Molecules of emotion, p.13
Molecules of Emotion, page 13
ENDORPHIN HIGH
My immediate superior in the early days at the Palace was Dr. William Bunney, head of the adult psychiatry branch and former director of the National Institute of Drug Abuse, whom I had first met two years earlier at the Hopkins press conference announcing the discovery of the opiate receptor. Dr. Bunney occupied an opulent suite, furnished with furniture and fine art he himself had purchased, a few floors above my lab. In a weekly ritual, I would ascend to his spacious office and deliver the update on my research projects. Dr. Bunney had a calm and clipped style that perfectly fit the Hollywood image of the classic psychiatrist, and he listened intently as I reeled off the week’s findings. He always wore a dark, pin-striped suit, which, I imagined, was one of dozens of identical ones in his closet at home.
Biff, a nickname I eventually felt comfortable using, had risen to his position within the Palace hierarchy by showing that lithium was an effective drug for manic-depressive psychosis. When I first arrived, he controlled a large corner of the funding empire through the NIH’s National Institute of Drug Abuse, an organization that had come into existence simultaneously with the opiate-receptor discovery. The purpose of NIDA was to support research that it was hoped would one day lead to the development of drugs to cure addiction.
Biff’s very first question took me by surprise. I was in his office for my weekly report when he leaned forward, looked me straight in the eye, and said in a flat, dry voice, “Do you realize, Candace, that for a heroin addict the first intravenous injection hits the brain like a sexual orgasm?”
“Gosh, no, Dr. Bunney, I didn’t,” I responded uncomfortably.
Biff explained that he believed the pleasure experienced during orgasm was accompanied by a surge of endorphins—the term that was being used to refer to Hughes’s enkephalin—into the bloodstream. Now, that caught my attention, as did any idea that might explain the influence of the opiates and how they worked to produce pleasure and relieve pain. Soon I was designing a test that could measure levels of endorphins in the blood and running a series of experiments to determine which kinds of behavior made these levels go up, and which made them go down.
My investigation of this question spanned a period of almost two years. We used hamsters for one study, the classic lab animals for studying sexual behavior because of their predictable cycle of sexual behavior—two minutes of licking this or that, three minutes of humping, etc., and the act was complete. The males are extremely prolific, ejaculating about twenty-three times per cycle. Later, we were joined by Nancy Ostrowski, an accomplished scientist who had left behind her desire to become a nun and gone on instead to become an expert on the brain mechanisms of animal sex. Nancy would inject the animals with a radioactive opiate before copulation, and then, at various points in the cycle, decapitate them and remove the brains. Using autoradiographic visualization of the animals’ brains, the two of us were able to see where endorphins were released during orgasm, and in what quantity. We found that blood endorphin levels increased by about 200 percent from the beginning to the end of the sex act.
With our newfound method of measuring endorphins in the blood, all kinds of other projects were now possible. We explored the question of how exercise affected the release of endorphins when I recruited twelve young Palace psychiatrists who were serious runners to let us take blood samples before and after their daily runs. The results showed a definite increase in endorphin levels, but the assay crashed at a few key moments, causing us to lose the precious samples that my subjects had literally sweated to produce. Nothing much came of these studies until Peter Farell, an exercise physiologist from outside the Palace, pulled a paper together that made use of my expertise, but was based mostly on his own efforts. He generously made me a coauthor of the paper, which was the first published study to provide the physiological validation of the phenomenon we now know as “runners’ high.”
My next project was the obvious biggie, the human-orgasm experiment, which presented a challenge in both recruitment and design. Since it wasn’t possible to have a technician present to draw blood at the ultimate moment, we had to settle for measuring the endorphins in our subjects’ saliva. Our subjects consisted of friends, as well as Agu and me, all of us agreeing to chew parafilm (which generates saliva) at various moments during sexual intercourse and then to spit into a test tube.
While enjoyable to do, these experiments were ultimately considered failures from a Palace point of view, because the results, suggestive as they were, lacked sufficient clarity to be written up and accepted by a medical journal. The work did produce a number of very interesting abstracts, which were presented at some early neuroscience meetings and were, understandably, very popular. But the idea that human orgasm is accompanied by the release of the organism’s own pleasure chemicals has never quite seen the light of day in a prestigious journal.
SUCCESS
And so it goes, month after month, planning experiments, brainstorming with your postdocs, and gathering data with an eye to publication. I was usually a pushover when it came to believing that data. If it looked crisp, and if, after massaging it this way and that, my gut reaction was still affirmative, I’d give the green light for a paper to be prepared. Most lab chiefs were just the opposite, making their postdocs repeat experiments ad nauseam, terrified of attributing truth to something that turns out to be a trick of the numbers, or an artifact—an error created by the method, which leads to a false conclusion.
