Darwinian Medicine -- It's A War Out There And Margie Profet, A Leading Theorist In A New Science, Thinks The Human Body Does Some Pretty Weird Things To Survive

BEFORE WE LIVED AS we live today, which is to say before we were organized, stratified, classified, specialized and sorted square pegs into square holes, round into round and polygonal into polygonal, human societies tended toward generalization. So did the humans in them.

Leonardo da Vinci, undoubtedly a genius in any age, was more apt to become a Renaissance man because he lived during the Renaissance. That is, generalists were common, specialists rare.

Today, if a person wants to be a scientist she becomes a particular kind of scientist, a physicist, for example; and not just a physicist, but a still more specific type; say, a particle physicist. To do this, the would-be scientist will spend 20 years in increasingly specialized education.

Twenty years, in Margie Profet's mind, in jail.

A decade ago, Profet, having just received her second undergraduate degree, this one in physics from the University of California at Berkeley, decided, unaccountably, to become a biologist.

She also decided she hated school. So she went out and bought a good basic biology textbook, took it home to her cramped San Francisco apartment and began reading and thinking.

To succeed as a self-made scientist is to overcome almost impossible odds. Yet today Profet has a growing reputation among evolutionary biologists and is recognized for pioneering work in a nascent field known as Darwinian medicine. She has published three significant, in some ways revolutionary, papers. She is finishing work on a book on early pregnancy to be published worldwide. She is the recipient of a quarter-million-dollar MacArthur fellowship, the so-called genius grants that allow people to work unencumbered by jobs. With it, she has escaped California and moved to Seattle where she is affiliated with the University of Washington's Department of Molecular Biotechnology. At 35, she has rented her first house and bought her first car.

She has yet to take her first college biology class.

MARGIE PROFET IS, almost without doubt, the only working biologist in the world today whose work, while published in specialized academic journals, also has been featured in general publications such as Time, Newsweek and People magazine, the one with Shannen Doherty's "secret wedding" on the cover, and in a whole slew of fashion magazines, including an issue of Elle whose cover story was "Good Hair Days."

This is not normal company for biologists, people more accustomed to seeing their work buried in library stacks than displayed at checkout stands. Most biologists don't get asked, as Profet was by Harper's Bazaar, if she had her own hair and make-up artists, or should they send someone out to help her prepare for a photo shoot?

Profet, by every account including her own, is not a normal scientist. She is odd in almost every important way, from her background to her research methods, which on a typical day might amount to puttering around the house or listening to Pink Floyd and chatting amiably with the neighborhood cat, or heading for the library with no particular goal in mind.

"I'd go to the library and just say, `What do I want to search for today? ... Something about the eye, about the heart, anything. My family's life, somebody's fever, thymus evolution? I'd pick a topic that intrigued me for some reason ... and follow it down little trails and tangents."

One of these tangents is responsible for landing Profet in People and Glamour, amid the gossip and the celebrities and the cosmetics ads. It had to do with something that had been bugging Profet for 20 years.

"I first learned about the phenomenon of menstrual bleeding when I was 7 years old," she says. "I found a tampon applicator, and I wanted to go play spy with it."

Her mother told her what the applicator was.

"When she told me I'm going to do this, you know, every month I'm going to bleed, it made no sense. I mean, it was, `God hates us.' It was like the lamest thing I had ever heard in my life. And I grew up Catholic, so I heard a lot of lame things.

"I never thought it was something I was going to spend years of my life working on. But I'm very opportunistic and if I think of a neat idea, I work on it."

Profet's neat idea came to her decades later in a dream. The dream, animated in the style of the grade-school filmstrip that tried to explain menstruation with cartoons, featured little creatures swimming valiantly upstream, carrying some dark, indefinite cargo with them. When Profet awoke, she knew exactly what those creatures were, what their cargo was, and where they were headed. They were sperm en route to the uterus carrying bad news, germs.

Eventually, she summarized the dream and the five years of research it inspired in a single sentence:

"Sperm are vectors of disease."

You do not expect and usually don't find sentences of such economy and weight in the scientific literature.

