By Beth Saulnier
Before you treat that fever, consider the emerging field of evolutionary medicine. The symptom just might speed the cure.
Thirteen years ago, evolutionary biologist Paul Sherman was in central Idaho doing fieldwork on the social behavior of ground squirrels when he decided to go rock climbing near Hell's Canyon. The weather was somewhere between rain and snow, the basaltic cliffs were slippery, and Sherman lost his grip; he plunged thirty feet and only avoided breaking his neck through a lucky bounce off a rock. The professor emerged with a broken shoulder and a badly skinned thigh - and the shoulder got him thinking.
It turned vibrant shades of purple and yellow, got blazing hot to the touch, swelled up, and hurt like crazy. Medically speaking, these were perfectly normal symptoms of a broken bone. But for the first time, Sherman wondered why they happened. Were they misplaced reactions by his body, and therefore something to be avoided, or was there some point to them? And if there were, did that mean that the standard treatment he received - ice, an anti-inflammatory drug, and pain medication - might not be such a good idea after all?
The answer, Sherman found, is that the body has a lot on the ball. Heat makes cells divide faster; swelling pushes them apart and enables fluid to go between them, carrying necessary nutrients and taking out dead cells; and the pain, of course, keeps you from moving. "All of it," says Sherman, "is the body's own defenses working."
More than a decade later, the effects of the accident linger. His shoulder still hurts once in a while-and the suspicions he had about the innate wisdom of the human body have shaped his academic career. Sherman is on the vanguard of Darwinian medicine, an emerging field that takes an evolutionary perspective on human health. "Traditionally, doctors have been interested in treating symptoms," he says. "That's what physicians do. But the new field is asking, 'Is every symptom something to be suppressed? Or is it possible that some of the symptoms can actually be beneficial?'"
Traditional medicine asks how the body responds to injury or illness; a Darwinian approach wonders why it responds that way. Fever is a common example. Is it simply a reaction to infection - and a potentially harmful one at that - or does it have a purpose? "The answer is that a moderate fever, below about 103 degrees, actually can speed the healing process," Sherman says. "It makes the body's environment less able to be invaded by the pathogen, and it enables its immune system to work faster."
And the response isn't limited to humans. Other mammals (as well as amphibians, reptiles, and even insects) also either experience fever or seek a hot place when they get ill. "What's being suggested is the idea that not every symptom must immediately be suppressed," Sherman says. "Not every symptom is evidence of a failure of the body. Some are evidence of the body doing something beneficial, which has evolved through eons of selection."
This new approach, he says, can add weapons to the physician's "mental toolbox." When treating a patient with a bad cold, for instance, the doctor can offer some options. If you really can't miss work for the next few days, she can give you something to lower your fever, and you'll feel better sooner - but you'll be sick (and infectious) longer. If you can spend the next couple of days in bed, she might advise you to let your fever run, as long as it's moderate; you'll feel lousy in the short term, but you'll be healthy faster. If the fever's dangerously high, though, she'll prescribe drugs right away. "In the twenty-first century, as this kind of thinking becomes more widespread, the doctors' challenge will be to work with the patient to find the appropriate balance," Sherman says. "Which of these responses is of immediate medical concern, and which are of some value so we should work with them instead of against them?"
Sherman stresses that Darwinian medicine is not alternative medicine, nor is it homeopathy. It doesn't suggest that modern medicine is unnecessary, just that an evolutionary understanding of the body can help doctors and patients make better choices. "It's totally complementary," he says. "Physicians can only benefit from this. They're asking how something works. We're asking, 'Why does it work that way?""
Sherman cites computers as an analogy. Most people use their laptop without ever worrying about what makes it run, while some know the ins and outs of microelectronics. Similarly, some doctors-for instance, those in the "repair" business, like surgeons - may not find a Darwinian approach particularly interesting. General practitioners, on the other hand, may consider it immensely helpful in day-to-day patient care. "What he's presenting holds a lot of promise," says Dr. Frank Chervenak, chairman of the Department of Obstetrics and Gynecology at Cornell's Weill Medical College in New York. "Instinctively, a doctor has a knee-jerk reaction if something is abnormal to make it normal. The exciting thing about Paul's work is it makes you ask, 'Is that the right course to pursue?"'
Sam Flaxman '98, who studied with Sherman as an undergrad and is now pursuing a PhD in neurobiology and behavior on the Hill, got interested in Darwinian medicine because of his allergies. He'd always thought his body's reaction to cat hair and other substances was inherently negative; now he wonders if it might have some useful purpose. "It's a different way of looking at our experiences," he says. "We have an idea of what it means to be healthy, and when we don't fit that, we think that's bad. This puts symptoms in a whole new light."
