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Candace Pert on Molecules of Emotion

Editor’s note: This extraordinary interview with neuroscientist Candace Pert, who died in 2013, takes us back to the discovery of the opiate receptor, which binds to the natural joy-inducing, pain-reducing molecules — the endorphins — in the body and the brain. The work Pert pioneered, today a cornerstone of neuroscience, showed that the mind-body connection is profoundly real.

by Judith Hooper

Visitors wander through a labyrinth of olive-drab corridors until they find the office with the name CANDACE PERT and a child’s drawing signed VANESSA posted on the door. Next door, rats slumber or scratch in their cages, dreaming of the day they can escape electrodes, syringes, and imperious gloved hands. Here at the Biological Psychiatry Branch of the National Institute of Mental Health (NIMH) in Bethesda, Maryland, the business is the mind: slices of cortex aglow with chemicals that, if you heed Candace Pert, contain all our joys and sorrows. In 1973, when Pert was a twenty-six-year-old pharmacology graduate student working under Solomon Snyder at Johns Hopkins University in Baltimore, she startled the neuroscience community with her discovery of the opiate receptor. A receptor is a site in the brain where molecules of a drug or naturally produced chemical fit like keys in a lock. The fact that the brain possesses receptors for morphine and heroin, Pert said, suggested that it must also produce its own version of these substances. And two years later, the Scottish scientists John Hughes and Hans Kosterlitz discovered our body’s natural opiates — the endorphins. A new era in neuroscience was born.

The discovery of the opiate receptor heaped instant renown on Pert and Snyder. Then, in 1978, Snyder, Hughes, and Kosterlitz received the Lasker Award, commonly considered a steppingstone to the Nobel Prize. Candace Pert did not. But she did soon find herself unwittingly famous, as the controversy over her exclusion from the award seeped out of the hushed chambers of dispassionate research into the streets of public opinion. The young graduate student’s name began reverberating even in the sacred editorial pages of Science. The opinion of many informed researchers was that Dr. Pert had been denied her due.

Today, still reluctant to talk about the Lasker Award controversy, Pert has only cordial words for her former mentor. The opiate receptor may have been a cause célèbre, but she’d rather discuss her current work on the Valium receptor, which she flippantly refers to as the Hoffman-La Roche receptor, for the mysterious target sites in the brain where angel dust works its black magic. Her photographs of intricate brain-receptor patterns, illuminated like so many inner galaxies, remind us of how little is known about the workings of the human mind. From where do our thoughts arise? How does the brain regulate behavior? Do our neurochemicals, like seasonings in a biological soup, make us sad or happy, psychotic or sane? Pert intends to find out. “I’m tinkering around inside the human computer,” she has said. “People are just very complicated electronic mechanisms, and our emotions of love, hate, anger, and fear are wired into our brains.”

A graduate of Bryn Mawr College, with a Ph.D. from Johns Hopkins, Pert went on to work at the NIMH right next door to her first husband, Agu Pert, a behavioral psychologist. “I’m his biochemistry consultant, and he’s my psychology consultant,” she said at the time.

Judith Hooper interviewed Candace Pert in 1981, both at her lab and at her Bethesda home.

Pert later co-founded a company, Rapid Pharmaceuticals, with her second husband, Michael Ruff, to develop a novel peptide treatments for pain, multiple sclerosis, Alzheimer’s, and AIDS; she also wrote an influential book, Molecules of Emotion, about the deep connection between mind and body. She died of cardiac arrest in 2013.

(For more information on Candace Pert’s life and work, visit http://candacepert.com.)

OMNI
Some people have compared the present explosion in neuroscience to the splitting of the atom. Do you think we’re on the verge of a neuroscience revolution?

Pert
Yes. There used to be two systems of knowledge: hard science like chemistry, physics, biophysics on the one hand, and, on the other, a system of knowledge that included ethology, psychology, and psychiatry. And now it is as if a lightning bolt had connected the two. It’s all one system: neuroscience.