But when the data held true, and it looked like we’d uncovered a legitimate piece of the picture, then we’d move ahead to getting it in print. As I said earlier, we scientists measure our success in terms of papers—how many we’ve published and where they’ve appeared, in journals considered top of the line, middle of the list, or bottom of the barrel. That, in a nutshell, is what scientific life is all about. The pay is comfortable but not spectacular, and the only real glory comes from seeing your name in print under the title of a paper. Even more thrilling, at times, is seeing your work cited in another scientist’s paper, which is significant because it affects your status in the professional hierarchy. Your position is determined by a huge database called the “citation index,” a listing of every paper that has ever been referred to in another paper, ranking each paper according to the number of times it has been cited. For many years Sol has been the very top-cited scientist in biomedicine! For one ten-year period, my ranking was 130 among the most highly cited scientists in the world.
The percentage of papers that get cited more than a few times is very small, and for this reason everyone always refers to their own previous papers as much as is practically possible. Because appearing in print is so important, and because modern scientific projects can involve several collaborators, more bitter and intense arguments arise over the order of authorship on a paper than over the thorniest of theoretical issues. As was the case with the opiate-receptor paper that Sol and I published, the first author cited is generally the person who took the lead in designing and implementing the experiment. Then come the names, in descending order of importance, of all those who participated, either by advising or assisting, sometimes as many as ten or fifteen names. The last name to be mentioned is the person who either runs the lab or has raised the money to make it all happen. Traditionally, the names of the technicians who do all the actual lifting and hauling are left off of papers, but I always thought it was the decent thing to do to include them on my papers. I was also glad to let my postdocs take the first-place position, especially if the paper was an important one. I had learned from my work with the opiate receptor that first authorship on a key paper could go a long way toward assuring a person’s career.
It was this name game that was partially responsible for my own swift rise to the top, and would soon be a pivotal element in an unfolding drama that would completely change the course of my career.
In a prophetic glimpse of things to come, John Hughes had dropped by my house for a casual visit in the spring of ’78. As we sat out on the back deck sipping cool drinks, he turned toward me and asked rather abruptly, “Candace, have you ever heard about an award called the Lasker?”
“No,” I responded. “What’s it for?”
“Well, it’s kind of an American Nobel Prize, given each year to scientists who have done outstanding medical research,” Hughes explained. “In fact, the scientists who receive it usually go on to win the Nobel. It’s sort of a stepping stone.”
Now he had my attention. I knew the Nobel was the biggest prize in science, but I hadn’t a clue as to how the scientists who won it were selected.
“What if I told you that Hans, Sol, and I were about to receive this year’s Lasker for the opiate work?” John asked.
It took a moment for his words to register, but when they did, I blurted, “You’ve got to be kidding, John! And leave me out? Why, I’d be furious, of course!”
6
BREAKING THE RULES
INVITATION
Science in the big leagues is a lot like what goes on up at the basket at the NBA play-offs: very competitive, with sharp knees and elbows flying hard and fast. As individuals vie fiercely for credit, everyone knows you have to take care of yourself, because no one else will. The exception, of course, is your scientific family, your collaborators, whose job it is to watch out for you, scratch your back, and see that you get a chance at the basket when it’s your turn.
While I found the game thrilling to play, I had not been sufficiently conditioned to accept the code of loyalty that it demanded. In a series of events that caused me much heartbreak and earned me much notoriety, I broke the rules and was dealt the cruelest of punishments, alienation from my scientific family. Later, in a popular book entitled Apprentice to Genius, Robert Kanigel would make a dramatic case for how I’d embarrassed a most royal medical dynasty, although this had never been my intention. In retrospect, I can see how my actions were part of a greater force at work to bring about a major shift from old-boy rule to a more egalitarian system.
It all began in the fall of 1978, when Sol Snyder, John Hughes, and Hans Kosterlitz were recognized for their opiate receptor/endorphin research and received a prize nearly as prestigious as the Nobel, the Lasker Award. My name wasn’t mentioned.
John Hughes had tried to tip me off when he paid a friendly visit to my home the summer before the awards ceremony in October. But I was so stunned when he mentioned that the Lasker might be given to him and the other researchers, that I blocked all further conversation on the topic. Later, I realized that John had tried to alert me to what was already in the works, so that if I had wanted to do something about it, I still had time. But I was so naive politically that I chose to stick my head in the sand and reject the possibility that such a scenario would ever take place.
I didn’t give it another thought until some months later, when I got a phone call from Sol, inviting me to a luncheon in New York City.
“Hello, my little baby girl,” he cooed affectionately, with the usual politically incorrect term of endearment I had tolerated with mixed pleasure and horror for nearly seven years. We chatted briefly, and then he announced, an audible tension coming into his voice, “Candace, I’m receiving an award in New York City next month, and I want you to be one of the five invited guests I’m allowed to bring.”
