"I don't know about this book tour thing," she finally says, referring to the upcoming publication of her Molecules of Emotion (Scribner), an exploration of the biology behind feelings. "It just scares me to death!" Then she tosses the toy to her husband, fellow scientist and research partner Michael Ruff, a stocky 44-year-old with light brown hair and glasses. He yelps her message a few times. The gravelly voice is out of some late night film noir, with snatches of almost-words—eerily misplaced in this sprawling wooden house with its wraparound deck, pool, and hot-tub out back. Pert interprets the apparent gibberish as best she can:
"'What did you think, the books would never relax?' See, it means I'm never going to relax."
Then she instructs me to try the Yalp, to say anything, but to speak with emotion, because "emotion is what creates the hidden message." That's a surprising statement from a neuroscientist, but emotion is the lodestone of Pert's work and life. She was one of the key researchers who, a quarter of a century ago, discovered and mapped the brain's opiate receptors. A receptor has often been described as a chemical lock on a cell, into which a particular substance, or key, fits. In truth, notes Pert, receptors are far more fluid and amazing than locks. A typical nerve cell has millions of receptors on its surface, dancing and vibrating, each waiting for another molecule to wander by and bind to it. When the two join into one, the receptor changes shape, and that shift sends a message into the cell itself.
"It was the killer experiment of my dreams," she recalls of the study that first proved that the brain is hard wired to respond to the body's internal morphine. "It didn't matter if you were a lab rat, a first lady, or a dope addict—everyone had the exact same mechanism in the brain for creating bliss."
That single finding opened up a monumental new field of research and led to the discovery of the body's natural opiates, known as endorphins. "The study of the opiate receptor became so incredibly hot," recalls Pert, "that world-class scientists from all over were coming into the field. It became totally interdisciplinary." Eventually, a class of tiny proteins known as peptides—including the opiates and serotonin—were found to regulate our behavior, mood, and health.
Our bodies are studded with peptide receptors. For Pert, this means consciousness operates at a cellular level, involving the mating dance of each receptor and the particular peptide that binds to it. Or, as she puts it, "Your subconscious mind is really your body. Peptides are the biochemical correlate of emotion." She has even stated that our white blood cells, which boast many of the same receptors and chemicals as the brain, are "bits of the brain floating around the body." She's talking a kind of molecular psychology, a true biology of emotions.
Part mystic, part scientist, Pert herself is nothing if not emotional—controversial, flamboyant, embracing, bossy, flirtatious, at moments unabashedly neurotic and even over-the-top—a woman who meditates daily and is friendly with Deepak Chopra, shows up at a cousin's past-life regression therapy group, and still publishes papers in Science about substances like chemoattractants and octapeptides. And her cup overflows with stories, from the bitter, public rift with her mentor, Sol Snyder, to the scientific conference where, while speaking of new research into peptides and AIDS, she heard what she jokingly calls "the voice of God" murmuring in her ear. From the beginning, Pert has stood apart, an outspoken, iconoclastic female in the male bastion of science.
From Lab Rat to Faith Healer
"To think I'm being viewed as a healer—God forbid, a faith healer!" says Candace Pert when I first meet her and Micheal Ruff at a restaurant in New York City. The couple is exhausted from a long day of fundraising for their research on Peptide T, which they believe may help prevent the wasting and demetia caused by the AIDS virus. It seems that the virus attaches to a crucial receptor on the immune system's T4 cells, thus preventing the cells from recieving peptides that are vital to their health and to the health of the entire organism. Peptide T—so named because its dominant component is the amino acid threonine—might offer a strategy to fight the virus.
It's a project the couple has been working on for 11 years, but in spite of initial encouraging experiments, other scientists have not been able to replicate their early results on AIDS. Still, Pert speculates that peptides may eventually spark a whole new generation of antiviral drugs. "Why do I never get a cold on a ski trip?" she muses. "Because I love to ski and it makes me happy and excited. The peptide norepinephrine is the chemical that stimulates excitement, and the cold virus uses the same receptors." When you're happy, the virus can't lock on to the receptors. That's why, she notes, depressed people get sick more often.
