defence mechanisms to detect these cells, however, they rarely get to proliferate. There exists a web of defences, though eventually a cancerous cell can fall through the cracks—especially as we age, and senescence causes cell regulatory capability deterioration
• A cancer’s success can never be more than short term, because it has no way to disperse to other hosts, and its host’s death means its death too
• The more menstrual cycles a woman has, the more likely she is to develop reproductive-system cancer. This could be because historically women would have a later menarche (harsher living conditions), then would be pregnant or lactating, which both inhibit menstruation. Perhaps the reduced frequency of these processes lead to reduced cellular processes in the mammary glands and gonads that protect against cancers
• Oral contraceptives may reduce ovarian and uterine cancer risk, though they have their own side effects

  Chapter 13: Sex and reproduction

• The reason sexes exist at all, and that asexual reproduction isn’t as prevalent, is that:
  • It introduces more genetic variation;
  • It can prevent the accumulation of deleterious mutations; and
  • It decreases vulnerability to pathogens. If a pathogen finds the key to exploiting a genetically identical colony it will be able to wipe out all of them. If they are more genetically diverse, this is more difficult to accomplish. This idea is support by the fact that asexual reproduction occurs in areas with fewer parasites
• Large gametes have abundant energy stores, but are expensive to make; small gametes are inexpensive and can be produced in enormous numbers, but can’t survive for long
• Trees are hermaphrodites, carrying both eggs and sperm(?) cells, can do so because reproduction can be done by vector transport by air currents or insects. This is not possible with mammals, thus there are no mammal hermaphrodites
• Extra nutrients in sperm are more likely to retard its swimming, so low nutrient, fast sperm have been selected for
• There exists a battle between fetus and mother, as both share only 50% of genes with each other. As such, fetuses have strategies to increase nutritional consumption from the mother, and the mother’s system has methods to counter act these exploitative tactics
  • Fetuses secrete a hormone that increases and retrieves glucose from the blood, which increases the mother’s insulin production. This can produce pregnancy onset diabetes
  • Fetuses also secrete substances that increase blood flow to the placenta by constricting blood vessels throughout the body and increase blood pressure. Moderate increases in maternal blood pressure are associated with lower infant mortality
• Fetuses produce human chorionic gonadotropin (hCG), which blocks menstruation so that the fetus stays implanted. The mother’s body likely measures levels of hCG as means of detecting whether a fetus is viable or not. High hCG levels are the fetuses way of screaming “wait, don’t abort me!”

  Chapter 14: Are mental disorders diseases?

• Definitions of mental disorders were formed so research findings across different studies could be compared, however this emphasized sharp boundaries around symptoms instead of a continuous emotional process influenced by psychological factors, past events, and life situations
• Sleep tends to be dominated by visual sense. We’re hard pressed to reimagine sounds, smells, taste, and touch from our dreams. This could be because sight is rather useless as night, so dreams can fully employ sight, whereas sound, smell, and touch may have been necessary to stay online in the background to detect threats during sleep

  Chapter 15: The evolution of medicine

• Genetic instructions are assembled in preparation for the future, but are caused by the past