The Scientist: Volume 27 Issue 10 | October 2013

Dr. Darwin at the Bedside

It’s time for evolutionary medicine to fully inform clinical research and patient care.

By Robert Perlman | October 1, 2013

Shakespeare memorably described the human life course, from “the infant,/ Mewling and puking in the nurse’s arms” to the “mere oblivion” of the aged, “Sans teeth, sans eyes, sans taste, sans everything.” Scientists now appreciate that human life histories have been shaped by natural selection. Evolutionary life history theory provides a valuable, if less poetic, framework for understanding our life cycle and the diseases that accompany aging.

Natural selection adjusted how humans use energy and other resources throughout our life cycles in ways that optimized the reproductive fitness of our evolutionary ancestors. Optimizing fitness has meant devoting energy to growth and development and to reproduction, at the expense of maintaining and repairing our bodies. Our evolved mechanisms of bodily maintenance and repair are sufficient to keep us alive and healthy long enough to have and raise our children, and perhaps contribute to the development of our grandchildren. But these mechanisms are not perfect. Over time, we accumulate unrepaired damage that leads to the diseases of aging and, ultimately, to death.

In my new book, Evolution and Medicine, I discuss the emerging field of evolutionary medicine. I show how integrating life history theory and other evolutionary concepts into medicine has the potential to improve our understanding of disease and, most importantly, clinical practice.

Perhaps the most dramatic contribution of evolutionary medicine to patient care has been the development of highly active antiretroviral therapy (HAART) for HIV-infected patients. HAART typically includes two reverse transcriptase inhibitors to block the activity of the enzyme that retroviruses use to replicate. The development of HAART was based on the recognition that mutant virus strains that were resistant to both drugs would have two or more mutations in the reverse transcriptase gene, and so were likely to have decreased fitness. HAART has revolutionized the treatment of HIV. The use of combination therapy for patients with hepatitis C infections and other diseases—and more broadly, our increased concern with resistance management to prolong the useful lives of new antibiotics—shows the reach of evolutionary medicine into the clinic.

Until the 20th century, most if not all humans were chronically infected by parasitic worms, or helminths. Helminths used to be so common in the environment that our ancestors evolved traits that optimized fitness in their wormy world. The effect of living in relatively worm-free environments is thought to underlie the increasing incidence of allergic and autoimmune diseases in economically developed, modern countries. These considerations have led to novel clinical trials using helminth extracts or eggs to treat patients with multiple sclerosis or inflammatory bowel disease. Although it is too early to know if these trials will be successful or will lead to new therapies for patients, they illustrate another way in which an evolutionary perspective can inform clinical research.

Evolutionary life history theory has great but as yet largely untapped potential to improve medical practice. We now know that although aging is inevitable, its time course is not fixed. Life expectancy in the United States has increased dramatically over the last century, from about 47 years in 1900 to almost 80 years today. Because of better nutrition and a decline in infectious diseases, we are born with greater amounts of physiological reserves, we experience lower rates of bodily damage, and we live longer than our grandparents and great-grandparents.  

Many hormones regulate energy utilization and so play important roles in our life histories. Physical and psychosocial stresses, acting through neuroendocrine regulatory mechanisms, appear to accelerate the aging process. Better understanding these mechanisms may help us modulate the rate of aging and extend life. The integration of evolutionary medicine with biomedical research offers untold and exciting new opportunities for improving human health and well-being.

Robert Perlman is Professor Emeritus in the Departments of Pediatrics and Pharmacological and Physiological Sciences at the University of Chicago. Read an excerpt of Evolution and Medicine.

Book Excerpt from Evolution and Medicine

In Chapter 11, “Man-made diseases,” author Robert Perlman describes how socioeconomic health disparities arise in hierarchical societies.

By Robert Perlman | October 1, 2013

Socioeconomic disparities in health are among the most troublesome and refractory problems in medicine. Simply put, poor, disadvantaged, or marginalized people have poorer health and shorter life expectancies than do rich or more privileged people. The cause of these health disparities is hotly debated. People who have poor health may be unable to work, or unable to work at higher skilled or higher paying jobs, and so poor health may sometimes lead to poverty, but this factor must account for only a small fraction of the association between poverty and health. In countries such as the United States, disparities in access to health care may contribute to health disparities but this too must be only a small part of the problem, because health disparities exist in countries such as the United Kingdom, which has a national health service and in which there is less inequality in access to health care. Absolute levels of poverty compromise health and longevity in the poorest countries in the world, where life expectancy is correlated with the per capita gross national product, but poverty alone does not account for the health disparities in developed countries. The epidemiologists Michael Marmot and Richard Wilkinson have been the most forceful proponents of the view that socioeconomic inequalities themselves are the cause of inequalities in health.