When researching symptoms, Darwinian medicine first asks a basic question: whom do they benefit? Some, like fever, aid the patient, so you probably don't want to suppress them; others can be harder to call. "A good example is a sneeze or a cough," Sherman says. "On the one hand, they might be your body's way of getting out an irritating substance. Alternatively, sometimes when you have a cold or flu you cough and sneeze and it's not doing you any good, but it's doing the pathogenic microorganism a lot of good, because it's spreading it."
For Darwinian doctors, understanding how viruses and bacteria propagate is a key part of infectious disease control, Sherman says. Those that spread through direct contact, like colds and flu, don't benefit themselves by being so virulent you can't get around enough to pass them on. So-called "vector-borne" diseases - those like malaria, cholera, and yellow fever that spread through vectors such as insects or water - are more deadly; they can reproduce faster since their transmission doesn't depend on their victims being well enough to move. (Sherman notes that HIV is a particularly frightening disease because it's transmitted through a vector and by direct contact; needles are manmade vectors that increase the virulence of an HIV strain every time it's passed on.) "A disease's effects on us can be understood by knowing what the disease itself is trying to do - what it evolved to do," he says. "It's not a passive particle doing nothing. It's evolving, too, and if we think about it that way we suddenly have new insights into the kinds of diseases that are deadly and those that aren't."
Darwinian medicine traces its roots to the mid-1980s, when physician Randolph Nesse and evolutionary theorist George Williams met and, eventually, put a name to a field that had seen disparate pockets of research over the previous few decades. In March 1991 their seminal article on the subject, "The Dawn of Darwinian Medicine," appeared in the Quarterly Review of Biology, and two years later the world's first symposium on the topic was held in Boston at a meeting of the American Association for the Advancement of Science. In 1995 Nesse and Williams published Why We Get Sick: The New Science of Darwinian Medicine, still the field's leading text.
"The great mystery of medicine," they write, "is the presence, in a machine of exquisite design, of what seem to be flaws, frailties, and makeshift mechanisms that give rise to most disease. An evolutionary approach transforms this mystery into a series of answerable questions: Why hasn't the Darwinian process of natural selection steadily eliminated the genes that would make us susceptible to disease? Why hasn't it selected for genes that would perfect our ability to resist damage and enhance repairs so as to eliminate aging? The common answer - hat natural selection just isn't powerful enough - is usually wrong."
The real answer, they say, is that the body is "a bundle of careful compromises." Like any machine, it has design trade-offs - the ultimate goal is not human health and happiness, but the perpetuation of our genes - and by understanding how evolution has shaped that design, modern medicine can become more effective. "Inevitably, this will become a standard part of medical education," Williams says. "As far as I'm concerned, for any medical problem you can think of, there's a way evolutionary history and natural selection can guide research and treatment."
But as Sherman notes, it's a brand new field. Williams, a professor emeritus of ecology and evolution at the State University of New York, Stony Brook, and Nesse, a psychiatry professor at the University of Michigan med school, are among a handful of scientists who research it full time. "It's not a specialty yet," Sherman says. "What we're looking at is probably a twenty- to thirty-year horizon before everybody in the world picks up on it."
The subject has yet to gain a significant presence in medical schools, he says, and no university has a department dedicated to it; the advanced seminar he's taught on Darwinian medicine for Cornell juniors, seniors, and first-year grad students since the mid-1990s is one of the few such courses offered anywhere in the country. "This is coming in from biology and entering into medicine," he says. "It's so new there's no track record on it. Many doctors have never heard of this." (The field has its highest profile in Norway, where it's included in a standard reference work for general practitioners and is making inroads into the curricula at medical and nursing schools.)
Sherman, who studied pre-med at Stanford and went on to earn a PhD in zoology at the University of Michigan, teaches in the Arts college's neurobiology and behavior department. He's an expert on the cooperative and competitive behavior of social animals, particularly the ground squirrel and naked mole rat; the latter, mammals that live in large colonies akin to anthills, are the subject of a children's book he co-authored. When he came across Williams and Nesse's work, he says, he was hooked. "The more I read about it," he says, "the more I became convinced this would be something useful, both for society and for students."
