Molecules of emotion, p.20
Molecules of Emotion, page 20
I remember thinking about all this as I sat across from my lunch table combatant, barely listening as his booming voice harangued me for well over an hour. I also remember feeling the late-term stirrings of my unborn child, which made me oddly peaceful in the midst of this ordeal. Perhaps the message that new life was on its way gave me strength and afforded me some distance from the attack I was now being subjected to.
The next morning, I received a four-page, single-spaced letter from the cancer lab director that read like a formal contract, spelling out exactly who would do what, when and where, in regard to further research. I read it with a dulled responsiveness, having no intention of ever bothering to reply. Clearly, my ex-collaborator believed I had been poaching on his turf, and I believed, just as clearly, that his territorial maneuvering, driven by a self-aggrandizing motive to get as much credit for the research as he could, was the stuff that kept medical science from finding desperately needed treatments. My father was dead, and I no longer had a shred of a reason to stay in the cancer doctor’s good graces.
I returned to my brain maps, my receptors, my peptides. What had been a thrilling and meaningful search for answers to the questions of why these lung cancer cells were full of peptides, why they didn’t fit the profile of other lung cells, was now being shelved. I fantasized that someday it would be resurrected, perhaps in a time when cold-hearted ambition mattered less than a genuinely motivated search for the truth. But for now, I let it go, thinking of it only in those moments when I remembered, with an ache, my father and how I had tried in vain to save his life.
CONNECTION
My weariness and disillusionment would soon fade, however, as I began a new intellectual journey, one that started with a casual social encounter, picked up steam as it involved me in yet another major quest for a disease cure, and had such momentum that it sustained me through criticism and adversity that would make what I’d already endured look minor. I met Dr. Michael Ruff in the fall of 1982 at the now-defunct Palace bar, a clubhouse and watering hole for brain-weary scientists, located in a donated stone house right off the campus grounds. Next to the cafeteria, it was the most interdisciplinary spot in the Palace, a fruitful place where the usual boundaries dropped away, and the talk flowed freely.
I rarely went there, but late one afternoon, several months after my separation from Agu had been formalized, I stopped by on a psychic hunch. With my new baby tucked securely into a carrier strapped on my chest, I certainly didn’t feel very glamorous or sexy. But I had a premonition as I climbed the stairway to the main room that I was about to meet someone very interesting.
I found myself gravitating toward the end of the bar, where two young, good-looking postdocs were holding forth. A few flashes of friendly eye contact passed between us, and I could tell that they had recognized me. “That’s Candace Pert,” I could see one mouth to the other. Soon we were all talking.
Michael Ruff and Rick Weber, I found out, had studied immunology in graduate school together, and were now getting some seasoning as postdoctoral students at the Palace. Mike told me later that he’d remembered seeing me on a TV science documentary, talking about how endorphins from the testes caused the orgasmic spasms of the vas deferens. I have to admit that my feminine ego soared as I contemplated playing the alpha, older, wise-woman scientist to these betas. But what really excited me was the fact that both guys were immunologists. Because I’d had an idea in the back of my mind for a long time—a notion that schizophrenia might be an autoimmune phenomenon—I’d been hankering for a congenial immunologist to grill.
Rick’s specialty was the study of the chemistry of antibody molecules, those spongelike substances made by certain immune system cells to recognize and eliminate invading pathogens (disease-causing agents) that threatened the organism. Rick was eloquent in his description of how these antibodies vibrated and changed shape as they encountered the bacteria, virus, or tumor cells, latching on to them and escorting them out of the system. We all had a good laugh when he described the scene in the movie Fantastic Voyage where Raquel Welch enters the bloodstream and is engulfed by a swarm of antibodies, each perfectly shaped to cup on to her amazing breasts.
Michael, who seemed quieter, more reserved, was interested in the cellular portion of the immune system, in particular the highly mobile scavenger cells known as macrophages, whose function is to keep the blood clean of debris left over from the battle to kill invaders. He talked about how “eating dirt” was but one function of these cells. They also played a key role in repairing the body fabric, manufacturing tissue when needed and orchestrating a chemical and cellular cascade that resulted in a healing response. Michael was beginning to question how they did all of this without some ability to communicate with each other or with the rest of the body—a concern that didn’t bother other immunologists in the least.
Like Michael, I, too, had some radical ideas stewing on the back burner of my imagination. One of these involved my hunch that schizophrenia might be the result of an autoimmune response, which is what we call the phenomenon in which the immune cells go awry and attack part of the organism itself rather than the invaders they are supposed to attack. In schizophrenia, I theorized, the immune cells were secreting antibodies that targeted brain cells via their receptors. Throwing caution to the winds, and trusting my sense that Mike and Rick were young and open enough to follow me, I put it right out: “I want to find a real cure for schizophrenia,” I announced, noticing their attention shift rather dramatically. “My idea is that the disease is caused by antibodies being made against the brain-cell receptors.”
There was a thoughtful silence as they pondered this possibility.
“Do you guys know if there’s a way to test this?” I asked more tentatively.