When published in the Quarterly Review of Biology last fall as the lead of Profet's article proposing a new theory of menstruation, this was a high-volume grunge-rock power chord in the sleepy halls of academe. The conventional wisdom holds that menstruation occurs because of an accident of evolutionary history. It is usually described as an unnecessary and inconvenient by-product of the female reproductive cycle.

Profet declared this scientific nonsense, useless at best, harmful at worst. If menstruation was unneeded, it would have been eliminated ages ago, she said, because it inflicts such a heavy cost on women. It is not just an inconvenience, it diverts resources the body could use profitably for other purposes.

Some evolutionary theorists see evolution as improvisational, proceeding almost haphazardly. Others, like Profet, see it as more disciplined, as a careful weighing of costs and benefits. If some significant feature of life evolves in a certain way, there must be a reason for it.

Profet says menstruation is just such an adaptation. It evolved to help women fight disease. "I propose," she wrote, "that menstruation functions to protect the uterus and oviducts from colonization by pathogens." The most likely means by which those pathogens would reach the uterus would be to hitch a ride on sperm headed that way for other purposes.

Profet was hardly unaware that in the war between men and women, in which she insists she is not engaged, will not enlist and will not be drafted, those words carried powerful political content. But Profet wasn't aiming at men; she was opening another front in her continuing war with business-as-usual biology.

THERE IS IN ANY POPULATION variation among its members. With human beings, for example, some are tall, some short, some of medium height. A statistician wanting to describe how tall a person was relative to other people might plot the distribution of heights on a graph. When plotted, heights describe a bell-shaped curve. A very few, very tall people are at one edge of the bell; a very few, very short people are at the other. Most people fall somewhere in between, bulging along the middle of the graph, the so-called norm. One common measure of distance from this norm is called a sigma after the Greek letter that is used to represent its formula.

So if the average height of American women was 5 feet 4 inches, someone who was 5 feet 7 might be one sigma away from the norm. A 6-foot woman might be three sigmas, a 7-footer five sigmas.

Margie Profet's father, Bob Profet, an admirer of hers, once said jokingly that Margie was a 10 sigma. Off the chart for weirdness. A 9-foot giant. He was exaggerating, of course. She's more like a six or seven.

Bob and Karen Profet are both physicists, employed by California aerospace companies. They raised four children in the glow of eternal summer on the suburban beachfronts south of Los Angeles. All the children were bright, Margie especially so.

"In first and second grade, she would get up early, sit on the heat register and study by herself before school," Bob Profet says.

Margie recalls being bored with school from the age of 7. She nonetheless vowed to herself she would make an effort in school, so she didn't foreclose future choices. She was precocious in math and by the sixth grade was taking high-school algebra exams.

"I just knew I didn't want a suburban little life," she says now. "I didn't know what I wanted in life; I just knew I wanted to do something stimulating, and I hadn't a clue what that would be."

She was accepted at both Harvard and Cal Poly, San Luis Obispo. Choosing Harvard was intended as a conscious move away from science.

Profet majored in political philosophy. Her faculty adviser was Harvey C. Mansfield, a philosophy professor so renowned for toughness that his nickname was C-minus. Profet had the same effect on Mansfield she would have on a succession of mentors.

She "looked like she just came in from the beach even in mid-winter," Mansfield says.

When she wanted to, Profet was an exceptional student, he says, who "somehow transcended the usual distinction between ordinary and weird."

Writing her senior thesis on the German philosopher Nietzsche was a defining experience. She discovered she was actually capable of doing what she had always wanted - original thought.

She did not, however, discover what she would do with her life.

"It came time to graduate. I didn't have a clue what I was going to do."

A younger sister who came east for the graduation ceremony took one look around and summarized things nicely. "She said, `Margie, everybody here has a plan about what they're going to do, and all you know is that you're going to Maine for the weekend.' "

Profet had a plan that extended somewhat beyond the weekend. She had learned to think. She had learned she liked it. She had also learned that many of the questions that absorbed her - what she calls "why questions" - might be answered by science. After a period of bumming around Europe, working as a computer programmer in Germany, trekking in Nepal, climbing mountains in Africa, she returned to California and enrolled at Berkeley as an undergraduate physics student.

If her first stretch in college had been liberating, this second was imprisoning. She struggled, getting a second degree but hating the regimentation of it. She knew further schooling was out of the question, but she also knew she wanted to continue to work in science.