Sherman is now one of only a few dozen American researchers delving into the field. On the Hill, he touches on Darwinian medicine in his courses on animal behavior; as a result, he says, "I'm overwhelmed with students wanting to do projects." Two ofthose projects turned into Sherman's highest-profile work on the subject to date. The first, conducted with Jennifer Billing '96, studied why residents of hot climates tend to cook with fiery spices. (They found that the spices themselves contain antibiotics that kill pathogens, so the people who craved them were less likely to die from eating contaminated food - and they taught those cooking techniques to their children.) Another, instigated by then-junior Sam Flaxman, looked into why women get morning sickness. The results, published in the June 2000 issue of the Quarterly Review of Biology with Flaxman as lead author, have been lauded by women - including Katie Couric, who interviewed Sherman about the study on "Today." The work, like most Darwinian inquiries, was based on a "why" question: Why do women's bodies reject food at a time when their fetuses need nourishment the most? Is it an evolutionary mistake, or is there a purpose to it?
The researchers found that women don't suffer for nothing; in fact, those who experience moderate morning sickness are less likely to miscarry, so eliminating it may not be a good idea. The very foods that expectant mothers dislike the most - meat, eggs, strong-tasting vegetables like broccoli, caffeinated beverages - are most likely to contain chemicals or pathogens potentially harmful to the developing fetus. By rejecting those foods through nausea or vomiting, the mother's body is protecting the baby - and women with a genetic tendency toward morning sickness are therefore more likely to reproduce and pass on the trait to the next generation. "The bodies of 70 percent of the women in this world aren't failing in the face of a pregnancy," Sherman says. "Rather, they're responding in a defensive way against potential microorganisms and plant toxins in food. Yes, you feel miserable for a while, but there's an evolutionary reason behind it and it makes some sense." (Williams says their work is "an enormous improvement" over previous evolutionary studies of morning sickness, and calls Sherman "among the most important people" in Darwinian medicine research.)
Morning sickness, like fever, is an example of the body's protective response being misunderstood. But that's just one category of phenomena Darwinian medicine covers; another is the conflict between ancient traits and modern society. "Human biology," as Nesse and Williams note in their 1991 article, "is designed for Stone Age conditions." Once upon a time, for instance, the craving for fat was a distinct evolutionary advantage, since it contains more calories than other types of food. But now we live in an age of abundance - and that same craving can be a one-way ticket to obesity and heart disease. "During our ancestral past, more was always better," Sherman says. "Within the range of what we could get our teeth on, the more of it you got, the better your nutrition. Today, the craving for fat is something we'd be better off without, given the serious consequences of overconsumption. That's an obvious example, but how many more are there?"
The same logic can be applied to vision, Nesse and Williams theorize. The issue of nearsightedness has always been a thorny one, evolutionarily speaking. Following the Darwinian principle of survival of the fittest, wouldn't people with a genetic tendency toward bad eyesight be winnowed out - be eaten by the proverbial lion? But the authors propose that nearsightedness is actually caused by modern society. Although many people have a genetic tendency toward myopia, it wasn't expressed as often, or as severely, until the advent of literacy. For millennia, they note, people were constantly focusing far and near, near and far, from the hearth to the horizon. Focusing close for long periods of time, particularly during childhood eye development, is a relatively recent phenomenon; it may be the price we pay for reading. "Technology has advanced at a very rapid rate, but we still carry three and a half billion years of evolution with us," Sherman says. "We are the way we are, we see the way we see, because of that evolutionary past."
Still another category of present-day ills can be traced to the fact that, in an earlier environment, they actually presented advantages. The gene that causes sickle-cell anemia protects heterozygous individuals (those that have one copy of it instead of the deadly two) from malaria; similarly, the gene that causes Tay-Sachs disease protects heterozygotes from tuberculosis. Since only a few people suffer the consequences of getting two copies of those genes and thereby develop sickle-cell or Tay-Sachs - and the ability to survive malaria or TB is such an advantage during an outbreak - the gene was once worth the cost. But take away the threat of malaria and TB, and all you're left with is the risk of sickle-cell and Tay-Sachs.
Other evolutionary trade-offs affect everyone. Take aging, senescence (decrepitude), and death. The question of why people get old and die may be one for the philosophers, but it's also one for evolutionary theorists. The answer to it, like all Darwinian queries, lies in the genes. Common wisdom might say that people die to make room for others, but Sherman only chuckles. Natural selection doesn't favor individuals that sacrifice themselves for others, unless they're close relatives; that famed footage of migrating lemmings leaping to their deaths, Nesse and Williams note, was generated not by nature but by broom-wielding documentarians. "Darwinian logic has to do with the survival of the individual and its genes, its family," Sherman says. "Organisms in nature do not do things to benefit their species, their ecosystem, or their world. They do things to benefit themselves and their genetic material."
