The Scientist: Volume 27 Issue 10 | October 2013
Dr. Darwin at the Bedside
ItÕs
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 Òthe infant,/
Mewling and puking in the nurseÕs armsÓ to the Òmere oblivionÓ of the aged,
ÒSans teeth, sans eyes, sans taste, sans everything.Ó 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, ÒMan-made diseases,Ó 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 Ò1. Higher professional and
higher managerialÓ (senior government officials, physicians, scientists, etc.)
to Ò7. RoutineÓ (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 isnÕt 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 Òsolitary, poor, nasty,
brutish, and shortÓ lead to the diversion of resources away from bodily
maintenance into early reproduction and to coping with and surviving acute
stresses. HobbesÕs 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.
Reprinted
from Evolution and Medicine, by Robert
Perlman. Copyright © 2013 by Robert Perlman.
Reproduced with permission from Oxford University Press.
Contributors
Meet
some of the people featured in the October 2013 issue of The
Scientist.
| 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
universityÕs 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 materÕs 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 ÒDr. Darwin at the Bedside.Ó