July 24, 2018

Evolution Does Not Make Mistakes

     Evolution does not make mistakes, but it does routinely conduct experiments.  "But Robert, what about genetic diseases, birth defects, and other inherited pathologies?  Those sound a lot like mistakes!"  To this I would say that if you believe these are examples of 'mistakes' of evolution, then our definitions of 'evolution' are probably a bit different.  As a general theme in this piece of writing, I will explore why I believe it's worth questioning what it means for something to be described as a 'defect', a 'disorder', or even a 'pathology'.  Furthermore, I hope to convince the reader that our over-eager tendency to consider even the slightest deviation from the average to be 'mistakes' of evolution is itself a mistake:  Many things that we call a 'disease' are simply an attempt by evolution to exploit a environmental 'niche', and I believe that our failure to realize this is negatively impacting our ability to make scientific and social progress in treating these 'diseases'.

     How do I define 'evolution'?  In keeping as consistent as possible with modern scientific terminology, I would describe it as 'phenotypic natural selection', but in a more general sense that can include Non-Mendelian inheritance, epigenetic factors or any as of yet undiscovered mechanisms for passing on traits:  Evolution is the ultimate decider of the universe.  It is the force of nature that causes anything to be the way it is:  Not as in intelligent design, but as in the laws of physics.  If something is a certain way, it is because it evolved to be that way.  It exists independent of morality, politics, good, evil or externally-imposed assessment about whether evolution should truly work the way it does.  Our artificial social or political value-systems cannot mandate what should or should not evolve in the same way that these systems cannot mandate that water should flow uphill.  No event has ever happened that has been inconsistent with evolution, and no event that has not happened has been consistent with evolution:  These two concepts are the same by definition.

     Now I must acknowledge that the more colloquial definition of 'evolution' is usually restricted to biological systems, but since every biological system is fundamentally a physical system, I think that my definition is appropriate.  Furthermore, since there is no sharp distinction between living and non-living things at the atomic level (at least that we know about), there is no reason not to generalize observations made in the context of biological evolution to non-biological systems.

Sickle Cell Anemia

     Sickle Cell Anemia is a blood disorder that causes swelling in the hands and feet, bacterial infections, stroke, long-term pain and decreased life expectancy.  If you live in north America, it is purely a disadvantage, but if you live in areas where malaria is prevalent then it might just save your life.  Due to the malformed blood cells that can be associated with sickle cell anemia, the malaria parasite is unable to complete its life-cycle in those who have the disorder.  This provides an advantage for those that have the disorder over those who do not, with dramatically higher rates of carrying this genetic trait seen by those who live in places where Malaria is prevalent.  According to the US government Center for Disease Control: "SCD affects approximately 100,000 Americans; SCD occurs among about 1 out of every 16,300 Hispanic-American births; SCD occurs among about 1 out of every 365 Black or African-American births; About 1 in 13 Black or African-American babies is born with sickle cell trait (SCT)."[6]

Colour Blindness

     Color Blindness is extremely common with up to 8% of the male population experiencing it.  Given that colour blindness is so common, this leads to the obvious question:  Is there some kind of evolutionary pressure keeping it in the gene pool?  Research suggests that are tasks that colour blind perform better on: "To explain the surprisingly high frequency of congenial red-green colour blindness, the suggestion has been made that dichromatics might be at an advantage in breaking certain kinds of colour camouflage.  We have compared the performance of dichromats and normal observers in a task in which texture is camouflaged by colour. ... We conclude that colour can interfere with segregation based upon texture and that dichromats are less susceptible to such interference."[1]  This effect has been speculated to play a role in our ability to see predators, or to find food when foraging.  There are anecdotal reports from people with certain types of colour blindness that they have better vision in the dark.  I attempted to find research evidence to support this claim, but instead I found evidence against it: "No evidence was found that red-green color deficiency or monochromatism confers a selective advantage under scotopic (dim light) conditions."[4]  I did, however, find research that suggests that there is a relationship between genetic abundance of colour blindness, and the amount of twilight that each region receives: "The above data, which provide equivocal support for the twilight hypothesis, clearly indicate an African and Eurasian north/south cline in frequencies of color vision polymorphyisms which span different cultures and continents.  Thus, at the equator, where twilight is only a minor component to total daylight, color vision deficiencies are generally rate, yet in northern regions, where twilight represents up to 25 percent of day-length, color vision frequencies are common."[5]

Huntington's Disease

     Huntington's disease is a case that I once considered to be evidence against my idea that diseases could be considered as evolutionary adaptations.  This was until I watched this lecture by Robert Sapolsky. "Huntington's disease is a neurological disorder; Huntington's chorea (other term chorea, choreography, body movement) Huntington's uncontrolled writhing that eventually consumes the entire body 24/7. The person eventually, not so long, dies from choking on their saliva because their muscles aren't co-ordinated anymore. Totally horrible neurological disease.  But what has taken people years to realize is that is not what Huntington's disease looks like at the beginning." "And what people have now figured out is that two or three years before Huntington's is a neurological disorder of movement, it's a psychiatric disorder of dis-inhibition." "Dis-inhibited behaviour a couple of years before the neurological symptoms do you in, during that time window individuals with Huntington's out-reproduce their unaffected siblings.  They become, among other things, sexually promiscuous."

