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Should we treat the symptoms of disease, or are they there to aid recovery?
Can phobias, panic attacks and morning sickness be of any advantage to people
who suffer from them? Might common diseases of old age such as Alzheimer’s
and osteoarthritis be associated with a genetic advantage in youth? Is the
phenomenon of the couch potato an unavoidable legacy of our past life as
hunters and gatherers?

Such questions are far from rhetorical. In fact, they are central to
an ambitious new movement in medical research which threatens to overturn
many of the conven-tional wisdoms at the heart of medicine. The underlying
message is uncontroversial enough: human beings and their illnesses are
the products of a long evolutionary history. Yet modern medicine, for all
its high-technology treatments and preventive strategies, has so far largely
ignored this fact. And the few researchers who haven’t have been scattered
across the world, working in disparate pockets of medical science. Now these
quiet revo-lutionaries are linking their ideas together, and the discipline
they are forging has acquired a name: Darwinian medicine.

Modern medicine is founded on reductionism. Organisms are viewed as
a collection of organs, not as functional wholes, and still less as members
of a species. Diseases and their symptoms are considered as discrete defects
of the body that can and must be eliminated. Evolution is not an issue.

In 1991, the scope of this approach was questioned by Randolph Nesse
and George Williams in a paper which served as a rallying call to those
with an evolutionary theme to their biomedical research. Nesse, a psychiatrist
at the University of Michigan, and Williams, an evolutionary biologist at
the State University of New York at Stony Brook wrote: ‘Advances (in medicine)
would be even more rapid if medical professionals were as attuned to Darwin
as they have been to Pasteur.’

The core of Darwinian medicine, Nesse explains, is the search to find
for each disease an evolutionary as well as a proximate explanation. For
instance, infection is not just the outcome of an encounter with a pathogenic
microorganism, but an arms race between host and parasite. Trauma is not
just a question of damaged tissue, but an interplay of protective mechanisms
and repair processes that have been shaped by natural selection. Genes that
cause diseases are not just the product of harmful mutations, but may be
selected for benefits we have yet to discover. Cancer, heart disease and
other ‘diseases of civilisation’ are not just the product of metabolism
gone awry, but the result of today’s humans living in conditions different
to those for which they evolved. In other words, Darwinian medicine considers
disease from the viewpoint of the species not the individual human.

Underpinning Darwinian medicine is the theory that evolutionary adaptation
may have apparently negative as well as positive consequences. In a sense,
say Nesse and Williams, any adaptation should be seen as a compromise. Back
pains are commonly the price of bipedal posture, for example; the price
of effective tissue repair is cancer; the price of a powerful immune system
is immune disorders; the price of anxiety, which is an adaptive response
to danger, is panic disorder. Natural selection is a powerful force, but
it is not all-powerful. Organisms are not perfect machines, but cobbled-together
compromises.

Rehabilitating symptoms

Take infectious diseases. With a few exceptions, like HIV, TB and yellow
fever in some urban ghettos, infectious diseases have been virtually conquered
by antibiotics in the developed world. The process and dynamics of infection
– what we see as the symptoms – are complex, however, and modern medicine
has tended to take a narrow look at them. Darwinian medicine argues that
the human body’s response to infection is likely to be an adaptation that
helps to fight the disease. Paul Ewald of the University of Massachusetts
at Amherst, pioneered this way of thinking in an influential paper published
in 1980.

Although doctors are aware of the beneficial effects of certain symptoms,
such as coughing induced by pneumonia, many symptoms are regarded as harmful
and are routinely treated – sometimes to the detriment of the patient. Fever
is the best example. Long suspected as having adaptive value, fever has
only recently been revealed as a beneficial response to infection. The response
is triggered by bacterial toxins, and the resulting increase in body temperature
is hostile to the invading microorganisms. Reduce the fever – using aspirin,
for instance – and the disease may last longer, as Timothy Doran of Johns
Hopkins University, Baltimore, has recently demonstrated in the case of
chickenpox.