We agreed on the spot to explore the hypothesis. A first step would be for me to teach them brain-receptor science and for them to teach me immunology, a project we began that afternoon in the bar! I didn’t know it then, but the deal we had just struck marked the beginning of a collaboration that would bear much fruit by merging our two fields to bring about a new approach to healing and disease. The research we would do would circle out from schizophrenia, leaving it temporarily behind as we explored the connection between nervous and immune systems, mind and body, as it pertains to cancer and AIDS, returning only years later to the question of schizophrenia.
Soon after our meeting at the clubhouse, the three of us took to hanging out together. One afternoon, we were bouncing up and down in Rick’s open Jeep when he pushed a journal reprint toward me.
“Look at this, Candace,” he said. “It’s written by my buddy Ed Blalock from the University of Texas.”
“What is it?” I asked, since I was jiggling around too much to be able to read the title.
“He’s found immune cells that make endorphins.”
“Really?” I said, hesitating while I let this astounding piece of information settle into my consciousness. “Does this guy know what he’s doing?”
“It looks rock solid to me,” Rick responded. “Read it yourself.”
Rick pulled the Jeep over, and with both him and Mike leaning over my shoulder, I read the paper. Blalock, an immunologist who had been in graduate school with both Mike and Rick only a few years earlier, had been studying interferons, peptides that are made by certain white blood cells known as lymphocytes. Like antibodies, interferons have the job of fighting off invading pathogens and thus help to preserve the integrity of the body. In his studies, Blalock noticed that interferons sometimes mimicked the activity of hormones, an observation that prompted him to put the lymphocytes in a dish and stimulate them to produce interferons, so that he could see if they produced anything else at the same time. To his shock and surprise, he found the lymphocytes were also secreting the mood-altering brain peptide endorphin, as well as ACTH, a stress hormone thought to be made exclusively by the pituitary gland, the main gland in the endocrine system.
“My God!” I exclaimed. “If this guy’s right, it makes the immune system look like a floating endocrine system, a bunch of tiny pituitary glands!”
In our excitement, we jumped rapidly to a possible conclusion: The immune system was communicating not only with the endocrine system but with the nervous system and the brain, as well, by using a chemical mechanism that consisted of the neuropeptide endorphins and their receptors to code for information. But there would be many steps—and about two years—between formulating this hunch and feeling confident enough about it to put it in print.
As the news of Blalock’s discovery spread, very few of my colleagues shared my enthusiasm. They either ignored Blalock or dismissed him as wrong. This was to be expected. Whenever something doesn’t fit the reigning paradigm, the initial response in the mainstream is to deny the facts. To suggest that systems historically defined as separate were actually interrelated was paradigm-busting at its best! For a while after his discovery, wherever Blalock went, he heard the whispered charges: “Sloppy work! Artifact! Dirty test tubes!” And they kept up until the number of labs that had repeated Blalock’s observation grew too great to ignore. What he had seen was no “artifact,” that is, something that was a product of the experiment itself. Finally, in 1983, an editorial in Nature admitted the presence of brain peptides in the immune system, but warned the scientific community against those “radical psychoimmunologists” who might prematurely interpret this work to mean that “no state of mind exists that is not reflected by a state of the immune system.” Rick, Mike, and I embraced the moniker with pride, proudly referring to ourselves as radical psychoimmunologists from then on.
But even while the weight of the evidence compelled Blalock’s critics to accept the data, those critics still had no intention of addressing how that data challenged the ordained view of the body.
As a budding radical psychoimmunologist who didn’t think twice about disregarding traditional boundaries to get at the truth, I immediately plunged into extending and exploring the implications of Blalock’s work.
Michael, whose home base was the Dental Institute over at the NIH, moved into my lab temporarily so we could do the work together. Rick joined us frequently. The first idea we investigated was that if the immune cells were secreting endorphins, there were probably opiate receptors on the immune cell surfaces. I knew there had been numerous papers published claiming to show opiate receptors on immune cells; one was even written by Pedro Cuatrecasas, my former teacher at Hopkins. He had found opiate receptors on immune cells using the traditional grind-and-bind method to isolate the receptors, but his paper, as well as several others, had been ignored because of various anomalies. Again, this kind of finding was far out in front of what the current paradigm accepted. Receptors for brain peptides on immune cells? What could that possibly mean? You’d have to have been some kind of radical psychoimmunologist—a scientific category that didn’t even exist when Pedro wrote his paper—to be interested!
We decided to take a more compelling route, one that would be harder for our colleagues to ignore. We would prove our hypothesis through what is called a “functional assay,” one that would elicit a specific and measurable activity, rather than one that simply showed the receptor. The main question we asked was: What function of the cell changes as the result of binding?
As part of his work on tissue inflammation at the Dental Institute, Michael had studied a process known as chemotaxis, the ability of a cell to pick up the “scent” of a peptide by the receptors on its surface, literally getting on its track and traveling toward where the peptide was most concentrated until it could bind with the peptide, whereupon the peptide commences its job of ordering the cell’s activities. We decided to use chemotaxis as a tool to demonstrate the action of opiates and their receptors on immune cells.