Behavior isn’t such a mysterious thing. I think it emanates from microcircuits of electrons flowing from one neuron to another. What we’re working on now is connecting up neurochemical facts, the brain’s juices, with circuit diagrams of the brain. Circuit diagrams are what people called neuroanatomists have been concerned with for years. They study the actual connections between the neurons, the wiring of the brain. What’s happening now is that we’re learning which neural pathways secrete endorphins and which secrete other neurojuices. There’s no doubt in my mind that one day, and I don’t think that day is all that far away, we’ll be able to make a color-coded map of the brain. A color-coded wiring diagram, with blue for one neurochemical, red for another, and so on; that is the neuroscientist’s ambition. We’ll be able to describe the brain in mathematical, physical, neurochemical, and electrical terms, with all the rigor of a differential equation.

OMNI
Will such a diagram account for consciousness?

Pert
No, it won’t. Just as a person may totally understand a television set, can take it apart and put it back together again, but understand nothing about electromagnetic radiation, we may be able to study the brain as input-output: sensory input, behavior output. We make maps, but we should never confuse the map with the territory. I’ve stopped seeing the brain as the end of the line. It’s a receiver, an amplifier, a little, wet mini-receiver for collective reality.

OMNI
In The Doors of Perception, the book Aldous Huxley wrote about his mescaline experiences, he theorized that the brain and the nervous system function as a filter that enables us to experience only a fraction of reality. Is brain research validating Huxley’s theories?

Pert
Yes. Huxley’s mind would be blown by neurochemistry. Our brain defines how much reality is let in. Reality is like a rainbow or like the electromagnetic spectrum. Each organism has evolved so as to be able to detect the electromagnetic energy that will be most useful for its survival. Each has its own window on reality. Humans can perceive the part of the color spectrum between infrared and ultraviolet. Bees can’t see red at all. They can see up through several shades of purple. We cannot. In fact, our team at NIMH has proposed that the endorphins, our natural opiates, are a filtering mechanism in the brain. The opiate system selectively filters incoming information from every sense: sight, hearing, smell, taste, and touch, and blocks some of it from percolating up to higher levels of consciousness. Nobody really knows what the world looks like, as philosophers like Bishop Berkeley and David Hume observed. Everybody’s version of the world is significantly different.

OMNI
While we’re on the subject of the natural opiates, let me ask you about the discovery of the opiate receptor in 1973. You were a graduate student, but yours was the first name on the paper you published with Solomon Snyder. So I assume you did the actual lab work?

Pert
Yes. I was a graduate student in Dr. Snyder’s laboratory at Hopkins. He was my mentor, and I have nothing but the fondest feelings for him. He’s a brilliant and wonderful teacher. The importance of our work is that the opiate receptor was the first receptor ever found in the brain. But the opiate receptor turns out to be one of thirty or forty different receptors in the brain that can be detected by using the technique I developed. My method was to use radioactive compounds to bind to a drug. We just ground up the brain tissue and measured how much of various radioactive drugs stuck to various brain tissues. We found the sites to which the radioactive opiates attached. And that led to the discovery, in 1975, by Hughes and Kosterlitz, of our naturally produced opiates.

OMNI
Then Snyder, Hughes, and Kosterlitz were awarded the Lasker Award. Why were you excluded, when you obviously did the seminal work?

Pert
That was a long time ago, and, to tell you the truth, I’m sick of being asked about the Lasker Award, as if I were a grumbling lady scientist who had done nothing else since then. I think there is other research for which I’m known. The politics of science is far less important , to my mind, than the core of scientific inquiry, which is the search for truth. That’s the awe-inspiring part of it.

OMNI
Still, didn’t you write to Mary Lasker, declining your invitation to the award ceremony? And isn’t it true that you did not entirely ’hold your tongue’, as is expected of women, graduate students, and others low down in the scientific hierarchy?

