“Nothing in biology makes sense except in the light of evolution”
-Theodosius Dobzhanksy
If there’s one thing I’ve learned to be absolutely certain as a medical student, it’s that the human body is an elegant and highly complex biological device; so complex in fact that it’s remarkable it even works in the first place. Just think about the idea that every cell in your body contains instructions to build a structure comprised of trillions of individual cells organized in such a way that allows you to do things like walk in a straight line, throw a frisbee, build a car, or invent the wheel in the first place. I can barely build a shelf from IKEA correctly due to crappy instructions, yet thousands of babies are born every day that will develop into perfectly normal, functioning human beings capable of remarkable things.
All of these behaviors that humans (and really any living being) have and do every day are constantly thought of in the context of evolution (i.e. why did we develop emotions or evolve to walk upright or have a brain in the first place?). In the biological sciences, evolution is the most widely used theory for building frameworks on how life works. So if we use evolution to understand why things like the human body work based on the environment we adapted to, why not ask why the body sometimes doesn’t work perfectly in the context of evolution?
In the remainder of this article, I will explain a framework for understanding all disease as some form of an adaptation made by the human body.
Before we begin, however, I would like to take a minute to include a few disclaimers: I don’t like the term “western medicine” to describe what doctors in America do, I prefer “evidence based medicine,” as everything in both research and the clinic is driven by our understanding of the data we have; second, from here on I will be presenting evidence to support a general philosophy for our current thinking of how pathology arises, however, I WILL IMPRINT MY OWN OPINION ON THE TOPIC. As such, this should not be taken as fact but rather as a traction point for further discussion on the matter.
Framing disease in the context of adaptation in contemporary evidence based medicine
Photo credit: Al Quora
To put it simply, a potential model for understanding the context (the why?) of disease is that all pathological processes arise from an initial adaptation that becomes maladaptive at a different time point or in a different compartment of the body (de novo or sporadically). Darwin’s theory of evolution revolves around survival of the fittest, i.e. those adaptations that are beneficial to life produce a higher chance of reproduction for that organism and thus generate a higher presence of that adaptation in the population through iterative generations (it’s like passing organic chemistry sophomore year of college: only the strong survive).
But what about all those adaptations that didn’t make the cut (RIP to our fallen soldiers who switched to a business major after failing OC) or those adaptations that begin as beneficial adaptions but come with maladaptive baggage alter on (passed organic chemistry but dropped after biochem 1 to a BA)?
The easiest disease example to understand would be a genetic disorder like Phenylketonuria (PKU), something that our very own writer Blaide Woodburn suffers from. In PKU and other genetic disorders, a genetic mutation occurs at some point during the conception process, whether it be in mom’s eggs, dad’s sperm, or in the one celled embryo itself. Since all evolutionary adaptations are derived from genetic mutations, it’s easy to see how a genetic disorder like PKU is just a mutation that is maladaptive rather than adaptive.
Those with sickle cell disease possess a rare but significant advantage over those without in that they are resistant to malaria.
Furthermore, in other diseases, the disadvantages that come with certain genetic mutations are balanced by a clear advantage in other aspects of life. Take sickle cell disease, for example. We know now that mutations to hemoglobin (characteristic of the disease) are actually protective against certain malaria infections. So while it may seem to be a disadvantage to have misshapen red blood cells that limit the bloods oxygen capacity, it’s actually a major advantage to be a carrier for the sickle cell gene in Sub-Saharan Africa where malaria incidences are extremely high. This co-evolution between certain infectious agents and humans is a clear example of how certain diseases arise as adaptations that are in some way maladaptive to other parts of human life.
These examples are more clear, but what about highly complex diseases like diabetes? How could that possibly be adaptive? In 2005, an interesting theory came out justifying the higher incidences of type 1 diabetes in Scandinavians and those from more northern climates as a protective adaptation to cold temperatures; i.e. a high blood sugar actually lowers the bloods freezing point.
With the dawn of the era of bioinformatics, others are taking a different approach to understanding multifactorial disorders like diabetes in light of protective adaptations. For example, Dr. Atul Butte at Stanford University is attempting to understand why certain single nucleotide polymorphisms (SNPs) associated with increased or decreased risk of diabetes are being selected for in uneven patterns (I.e. some SNPs are being positively selected for in the population despite their increased risk developing diabetes). Some of the SNP’s, while carrying an increased risk for developing diabetes, also carry increased protection against certain infections (Ex: IFIH1 protects against enteroviruses but increases risk for type I diabetes).
Type 2 Diabetes. Photo credit: Kate
Others have speculated that the development of type 2 diabetes occurs as an adaptation to selectively protect the brain and heart from metabolic collapse, particularly in type 2 diabetes. Too many nutrients entering a cell, specifically cardiomyocytes, can burden the cell and potentially lead to metabolic collapse, something that would be immediately fatal if it occurred in the heart. One group has even proposed that improving insulin sensitivity, a potential target of treatment for type 2 diabetes, could be more harmful than it is helpful (See the following papers for evidence in the literature of type 2 diabetes as an protective adaptation)!