Then consider the sequestration of iron. Early in bacterial infection,
iron becomes more tightly bound to protein, and is removed from circulation
by the liver. From an adaptive point of view, the response is beneficial
to the host because the bacteria need a plentiful supply of iron to thrive.
Together with fever, low levels of iron help to fight the infection. And
yet this ‘deficiency’ is often treated with dietary supplements, thus prolonging
the disease process. Another example is using drugs to block diarrhoea.
In certain diseases, such treatment will slow the evacuation of pathogenic
organisms and prolong the condition.

Darwinian medicine doesn’t go so far as to say that all symptoms are
likely to be beneficial and must be allowed to run their course: suppressing
a severe cough, for example, may help the patient. But a better understanding
of the disease process would enable the doctor to decide when and if to
intervene. As Nesse and Williams put it, treatment ‘should be informed by
an understanding of the evolutionary nature of the host-parasite contest’.

Drug resistance

Recent advances on this front have come from the mathematical analyses
of the interaction between predators and prey, a technique known as conflict
modelling. Parasites can mutate more rapidly than their human hosts but,
as Williams says, the implications of this have only recently been recognised.
The most obvious consequences are the development of drug resistance in
bacteria, and the ability of some microorganisms to change the surface proteins
by which the human immune system recognises them, thus eroding the value
of long-term vaccination. Less understood is the evolution of virulence.

According to conventional wisdom, a prolonged association between a
parasite and its host should reduce the parasite’s virulence. The parasite
must look after its interests by keeping the host in a relatively healthy
state, thus maintaining its own food supply. However, conflict modelling
shows this argument is flawed; it fails to take into account the speed of
parasite evolution. This allows the parasite to respond quickly to changes
in the host, continually maximising its virulence. Moreover, mechanisms
for spreading the parasite, such as coughing and diarrhoea, may be triggered
only by high virulence. Ewald has used conflict modelling to unravel the
complex way that host-parasite interactions can affect virulence.

In parasites which have an insect or other animal vector, virulence
will be high in the human host and low in the vector. For instance, serious
damage to the mosquito that carries malaria may slow transmission of the
parasite to new hosts, and should be avoided. But high virulence in the
human host, may benefit the parasite because the human body simply represents
a food resource, and severe illness may make the vector more accessible
to the parasite.

Parasites, like the cholera organism, that are spread by inanimate carriers,
such as water, are also likely to evolve high virulence, for the same reason:
transmission from host to host is the limiting factor, not the availability
of the host. By contrast, low virulence is likely in parasites that are
transmitted from parent to offspring. An example in humans is HTLV-I, a
close cousin of HIV, the virus that causes AIDS. Death from HTLV-I infection
often takes many decades. Healthy survival of the two hosts is essential
for the long-term success of the parasite. By using conflict modelling predictions
can be made about how effective drug treatment or attempts to block disease
transmission might be.

Compared with the infection process, response to physical trauma is
relatively simple because only one organism is involved. Nevertheless,
an evolutionary perspective may be enlightening. For instance, when a joint
is sprained, a sequence of physiological events is set in train, including
pain, bruising, swelling and an influx of scavenger cells to begin removing
damaged tissue. Questions that should be asked, suggest Nesse and Williams,
include the following. Is the swelling an incidental consequence of the
trauma, or an adaptation to immobilise the joint and promote healing? What
harmful consequences may result from reducing swelling? What effect does
increased temperature have on the healing process? How is pain produced,
and what is its role in immobilising the joint? Only by answering these
questions can we choose the correct treatment.

Panic attack

The human body has also developed responses to avoid trauma. These
include extreme fears (phobias) and symptoms associated with stress. Phobias
are often directed at real threats which has led Nesse to suggest that they
may be ‘prepared fears’ against threats experienced by earlier generations.
He also argues that panic attacks are not chaotic but instead are ‘a carefully
coordinated pattern that is adaptive in life-threatening situations’. As
a psychiatrist, Nesse’s main interest is in human emotions. As yet, however,
very little is known about the functions of emotions. ‘A Darwinian approach
would, in principle, allow clinicians to know when it is helpful to block
emotions and when it is not,’ he says. ‘This would lead to a wiser use of
psychotropic drugs.’