Allergies

     Allergies are caused by an over-active immune response that occurs in response to what one would otherwise consider a harmless environment.  What possible evolutionary advantage could it be to have a body that attacks itself?  There is an interesting CBC documentary called 'The Allergy Fix' that describes a hypothesis that allergies come from an attempt by our bodies to compensate for immune system suppression caused by various infectious diseases and parasites.  The hypothesis notes that various parasites such as gut worms suppress the immune system.  According to this hypothesis, in order to get back to a normal level of immune activity, the body must naturally modulate the default immune response to be higher in anticipation of being infected by these parasites.  Therefore, the trait of increasing immune system activity by default would be beneficial to most of our ancestors who were almost persistently infected with parasites from untreated water or undercooked food.  In a modern day environment where these parasites have been effectively eliminated, this immune system over-activity would provide no benefit.

Down's Syndrome

     Down's Syndrome is one of the most common chromosomal abnormalities in humans.  It causes mental disability, poor immune system function, heart defects, Alzheimer's disease and a number of other problems.  At first glance this basket of symptoms doesn't at all seem to imply any evolutionary advantage, but it does if you consider living in a highly resource constrained environment. "Reports have indicated that the resting metabolic rate of both children and adults with Down syndrome is significantly lower than those of normal individuals (Luke, 1994; Allison, 1995). This is thought to partially explain the high proclivity for obesity in DS groups as observed in modern times (Cronk, 1985)."[2] We haven't always been able to walk down the street to McDonald's and buy 2000 calories for $10, and this makes it easy to overlook how difficult it was for our ancestors to find enough food.  Especially in times of famine, or other near-extinction events that may have pruned the entire population down to only those who are the most calorie-efficient.  The mental impairment that often comes with Down's syndrome doesn't seem to be much of an advantage unless you consider how calorie expensive brain function is:  "In fact the mass specific metabolic rate of brain tissue is over 22 times the mass specific metabolic rate of skeletal muscle (Aschoff et al., 1971).  The microencephaly, or small brain size seen in DS individuals may in fact be an advantageous decrease in this metabolically expensive organ."[2]

     There is another chromosomal abnormality called William's Syndrome that results in similar reduced brain size, but it affects different areas in different proportions compared to Down's syndrome.  "Children and young adults with DS or WS have an overall smaller brain volume compared to TD individuals of similar age; however the specific brain areas that show significant volumetric differences compared to TD are distinct for each of the neurodevelopmental disorders. Individuals with DS have smaller frontal, amygdalar, and cerebellar volumes compared to TDs; whereas individuals with WS have smaller midbrain, thalamic, basal ganglia, and occipital and superior parietal lobe volumes compared to age-matched TDs."[3]

     An important point worth considering regarding any potential evolutionary adaptation of Down's syndrome is that of fertility:  Down's syndrome individuals (especially men) are commonly reported as being infertile.  However scientifically speaking, there is evidence that fertility among those with Down's syndrome is under-estimated simply due to the fact that Down's syndrome individuals generally have less opportunity to conceive because of cultural and social reasons.  Quoting from a case report where a man with Down's syndrome fathered a healthy, non-Down's syndrome child:  "A 26-year-old man presented with characteristic features of Down syndrome. His mother was 28 years old at the time of his birth, and he had three normal siblings. His karyotype revealed nonmosaic trisomy 21 on two occasions. He was married to a 22-year-old normal female."..."Antenatal ultrasound and fetal echocardiography were normal. She delivered a healthy male child weighing 3 kg at term."..."To rule out the possibility of false paternity, DNA of the father of the Down syndrome patient was also genotyped for the same panel of 14 STRs. As expected, the same allele was found in both the grandfather and the putative son on all the Y-STRs but no common allele was found on four out of 10 autosomal STRs genotyped."[7]

Prader–Willi Syndrome

     Prader-Willi syndrome is a genetic disorder that is associated with weak muscles, poor feeding, and slow development as an infant.  Early in childhood, those with PWS begin to experience a near constant hunger which often leads to obesity and diabetes.  The extent of their hunger is incredible.  To convey this point, here are several quotations from the documentary Eating to Death: Living with Prader-Willi Syndrome | UK:  "They told us when she was diagnosed at 4, she'd eat herself to death by the time she's 20." "She's completely obsessed by food. From nursery age, every drawing, every painting, every piece of work, every story, all have food in it." "It's like living with somebody that's an addict. Her whole life is governed by when the next meal is coming and what she's going to eat for the next meal. She'll finish breakfast and she'll be talking about what she's going to have for lunch." "'Have you ever stolen money from your dad?' Yes...quite a few. 'For food?' Yes." "We did put a lock once [on the fridge], but he just took the bolt cutters and cut it off. It's a horrible disorder because they live and breathe only for food. How to get the next meal, how to get the next piece of fruit, or anything. Their mind is only on food. Nothing else matters in life. Food. James' father was his best friend, but in 2009, his dad died suddenly. The grief was too much for James, and at the age of 22, he made the decision to eat himself to death." "'To what extent will they go to, to get food?' Some people will eat inappropriate inedible things, some people will food seek after meals.  If there's a crumb on the floor, they'll try and pick it up."

