Best known for three landmark papers in the prestigious Quarterly Review of Biology (QRB) and Evolutionary Theory, Profet recast a trio of everyday curses into a trinity of evolutionary blessings. Allergies, menstruation, and morning sickness, she argued, eliminate germs, carcinogens, and mutation-causing toxins from the body. Her theories were hotly debated among scientists but embraced by mainstream media. In quick succession, Profet landed a six-figure MacArthur Foundation “genius” grant and published two books, including Protecting Your Baby-to-Be, on what to eat—and avoid—during pregnancy.
Magazines and newspapers played up her model looks and touted her beautiful mind. Her “radical new views,” the New York Times announced, gave “ordinary annoyances an active and salutary spin.”
Though controversial to this day, Profet’s work is “a paradigmatic example of how evolution can offer new solutions to old medical riddles,” says Michael Jones, a retired psychiatrist who discovered her papers while researching evolutionary biology at the University of Missouri.
Now, converging research suggests that Profet’s allergy theory, which has thus far received less attention than her other work, may be her most important. Scientists have generally confirmed an inverse relationship between allergies and many types of cancer, but struggle to explain the observation. The traditional view is that allergies are an accident of nature. Profet argued that allergic reactions evolved to expel toxins, including deadly carcinogens, from the body.
Prior to Profet’s work, the only discussion of allergies as protective pertained to the finding that food intolerance expels such pathogens as parasitic worms. Profet observed that the sneezing, scratching, watery eyes, and blocked sinuses of pollen allergies all combat toxins, as do the nausea, vomiting, and diarrhea of food intolerance. In extreme cases, blood pressure drops like a rock during allergy-driven anaphylactic shock, to slow circulation when toxins come calling.
If allergies are a broad filter against toxins, then they could presumably combat known and unknown carcinogens. Might irritants that trigger hives also cause skin cancer? Could a heretofore unknown risk factor for brain tumors reside in an allergen that swells sinuses? Profet argued “yes” to such questions, filling her work with intriguing clues. Heavy metals such as arsenic and nickel are the most likely metals to cause cancer; they are also the most allergenic. Aflatoxins from fungus that grows on hay and grain are so allergenic that just thinking about them can cause an itch. They are also among the most carcinogenic substances known. Profet learned facts such as these while working with University of California at Berkeley toxicologist Bruce Ames.
In 2008, neurobiologist Paul Sherman and evolutionary biologist Janet Shellman-Sherman applied Profet’s allergic “prophylaxis hypothesis” to 646 studies dating back to 1953.
“We examined inverse relationships between allergies and cancers of tissues and organs directly exposed to the environment versus those not directly exposed,” says Sherman, who with his wife works at Cornell University. Food-borne carcinogens travel to the stomach and colon and circulate into the bloodstream; airborne carcinogens enter the lungs and brain through sinuses and airways. If Profet was correct, allergy sufferers should get fewer cancers in directly exposed areas.
After an exhaustive review, the Shermans and coauthor Erica Holland, a University of Massachusetts medical student, found this very correlation. Inverse associations with allergies are more than twice as common among cancers of the nine tissues and organ systems that interface with the external environment—mouth, throat, colon, rectum, gray matter, pancreas, skin, cervix, and lung—versus the nine that do not, including the breast andprostate gland.
The brain affords a particularly exacting laboratory for Profet’s theory, the Shermans claim. Dozens of research teams worldwide have shown allergies significantly reduce the risk of gray matter, or glial cell, cancers such as glioma, but have no measurable impact on cancers of the sheath that surrounds gray matter, the meninges. Eight studies since 2002 have shown that when ultrafine airborne particles are deposited on nasal membranes, they cross the blood–brain barrier via routes that come into contact with gray matter, but not with the meninges.
Other studies have shown allergies slash ovarian cancer risk up to 30 percent and leukemia by 40 percent. Cancers of the lung, pancreas, colon, and more than a dozen other areas of the body reflect the same “inverse allergy” effect. The Shermans published their findings in the journal that started Profet’s career—the Quarterly Review of Biology.
Despite the supportive findings, Profet’s allergo-oncology arguments are largely unknown, especially among cancer researchers. Joseph Wiemels, a University of California, San Francisco epidemiologist who has published several studies about the allergy-cancer connection, says he took a “quick look” at Profet’s work and prefers a different explanation: Allergy sufferers get fewer cancers because their immune systems are on high alert, attacking tumor cells with “hypervigilant immunity” before the mutant cells even become visible.