It's the kind of message that advocates of alternative medicine love, and Pert has become a veritable mind-body medicine guru. She's now on the staff of Deepak Chopra's Institute for Human Potential and Mind/Body Medicine in San Diego, and has adopted some of his ayurvedic health practices, such as sesame oil rubdowns, which "have a very calming influence. I have one before heavy duty meetings." She has even tried guided visualization sessions uniquely tailored to her own expertise: she imagined a flood of beta-endorphins spurting out of her pituitary gland." I had very little trouble bringing the pituitary into sharp visual focus," she recalls, "and the beta-endorphin was there on my inner screen, all thirty-one of its amino acids strung together in a bead chain." When she visualized releasing the endorphins, she felt an instantaneous rush of bliss. Yet for all her mind-body wisdom, she's clearly worried at this dinner: about fundraising, the future of her research, the launching of her book, and a relapse into an old addiction. "I quit smoking on the stroke of midnight in 1970, but two months ago I started again. I'm not going to do it forever, but Michael's on the verge of leaving me over this. Are you, honey?"
A few weeks after our dinner I take the train down to Potomac to spend two days at her house, shopping with the scientist and her husband, cooking dinner together, observing them in the lab. It's an experience that is absolutely unnerving, for Pert rolls out her passions, obsessions, aspirations, and frailties as if she were a one-woman stage act, seeming to censor nothing. "I have a pathological desire to mother people," she announces spontaneously. "It's horrible if you're one of the men in my life." She sits a little too close, with a big smile. She urges me to stay longer so that we can go on a sailing trip, offering to lend me her daughter's old bathing suit. She tells me she had a crush on one of her cute postdocs earlier this year. She admits she suffered a major depression when she was in college, which she blames on a diet of peach pie that "blew out my thyroid." She bickers with her husband, and he bickers back, and the bickering sometimes has an uneasy intensity, perhaps born of their 24-hour-a-day partnership. Ruff himself was a postdoc a decade younger than Pert when—divorced with three children—she apparently took him under her wing, romantically, sexually, and scientifically. "We were at a party and he told me that it was his 30th birthday and that he wished he could go home with the sexiest woman at the party. I said, 'How about me?'" As Pert herself admits, "I say all kinds of things I shouldn't."
Yet when the subject turns to science, she shows a fluidity, passion, and ease of expression that is rare. As her ex-husband, Agu Pert, Chief of Behavioral Pharmacology at the National Institute of Mental Health (NIMH), says, "Candace has a very fertile mind. Some of the things she's conjured up are really excellent, others are off the track, but she has a unique way of looking at things." Her attempt to stitch together fields as diverse as molecular biology, immunology, psychology, and alternative medicine is at the very least courageous, at best inspiring. No wonder she came to national attention when she was featured on Bill Moyers' landmark 1993 PBS series, Healing and the Mind. Critics, enchanted by Pert's ideas and enthusiasm, said she deserved her own series.
Scarlet Woman of Science
Healer wasn't a role Pert could have conceived of when, in her early twenties, she joined the already famous lab of Solomon Snyder, M.D., a neuropharmacologist and psychiatrist at The Johns Hopkins University. Neither did she imagine that she'd soon be involved in a bitter political rivalry with her mentor over America's most prestigious scientific award. She was newly married, with a toddler son and a husband finishing a deferred military obligation.
Snyder was a prodigy at 34, the youngest full professor at Hopkins and heir apparent to a stunning scientific lineage. Snyder's mentor, Julius Axelrod, was a Nobel laureate; Axelrod's mentor, Bernard Brodie, was widely considered the most important figure in modern drug research. "When 'Julie' won the Nobel we felt forever blessed." she recalls. "And we saw Sol as just short of God. Most labs are really dull, and people almost bask in the tedium of the research, but we were always at a fever pitch." Students called Snyder's office the "throne room," and already, recalls Pert, he was "jetting around the world to get the latest, hottest news from other labs."
Pert seemed driven by the same hubris and passion as her mentor. "The opiate receptor!" she writes, describing Snyder's decision to let her search for it. "To find a receptor for morphine, the drug over which wars had been fought, kingdoms lost, the mystical substance that suffused the writings of Coleridge and De Quincey, named in the honor of Morpheus, the god of dreams. Now here was a project worthy of my ambitions."
After months of failed experiments, Snyder finally took her off the opiate project, but Pert claims she disobeyed his instructions and ordered radioactive naloxone (a drug that blocks the effects of morphine) without his knowledge, completing one last experiment over the weekend while her toddler son played with vials and caps a few yards away Pert contends that it was then, mother and child alone in the lab, that she discovered the opiate receptor, adding that the elated Snyder guided almost instant publication of the results in Science. Others at the lab and around the world soon did equally important work on the receptor and on endorphins.