     Interestingly, not only are people with PWS pre-disposed to consuming more calories than the average person, but they also burn fewer calories than the average person.  "Children with PWS have an energy requirement of approximately 8-9 kilocalories per centimeter (kcal/cm) of height for weight loss, and 10-11 kcal/ cm for weight maintenance. This is approximately 20-30% less than their same age and sex peers."[8]

     This combination of extremely active appetite and low calorie burn rate combined with weak muscle tone (requiring less protein and calories) would have obvious benefits in surviving extreme famines.  Famines don't happen every day, but when they do happen, we need to someone to carry on our genes to the next generation.

     In reading the last paragraph, you might point out that people who suffer from PWS are usually infertile.  However, according to the International Prader-Willi Syndrome Organisation[9], "Until recently there were no known cases of either men or women parenting children. However, the first two cases of live births to women with PWS were reported in 1999 and there have been two more since then; one a normal birth, the other resulting in a child with Angelman's Syndrome."  Furthermore, from the same source: "Girls with PWS are often pre-occupied with wanting to have a baby. They fantasize about having boyfriends and getting married without worrying in the least about any of the consequences."  Another consideration regarding fertility is that PWS usually comes with emotional and mental under-development.  In contemporary society, this significantly reduces the number of opportunities one has to actually conceive, which may skew the actual fertility rate of PWS to be lower then it truly is.

The Thrifty Phenotype

     There is a concept known as the Thrifty phenotype hypothesis that suggests that a number of chronic diseases (such as diabetes, heart disease, hypertension, etc.) can be explained by an adaptation that has benefits for surviving in an environment with limited resources.  In the preceding sections on Down's syndrome and Prader-Willi syndrome, I have aimed to give you the impression that this 'thrifty phenotype' would be an excellent explanation for why these conditions exist in the first place.  After all, humanity really has gone through some exceedingly difficult to survive famines many times throughout history.  Given this fact, we must ask "If Down's syndrome, Prader-Willi syndrome are not examples of individuals that would survive a famine, then where are the phenotypes that would?"

Extinction Events

     About 75,000 years ago, a supervolcanic eruption event occurred in Sumatra, Indonesia.  There is a theory known as the Toba catastrophe theory that suggests that this event was followed by a global volcanic winter that altered the climate enough to reduce the entire human population down to about 3,000 - 10,000 surviving individuals.

     Extinction events like this, and other similar, but not as severe, events such as the Irish potato famine of 1845-1849, The Year Without a Summer, or the Extreme weather events of 535–536 have a dis-proportionate effect on the genes that survive in a given population.  On a day to day basis these events don't happen that often, but looking historically over long periods of time there with surprising regularity.

     Apocalyptic extinction events don't occur every day, so it's tempting to consider someone who is preoccupied with thinking or preparing for these events as suffering from some pathology.  The irony of this is that the only people who will be around to carry the human race forward after such an event, are the people with the 'pathological' tendency to prepare for it.  This might explain why doomsday cults, religious prophecies of judgement day, and predictions that the stock market will crash are so popular:  We need a few of these people to get through extinction events, even though we typically just ignore them.  After the event has passed, the genes that code for producing relaxed and carefree individuals survive through those with neurotic and thrifty pre-occupations.  After a few generations, everything returns to normal and the species flourishes again.

     It's worth including in this section, although somewhat tangentially, the concept of Mitochondrial Eve.

Addiction

     The contemporary way to look at addiction is to focus on splitting it up according to the various vices that are targets of that addiction:  drugs, sex, video games, internet, alcohol, etc.  Since the target of an 'addiction' is usually considered an undesirable behaviour, we usually don't consider any connection to virtuous behaviours that could conceivably be part of the same underlying mechanism:  working, socializing, grooming, eating, planning, dancing etc.

     Consider the following idea:  What is 'addiction' is simply part of the underlying mechanism that motivates us to do anything at all?  There are a number of pieces of evidence that suggest that there are deep associations between dopamine, motivation and behaviour:

     A common theme here is that high dopamine activity tends to be associated with high motivation, high physical activity, mania, psychosis and addiction.  Whereas, low dopamine activity tends to be associated with low motivation, physical slowness, depression and abstinence from behaviour.

     However, it's not as simple as defining a 'dopamine spectrum' to explain all of these behaviours:  For example, symptoms such as Parkinson's disease (abnormally low dopamine activity) and psychosis (abnormally high dopamine activity) can occur at the same time in the same individual, invalidating any kind of idea that everything can be explained by one common neurotransmitter.  The reality is that dopamine isn't the only neurotransmitter involved in moderating behaviour (although it is a major one).  Neurotransmitters such as serotonin, norepinephrine, epinephrine, and many others.  Each of these neurotransmitters has many different sub-types, and for each sub-type there are many different variations of corresponding receptors that responds to these neurotransmitters in different ways.  Some people are genetically pre-disposed to having special proportions of these receptors, and to make it even more complicated, the rate at which each different neurotransmitters is used up and recycled can change from person to person.  A final complication is that different areas of the brain can and do have different proportions of receptors for each of these neurotransmitter receptors which, of course, can vary between individuals based on genetic environmental factors.

     As an example of this complexity, in Parkinson's disease, the death of dopamine receptors is localized to the substantia niagra, but dopamine replacement therapy offered to these patients raises dopamine levels, not only in the substantia niagra, but also "in the ventral striatum and mesocorticolimbic system. This fact causes problems in reward and in the motivational-related processing"[19].  It also explains why controlling motivation related illnesses is so hard:  Attempting to cause desirable changes to the level of neurotransmiter activity in one area of the brain can have undesirable effects to another area of the brain.