Toxins act as a chemical trauma to the body, and a pocket of nerve cells
in the brain stem is in a state of constant vigilance. Toxins cause these
cells to trigger a defensive response that includes vomiting. In an innovative
line of reasoning, Margie Profet of the University of California at Berkeley
linked this response to the kinds of sickness and aversions to certain food
that women experience during pregnancy. So common a condition could not
be a ‘mistake’, she reasoned. Might it be a mechanism for protecting the
developing fetus from toxins? One observation that supports Profet’s hypothesis
is that miscarriages are three times more common in women who suffer only
mild sickness as compared with severe sufferers.

The evolutionary approach is probably more directly applicable to genetic
diseases than it is to any other area of medicine, because it can address
the selective influences on specific genes. Most mutations are deleterious,
are rapidly lost, and are therefore rare in the population. So why are some
genetically based diseases so common? Proponents of Darwinian medicine suspect
that many will turn out to have some associated benefits. This has already
been shown for sickle-cell anaemia, where a single copy of the defective
gene confers immunity to malaria without causing sickle-cell anaemia. Other
likely candidates are diseases of old age: genes that cause diseases such
as Alzheimer’s and osteoarthritis, for example, may confer beneficial effects
early in life. ‘If we naively assume that ridding the population of the
genetic capability for Alzheimer’s disease is an unconditionally desirable
goal,’ caution Nesse and Williams, ‘we might incidentally eliminate unsuspected
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For these three areas of medicine – infection, trauma and genetic diseases
– the message of the Darwinian approach is that things may not be as they
seem. By asking questions about evolved function, doctors will be in a stronger
position to choose the best course of treatment. For the fourth area of
medicine – broadly, the diseases of civilisation – the Darwinian approach
tries to understand the mismatch between the evolutionary and modern context
of Homo sapiens. From it flows an approach to preventive medicine that,
although considered distinctly unglamorous in the medical profession, promises
enormous benefits. Diseases of civilisation, such as heart attacks and cancers,
account for more than 70 per cent of deaths in affluent Western nations.

Boyd Eaton, a diagnostic radiologist at Emory University, Atlanta, starts
from the premise that ‘Twentieth-century humans are Stone Agers displaced
through time’. For most of our evolutionary history, humans have lived as
hunters and gatherers. When food production was first adopted ten thousand
years ago, a dramatic change in lifestyle ensued. The cultural change has
been enormous in this time, yet the genetic change has been minute, measuring
no more than 0.005 per cent. ‘Designed as hunter-gatherers, humans are now
suffering the consequences of living in an alien environment,’ says Eaton.

The most obvious differences in lifestyle between pre-agricultural and
modern times are in exercise and diet. Much ill health stems from overconsumption,
particularly of saturated fat and salt. The problem, however, goes deeper;
the evolutionary perspective shows it is also a predictable outcome of the
human genetic make-up. Designed by natural selection as hunter-gatherers,
humans are programmed to store fat reserves when possible, against lean
times. And, suggest Nesse and Williams, a tendency to minimise physical
activity when it is not absolutely necessary might be an adaptation to conserve
those stores – the couch potato might be an evolutionary inevitability.

Hunter-gatherer lifestyle

Eaton’s research interest is in cancers, but ones related to lifestyle
changes other than diet. He argues, for instance, that changes in reproductive
patterns in Western women mean that they have up to a hundred times increased
risk of breast cancer and increased risk of endometrial and ovarian cancers
compared with women who still have a hunter-gatherer lifestyle. The increased
risk is a consequence of a combination of earlier menarche, later first
birth, fewer births and later menopause; in addition, modern women breast-feed
for much shorter times. One consequence of these differences is that during
their lifetime, hunter-gatherer women ovulate on average 158 times, while
the average for modern affluent women is 451 times.