Yet two years later Pert failed to receive the Lasker Prize, often called "the American Nobel," when it was awarded to Snyder and two other male scientists, John Hughes and Hans Kosterlitz. Told "that's just how the game is played," the infuriated Pert believed she'd been cut out because she was a woman, and went straight to the scientific press, triggering a public scandal that eventually inspired a book, Robert Kanigel's Apprentice to Genius. Pert refused to cooperate in Snyder's nomination for the Nobel Prize, and even accuses Snyder of nominating himself by asking his department chairman to nominate him and then filling out the forms himself. To this day she believes he feels she cheated him out of the prize, and admits she was soon nicknamed "the scarlet woman of neuroscience."
It's a nickname that has stuck, especially since Snyder tells a radically different story (Harvard University Press published his version in a book called Brainstorming: The Science and Politics of Opiate Research): "First, no graduate student can order a radioactive substance on their own," says Snyder, now director of the department of neuroscience at Hopkins. "The regulations are too stringent." Snyder says he guided Pert's research, and had applied for an NIH grant a year earlier to look for the opiate receptor using radioactive drugs. As for nominating himself for a Nobel, "That's absolutely not true," insists Snyder, somewhat outraged. "Those nominations are carried out in great confidence."
For a long time, says Pert, "I was trying to make up with Sol. It was a major subplot of my life. When will Sol forgive me? When can we live happily ever after? Those days are over." Now, Pert plugs away at Peptide T, still convinced she may have a potent treatment for AIDS in her back pocket, and explores the frontiers of alternative medicine and spirituality. "I've earned myself a reputation as the body-mind scientist. Somehow I've found myself able to straddle both worlds."
Pert first "came out" as a different kind of scientist in 1985, when she spoke about the mind-body connection in a keynote address at a symposium for the Institute of Noetic Sciences, an organization that supports studies into consciousness. A version of her talk was published in the Journal of Immunology, titled "Neuropeptides and Their Receptors: A Psychosomatic Network." It detailed her view of emotions and health.
According to Pert's talk, peptides provide our body's most basic communication network. To study the molecules' specific function, Pert and colleagues at NIMH began taking wafer thin slices of rat brains and, using radioactive molecules, mapping peptide receptors in the brain. Dense clusters appeared in parts of the brain long associated with emotion. According to Pert, the hippocampus, a small, almond-shaped structure that is crucial in memory, is the brain's emotional gateway. Almost every variety of peptide receptor is found there, she notes. The frontal cortex and another brain structure, the amygdala, are also densely populated with peptide receptors. Since emotions are regulated by neuropeptides, and the brain's memory centers are filled with receptors for these peptides, it's likely that emotion and memory are intertwined. However, the peptide network reaches into all the organs, glands, spinal cord, and tissues of the body.
"This means," says Pert, taking a huge theoretical leap, "that emotional memory is stored throughout the body." Emotions, ranging from anger to fear, sadness, joy, contentment, courage, pleasure, pain, awe, and bliss, engender a constellation of bodily changes, of which facial expressions are simply the most obvious. "And," concludes Pert, "you can access emotional memory anywhere in the network." How else, she speculates, could therapies based on massage, therapeutic touch, and chiropractic, trigger profound transformations? "Repressed emotions and memories might actually be stored in receptors throughout the body." In fact, says Pert, body and brain are not separate. "We are one bodymind."
Pert envisions emotions traveling in both directions, from the brain into the body, and up the body into the brain, where they are integrated and expressed. She has called herself a "molecular Reichian," after the theory of radical psychotherapist Wilhelm Reich, who believed that body "armoring" and muscular tension were a result of emotional repression, and led to illness. Breathing deeply—as recommended in yoga and meditation—may alter the flow of peptides. "There is a wealth of data showing that changes in the rate and depth of breathing produce changes in the kind of peptides that are released from the brain stem." "Gut feelings" may be more than a cliche: the stomach is thickly laced with peptide receptors.
Even the immune system may be a different kind of emotional brain. Pert's husband, Ruff, has theorized that special immune cells called macrophages may function like nomadic brain cells, because their receptors accommodate virtually every neuropeptide known. Perhaps the connection between emotions and health is more than folklore: it may indeed have a very precise scientific basis. "Could being in touch with our emotions facilitate the flow of the peptides that direct our immune system's natural killer cells?" she asks. Might that explain why women with breast cancer live longer when they participate in support groups?