     It's worth emphasizing that Parkinson's disease is an affliction of movement planning and anticipation and not motor control in general.  Take for example the following incredible insight from a research paper on Parkinson's: "...One of these is 'kinesia paradoxica,' the seemingly paradoxical ability of Parkinson's disease patients to move considerably faster than the maximum speed at which they could otherwise move (Souques 1921; Broussolle et al. 2010). The example typically given is that a patient with advanced PD, who is normally confined to a wheelchair, might be able to get up and run out of a theater if there is a fire. The situations described are characterized by a powerful urgent stimulus."[20]

     Now getting back to the general discussion on analyzing addiction and motivation, the following general themes can be either extrapolated from the above, or are directly stated in the linked research papers:

     What does this all have to do with evolution?  Well, one can reason that the different idiosyncrasies of addiction are due to genetic specializations (achieved through a carefully evolved collection of neurotransmitter sensitivity levels) that have favoured certain types of behaviours.  Some situations may select for people who like to eat more than they like to have sex.  Some situations may favour the reverse.  Some situations may select for people who like to exercise constantly to improve fitness to defend against predators.  Some situations may favour eating foods that contribute to endogenous ethanol (minute quantities of alcohol produced naturally in the stomach) or altered metabolism leading to high endorphin levels.  The 'correct' behaviour depends on the environment and how many resources are available.

     In writing this section, I was reminded of one day when my father came home one day after looking for some spare car parts at a local junk yard:  Growing up in rural New Brunswick, it was not uncommon to visit a rather 'rustic' looking junk yard filled with old broken down cars to get a bargain on used parts.  These junk yards were often run by similarly 'rustic' looking people.  On this day, when my father came home he recounted how there was a very animated and somewhat over-active young man working at the yard.  My father had a brief conversation with the young man's father who declared without being prompted (in reference to his son): "When he was on the drugs we couldn't get him to do anything.  Now that he's off the drugs we can't get him to stop working!"

     The famous polar explorer Ernest Shackleton acknowledged his own disposition for addiction:  In the book, 'Polar Wives: The Remarkable Women behind the World's Most Daring Explorers' there is a section that reads: "A drinking spree at Christmas upset his equilibrium, and he realized that he was in danger of losing himself entirely. "I am strictly on the water wagon now," he reassured Emily. "It does me no good and I can tell my imagination is vivid enough without alcohol -it makes me extravagant in ideas and I lose balance... If I had not some strength of will I would make a first class drunkard.""

Suicide

     Why would a tendency toward suicide or suicidal ideation ever be positively selected for?  I would reason that in a competitive environment, a population containing individuals who have a willingness to sacrifice their lives for no reason will have more individuals willing to sacrifice their lives for a noble reason than a population consisting of individuals who refuse to sacrifice their lives for any reason.  Purple heart earners, emergency responders, and police officers all need to suspend their safety for the good of protecting others.  I'm not claiming that every suicidal person is a fearless warrior, but I would claim that if you want to be among the most fearless warriors, it might help to be a bit suicidal.  In May 1786 Napoleon wrote "But what can be done in this world?  Since I have to, is it not better to kill myself?  If I was over sixty years of age I would respect the prejudices of my fellow-creatures, and would wait patiently for nature to accomplish its work; but since I commence to experience unhappiness, and since nothing gives me pleasure, why should I endure days in which I succeed in nothing?"  It's clear that Napoleon's mind craved for some sort of noble purpose to assign meaning to his life.  A few sentences later he continued "What is the spectacle I shall witness in my country? Fellow-countrymen loaded with chains, all trembling, kissing the hand that oppresses them.  They are no longer brave Corsicans animated by heroic virtues, and the enemies of tyrants, luxury, and base courtesans."[21]  Napoleon, of course, became the ruler of France and is now viewed as one of the greatest military commanders in history.  To this day, Napoleon is still considered a relevant figure of study even for the US military.[22]

     In writing this article, I spent some time looking to see if there were any studies on pre-disposed risk for suicide and military enlistment.  Interestingly, I found that this topic simply isn't studied: "The U.S. Army does not use secondary screening tools, because of their historical failure to reduce neuropsychiatric casualties and to predict combat military performance." "Current accession screening continues [...] by identifying only gross mental health disability."[23]

     I also found a historical review of psychological reviews for military screening that takes into considerations multiple wars across the world, and this study also came to the same conclusion:  That psychological pre-screening was not effective.  "Despite the optimism shown in World War I and the concerted efforts of World War II, followup studies showed that screening programmes did not succeed in reducing the incidence of psychological casualties. Furthermore, they had a counter-productive effect on manpower, often rejecting men who would have made good soldiers. Continued experimentation with screening methods for psychiatric vulnerability failed to yield convincing results during the post-war period."[24]

     In addition to the above hypothesis of suicide as a protective self-sacrifice mechanism that benefits the survival of the larger group, there is a paper published in the journal of Environmental Research and Public Health[25] that suggests several other hypotheses:  'The Altruistic Suicide Hypothesis' which suggests a similar self-sacrifice idea, but one more focused on preserving resources for the surviving kin; 'The Bargaining Hypothesis' which suggests that suicidal ideation or near-suicidal behaviour benefits the individual by drawing attention to them when they are in legitimate need of help; and 'The Parasite Manipulation Hypothesis' which describes cases where the suicidal behaviour can be explained by the evolutionary fitness of the parasite rather than the host:  The parasite can manipulate the behaviour of the host in order to cause its death allowing the parasite to complete it's life-cycle.