Eaton acknowledges that altering this pattern will not be simple. ‘Increasing
the popularity of breast-feeding has a good chance of being accepted,’ he
says, ‘but the other factors would have to be addressed mainly through hormonal
therapy that mimics the hunter-gatherer reproductive pattern, rather than
seeking to restore the pattern itself.’ For instance, hormone therapy could
induce early maturation of mammary ducts, decrease ovulatory frequency,
and lower the level of the reproductive hormone gonadotropin in the blood.
Each of these features is associated with low incidence of female cancers.

Modern methods of infant care may also put babies at risk, according
to several researchers. For instance, the Western cultural practice of
having the baby sleep in its own room, isolated from its parents, may be
a cause of infant problems, and perhaps even death. Mothers and infants
who sleep together become physiologically entwined in their breathing, heart
rate, and arousal patterns: each responds to the other. This is important
in the baby, who learns normal sleep patterns, including occasional periods
of waking up. All babies experience brief periods of extremely shallow or
halted breathing several times a night. Learning to awaken periodically,
through being attuned to its mother, a baby is at less risk of succumbing
to sudden infant death syndrome (SIDS), suggests James McKenna of Claremont
McKenna College, California.

McKenna, who has been researching SIDS for eight years, says, ‘The difficulty
is explaining to trained specialists what it means to apply evolutionary
theory in the context of infancy and parenthood.’ He is not alone in facing
this problem. A radical change of the kind implied by a Darwinian medicine
approach is certain to be resisted, especially by so conservative a body
as the medical profession. Even the most optimistic proponents, such as
Nesse, Williams and Eaton, acknowledge that so far Darwinian medicine has
had little or no impact on traditional medical education and practice. ‘There
is increasing interest in the subject among the public, however,’ says
Eaton. ‘I believe the medical profession will soon begin to embrace it.
It has to.’ Nesse and Williams have a clear view of how the subject should
affect modern practice: ‘We hope that Darwinian medicine never becomes
a sect or a rallying cry for a branch of medicine,’ they wrote in their
1991 paper. ‘Instead we hope that the addition of an evolutionary perspective
can help to integrate every practitioner’s knowledge as it is applied to
individual cases.’

* * *

The battle of the bulge

When a pregnant woman and her child are viewed through an evolutionary
lens, many of the problems of pregnancy become explicable. Although mother
and child share some goals in the business of gestation and birth, the relationship
has an underlying conflict. The reason is that the child is not a genetic
copy of its mother, but inherits half its genes from the father. A mother
must balance the investment she makes in the child she is carrying against
future opportunities for bearing more offspring. The child is 100 per cent
selfish in its need to survive.

Harvard biologist David Haig has been studying the battleground of pregnancy
for two years, focusing on certain chemical conflicts. One of them concerns
human chorionic gonadotropin (hCG), the hormone that is the signal in home
pregnancy tests. Shortly after ovulation, the ovary begins secreting luteinising
hormone, which halts menstruation and allows pregnancy to become established.

By the end of the seventh week, the placenta (which genetically is part
of the embryo) is secreting human chorionic gonadotropin, which does the
same job as luteinising hormone. This apparent cooperative effort can be
seen as conflict: the mother has an interest in establishing the pregnancy,
but wants to have the option of ending it through miscarriage if the fetus
is defective in some way; the fetus wants to survive at all costs, and so
wrests control of maintaining the pregnancy away from the mother, by producing
sufficient hCG to do the job. Despite this, between 10 and 30 per cent of
pregnancies end in miscarriage.

A second chemical conflict arises in the mother’s production of insulin,
which regulates the level of glucose in her blood. For the mother, maintaining
glucose within normal bounds is important for her health; for the fetus,
high glucose levels in maternal blood boost growth. The consequence of this
conflict is an escalating chemical warfare, with the fetus producing ever
higher levels of a hormone, lactogen, which makes the mother less sensitive
to insulin; and the mother constantly boosting her insulin output to combat
the effect of the fetal lactogen. By the end of pregnancy, placental lactogen
output is 2000 times higher than it was in the beginning.

Haig’s evolutionary perspective helps explain the problem of diabetes
during pregnancy, and he extends the analysis to include high blood pressure,
which may be the result of the fetus’s attempt to increase the flow of blood
to the placenta.