Pert
I wrote to-Mary Lasker at the time because I was not about to sit through a luncheon and be patted on the head. But I don’t care to perpetuate an image of Candace Pert, Scarlet Lady of Neuroscience. I have no feud with Sol, whom I respect very much, and the discovery of the opiate receptor itself is, in a sense, ancient history. I’m now working on the angel dust receptor and the Valium receptor. Our brains probably have natural counterparts for just about any drug you can name. No one has yet actually found the brain’s own marijuana, but I think that’s because marijuana doesn’t interact with the brain as THC [tetrahydrocannabinol], but as another breakdown product.

As far as women in science go, people have been analyzing the critical point at which women get stuck, and basically the problem is that they don’t get those faculty positions which you must have to get grants. The female position is postdoc for life or research associate. Eighty-five percent of the American scientists who have been stuck at the level of research associate for twenty-five years or more are women. Research associates are PhD’s with a lot of responsibility who are never really the boss, calling the tune. On paper, you work for this excellent person who received grant money, but you’re not good enough to be on the faculty yourself.

OMNI
It has been said that women hold themselves back by trying to please. Is that a stumbling block for women scientists?

Pert
Women scientists are women. Studies show that there’s some hard-wiring in that department; for example, women smile more than men do. I’ve observed it myself at meetings. In tense situations when important theoretical issues are being discussed, women smile a lot when they make their statements.

OMNI
Do you believe that all our behavior, even loftier emotions such as altruism or romantic love, can be traced to biological phenomena? E. O. Wilson and other sociobiologists propose, for example, that thousands of years of natural selection have shaped our brains into highly refined survival instruments and that, at bot tom, even the noblest sentiment is only survival instinct.

Pert
Well, many psychologists believe that there are only a few basic drives: sex, hunger, thirst, and escape from pain. They theorize that something more complex, say, the desire to discover a cure for cancer, can be traced back to a series of reinforcing events. Its source might be a very primitive feeling of well-being when your mother stroked your head and talked to you about medicine.

OMNI
How does brain chemistry work into the scheme?

Pert
Well, if you were designing a robot vehicle to walk into the future and survive, as God was when he was designing human beings, you’d wire it up so that the kinds of behavior that would ensure the survival of that species, sex and eating, for instance, are naturally reinforcing. Behavior is modifiable, and it is controlled by the anticipation of pain or pleasure, punishment or reward. And the anticipation of pain or pleasure has to be coded in the brain.

We’re starting to understand that emotions have biochemical correlates. The brain is just a little box with emotions packed into it, primarily in the limbic system below the cortex, the old mammalian brain. Remember the experiments conducted in the 1950s, in which rats were given the chance to self-stimulate different parts of the limbic system by pushing a lever? They stimulated the pleasure center in the brain until they fell from exhaustion. Well, it turned out that the electrical stimulation caused the release of brain chemicals associated with pain or pleasure. The endorphins, for instance, are very pleasurable. Larry Stein at the University of California, Irvine, has suggested that the natural opiates are the brain’s own internal reward system. It seems that when humans engage in various activities, neurojuices associated either with pleasure or with pain are released.

OMNI
Do all animals have these reward and punishment chemicals?

Pert
Absolutely. Endorphins are being studied in the leech. Insects have endorphins and many of the other neurochemicals that regulate our own emotional circuitry. There’s evidence that even unicellular organisms have these chemicals. I’ve always understood theoretically about the unity of life, that we’re all composed of DNA molecules and protein. But I’ve never experienced that understanding as directly as I have in the last few years. I’ve been looking through the microscope at the brains of different mammals, and when you’ve seen one brain, you’ve seen them all: a cat brain, a dog brain, a monkey brain. We’re all made up of the same building blocks, the same structures. A lot of the key work in neuroscience has been done on invertebrates like clams, spiders, crabs, octopuses, and leeches, creatures that are very primitive.

OMNI
Would we be anthropomorphizing to suppose that, say, cockroaches feel some sort of emotion?

Pert
Not at all. They have to, because they have chemicals that put them in the mood to mate, and chemicals that make them run away when they’re about to be killed. That is what emotions are often about: sex and violence. We humans are stuck with some sex and violence circuitry, but we have the intellectual ability to transcend our programming.