Violence

     In contemporary culture, violence is generally considered a maladaptive behaviour.  Interestingly though, there is one very specific genetic variation that runs in some families and very accurately predicts violent behaviour:  The 2R variant of the MAO-A gene.  One study found "The association analysis shows that men with a 2R report a level of serious delinquency and violent delinquency in adolescence and young adulthood that were about twice (CI: (0.21, 3.24), P = 0.025; and CI: (0.37, 2.5), P = 0.008 for serious and violent delinquency, respectively) as high as those for participants with the other variants. The results for women are similar, but weaker."[26].  Reading further from the Wikipedia article on the subject: "Low MAO-A activity alleles which are overwhelmingly the 3R allele in combination with abuse experienced during childhood resulted in an increased risk of aggressive behaviour as an adult" and "The low-activity 3-repeat allele variant of the MAOA gene has also been found to occur frequently in men who join gangs.".

     There is a rather interesting talk by a neuroscientist named James Fallon[27].  In this talk he discusses his experience reviewing the neurophsiology of the brains of violent offenders.  After unknowing reviewing a PET scan of his own brain and suggesting that it may be one of the worst among the group of offenders, he does more research on his own genetics and discovers that he has the same MAO gene variant that is associated with violent behaviour.

ADHD

     ADHD, or Attention deficit hyperactivity disorder, is usually associated with problems paying attention, excessive activity, and difficulty controlling behaviour.  According to the US CDC it affects about 5% of the population[28].  It is typically described in terms of how difficult it can be for parents or teachers to manage the attention of children with ADHD.  One study states as follows: "At home, common problems targeted for behavior management treatment may include[29]:

     But since when does evolution optimize for creating individuals who are obedient to authority and do what they are told?  Is it so ridiculous to suggest that every once in a while, our genetics produces an individual who says  "Nope, I'm going to do what I want to do and ignore everyone else." because that happens to occasionally be a successful phenotype for surviving?

     There is an idea called the 'Hunter vs. farmer hypothesis' that provides a suggested explanation for the evolutionary role of ADHD.  The hypothesis suggests that many traits of ADHD, excessive activity, inability to sit still, easily distracted, shifting attention, etc., are all traits that would benefit humans in hunter-gatherer roles.  Being able to react immediately to the sound of a crunching leave in the distance, and constantly being on the edge of excitability would have obvious advantages not only for hunting, but also for escaping predators in the wild.  These advantages would be contrasted from the advantages that a farmer would need:  Ability to sit quietly and focus for hours on end, doing repetitive work.  When all of your food comes from staying focused on growing crops, the types of high-stimulation excitement that individuals with ADHD crave would not be considered a benefit.

     The general cultural awareness of ADHD generally focuses on the 'attention defecit' part of the acronym, although among those who have ADHD, many will note that this can be somewhat of a misnomer:  There is a concept known as hyperfocus that those with ADHD purport to experience.  When hyperfocused, individuals experience a state of complete absorbtion in a task that is not easily broken.

     Reading from the book 'Recent Developments in Neuroscience Research': "People with ADHD can only focus on stimulating things, and that focus is often extreme, taking the form of Absorbtion. They have short attention span for subject matter that not does trigger absorbtion. ADHD has been proposed to represent adaptive responding to highly urgent situations, and absorbtion in ADHD has been proposed to be a gift of benefit under appropriate circumstances. Glickman and Dodd (1998) found that adults with ADHD scored higher than normal adults on ability to hyperfocus (get absorbed in) 'urgent tasks,' such as last-minute projects or preparations. Adults in the ADHD group were uniquely able to postpone eating, sleeping, and other personal needs and stay absorbed in the 'urgent task' for an extended time."[30]

     There is also a study which demonstrates an association between individuals with ADHD and workaholics:  "The present study utilized an open web-based cross-sectional survey assessing symptoms of psychiatric disorders and workaholism among 16,426 workers" ... "The present study suggests that having symptoms of an underlying psychiatric disorder is associated with workaholism. A synthesis of individual (1.2%), work-related (5.4%), and mental health (17.0%) variables, explained 23.7% of the variance in workaholism, which is considered a large effect. ADHD, anxiety, lower age, and managerial positions stood out as most consistent and conceptually meaningful in the linear regression." ... "it became evident that individuals that were younger, female, not in a relationship, managers, self-employed, and met clinical cut-offs for ADHD, OCD, anxiety, and depression, were more often categorized as workaholics than their comparison groups."[31]

Mental Illness

     Schizophrenics sometimes believe that everyone is out to get them.  However, sometimes everyone is out to get you.  Someone who acquires PTSD from a horrific car crash, might tend to avoid using a car after the accident.  But avoiding any form of driving sounds like a pretty good way to reduce your chances of being in another car accident.  A common autistic trait is to have repetitive and narrowly-focused behaviours.  But some behaviours, taken to an extreme, do benefit survival, especially in niche environments.  In each case, regardless of how 'mal-adaptive' a particular phenotype may appear to us in contemporary modern-day society, there is almost always an extreme environment where the underlying heritable traits could, individually, be considered a benefit.