But the scientist who published one of the first allergy-glioma studies in 2003—Ohio State University epidemiology professor Judith Schwartzbaum—said she finds Profet’s hypothesis worthy of serious inquiry. “We haven’t settled on an explanation, so all options ought to be examined,” she says. Regardless of the ultimate answer, Wiemels, Schwartzbaum, the Shermans, and other researchers hope the allergy connection will provide new ways to identify and combat cancer-causing substances.
The next step is to look for key associations between substances known to cause cancer but not known—as of yet—to prompt allergic reactions, Paul Sherman explains. Are nasal dripping and sneezing triggered by substances known to cause glioma? Is allergic diarrhea triggered by substances also implicated in colon cancer? Cigarette smoke causes coughing—a common allergy symptom—and it also causes cancer. The hints are “indeed exciting,” Sherman says.
Manhattan Beach, 1960s and 1970s: Profet read obsessively from her earliest years and by sixth grade was doing high school algebra.
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Bruce Ames met Margaret Profet while he was teaching a toxicology seminar to physics students at Berkeley. Her soft-spoken yet astute remarks stopped him mid-stride. In a “who are
you” moment, Ames asked Profet about her background. He “almost fainted” when Profet told him she was a waitress.
Amazed, the professor hired Profet—who had degrees in physics and philosophy but no biology background—for a position more fitting her interests. She edited his academic papers, becoming, in effect, guardian of a scientific legacy that included an important test—the Ames Test—for how likely a substance is to cause cancer or genetic mutations.
Ames—who remembers Profet as a stickler for details—became one of several important supporters, including evolutionary psychology pioneer Don Symons; the biologist George Williams, known for his theories about evolution and aging; and Harvard political science professor Harvey Mansfield.
Profet was just under 30 when the Ames Test helped validate the intuition that started it all. Why, she wondered, do pregnant women avoid coffee and what she called “the pungent vegetables” like cauliflower and Brussels sprouts? Morning sickness and food aversions, she concluded, keep expectant mothers away from even the smallest amounts of naturally occurring toxins. Where many saw healthful properties in veggies such as cabbage, cauliflower, and Brussels sprouts, Profet saw psoralin, hydrazine, L-isothiocyanate, and other noxious chemicals produced to ward off insects and deer.
Yet Profet’s best known and most controversial theory focused on menstruation, a seemingly inefficient and taxing biological process that has long escaped clear understanding. Menstruation, she argued, is nature’s way of cleansing reproductive canals. “Sperm are vectors of disease,” she famously stated. Bacteria from male and female genitalia cling to sperm and travel to the uterus, a concept she suggested in a 1982 Obstetrics and Gynecology journal paper entitled “Evidence for Microbial Transfer by Spermatozoa.”
Women should stay away from oral contraceptives that suppress menstruation, Profet insisted. And when patients complain of heavy periods, doctors should test for cancer and infections.
Rethink contraception! Avoid vegetables during pregnancy! Profet’s ideas stirred controversy. But she also emerged as a crossover celebrity rarely seen in academe. People, Elle and Harper’s Bazaar came calling. Even Scientific American and Time swooned.
Profet’s backstory was irresistible: A Renaissance mind in an alluring package, she published serious research without a doctorate or a steady place to call home. At the age of 35 she had just bought her first car and rented her first house.
“Margie was unusual in so many good ways,” remembers MacArthur Foundation administrator Maureen Atwell. “She was sweet, innocent, and easy to like.”
Innocence and likability, however, go only so far in the rough-and-tumble brawls of academic politics and public opinion. Profet would face a dilemma her personality and thin curriculum vitae left her ill-equipped to resolve. Scientific success means not just publishing your work, but defending it—something Profet was called upon repeatedly to do.
By proclaiming healthy vegetables “toxic” in her 1995 book, Protecting Your Baby-to-Be, and its 1997 sequel, Pregnancy Sickness: Using Your Body’s Natural Defenses to Protect Your Baby-to-Be, Profet incurred the wrath of prenatal nutritionists and the March of Dimes, who said she was pushing expectant mothers toward unhealthy eating at the worst possible time.