OMNI
Is there a schism these days between biologically oriented brain researchers like yourself and analytical psychiatrists who think free association and dream interpretation are the ultimate tools for understanding human behavior?

Pert
Yes. The present era in neuroscience is comparable to the time when Louis Pasteur first found that germs cause disease. Before that, disease had been attributed to demons, bad air, or an imbalance of the bodily humors. But do you think every doctor said, Oh, it’s bacteria; let me find out how to give those vaccinations that Louis Pasteur discovered? It didn’t happen that way. They were still bleeding people to cure infections. The old guard had to die out.

There are people who theorize that autism is caused by something like a father’s not paying enough attention to a child and a mother’s being a little too pushy. Yet there’s scientific evidence that it may be associated with something as physical as the mother’s bleeding during a certain month of pregnancy.

OMNI
With the advent of psychiatric drugs, our understanding and treatment of mental illness have become increasingly biological.

Pert
That’s right. Incredible shame is associated with mental illness. People will confide the most intimate details of their love life before they’ll mention a relative who has had a serious mental breakdown. But the brain is just another organ. It’s just a machine, and a machine can go wrong. One neurochemically coded system may have a kink in it. In the last twenty years, psychiatry has come out of the Dark Ages. We know that many forms of mental illness are associated with an imbalance in brain chemicals, and we have drugs that are closely related to those chemicals to treat that imbalance. All psychiatric drugs work at the vulnerable part of the brain, the synapse [the point at which a nerve impulse passes from one nerve cell to another], where they mimic or block the brain’s natural chemicals. But our drugs are still very crude. In fact, there are only three basic psychiatric drugs: neuroleptics like Thorazine for schizophrenia, anti­depressants for depression, and lithium for manic-depressive illness. Similarly, when antibiotics were first being used, we had only sulfa drugs given for everything. Later, we had penicillin and other very specific drugs.

OMNI
In the year 2000 will we have recourse to the ampicillins and the tetracyclines of the mind?

Pert
2000? Much sooner, I think. I had envisioned the impact our discovery of the opiate receptor would have on biochemistry and pharmacology, but I had no idea of its impact on psychology. The future of psychiatry will be totally changed. Our future treatment of mental illness will probably deal with receptors, which we now know are constantly fluctuating. With some receptors, the actual number of receptors decreases; with others, the actual number may not change, but the way the receptor is coupled to the neuron’s membrane does. William Bunney, here at NIMH, thinks that the waxing and waning of receptors is the key to understanding mental illness. He has found that some manic-depressives cycle between depression and mania every twenty-four hours. Every afternoon at four o’clock, say, they’ll click sharply from depression to mania. It’s called the switch. And there’s only one cure: lithium. My husband, Agu, demonstrated that lithium stops the sharp oscillations and stabilizes the receptor for the neurochemical dopamine. There’s evidence that the insulin receptors fluctuate in diabetes. Manic-depressive psychosis is like diabetes of the dopamine receptor.

OMNI
How will this knowledge transform psychiatry? What will a psychiatric consultation be like ten or fifteen years from now?

Pert
We’ll do a total receptor work-up with a PET [Positron Emission Tomography] scan, which measures metabolic activity in various parts of the brain. We’ll drop in a very selective drug with a radioactive isotope, which will light up the brain, and then we’ll be able to get a three-dimensional look at the receptors: which areas are okay, which need tuning. We’re going to have computerized maps of the brain of all the different substances we know of, and some we haven’t yet discovered. One day we will have each neurotransmitter on a separate floppy disc. We’ll know the different distributions in the brain, and we will find out a lot about what goes wrong. Then maybe the patient will be given a highly specific dose of, say, ten drugs that will straighten things out. On the other hand, it is all in the mind anyway. Perhaps what this is telling us is that drugs can never be as subtle as our own neurochemicals, which can be released in one spot and not another. Drugs assault the whole brain at once. Who knows? The future psychiatric treatment may consist of autohypnosis, meditation, exercise, diet modification, and so on.

OMNI
Is it true that researchers are already looking into the brains of schizophrenics using PET scans?

