Getting the whole story- attempting to make sense of disease through evolutionary medicine

Student guest post by Anne Dressler

The idea of evolutionary medicine is new to me and my understanding is quite shallow but it has piqued my interest. Currently, the book "Why We Get Sick" by Randolph M. Nesse and George C. Williams has been satisfying my curiosity during the 15 minutes of intellectual thought I have left at the end of the day while reading before bed. From what I've read, I'm finding how useful it can be to consider disease in light of evolution and I'm left wondering how I haven't heard of it before. I'm guessing I'm not the only one interested, so let's talk evolutionary medicine, starting with some of the basics and finishing with why I find this particularly interesting for the nexus between infectious and chronic disease.

If basic biology and traditional medicine make up the plot of our disease "stories", evolutionary medicine would be somewhat like the moral. My roommate is a medical student and when asked, she can tell you how just about anything in the human body works and what is happening when things go wrong. When asked why things go wrong, her answer will refer to a proximate cause, such as certain foods leading to plaque build up which can lead to heart disease. If the question of why is rephrased, as in why does the disease even exist at all, then she's stumped. This is the question considered by evolutionary medicine. Why aren't our bodies able to repair clogged arteries? Why are we prone to infections? Why are our bodies so good at some things but so inept at others? At first I found theses questions strange- after studying epidemiology's risk factors for the past year, I had started viewing them as the sole reason for the existence of disease. And that kind of makes sense...if you completely ignore evolution. Enter famous and ubiquitous Dobzhansky quote:

"Nothing in biology makes sense except in the light of evolution."
-Theodosius Dobzhansky

It is through the perspective of evolution that one can consider why a disease exists beyond the obvious.

In their book, Nesse and Williams propose six categories for evolutionary explanations of disease: infection, novel environments, genes, design compromises, evolutionary legacies, and defenses. The basis for all these explanations is evolution through natural selection thus I think it is wise to keep in mind some key points. First, natural selection occurs when survival and reproduction are affected by genetic variation among individuals. Genes are only passed on by the organisms that survive to reproduce. Note, surviving to reproduce doesn't necessarily have anything to do with health or survival later in life nor does it necessarily mean good health before reproduction either.

"If tendencies to anxiety, heart failure, nearsightedness, gout, and cancer are somehow associated with increased reproductive success, they will be selected for and we will suffer even as we 'succeed,' in the purely evolutionary sense."
-Randolph M. Nesse and George C. Williams, Why We Get Sick

Also, think Richard Dawkins and "selfish genes"- selection doesn't consider populations, but rather benefits genes. With this in mind, let's go over one of the proposed categories for explaining disease- infection (even if it is just skimming the surface).

Infectious agents have long been a cause of human disease. As we have evolved means to avoid infection, pathogens have evolved means to counter us leaving us prone to infection. Due to their relatively rapid reproduction, pathogens can evolve much more quickly than we can. One way we attempt to make up for this deficiency is by using antibiotics. Interestingly, by using antibiotics we are essentially taking advantage of the evolutionary advantages of another organisms. Toxins produced by fungi and bacteria are a result of millions of years of selection to combat pathogens and competitors. Dangerously, many believed that with antibiotics we would finally be in control of infections. Unfortunately, that was an underestimation of evolutionary forces and while almost all staphylococcal strains were susceptible to penicillin in 1941, today nearly all are resistant. This pattern is standard for most newly introduced antibiotics

The concept seems simple enough, but it's not the only thing we've misunderstood about the evolution of pathogens. A common misperception is that a pathogen will evolve from being virulent to being more and more benign in order for the host to live long enough for the pathogen to pass on offspring to new hosts. This makes sense, yet doesn't fully take into account the need to pass on offspring. Being able to disperse offspring to new hosts may mean it is most beneficial to the pathogen for the host to be sneezing, coughing, or laying prostrate. Another force behind pathogens evolving increased virulence is within-host selection. Simply, if there is more than one strain of a pathogen within a host, the one that uses the host's resources most effectively will be the one to disperse the most offspring.

So if infections are one evolutionary explanation for disease, what's an example? I recently came across an interesting article about infection and it's relation to premenstrual syndrome. In the article Premenstrual Syndrome: an evolutionary perspective on its causes and treatment, Doyle et al. propose premenstrual syndrome is due to an exacerbation of a set of infectious diseases during cyclic changes of immunosuppression by estrogen and progesterone. While genetics and non-infectious environmental influences have been examined and found largely unable to explain PMS, infectious causes have been overlooked. However, it is know how immune function varies throughout the menstrual cycle in such a way that there could be less effective control of fungi, viruses, and intracellular bacteria, so making the leap to a persistent infection contributing to PMS doesn't seem too difficult. Supporting this hypothesis is a long list of chronic diseases with suspected infectious causes that are exacerbated premenstrually including Crohn's disease with Mycobacterium avium and juvenile onset OCD with Streptococcus pyogenes.

I think the most important point to take from this article is that there may be many other chronic diseases we don't yet fully understand that are caused by infectious agents.

Yet even while the who, what, when, and where of some diseases may already be understood, the why of a disease is usually ignored. With an evolutionary perspective, we can try to answer the question of why diseases arise and persist under the forces of selection. These insights could help answer some old questions, such as those regarding unknown causes of chronic diseases, and ask some new ones, such as how could PMS be treated if it's cause really is infectious. Finally, while guiding health care practices to improve health is the ultimate goal, at the very least evolutionary medicine reminds us to keep thinking about things in new ways.

Sources:

Doyle, C., H. A. Ewald, and P. W. Ewald. "Premenstrual Syndrome: An Evolutionary Perspective on its Causes and Treatment." Perspectives in biology and medicine 50.2 (2007): 181-202.

Gammelgaard, A. "Evolutionary Biology and the Concept of Disease." Medicine, health care, and philosophy 3.2 (2000): 109-16.

Nesse, Randolph M., and George C. Williams. Why we Get Sick. New York: Vintage Books, 1994.

Nesse, R. M. "How is Darwinian Medicine Useful?" The Western journal of medicine 174.5 (2001): 358-60.

Stearns, S. C., and D. Ebert. "Evolution in Health and Disease: Work in Progress." The Quarterly review of biology 76.4 (2001): 417-32.

Williams, G. C., and R. M. Nesse. "The Dawn of Darwinian Medicine." The Quarterly review of biology 66.1 (1991): 1-22.