     Now I must acknowledge that the reason so much literature is written about mental illness is because the cases that get most of our attention are ones where there is tremendous evidence that the underlying mental illness doesn't have any hidden benefit for the individual.  Instead it has a very negative effect on their life due to the severity of the illness.  How can this be explained?  In considering this, I am reminded of a documentary called Children Of Darkness.  In this documentary, a mother speaks about her child: "Why is this child?  Why did God create it?  That's all I've always wondered.  What does it mean?  It has to have a meaning.  Everything has a meaning.  What is his meaning?  Why is billy here?  I don't know."

     The explanation I would propose for why Billy is here is that Billy likely received too much of a good thing.  In different environments, some individuals may adapt to filter more or less sensory input.  It is often the case, as it is for autism spectrum disorders, that many different genes can affect the way they process sensory input.  An individual that ends up with a couple copies of the gene that make them more sensitive to sensory stimulation can give them the benefit of being more aware.  However, if you receive too many genes that would individually give you a benefit, the balance tips the other way:  Too much sensory input overloads the mind.  The world could become a blur of lights, sounds, painful touch, and a confusing mess where learning is impossible.  The same process could occur with other illnesses like schizophrenia, or a pathological addiction:  Receive just enough genes that code for a specific dopamine receptor sub-type, and you'll be more motivated to find food.  Receive too many, and you either hallucinate or become addicted to cocaine.  The individual genes stick around because they are so positively selected for, but when they occur together in an unfortunate individual, it's effectively 'collateral damage' of the evolutionary process.

     The fundamental unit of survival is, therefore, not the individual, but the individual heritable traits.

Evolutionary Neuropathology

     There is a term called 'Evolutionary Neuropathology' that isn't quite popular enough to have it's own Wikipedia page, but it does have a number of references in academic literature.  The term describes an approach to understanding neurological and neurodegenerative diseases in terms of adaptation to an environment.  I don't have much more to say on the topic, but an interested reader might find it interesting because it describes exactly the concept I'm trying to convey in this piece of writing.

The Illness of Believing You're Healthy

     I would posit that believing that evolution does make mistakes is likely something that is positively selected for.  Furthermore, it isn't unreasonable to suggest that believing your own evolutionary idiosyncrasies are the 'correct' or 'best' ones is something that would contribute to the proliferation of those same traits.  If you believe your traits are an illness or defect and therefore inferior, you'll probably try to change them and associate more with what you perceive to be the successful group.  You might also become prone to limiting yourself other ways that inhibits your reproductive success.

     Nowhere is this idea more evident than when it comes to the consideration of what it means to be mentally 'healthy' or mentally 'ill':  Do you dislike someone's thinking or behaviour?  All you have to do is convince them and everyone else that they're mentally ill.  Regardless of your political affiliation you can probably agree that, among members of your favourite political party, it's common knowledge that the opposition is crazy.  What are they thinking!

     One of the things that convinces me the most that I'm probably right about this idea is how vehemently some people will declare that it's wrong.  There's a certain amount of opposition you'll get if assert something that's clearly wrong such as saying that "1 + 1 = 3", but for some people the slightest suggestion that they should question their own biases or conflicts of interest evokes a uniquely visceral reaction of hatred.  They cannot even consider for a moment that their way of being isn't the 'optimal' way, and they interpret even hypothetical discourse on the subject to be a personal attack on their being.

Nature Is Metal

     It's likely that different people will interpret this article in remarkably different ways.  Some people might suggest that I'm trying to trivialize their own afflictions or suffering, while other people might suggest that I'm trying to glorify them.  Make no mistake, my goal is to do neither:  From a purely scientific perspective, no consequence of evolution is good or bad, it simply 'is'.

     You might also get the idea that I'm trying to claim that there's always a silver lining, and that everybody is somehow 'special in their own little way'.  A sort of optimist's approach to dealing with the harshness of life.  This really isn't the tone I want to set either, and I would instead compare it to the phrase that 'nature is metal' (a reference to the fact that nature is often cruel and indifferent, even in the face of extreme hardship, a theme often explored in heavy metal music).  Evolution doesn't optimize for the comfort and happiness of the individual, it optimizes for that which survives.  

Specialization Vs. Unconditional Advantage

     There are some adaptations and advantages that nearly all humans have that arise when there is a possibility to evolve toward an unconditional advantage.  All surviving humans can breathe air, drink water, and eat food.  They have a brain that functions somewhat, a heart that pumps blood, and a circulatory system that delivers oxygen and nutrients.  These, and many others, are the adaptations that we all have in common because they never require a trade-off in terms of resources.  You either have them and survive, or you don't, and we therefore don't think about them as 'adaptations'.  The instant that evolution can make these improvements, it does, and it never looks back.

     But then there are a great number of potential improvements, but they come with a resource trade-off of some sort:  Increased survivability when living during a famine at the cost of diabetes if food is plentiful.  Increased resistance to persistent infections and parasites, but alergies if the infections are not present.  Resistance against certain types of mould, but slightly different lung function.  Ability to run faster in short bursts, but an inability to run longer distances.  Big calorie-hungry brain with lots of intelligence Vs. small calorie-conserving brain with low intelligence, etc.