In facing her own emotions, Pert says she has sometimes experienced a healing crisis. "One night I stayed up all night and prayed. I felt like I was going to die. It was as if I was re-experiencing every cough, ache, and pain I'd ever had as a kid. There's this unbelievable skepticism that scientists have. I don't have it anymore. People said the opiate receptor didn't exist. I saw it go from something people couldn't conceive of to something that was invoked to explain everything from orgasms to runner's high."
That optimism may be why she persists in her research on Peptide T and AIDS, which has gotten a frosty reception from her colleagues. Or perhaps it's the mystical experience she had in 1985, after Pert and Ruff decided to marry. They hiked up the famed Haleakala Crater on Maui. Returning in an exhausted and altered state of mind to a scientific conference on the island, Pert presented her findings on the AIDS virus, which she says looks like a Star Wars "sphere whose surface is covered by hundreds of sharp protein spikes." These spikes allow it to bind to cell receptors, including T4 receptors in the brain and certain immune cells. That may be the virus' entry point into the immune system and the brain—and if so, could explain how the virus causes dementia. If we could find the peptide for that receptor, she told scientists at that meeting, we might have a nontoxic therapy to prevent AIDS.
"And then I heard a male voice inside my head," she recalls. "It said, 'You'd better find it!'"
She did find Peptide T, but thus far its potential has not panned out. Pert believes the scientific community is still antagonistic toward the "scarlet woman of neuroscience." But, in looking back at the Lasker fracas, she would not have played the game differently. "I would not have been who I am, [the woman] who went on to meet Michael and think in a new way and try to merge neuroscience with immunology. I've run into obstacles, but it's kept me close to the bench, to real lab work. I used to be angry about it all, but somehow that pales in comparison to having the potential treatment for a devastating disease."
She also faults the scientific community for its rigidity. "There are turf battles. For instance, neurology 'owns' multiple sclerosis. It's considered a neurological disorder. So they've been working happily for 20 years on myelin (the protective coating of nerves), and they just keep barking up the same tree. And they're very upset that the disease might possibly be viral in origin. If you find infected cells they say, 'Well, that's very interesting, but what relevance does it have?' And they walk out of the room. Why? Because if multiple sclerosis turns out to be viral, suddenly infectious disease researchers will own it. The different fields just won't hold hands. So how can they have original ideas?"
A Fabulous Happy Ending?
But Pert, in marrying an immunologist, long ago broke with that tradition. At Georgetown, she and her department chairman, neuroendocrinologist Michael Lumpkin, are collaborating. They've found that AIDS wasting seems linked to a disruption of growth hormone, and possibly a disregulation in Peptide T.
Pert's view of Peptide T is romantic, even transcendentally mystical. "Whenever Peptide T research is at a pivotal point, it seems, meteorological weirdness strikes: ice storms, heat waves, hurricanes, earthquakes...and rainbows," she writes. "Michael and I call it 'Peptide T weather.'"
"Do you really believe that?" I ask as we drive toward her lab at Georgetown University in the late morning. "That Peptide T is holding so much energy and being blocked so strongly that it's actually disrupting the weather?"
"Yeah, something like that," she says, soberly. "There'd be a meeting on it at NIH and we'd have the biggest ice storm of the century. It got to where Mike and I would just laugh about it."
Peptide T, she hopes, may be the beginning of a whole new avenue of research as big as the opiate receptor. Viruses, triggers in so many diseases, from the common cold to cancer, may imitate peptides. Perhaps the most damaging viruses wreak havoc because they are able to bind to multiple receptors in the body. Peptides, then, may be more than the language of emotions, they may be a language that viruses have stolen and imitated. Think of viruses as peptides' evil twins.
"I think this is all going to have a fabulous, happy ending. Let's say Peptide T really does block the virus, and somebody inside the system shows that it works. Somebody else stands up and says, 'We got the same result she did.' Then it will explode." As she writes at the end of Molecules of Emotion, "I've come to believe that science, at its very core, is a spiritual endeavor. Some of my best insights have come to me through what I can only call a mystical process. It's like having God whisper in your ear, which is exactly what happened on Maui. It's this inner voice that scientists must come to trust."