Pert
Yes. The technique is still in its infancy, but they’re already finding startling differences between normal brains and those of schizophrenics. Parts of the front of schizophrenics’ brains are dark on the scans, as if they were turned off.

OMNI
Do such drugs as heroin affect the sensitivity or the number of receptors?

Pert
Absolutely. Heroin bludgeons the opiate receptors into submission, functionally shrinking them. And there’s evidence that the younger the brain, the more vulnerable its receptors are. If you give a pregnant rat one shot of Valium, for example, its babies will have half as many Valium receptors when they grow up. This raises frightening questions about current obstetrical practices. Babies whose mothers were given Demerol during pregnancy are affected by the drugs. For example, they fail to habituate to background noise as readily as normal babies do. There is hard evidence that this condition lasts at least two weeks. Whether it extends into adolescence is not known. And of course drugs are just analogs of our own internal chemicals anyway, and there’s evidence that life events prompt the release of neurochemicals. So our experiences probably affect the distributions of receptors.

OMNI
What would Sigmund Freud say? Are his theories concerning the Oedipus complex, wish fulfillment, and repression now as antiquated as the concept of the geocentric universe?

Pert
There’s nothing that Freud ever said that I can’t relate to. Not only was he an incredible genius, but he was also the first psychopharmacologist. His treatise on cocaine, which he wrote before the turn of the century, was a masterly psychopharmacological paper. And of course he experimented with cocaine himself. He was interested in the underlying neuromechanisms of mental disorders. If he were alive today, he’d be a neuroscientist. Also, he was right about the unconscious. In studying the way the brain processes information, we’ve learned that much information never reaches the conscious mind. As incoming information travels from the senses up through higher and higher levels of the nervous system, it gets processed at each stage. Some is discarded; some is passed on to the higher regions of the brain. There’s a filtering, a selection, based on emotional meaning, past experience, and so on. We think repression occurs at the synapse, where the message is either blocked or transmitted.

OMNI
Once we come up with highly refined maps of the brain, would you expect to find differences between the brains of men and those of women?

Pert
Well, at a certain level of consciousness, it’s very upsetting for a woman to think she’s any different from a man. I went through that phase in the late 1960s. I wore a lumberman’s jacket and boots and really denied any differences between men and women except for the most obvious difference in sex organs. Bu t you need a whole different brain circuitry to operate those different sex organs. So I think that in a few years, we’ll be able to look into the brains of a man and a woman and see differences. At Stanford, recently, researchers found an area in the rat brain that was bigger, it contained more neurons in males. And wherever you have different neurons, those neurons are secreting different neurochemicals. So, yes, I think we’ll be able to figure out the chemical coding for the differences between the sexes.

OMNI
Why should there be sex differences in the brain? Is it because evolution favored different characteristics in males and females?

Pert
Of course, men and women have entirely different attitudes toward sex, and those attitudes are due to physiological differences in the brain. Men derive an evolutionary advantage from spreading their seed as much as possible. Women, on the other hand, need to choose a mate who will stay around and take care of them and their offspring. So I’d expect to find a part of the female brain that is devoted to making that kind of choice. Women are programmed to fall in love with whomever they make love with, no matter how ludicrous the person. As soon as they look into the eyes of their partner, they’ve had it. Men can act as if they’re really in love, but it’s a case of out of sight, out of mind. The brain doesn’t know the Pill was invented. Women have been programmed since time immemorial to get that guy back to take care of any offspring that might ensue. After all, our mothers had babies, our grandmothers had babies; women alive today are the result of a long line of women who reproduced. When a woman chooses not to have children, it’s a momentous decision, at odds with her programming.

OMNI
Would you expect to find a kind of mothering or nurturing circuitry in the female brain?

Pert
Definitely. The female brain was designed to enable a woman to teach another organism to survive. I think the reason that the X chromosome is bigger than the Y chromosome is that it takes much more information to produce a brain that can raise a baby to the point where it can survive than a brain that merely impregnates and runs. Evolutionary theories have made too much of the bands of cavemen working together to hunt down a bull, and they’ve forgotten the women back at the cave, who have chosen which men to mate with; and I do think it’s a choice. Maybe when we look for the origins of language, we should look to the cavewomen communicating with their offspring and with one another.