     In the interest of making scientific progress, I think it would be very enlightening to go through the record of human history and enumerate all of the extreme environments that humans have ever survived.  For each of these cases, then ask the question: "Is there any slight evolutionary adaptation that helped this subset of individuals survive their situation?"  If the answer is "yes" investigate whether this adaptation manifests itself as a 'disease' in our contemporary environment.  If this analysis were properly done, I'm convinced that we would immediately solve a large number of outstanding medical mysteries surrounding pathology.

Conclusion

     The approach that seems to be used most often in the investigation of pathology is to explain the 'disease' as the result of something going wrong in a normal environment, but I claim that we should instead seek to explain it as something going right, but in an abnormal environment (the current environment).  The result is a much more scientifically actionable line of reasoning:  Instead of looking for a random, unfortunate and unjustified trigger for the disease mechanism you can look for a predictable, constructive and desirable response to some constrained condition.  Then, once you can explain the mechanism and circumstances under which the 'disease' happens for some benefit, you can explain why it's not the response we want in our modern day lives.

     Now some of you might not agree with the perspective of 'everything happens for a reason' and suggest that some diseases are just 'bad luck' or 'random', but I claim that is nonsense.  Any accurate model of what caused a problem should be able to make predictions about the mechanics of how that problem came to be in the first place.  If it can't then the model is not useful and it's purely pseudoscience.  And don't complain to me about Brownian Motion or cosmic rays.  Go model it using statistics!

     For debugging computer programs, an accurate model should be able to describe and predict the previous register states and contents of memory before the problem occurred. I/O operations, internal states, etc. Computers are not magic, and if the model can't describe these, then it's not a useful model.  For debugging biology, the same applies:  A useful model of an illness should accurately describe how the illness came to be.  No exceptions.  Coincidences, luck and chance are for the scientifically lazy.  For every pathology, a useful model describing it must be able to answer at least one of the following two questions:

     The only other possible case is a purely idiopathic disease that occurs for the first time in a single individual, but even in this case you can make arguments about how our reproductive processes physically evolved to be easily susceptible to this type of idiopathic pathology.

References

[1] M. J. Morgan, A. Adam and J. D. Mollon (1992) Dichromats detect colour-camouflaged objects that are not detected by trichromats. Proc. Roy. Soc. Lond. B 248, 291-295

[2] Article II; Evolutionary Neuropathology: Down Syndrome An Analysis of the Etiological and Phenotypical Characteristics of Down Syndrome Suggests that it May Represent an Adaptive Response to Maternal Deprivation; Medical Hypotheses, Volume 67, Issue 3, 2006, Pages 474-481; Jared Reser

[3] Differences in age-related effects on brain volume in Down syndrome as compared to Williams syndrome and typical development J Neurodev Disord. 2014; 6(1): 8. Published online 2014 Apr 9. doi: 10.1186/1866-1955-6-8 PMCID: PMC4022321 PMID: 24713364

[4] Is Color Vision Deficiency an Advantage under Scotopic Conditions? Accessed July 8, 2018.

[5] Human Color Vision Deficiencies and Atmospheric Twilight T.E. Reimchen, Accessed July 8, 2018.

[6] https://www.cdc.gov/ncbddd/sicklecell/data.html Accessed July 7, 2018.

[7] Fertility in men with Down syndrome: a case report December 2006Volume 86, Issue 6, Pages 1765.e1–1765.e3; Mandakini Pradhan, D.M.'Correspondence information about the author D.M. Mandakini PradhanEmail the author D.M. Mandakini Pradhan, Ashwin Dalal, M.D., Faisal Khan, M.Sc., Suraksha Agrawal, Ph.D.; Department of Medical Genetics, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India; Last accessed July 9, 2018

[8] Prader-Willi Syndrome Association USA Last accessed July 9, 2018

[9] International Prader-Willi Syndrome Organisation Last accessed July 9, 2018

[10] Daily physical activity and alcohol use across the adult lifespan. Health Psychol. 2015 Jun;34(6):653-60. doi: 10.1037/hea0000157. Epub 2014 Sep 15.; Last accessed July 9, 2018

[11] Tridimensional Personality of Adolescents with Internet Addiction and Substance Use Experience Chih-Hung Ko, MD1,2, Ju-Yu Yen, MD1,3, Cheng-Chung Chen, MD, PhD4,5, Sue-Huei Chen, PhD6, Kuanyi Wu, MD1 , Cheng-Fang Yen, MD, PhD4; Can J Psychiatry, Vol 51, No 14, December 2006; Last accessed July 9, 2018

[12] Drug-Induced Parkinsonism J Clin Neurol. 2012 Mar; 8(1): 15–21.; Published online 2012 Mar 31. doi: 10.3988/jcn.2012.8.1.15; PMCID: PMC3325428; PMID: 22523509; Last accessed July 9, 2018

[19] Dopamine Replacement Therapy, Learning and Reward Prediction in Parkinson’s Disease: Implications for Rehabilitation Davide Ferrazzoli,1,* Adrian Carter,2,3 Fatma S. Ustun,4 Grazia Palamara,1 Paola Ortelli,1 Roberto Maestri,5 Murat Yücel,3 and Giuseppe Frazzitta1; Front Behav Neurosci. 2016; 10: 121.; Published online 2016 Jun 14. doi: 10.3389/fnbeh.2016.00121; PMCID: PMC4906006; PMID: 27378872; ; Last accessed July 9, 2018