Although I’d been away from Hopkins for over a year, I was still flush with gratitude for Sol’s help in procuring for me a lab and a position as staff scientist at NIH, and I was thrilled that he would think to invite me to this obviously important event. He then mentioned that two other scientists were receiving the award with him, but failed to mention what it was for, or who the other two were.
I hung up feeling pleased, but in the back of my mind an uneasy question surfaced. Sol had been unmistakably uneasy in extending this invitation, and I wondered why the Golden Boy, the wunderkind of neuroscience, would be afraid of asking his former graduate student to a luncheon where he’d be receiving an award? It took only a few seconds for the answer to hit me square between the eyes. The Lasker Award! The one John Hughes had talked about! This is what he’d meant, that he and Kosterlitz were to join Sol in receiving the Lasker Award for the opiate receptor and endorphin findings, the very work I had played such a pivotal role in. And now Sol was inviting me to the awards luncheon as his guest!
My heart had already begun to pump furiously, even before my brain got the full news. I picked up the phone and dialed Sol back.
“Sol,” I said, barely concealing my anger, “do I understand that you, Hughes, and Kosterlitz are accepting an award for our work on the opiate receptor, and I’m not included?”
Taken off guard by my rawness, he admitted, half-apologetically, that, yes, it did seem strange, but that’s how these awards things went, they were unpredictable, not always going to the person you’d expect. And anyway, he assured me, it was too late to do anything about it now. To make it up to me, he would see that I stood up for a bow at the awards luncheon, which he thought I would enjoy, he told me, since Ted Kennedy would be presiding over the ceremonies at the famed Rainbow Room, and I’d have a chance to meet him.
I hung up again, and tried to see things from Sol’s point of view, but I could not put my rage to rest. The idea that I would be sitting in the audience while he and the others were honored for the work that I had played such an important part in seemed blatantly unfair. Was I really expected to stand down for my part in what had turned out to be a tremendous discovery, one that in the few short years since it occurred had been reshaping the entire field of the neurosciences? No, I resolved, this was not something I could watch happen. But what could I do?
DEEPER ISSUE
At the time all this took place, I had been reading several books that greatly influenced the development of my thinking and feeling. They were biographies of Rosalind Franklin, the brilliant scientist who had provided the critical link in the chain of reasoning that allowed Francis Crick and John Watson to show that the DNA structure was a double helix. As a result, the two men beat Linus Pauling to the punch and bagged themselves a Nobel in 1962. Franklin was a classic science nun whose life was totally given over to her work, and in Watson’s book, The Double Helix, we get to see how these women were viewed by their male colleagues. The contempt all but bleeds through the pages, as Watson justifies his and Crick’s actions in a graphic example of unabashed sexism in science.
But the truth of the matter is, the two men visited Franklin’s lab when she was out of town and persuaded her boss to let them take a peek at her data. In what must have been a moment of incredible rationalizing, they stole Franklin’s findings and got away clean, tossing her a bone of acknowledgment in their seminal paper, which won them the biggest award in science. In his best-selling book, Watson actually boasts about the theft, deriding their colleague for withholding her findings for publication in her own paper, which came out in the same journal—Nature—where theirs had appeared just a few months later. At the time, no reviewer, to my knowledge, cried foul, although in later years some heroic attempts at correcting the record were made.
To say I was livid about Rosalind Franklin’s plight is an understatement. Even more, the tale of this outrageous deception deepened my appreciation for all the women who had been my teachers. I no longer saw them as second-class scientists who had failed to achieve status as lab chiefs and had settled instead for academia. I now realized that they were the pioneers who, if I were ever to run a big lab, I could thank for trailblazing the way, enduring the rampant sexism of their male colleagues in order to level the playing field for future generations of women in science.
But even while I acknowledged the debt I owed to these women, I was appalled at how little had changed since their time. The deeply ingrained bias against women surfaced often at meetings, especially at the quarterly study section, where we would review grant applications. Whenever my male colleagues came across a grant whose principal investigator (the “PI,” as we call the controller of the government green) was a woman, they would unfailingly amuse themselves by subtly conjuring up an image of the eccentric, asexual lady scientist. This was followed by a silent consensus concerning her scientific untrustworthiness, an assumption that reverberated around the conference table until, finally, the application was given an inappropriately low rating. Most interesting was the discussion about the budget section of these female-initiated grants. While grants with a male PI requesting twelve postdocs never raised an eyebrow, the grants with a woman PI asking for a secretary and extra technicians would be chewed over ad nauseam. Like the attack cry of a flock of ravenous birds, the word she was repeated incessantly during the deliberations—Why couldn’t she manage with less? I once amused myself by scientifically documenting this male pack behavior, carefully marking the number of times the pronoun was mentioned during one long afternoon session. My record showed that “she” was used nine times more often than “he,” in spite of the fact that grants involving female PI’s were rarer by far than their male-headlined counterparts. In as humorous a way as possible, I would try to point out the subconscious prejudice, but my words fell on deaf ears.