Academe also cried foul. Three years after her QRB paper on menstruation, Profet’s most ardent critic surfaced with a rebuttal in the same journal. Point by point, University of Michigan anthropology professor Beverly Strassmann deconstructed Profet’s argument. Logic and prior research didn’t support her claim that menstrual bleeding reduces infections, Strassmann wrote. It happens too rarely in the life of a woman to have such significance. Profet also predicted that promiscuity would correlate with menstruation frequency. But no such correlation exists, Strassmann retorted: The comparatively chaste bleed just as much as the sexually profligate.
Though Strassmann had studied menstruation firsthand among members of a West African tribe, her arguments were “flawed and unpersuasive,” Profet told the journal Science News. “I consider them a waste of time.” For all her sweetness, Profet could be brutal when sizing up others’ intellect or arguments.
But what Profet thought about menstruation ultimately didn’t matter. The éminence grise George Williams delivered a blow that has stuck to this day. “I think Beverly [Strassmann] did a pretty conclusive job of demolishing the main idea of Margie’s paper,” Williams, who died in 2010, told Science News in 1997.
Berkeley, 1980s: Toxicologist Bruce Ames "almost fainted" when he discovered Profet was a waitress. She later became his editor.
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Williams’s decree effectively halted research into Profet’s menstruation theory, but he did recommend her allergy and morning sickness work to researchers, including Sherman, thereby tacitly endorsing her fundamental approach: the desire to find the adaptive purpose in biological processes. It is this emphasis on ultimate rather than proximate explanations that interests evolutionary biologists, who investigate the value of a certain response, no matter how painful or undesirable.
At Cornell, the Shermans teach premed students to understand both the “why” and “how” of medicine from this perspective. “To fix something as complicated as the human body, it is wise to start with an understanding of what it was designed by natural selection to do,” Shellman-Sherman explains. Whether or not Profet found the ultimate function of allergies, menstruation, and morning sickness remains an open question, intriguing enough that Sherman and colleague Samuel Flaxman—an evolutionary biologist at the University of Colorado at Boulder—approached her in 2000.
They had spent years developing a scientific extension of her morning sickness theory that should have prompted a fruitful collaboration. But Profet wasn’t interested, telling them “she was not reviewing papers on the subject,” Sherman says.
It was an unusual move that may have indicated trouble ahead.
Evolutionary psychologist David Buss once noted that Profet “seemed to possess a unique view of the world that included a paranoia consumed with invading pathogens and parasites,” recalls his former student Barry Kuhle, now a University of Scranton (Pa.) psychology professor. This paranoia may have fueled her genius. It may also explain her disappearance.
By the turn of the millennium, Profet was back in Cambridge taking math classes at Harvard. “We spoke on the phone about a math problem she was trying to solve and how she was having a lot of trouble concentrating,” says Deirdre Barrett, a professor of psychology at Harvard Medical School. “She wasn’t in good shape.”
The author of The Committee of Sleep, Barrett—a dream researcher—had followed Profet’s career in part because Profet told the media that her menstruation theory had had its genesis in a dream. (Profet’s dream involved black triangles embedded in red. The triangles were pathogens, she interpreted, red blood washing them away.)
“Margie and I spoke on and off for some years,” recalls Barrett, who said their final contact was in 2004 or 2005, at which point she says Profet had already stopped communicating with her mother, to whom she’d long been close. “Margie was a private person even in better days, but [by then] didn’t want to communicate at all. She kept quibbling about little things. Her speech was much more hyper than usual. She seemed aggravated and distressed.”
Profet was still living off her 1993 MacArthur grant. “She said she had to find a cheaper place to rent,” Barrett says. By 2004, the bright, inquisitive woman Mansfield remembered had become lonely and adrift. “I tried to help, but she became exasperated with me,” recalls Mansfield, who supervised her undergradaute thesis on Nietzsche. The last time Mansfield saw her, on a street in Cambridge, she “told me to get lost.”
Those who knew Profet best shed some light on her disappearance, but stop far short of elucidating the psychiatric factors that might offer clues to her whereabouts. Don Symons, now retired from the UC Santa Barbara department of anthropology, had a six-year relationship with Profet. “No one has more respect and admiration for Margie’s amazingly creative intellect than I do,” says Symons, widely regarded as a pioneer in the field of evolutionary psychology.
The couple lived together for six months in 1990, when Profet had returned to Harvard yet again, this time as a graduate student in anthropology. “I took a sabbatical and moved back with her to support her,” he told me. “The grad student part was a short-lived disaster, but we made a lot of headway on the allergy paper. The science is all hers.”