OMNI
What about violence? Are men innately more aggressive than women?

Pert
Each sex has to grapple with its own programming, and I think the female program is easier to deal with. Women don’t realize how much men have to struggle to control themselves. In their early teens, when testosterone starts to surge, young men feel angry. There is now a proven connection between violent behavior and elevated testosterone levels. A Y chromosome is a real cross to bear. It’s a predisposition toward angry, violent, competitive, macho behavior.

OMNI
Is the male program evolving, in your opinion, now that communication and peaceful coexistence are more important survival skills than physical prowess?

Pert
Yes. There was an article in Newsweek about men like the late John Lennon staying home to take care of their children. We’ve come a long way. Men have gradually developed paternal feelings, and bit by bit the concept of monogamy has grown. So men are becoming more civilized. Someday they may be as civilized as women. The women’s movement is also a sign that the female element is becoming respected by our society. It’s a sign of the civilizing process of the evolution toward peace.

It’s interesting that the main reason that many people oppose the Equal Rights Amendment is that they are threatened by the idea of women going into combat. Well, I think once you have women in the trenches, you’ll have no more war. My feeling is that if there had been women in every trench during World War One, the women on both sides would have communicated with one another, and they all would have celebrated Christmas Eve together. Women are natural peacemakers. The Christian mythology is just a very elegant and complex metaphor about mother love. Mary stands for mother love, forgiveness, and compassion. Jesus understood that love was the key. “Love thy neighbor.” “Blessed are the peacemakers.” I always say it was great for God to send his only son, but I’m waiting for him to send his only daughter. Then things will really be great.

OMNI
The size and structure of the human brain have remained unchanged for thousands of years. What do you think is the next step in evolution, if there is one?

Pert
Well, evolution has no purpose except to enable a species to reproduce and survive. Each creature is a finely evolved machine for that. Richard Dawkins, who wrote The Selfish Gene, says that a duck is basically a robot vehicle for the propagation of duck genes; a human being is a robot vehicle for the propagation of human genes. Yet somehow, it seems to be requiring greater and greater intelligence for human genes to propagate. We’re evolving toward perfect knowledge. Remember, all human beings alive today are the offspring of a long chain of ancestors, each of whom was smart enough to survive.

OMNI
Can the brain ever really understand the brain?

Pert
Yes, absolutely, in terms of matter, in Newtonian terms, if you like. Until recently I have visualized the brain in Newtonian terms. I’ve pictured the neurochemicals and their receptors as hard little locks, keys, and balls, like the drawings in textbooks. But now I’ve come to see the brain in terms of quantum mechanics, as a vibrating energy field, with all these balls, locks, and keys just being ways to perturb the field. As I’ve said, the receptors aren’t static locks; they’re constantly oscillating and moving. It’s like the difference between Newtonian and Einsteinian physics. I remember studying physics at Bryn Mawr and getting a glimmer of what reality is. I was just vibrating on the brink of experiencing everything as matter and energy. But you quickly return to your everyday consciousness. You can write equations about Reality, with a capital R, but you think in Newtonian mechanical terms. Consciousness is before the brain, I think. A lot of people believe in life after death, and the brain may not be necessary to consciousness. Consciousness may be projected to different places. It’s like trying to describe what happens when three people have an incredible conversation together. It’s almost as if there were a fourth or fifth person there: the whole is greater than the sum of its parts.

OMNI
Einstein and other physicists have described experiencing an almost religious awe when contemplating the laws of the universe. Do you ever feel that way about the brain?

Pert
No. I don’t feel an awe for the brain. I feel an awe for God. I see in the brain all the beauty of the universe and its order, constant signs of God’s presence. I’m learning that the brain obeys all the physical laws of the universe. It’s not anything special. And yet it’s the most special thing in the universe. That’s the paradox.

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