"For some people going to grad school is a very wonderful experience," Profet says. "I mean for some people. And they learn a lot. But so much of it is so regimented and it can be so long before you're doing anything on your own."

PROFET BEGAN HER independent education in biology and evolutionary theory. She took odd jobs to support herself and spent almost every spare minute thinking and reading. Even when her boyfriend came to visit, they would sit on opposite sides of her tiny dining-room table and read.

In 1986 she had her first real insight. Several relatives were pregnant at about the same time and, talking to them, Profet began to think about what was called morning sickness. She wondered what function it served.

"I went on a detective hunt," she says. "I discovered the Berkeley biology library. I'd never been in it. I had this phobia of libraries. They were dusty and old, and I was afraid of going to the stacks and finding some old 18th-century scholar rotting there. Now I love them. They're like my sanctuaries."

Profet eventually concluded morning sickness didn't necessarily occur in the morning, and its purpose was to shield the human embryo from plant toxins eaten by the mother. It had evolved as a defense mechanism designed to protect a pregnancy at its most vulnerable point, in the first three months before the embryo grows into a fetus and develops resources to defend itself.

It took a year to develop the theory, and publication was delayed beyond that for a variety of other reasons. By then she was off on another library adventure. This one also started in bed.

"I'm allergic to a lot of things, mostly detergents and things like that," she says. "One night, when I didn't know exactly what I was allergic to yet, I'm in bed scratching and I just remember thinking: `What is this for?'

"I knew because I had studied some immunology that there was this whole class of antibodies that does nothing but cause allergies. And I thought, `What on earth could it be there for?' I thought, `What are the symptoms of allergy?'

"It's immediate. It's unlike a viral illness or a bacteria, which are delayed, and might be days before you get any noticeable reaction. With allergies, it's immediate, within minutes. You're scratching it off, you're tearing, you're sneezing, you have diarrhea, or you vomit and you drop your blood pressure. All of these are ways to immediately expel something.

"I thought, `What could cause this? What could kill you within minutes? Viruses don't work that fast. Bacteria don't. Toxins do.' "

Profet had no idea at the time what the conventional analyses of allergy were. When she found out that most scientists believed it was either, one, a mistake, or two, a reaction to the potential presence of parasitic helminth worms in the digestive track, she was appalled.

"When I came across the helminth worm theory, I thought, `NO, they couldn't be taking this seriously. Maybe one or two immunologists think this is the reason, but this is beyond silliness.'

"It doesn't make sense from an adaptationist viewpoint because there's not a fit between the mechanisms of allergy and the problem of worm expulsion," she says. "Worms are a chronic problem, and allergies were designed for something acute."

All the while Profet was working on her pregnancy-sickness and allergy research, she was unable to get decent part-time jobs. She faced the daily problem of being poor.

"I was constantly applying for jobs, looking at the want ads," she says. "One of my versions of hell is a world populated solely by personnel directors."

Finally, she met toxicologist Bruce Ames, who ran a research lab at UC-Berkeley and outfitted it with scientific oddballs.

Ames recalls his first encounter with Profet. He was giving a seminar to physics students on current research in toxicology. Profet, who was long out of school, somehow got into the seminar, and began asking unusually insightful questions. After the class ended, Profet trailed Ames back to his office, "peppering me with some more really good questions. Finally, I said, `Hey, who are you, anyway?'

"She said she was a waitress or something like that.

"I said, `What do you mean, a waitress?' "

She told Ames that's what she did to make a living, and in her spare time she was a biologist.

Ames hired her to work half-time in his lab, where her job was intended to be clerical. She proved to be "a major contributor," Ames says, and was soon editing much of the research the lab published. She became a principal editor of Ames' own published works.

"She's a fanatic on getting every sentence right," Ames said. "There was a paper she contributed to, and I said I was going to list her as a co-author. She said no, she felt the paper wasn't up to her standards and she didn't want her name on it."

"She's a person who goes her own way in life."

By this time Profet's pregnancy-sickness paper had been published by a small journal and her allergy research, after surviving significant criticism during its peer review, was accepted by the Quarterly Review of Biology. George Williams, the Quarterly's editor and a highly regarded evolutionary biologist, thinks Profet is helping to form what amounts to a new science, uniting biology and medicine in a way that hadn't been done.