Symons hasn’t heard from Profet in more than a decade. “All I can tell you is that her disappearance may not have been as sudden or unexpected as you may imagine,” he says. “She suffered for years from serious psychological problems she was adept at concealing.” Symons declined to elaborate further.
Margie’s mother, Karen Profet, did not respond to multiple interview requests beginning in 2009, but recently broke her silence, stating that there is no electronic trace of Margie after May 2002. “I hired a detective, enlisted the help of her credit card companies, searched the streets and shelters with her picture, and filed a missing persons report with the Cambridge Police Department, updated subsequently with dental records, [but] no information about her fate or whereabouts has ever surfaced,” states Karen in an email. “Margie may have been the victim of foul play, though it is probably more likely that she chose to disappear. Over the past decade, I have sorrowfully chosen to honor her choice.”
Karen declined to discuss Profet’s behavior or psychological state, but her unusual mind was apparent from an early age.
The precocious daughter of two Berkeley-trained engineers, she grew up in Manhattan Beach, Calif., and consistently tested grades above her age. She was also eccentric—“off the charts weird,” in the words of her father, Bob Profet, who died in 2006. As a child, Margie told People in 1993, she “felt like an alien who didn’t belong.” But that was okay, she emphasized. “Throughout history, the really good scientists were misfits. It’s okay to be a misfit as long as your science is good.”
Cambridge, Early 2000s: Profet cut off contact with her family in 2002. The last reported sightings of her date to 2004 or early 2005.
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Profet’s high school boyfriend John Whitcombe, an attorney in Torrance, Calif., remembers her as “a vibrant writer who giggled a lot and enjoyed philosophical discussions in coffeehouses long before there was a Starbucks.”
“She was a joy, always up and positive, adventurous and confident,” he says. “It is inconceivable to me that she has vanished. I hope her story has a good ending.”
Another ex-boyfriend, Russell Eubanks, remembers a woman who was “beautiful and engaging” but also given to long spells of melancholy, depression, and antisocial behavior. “She knew she had great intellectual gifts, but at the same time, I think she felt isolated by her mind,” he says.
Now a software engineer in Centennial, Co., Eubanks has stayed in touch with Karen Profet. “Margie and her mother were close,” Eubanks explains. “I never saw any hint of family discord.” He talked to Karen in 2011, in an “emotional, tearful conversation” that shed no light on Margie’s disappearance.
“I’ve found their reaction to her disappearance odd,” Eubanks says. “But I picture three possible scenarios. One, she’s dead by her own hand or through foul play. Two, she’s alive and under the care of someone, but mentally unbalanced. Finally, she got tired of the hassle of fame and academia, maybe found someone she’s comfortable with, and decided to drop out and live a very private life. I hope it is the latter.”
Eubanks’ reaction mirrors that of many others, as one-by-one, Profet’s friends learned she was missing. When Karen Profet called the MacArthur Foundation looking for her daughter in 2005, Maureen Atwell and her colleagues were “stunned and heartbroken,” Atwell says.
In fact, people who cared for her deeply very much factored in Margie’s many successes, says Symons. “Margie was not an outcast, nor a lone voice in the wilderness,” he explains. “Bruce Ames is surely one of the most respected biochemists of our time, and George Williams one of the greatest evolutionary biologists of the 20th century. And of course, winning a MacArthur grant testifies to the support she received from some well-placed and established people.”
Despite all the support, by 2005, Profet had turned away from her friends as well as her family, and lost much of the footing they helped provide. She started calling Barrett at all hours of the night, “rambling about how badly her work was going or how she needed to be left alone. Some nights she sounded really suspicious,” Barrett says. “She told stories about people she was working with that didn’t make sense at all.”
When Barrett suggested Profet was isolating herself from the people who cared for her most, she relented. “Margie told me she was being treated for something—she didn’t say what, but it sounded like bipolar disorder. She was sure she would get better soon.”
A few blocks away, Mansfield says he “had been trying to help Margie for several months.” These many years later, “I hoped I would get some good news about her. But I did not really expect it,” he says.
Mansfield characterizes the final contradiction of Profet’s many sides as “an apparent case of schizophrenia.” Exhausted and bowed when he saw her on that lonely Cambridge street, she had apparently succumbed to the unrequited cloak that had hovered for so long.
“Margie was a wonderful, free spirit in the best, intellectual sense of the phrase—a charmer, and a beauty, too,” Mansfield says. “May God protect her, wherever she is.”