[13] Hedonistic homeostatic dysregulation in patients with Parkinson’s disease on dopamine replacement therapies J Neurol Neurosurg Psychiatry 2000;68:423–428; G Giovannoni, J D O’Sullivan, K Turner, A J Manson, A J L Lees; Last accessed July 9, 2018

[14] Cocaine: Discussion on the Role of Dopamine in the Biochemical Mechanism of Action Jorgen Scheel-KrügerClaus BraestrupMogens NielsonKrystyna GolembiowskaEwa Mogilnicka; Last accessed July 9, 2018

[15] A Receptor Mechanism for Methamphetamine Action in Dopamine Transporter Regulation in Brain Zhihua Xie and Gregory M. Miller; Division of Neuroscience, New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts; Received March 18, 2009; accepted April 10, 2009; Last accessed July 9, 2018

[16] Reversal of cocaine addiction by environmental enrichment Marcello Solinas1, Claudia Chauvet, Nathalie Thiriet, Rana El Rawas, and Mohamed Jaber; Institut de Physiologie et Biologie Cellulaires, Universite´ de Poitiers, Centre National de la Recherche Scientifique, Poitiers F-86022, France; Edited by James L. McGaugh, University of California, Irvine, CA, and approved September 17, 2008 (received for review July 17, 2008); Last accessed July 9, 2018

[17] Self-reported motivation to smoke in schizophrenia is related to antipsychotic drug treatment Volume 100, Issues 1–3, March 2008, Pages 252-260; Alasdair M.BarraRic M.ProcyshynbcPhilipHuibJoy L.JohnsondWilliam G.Honer; https://doi.org/10.1016/j.schres.2007.11.027; Last accessed July 9, 2018

[18] Antidepressant-induced mania: an overview of current controversies. Bipolar Disord. 2003 Dec;5(6):407-20., Goldberg JF1, Truman CJ; Last accessed July 9, 2018

[20] Motor Control Abnormalities in Parkinson’s Disease Cold Spring Harb Perspect Med. 2012 Jun; 2(6): a009282.; doi: 10.1101/cshperspect.a009282; PMCID: PMC3367543; PMID: 22675667; Last accessed July 9, 2018

[21] NAPOLEON ON SUICIDE South Australian Chronicle (Adelaide, SA : 1889 - 1895) Sat 9 Feb 1895 Page 7 NAPOLEON ON SUICIDE.

[22] Military History: Is It Still Practicable? Jay Luvaas; Originally published in Army War College's Parameters, March 1982, Last accessed July 9, 2018

[23] U.S. Military Enlisted Accession Mental Health Screening: History and Current Practice Robert Andrew Cardona, MD Elspeth Cameron Ritchie, MC USA; Military Medicine, Volume 172, Issue 1, 1 January 2007, Pages 31–35, https://doi.org/10.7205/MILMED.172.1.31; Published: 01 January 2007, Last accessed July 9, 2018

[24] Screening for vulnerability to psychological disorders in the military: an historical survey E Jones, K C Hyams, S Wessely; J Med Screen 2003;10:40–46, Last accessed July 9, 2018

[25] The Evolutionary Puzzle of Suicide Int J Environ Res Public Health. 2013 Dec; 10(12): 6873–6886.; Published online 2013 Dec 9. doi: 10.3390/ijerph10126873; PMCID: PMC3881146; PMID: 24351787; The Evolutionary Puzzle of Suicide; Henri-Jean Aubin,1,* Ivan Berlin,2 and Charles Kornreich3;, Last accessed July 9, 2018

[26] The VNTR 2 repeat in MAOA and delinquent behavior in adolescence and young adulthood: associations and MAOA promoter activity Eur J Hum Genet. Author manuscript; available in PMC 2010 Aug 17.; Published in final edited form as:; Eur J Hum Genet. 2008 May; 16(5): 626–634.; Published online 2008 Jan 23. doi: 10.1038/sj.ejhg.5201999; PMCID: PMC2922855; NIHMSID: NIHMS223559; PMID: 18212819, Last accessed July 9, 2018

[27] James Fallon, Neuroscientist - A Scientist's Journey Through Psychopathy ZeitgeistMinds; Published on Sep 16, 2014, Last accessed July 9, 2018

[28] US CDC Attention-Deficit / Hyperactivity Disorder (ADHD) Data & Statistics Last accessed July 9, 2018

[29] Behavior Management for School Aged Children with ADHD Child Adolesc Psychiatr Clin N Am. Author manuscript; available in PMC 2015 Oct 1.; Published in final edited form as:; Child Adolesc Psychiatr Clin N Am. 2014 Oct; 23(4): 731–746.; Published online 2014 Aug 10. doi: 10.1016/j.chc.2014.05.014; PMCID: PMC4167345; NIHMSID: NIHMS602817; PMID: 25220083; ; Last accessed July 9, 2018

[30] Recent Developments in Neuroscience Research on Human Motivation Volume 19 Sung-il Kim, Johnmarshall Reeve, Mimi Bong; Copyright 2017.; Last accessed July 9, 2018

[31] The Relationships between Workaholism and Symptoms of Psychiatric Disorders: A Large-Scale Cross-Sectional Study Cecilie Schou Andreassen , Mark D. Griffiths, Rajita Sinha, Jørn Hetland, Ståle Pallesen ; Published: May 18, 2016https://doi.org/10.1371/journal.pone.0152978 ; Last accessed July 9, 2018