To do this, we chose ten different opiate drugs, including the various endorphins, and showed that immune cells chemotaxed to them in the same order of relative potency that they bound to the receptor. Later, we extended this work and showed, using the same method, that there were receptors on immune cells for virtually every peptide or drug we had identified in the brain, such as Valium, Substance P, and many others.
We published our findings and moved to the next logical question, which was the inverse of the one we’d just answered: If there were neuropeptides in the immune system, would we find immunopeptides in the nervous system? Finding brain correlates of peptides that had originally showed up in other parts of the body was what our lab had been doing for years, and so we decided to take a look. This time, working with Mike and another immunologist, Bill Farrar, a collaborator from the Cancer Institute, I chose interleukin-1 as our first target immunopeptide.
IL-1, as it’s known in the jargon, is a polypeptide hormone produced mainly by macrophages in the immune system, and is one of fifty or so identified peptides that mediate the inflammatory reactions caused by injury, trauma, or an activated immune system. In a molecular cascade, IL-1 causes fever, activates the T cells, induces sleep, and puts the body in a generally healing state of being, allowing it to mobilize its energy reserves to fight pathogenic intruders with maximum efficiency.
Sure enough, there were interleukin-1 receptors in many areas of the brain, the second immunopeptide receptor found there. (The first to be discovered was Thy-1, short for thymus, and Rick Weber and Joanna Hill and I had done the autoradiographic mapping that showed its distribution pattern in the brain.) We weren’t at all surprised, but the immunologists, who had previously known only about the presence of Il-1 receptors in the hypothalamus, where they had long been recognized as a cause of fever, were quite puzzled by the finding that Il-1 receptors were also in the cortex and higher brain centers (mainly on glial cells and the tough membranes around the brain). Today we know that numerous—perhaps all—of the peptides discovered by immunologists can be made in the brain under some circumstances, and can act on receptors in the brain.
What we were now seeing was astounding and very revolutionary. The immune system was potentially capable of both sending information to the brain via immunopeptides and of receiving information from the brain via neuropeptides (which hooked up with receptors on the immune cell surfaces). Our work confirmed Blalock by pointing irrefutably to the existence of a chemical mechanism through which the immune system could communicate not only with the endocrine system but with the nervous system and the brain, as well. Previous work my colleagues and I had done demonstrated quite convincingly that the brain communicated with many other bodily systems. But the immune system had always been considered separate from the other systems. Now we had definitive proof that this was not the case.
POTENTIAL
It was in the spring of 1983 that Michael and I decided we were in love. The many hours we spent working closely together in the lab had certainly contributed to this happy state, but ours was more than an intellectual merger. We had recognized something in each other that promised a new direction, a common quest based on a desire to step outside what was ordinarily accepted and bring forth something greater, both personally and scientifically. This became our bond, which was to serve us well in the coming years when nothing we would do would be possible without the support and strength we gave each other.
I remember the moment I realized that Michael and I had a future, although never in my wildest imagination could I have guessed what that future would hold. I had taken to hanging out with some frequency at the clubhouse, often meeting on a casual basis with Mike, Rick, and other friends. Mike had been away from the lab for a week, and on his first day back had arranged to meet me at our usual corner for an informal update on the work we’d been doing together. I looked up as he slid into the booth and noticed his eyes were wider, more clear and deep, and he seemed present in a way I hadn’t notice before.
“Wow, Mike, where have you been?” I couldn’t help myself from asking. “You look like a different person!”
He smiled and in his low-key way proceeded to tell me that he’d been at a week-long bioenergetic workshop.
“It was great,” he responded enthusiastically. “We did all these exercises and made all these noises. I can’t believe how much better I feel!”
Bioenergetics, he went on to tell me, was a kind of alternative therapy that had been created by Alexander Lowen and inspired by Wilhelm Reich. Now, this was hardly a subject you’d expect to hear two Palace denizens deep in conversation about, especially since Reich had been banned from the realm of “real science” for his wild and crazy experiments with human sexual energy—but I was fascinated and pressed for more details. Bioenergetic therapy, Mike continued, made use of various physical postures and exercises to access deeply stored emotional traumas or blockages. The theory was that these emotions are trapped in the physical body and can only be released physically, through movement accompanied by loud, emotive expressions. The result was a freer, more abundantly flowing sense of energy, something I was certainly seeing manifested before me in Mike’s transformed appearance.
As we talked, I shared with him some of my own formal and informal personal excursions into the mind-body experience. One of these had occurred in 1977, when I took Est training at the recommendation of a colleague at NIH. Est personal-growth seminars were popular in the seventies, and were presented as a two-weekend affair with as many as two hundred people crammed into a hotel banquet room, literally sequestered for long stretches of time with few breaks. Although I had a lot of skepticism at first, I decided to throw myself into the training, intending to get the full experience and then make up my mind afterward. A team of sensitive if domineering trainers led us through the paces, from guided visualizations to confrontational dialogues, and on to mind-boggling explorations into the nature of reality. At one point, I witnessed a woman’s physical body change. As she re-experienced an incest trauma buried for years, the hunched shoulder she’d had since childhood appeared to spontaneously transform itself, healing before our eyes.
