What Do Women Want?: Adventures in the Science of Female Desire - Daniel Bergner (2013)
Chapter 9. Magic
Martina Miller, the coordinator, counted out tablets. Wendy filled out a questionnaire. She prided herself on efficiency, and she was efficient at this. She sat at Miller’s desk, facing photos of Miller’s carefree dogs in magnetized frames on a file cabinet. She removed the paper clip that fastened the questionnaire’s many pages, swiftly read each query, quickly checked the boxes beside her answers, straightened the pages by tapping them sharply—click-click—against Miller’s white enamel clipboard when she was finished, reattached the fastener, and passed the document back to the coordinator.
In return, Miller handed Wendy a new supply of medication. Red slacks, a canary yellow scarf with orange trim—Wendy radiated bright hues and optimism. She said thank you, gave a split-second’s giggle, zipped the pill jar into her glossy shoulder bag. But there was a glitch. Checking her computer, Miller pointed out that Wendy had been missing some of her reports, that she hadn’t been making an entry in her online diary every time she put a tablet on her tongue.
“I know, I know,” Wendy confessed. “It’s a mess. I keep forgetting.” For two or three minutes, her upbeat armor cracked. There were no tears, only fear expressed in cheerful tones, as she stopped in here at a center for sexual medicine in a Maryland suburb. Soon she would be outside, in her car, in the sun, away. She would be driving through the May afternoon to her ten-year-old daughter’s lacrosse practice. But now she explained to Miller that she’d taken the drug, felt nothing, done nothing with her husband, fallen asleep and ignored her diary the next day, with only failure to record. She hoped her first round of pills had been placebos.
Answering ads on the radio, in newspapers, on Craigslist, the women had arrived to enroll in the trials all fall and winter. I’d watched that stage of the process at another clinic, near downtown Washington, DC. The tiny drug company, Emotional Brain, had enlisted centers all over the country, clinics run by psychologists and gynecologists and everyday physicians, some taking part just because medical trials were a facet of their practice, others because they believed that EB’s inventions, Lybrido and Lybridos, might prove distinct enough from the earlier chemicals of other companies, might be ingenious enough in their composition and precise enough in how they would be prescribed, to be the first aphrodisiacs to make it past the FDA, the first to give doctors something, something reliably successful and government approved, to offer women like Wendy.
“They use terms with real emphasis, words that are violent,” Andrew Goldstein, who ran the DC center, said about his patients. The light in his office was soft. A close-up photograph of a cherry tree hung opposite his diplomas. “This is like someone cut off my arm; this is not how I see myself; this is like something’s been ripped away from me. Stripped away. Stolen.” He was among the most prominent gynecologists in the country, the president of the International Society for the Study of Women’s Sexual Health. And he was all but exultant. He didn’t stand to profit financially if the data from the trials panned out, if the two drugs outperformed the placebo, if the side effects were mild, if the FDA gave its blessing. He’d signed on for trials of other medications, molecules aimed by pharmaceutical giants at the same despair, the feeling of desire’s vanishing, aimed at the same market, worth over four billion dollars a year in America alone. Then, for the past two years, he’d taken a hiatus, out of frustration. But Lybrido and Lybridos had rekindled his hope. He sensed solutions. And it wasn’t only that. EB’s diagnostic method, its gleanings of the genetic and the learned through blood work and interviews and its algorithm that compiled and processed these gleanings, would allow new glimpses into women’s sexual brains.
“The tools we’ve had up till now have been like flint knives.” His field’s wherewithal, for comprehending, for treating, had been blunt, crude; it had belonged to the Stone Age. As we talked between his screenings of possible subjects, he wore a blue and white pin-striped shirt, a white lab coat. His voice was scratchy and high. He had a cherubic face and full gray hair, so that he looked sometimes childlike, sometimes stately. The gray seemed to disappear when he spoke about EB’s algorithm, its pills. “God bless! This is fine-tuned!”