Some of the most comprehensive and best-documented studies of health disparities have been carried out in the United Kingdom. The U.K. Office for National Statistics classifies occupations into seven socioeconomic classes, ranging from “1. Higher professional and higher managerial” (senior government officials, physicians, scientists, etc.) to “7. Routine” (occupations such as bus drivers and domestic workers), and analyzes health disparities in terms of this occupation-based scale. An ongoing longitudinal study of the U.K. population has documented a socioeconomic gradient in life expectancy. In the period from 1982–86, men in class 1 had a life expectancy of 75.6 years while men in class 7 had a life expectancy of 70.7 years. In the period from 2002–06, life expectancy of these groups increased to 80.4 and 74.6 years, respectively. Despite the dramatic increase in life expectancies during this time, the gap in life expectancy increased from 4.9 to 5.8 years. Similar data hold for women, except that women have higher life expectancies than men and the socioeconomic gap is a little smaller for women (3.8 years in 1982–86, 4.2 years in 2002–06).

Health disparities are not simply restricted to the most disadvantaged members of a society. There isn’t a cutoff in socioeconomic status such that people below some level have poor health and people above it have good health. Instead, there is a social gradient in mortality rates that runs through all socioeconomic classes. This gradient is not just a gradient in mortality from one specific cause but results from socioeconomic differences in mortality rates from a host of different diseases. In addition to the socioeconomic gradient in mortality rates, there is also a gradient in morbidity. People in lower socioeconomic classes exhibit earlier onsets of chronic diseases and disabilities. In terms of morbidity as well as mortality, people in lower socioeconomic classes appear to age more rapidly than do people in higher classes.

Studies of health disparities in the United States and in many other countries complement those in the United Kingdom. Together, these studies provide compelling support for the hypothesis that poor, disadvantaged, low status people age more rapidly than do rich, advantaged, higher status people and that there is a socioeconomic gradient in the rates of aging.

Recall that we have evolved mechanisms that alter our life history trajectories in response to our assessment of the security or insecurity of our environment and of our anticipated mortality rate. Signals which suggest that our environment is dangerous and that our lives may be “solitary, poor, nasty, brutish, and short” lead to the diversion of resources away from bodily maintenance into early reproduction and to coping with and surviving acute stresses. Hobbes’s description of the human condition may not apply to foraging populations, as he suggested, but it does fit the lives of poor and disadvantaged people in modern societies. Earlier, we discussed the developmental conditions that increase the risk of adult disease and early mortality. These conditions, which include poor nutrition and psychosocial stresses such as social isolation, lack of material resources, and fear of violence, as well as prematurity or low birthweight and exposure to toxins, are more prevalent in lower than in higher socioeconomic classes. Although socioeconomic gradients in rates of aging are distressing, they should not be surprising.

The physiological mechanisms that underlie our responses to environmental signals are still being investigated but they appear to involve neuroendocrine regulatory pathways, including the hypothalamic-pituitary-adrenal axis and the autonomic nervous system. Hormones such as cortisol and catecholamines suppress the immune system and reduce tissue repair. These hormones enhance our responses to stress at the cost of reducing somatic maintenance. Socioeconomic gradients in the levels of these hormones or in the reactivity of these neuroendocrine systems may contribute to gradients in life history trajectories.

Socioeconomic gradients in health behaviors are important proximate causes of health disparities. People of lower socioeconomic status are more likely to smoke and to engage in other risky behaviors, and less likely to take advantage of preventive health services, than are people in higher socioeconomic groups. We appear to have evolved psychological biases as well as physiological mechanisms that lead us to discount bodily maintenance and future health when we assess our environment as dangerous or stressful. Improved education or increased availability of preventive health services by themselves are not likely to alleviate the root causes of health disparities, which are disparities in wealth, status, and power, and the ways we have evolved to respond both physiologically and psychologically to the place we find ourselves in hierarchical, socioeconomically stratified societies.

Contributors

Meet some of the people featured in the October 2013 issue of The Scientist.

By Kate Yandell | October 1, 2013

Robert Perlman grew up around the University of Chicago, studied there, and is now a professor emeritus at the same institution. His father was a surgeon and faculty member at the university’s medical school. Perlman started college after his sophomore year of high school as part of a University of Chicago program for young entrants. He enrolled in his alma mater’s medical school immediately after graduation to avoid the draft, and stayed on at the university for a few years to do research before heading off for his internship and residency at Bellevue Hospital in New York City. He then got a commission in the public health service and studied bacterial genetics at the National Institutes of Health (NIH). At the NIH, he helped to discover the role of cyclic AMP in regulating bacterial gene expression. Perlman never made it back into clinical medicine. He taught at Harvard Medical School and the University of Illinois at Chicago, where he did research on the biology of adrenal chromaffin cells, before returning to the University of Chicago. In the 1990s, while serving as dean of biological sciences, Perlman became hooked on thinking about evolution and its connections to human biology and medicine. That topic became the focus of his recently published book Evolution and Medicine, discussed in his essay “Dr. Darwin at the Bedside.”