For reasons neither Williams nor Profet can fathom, physicians and biologists, who, after all, share the human body as a subject, seldom were aware of one another's work.

Profet says, "Physicians don't look at function. Physicians seem to think if you ask what's the function of something, it's teleological. It's an intellectual theory, and there's no practical utility.

"It's not important? It's the basis, it's the foundation for understanding physiology. And physiology is the basis for understanding medicine. Imagine if we didn't understand the function of the heart. How could you recognize heart disease? How could you define heart health? How could you do anything? How could you perform heart surgery? How would you know when to do it? What to do?"

"Say we have two theories about the function of the heart. One is that it pumps blood. The second theory is that it's there to give us love and heartbreak.

"In the second case it's removable. You had a bad loveship, take out your heart.

"These things have major implications. With pregnancy sickness, they did awful things to women. Not only did they think it was not a function, they thought it was dysfunctional, especially if you had severe pregnancy sickness.

"Of course, with the Freudian revolution a lot of people thought this was just in people's heads; they're just neurotic. So a woman with a lot of pregnancy sickness is super-neurotic. They would tell her, `This is an attempt at oral abortion. It's a loathing of femininity. A loathing of your husband.' "No matter what aspect of physiology you look at, the core question is: What's it there for? Maybe it is just a fluke or a by-product. But maybe it has a function. You have to know that. Otherwise you're doing blind medical intervention."

The reactions in the medical community to Profet's theories have ranged from the cool to the hostile. One criticism to her allergy theory complained that a new explanation of allergy wasn't needed. They already had one.

"Science isn't a democracy," Profet says. "Voting is not the basis for truth. You don't go to some allergist and say, can I have a show of hands? That's not how you demonstrate science. I find things like that mind-boggling.

"You know, you tell any lay person, `Guess what the immunologists think that allergy is designed for.'

"They say, `What?'

"And you say, `Little worms.'

"And they go, `Huh?' "

It is this intuitive grasp of the apparent failure of existing theory that is the basis for all of Profet's work. Her three major ideas - on pregnancy sickness, allergy and menstruation - all subject anomalous human behavior to an adaptationist critique. Why does this happen? What does it cost? What is the resulting benefit? The fundamental supposition of evolution, that all organisms are engaged in an evolutionary race for survival, is the main motivation of all of her explorations.

IT IS HARD TO IMAGINE someone of Profet's physical demeanor succeeding at any pursuit as sedentary as thinking. She is a small, preening rabbit of a woman, with a skittish hyperactivity that prompted me to ask her, not facetiously, how often she ran into walls.

She considered it a legitimate question.

She has developed the odd habits of the solitary, talking to herself, to animals, to people who aren't there. She hasn't enough patience to eat normal meals. She grazes at her desk, consuming low-calorie animal crackers, fruit, bread, milk and diet colas. "I don't like to cook," she says. "When I'm hungry I want to eat now. I don't want to eat in an hour."

When she went shopping for her first car this year, she decided that for the good of the public order it had to have a manual transmission. The need for constant shifting, she thought, would keep her attention focused on driving. Otherwise, it was hard telling where her mind, and the car, might wander.

True to her beachfront roots, she wears T-shirts and running shorts year round, changing the length of the shorts in carefully calibrated accord with the temperature.

George Williams, the biologist, asked recently to evaluate Profet's history and habits, concluded, "People don't always get born when they should."

Profet acts much more like a medieval hermit monk than a modern scientist. Her big social event of the week is going to the library. Her major expense last year was photocopying. Given her work habits and highly unconventional training, she would seem more in sync somewhere in the late Renaissance. In some fundamental way, Profet might belong to an even earlier era.

Most modern scientists are grown in much the same way as today's crops. They are lined up all in a row, standardized, carefully fertilized and watered, grown to uniform size. They have been domesticated. Profet is a throwback to the days before domestication. She is a precursor, foraging through the fields of human knowledge, searching for some things, happening upon others.

In her own evolutionary race, she seems to have outlasted her natural enemies. The hunter-gatherer has come back.

Terry McDermott is a reporter for The Seattle Times. Harley Soltes is Pacific's staff photographer.