So why do people die? Because once they reproduce, their genes no longer care what happens to them. Humans, therefore, are designed to be robust during their reproductive years - and any healthy life you have after that is just a fringe benefit. That logic also helps explain why women live longer than men. Men are even more "built for speed" than women are, their lives even more front-loaded. Historically, they had to be strong and robust to attract a mate when they were young, so their candle burns both brighter and shorter. (Women, furthermore, are evolutionarily predisposed to longer lives. Since they're assured of their genetic relationship to the children they bear, they can help promote their survival by living long enough to act as mother and grandmother.)
The bottom line, Sherman says, is that the search for a fountain of youth is futile. "It's a losing cause," he says. "It's not gonna happen." Although the average life expectancy has risen dramatically - mostly due to drops in childhood mortality - the maximum life-span has stayed pretty much the same. "The oldest people 1,000 years ago lived to be about a hundred," he says. "The oldest people today live to be about a hundred. What that should say is that doctors should concentrate on the quality of life, not on prolonging life."
Helping prioritize where medical resources should be spent is one of the field's biggest potential contributions, Sherman says. If morning sickness isn't something to be avoided except in extreme cases, for example, then working to develop a new drug for it is probably not a great idea. On the other hand, biologists know that the evolutionary contest between humans and pathogens will go on for eternity, so exploring new ways to treat infectious diseases should be a priority. "It's a coevolutionary race," he says, "a never-ending arms race. Every time we get better at treating a disease, the disease gets better."
Sherman is presently juggling three Darwinian projects: one on the causes of pre-eclampsia, an immense rise in blood pressure after about the twentieth week of pregnancy that can cost the lives of both mother and fetus; another on lactose intolerance, which has been found to be more common in non-dairying societies but is present even in dairying ones; and a third on the usefulness of allergies. "Darwinian medicine is an approach that says, 'Let's work with our bodies instead of fighting them,"' Sherman says. "Now, we go to doctors and say, 'I'm sick, fix me.' We want the latest miracle drug to ameliorate all our symptoms, take away the pain, change everything, make us live forever. It isn't the doctors imposing this on us, it's us imposing it on the doctors. We need to change our whole cultural attitude."
Darwinian medicine researchers are exploring a variety of health questions from an evolutionary perspective. Like, why do we ... Get old and die?
All our genes care about is reproducing themselves. So the human body is designed to be hardy during our reproductive years; anything beyond that is not an evolutionary imperative - particularly for men. Since women are certain of their genetic relationship to their offspring, they live longer to assist their children and grandchildren.
LIKE SPICY FOODS?
It's not to hide the taste of spoilage. Spicy foods have become popular in hot climates because the spices themselves have antibiotic properties that kill bacteria.
HAVE TO INVENT NEW ANTIBOTICS?
Because pathogens evolve much faster than we do - hundreds of millions of offspring an hour compared to two or three in a twenty-five-year human generation - thus creating many opportunities for a drug-resistant strain to mutate.
CHOKE?
The intersection of our air and food tubes isn't ideal, but it isn't so deadly that it inhibits reproduction. It's what evolutionary theorists call a "historical" rather than a "functional" design we inherited from our remote ancestors.
GET ALLERGIES?
Researchers aren't sure, but it may be another conflict between our Stone Age bodies and the modern environment; the increasingly common allergy to peanuts, for example, may stem from modern processing. Another possibility is that individuals have allergic reactions to get the toxins to which they're most vulnerable out of their bodies.
EXPERIENCE FEVER?
In humans and other creatures, a raised ttemperature creates a hostile environment for invading bacteria.
GET MORNING SICKNESS?
Nausea and vomiting during pregnancy appears to be an effort by the mother's body to protect the developing fetus from toxins and pathogens in foods such as meat, eggs, and broccoli.
GET CANCER?
Because we live too long. Our cells reproduce constantly; the longer we live, the more chances there are for a cancerous mutation to develop.
SUFFER FROM MYOPIA?
It may be caused by the modern tendency to focus close for long periods of time during eye development - in other words, reading. Our ancestors, on the other hand, constantly readjusted their vision to see far and near.
SUFFER FROM MENTAL ILLNESS?
Researchers theorize that conditions like anxiety, depression, and agoraphobia may be "overshoots" of appropriate survival reactions such as submissiveness, fear, or fight-or-flight - and that other conditions, such as schizophrenia, may be traced to infectious diseases contracted by the mother or infant.
CRAVE FAT?
For most of human history, there was never enough food, so a craving for calorie-laden fat was an advantage. In an age of overabundance, it's a drawback - but changes in environment have happened faster than evolution can keep up.