This also helps to explain why insulin resistance occurs physiologically during certain points of life such as puberty and pregnancy. So while we view type 2 diabetes as a disease that increases risk for cardiac disease, stroke, and mortality later on life (mostly due to damage to blood vessels), we might be missing it’s immediate cardioprotective effects!
As I mentioned above, our treatments are based on our understanding of disease processes, and if we mistake insulin resistance purely as a disadvantage, targeting insulin sensitivity as a treatment could be more harmful than beneficial. In fact, one study showed that intensive insulin therapy significantly increased risk of all cause mortality in a population of individuals with type 2 diabetes! This included a non-significant increase in fatal cardiac events and a significant increase in nonhypoglycemic serious adverse events in the intensive insulin treatment group as compared to standard treatment.
While there are clear mechanisms showing the negative affects of hyperglycemia in patients type 2 diabetes on blood vessel walls and eventually declining cardiovascular health, we might be missing the idea that type 2 diabetes arises in the first place to protect against immediate cardiovascular or neurological collapse. As with anything, however, more evidence needs to be obtained before we can absolutely support these findings.
The golden question is: what if the body weren’t able to undergo normal disease progression in response to an insult? That is to say, what if insulin resistivity could be blocked in an individual who would normally develop type 2 diabetes? What would 1, 5, and 10 year all cause mortality rates look like compared to those who develop type 2 diabetes?
The idea of diseases arising as protective adaptations is not a novel idea, however, in the modern era of medicine where access to massive amounts of population data is higher than ever before, our understanding of disease in specific populations is allowing us to see new patterns that were unthinkable 50 years ago. Using evolution to understand disease can help us justify why diseases arise in the first place and how treatments could be made most effective by trying to preserve the advantages of the bodies initial adaptation while halting the progression to maladaptations.
This theory for adaptation/maladaptation in disease processes and the way I’ve presented certainly isn’t perfect (a lot of detail is out of the scope of this article, but that’s why the references are there). But as an aspiring scientist and physician, it helps me personally understand every disease I learn about, especially for someone who’s going into neuroscience where idiopathic diseases reign supreme. As we move forward with our understanding of highly enigmatic diseases like Alzheimer’s, it might help to ask the question “what advantage could the body have for the changes we see?” For the sake of completeness, we’ll end by running through examples from the VITAMINS acronym (check out the introduction to pathology article if you’re unfamiliar with the acronym) of how diseases are adaptive in some way.
•V = Vascular
Example: Ischemic stroke (embolic)
Adaptation: One group suggests that proinflammatory states led to increased fitness in our ancestors, however, this global proinflammation paired with our contemporary environment lead to increased atherosclerotic events.
•I = Idiopathic/Iatrogenic
Example: Alzheimer’s (idiopathic) or a drug overdose (iatrogenic)
Adaptation: unknown by definition (idiopathic) or exacerbated response by they body to exogenous agonist introduction (i.e. overdose on beta blockers due to administered drugs that take advantage of beta receptor adaptations)
•T = Trauma
Example: Head injury from a car crash
Adaptation: This is a difficult example since trauma itself is not an adaptation by the body, however, the inflammation that ensues after a traumatic event is an adaptation and can sometimes be harmful, especially in head trauma where intracranial pressures can rise to potentially fatal levels.
•A = Autoimmune
Example: Multiple sclerosis
Adaptation: Many researchers believe that genes predisposing for autoimmune disorders were positively selected for during evolution to aid in fighting off infectious against. These genes make the immune system more reactive against foreign invaders, however, according to the hygiene hypothesis, our lack of exposure to antigens during early years leads to maldevelopment of the reactivity of the immune system. For more, check out this link and the work of Dr. Towfique Raj.
•M = Metabolic
Example: Tay-Sachs
Adaptation: Some evidence suggests a heterozygous advantage for Tay-Sachs disease which includes increased neuron growth and greater learning capacity.
•I = Infectious
Example: Bacterial meningitis
Adaptation: This is a classic example of a parasitic symbiotic relationship. Bacteria such as Neisseria meningiditis, E. coli, and Streptococcus pneumoniae that cause meningitis have adapted mechanisms to enter the brain and reside there. Our body responds by inducing an inflammatory response to the foreign invaders leading to excessive fluid production and subsequently increased intracranial pressure which can ultimately be fatal.
•N= Neoplastic
Example: Cancer (Glioblastoma multiforme would be a specific example)
Adaptation: One study found a strong inverse association between average temperature and risk for cancer. Their hypothesis is that certain genes that carry a higher risk for cancer can be adaptive to colder environments.
•S = pSychiatric
Example: Depression/anxiety
Adaptation: Head over to the neuro section to find out more ;). It’s mental to think about.
The examples provided are but a fraction of the many ways researchers around the world are attempting to understand the context of disease in the frame of evolution. Many more similar and competing theories exist. I would once again like to express that, while I presented evidence rooted in reputable scientific journals, many of my personal opinions were imprinted on the article and this should NOT be taken as something that is hard fact, but rather an interesting talking point moving forward.
-Daniel