If EB turned out to be on target, he said, there would be fantastic changes, specific, vast. He would have a drug to help a subset of his patients, women whose antidepressants suffocated their desire. He would have a way to understand one of the conundrums of his field: why birth control pills snuffed out sexuality in some—but far from all—women. He would have something much more accurate than the current blurry grasp of testosterone’s effect on female libido. And more than anything, for all sorts of women, he would be able to restore what they felt had been torn away.
An African-American law student who, after five years with her boyfriend, couldn’t trick herself into the wanting she’d once felt, could only trick him. “I use a lubricant, so he doesn’t know,” she told Goldstein, as he interviewed her for EB’s pools. A divorced mother of three who sensed herself, with her lover, slipping into a sexual indifference that was familiar from the demise of her marriage. “When we split up,” she said about her ex-husband, “it was like going through a second puberty. So I attributed what had gone missing to who he was.” She gave some attribution as well to her children, the energy they drained away, the physical and occupational therapy appointments her disabled son needed each week. But with the indifference returning, she was starting to doubt those attributions, starting to wonder if it was something about herself. A bank officer who, answering Goldstein’s questions about her past, mentioned where she’d met her husband. “It was at Nashville International Airport.”
“How’d you meet him at an airport?” This sort of detail didn’t matter at all to EB in deciding who to enroll in its trials, but Goldstein was that kind of doctor. He liked to get to know the women who sat across from his desk, even if they weren’t his patients, even if they would only be in and out of his office a few times over several months, to pick up tablets and answer follow-up questions, even if they would be gone forever after that.
“I was a screener,” the bank officer remembered. “I was in college, and I was a part-time screener. I was coming back from lunch in my uniform, and he was looking at me, and I said, It’s not polite to stare at a woman without saying hello. I turned around, and he followed me.”
“Obviously he had something to say.”
“Obviously,” she said, and she and Goldstein laughed together.
“How long did you date?”
“It was extremely fast. June we met, March we married.”
And for years, even with young kids, she’d felt that speed, that sense of something predestined; she’d counted on the rush of their combined bodies. Now, in her late thirties, all happened slowly, all waited at a receding distance. Often she faked her orgasms.
“When he initiates sex, do you feel anxious?”
“I try not to show it.”
For every woman who wanted to enroll, there were a range of reasons. There were the demands of law school, the disabled son, a self-consciousness about added weight, a fibroid surgery that seemed to have caused damage, though a neurologist could find no loss of sensation. “When he plays with me, when he tries to jump start me down there, I don’t feel it, I don’t understand,” the bank officer said. “That’s why I need to be in this study.” There were lots of factors, always, Goldstein told me. But as I listened, it sometimes seemed there was only one. There was no ripping away, no theft; nothing violent had occurred; there was only a leaving behind. Time had passed. Desire was back there. That was all. That was violent enough.
Lybrido, Lybridos, the pharmaceutical efforts that had come before them, the inestimable millions or billions that the industry had poured into research—the race was for a drug to cure monogamy. This was the main demand, the market with the biggest potential payoff.
“I just want to know,” one woman asked at the end of her interview, after describing the man she’d spent the past seven loving years with, “is this medicine going to work? Am I going to get my freak back?”
In her front yard, one May evening two years ago, Wendy sat with her neighbors on lawn chairs. Behind the women, their houses stood quiet, modest, in matching brick; beside them was a portable fire pit on iron legs, flames breathing heat into air on a cusp between spring and summer. Their upstairs windows were opened wide, letting that air transform the rooms. Their children swooped on a rope swing behind Wendy’s house; their husbands were at an Orioles game; the women sipped their wine.
A beeper went off, faint, then louder, more insistent, bleating into the suburban calm. Wendy’s next-door neighbor sprang up. The study Wendy and two of the others were in that year worked a bit differently than the EB trials; electronic diaries, logs of sexual acts and feelings, were to be updated every day, and Wendy’s friend sprinted inside to silence the company’s automated reminder before it began screaming across the neighborhood. They were taking Flibanserin. They tracked their responses for the company and talked with each other—and with their other friends at the fire pit, who were monitoring their progress—about whether the experimental pill was working. They wondered together what the odds were that two or all three of them had been given the placebo. They agreed, on evenings like this, or in the mornings, over coffee after putting their kids on the school bus, that whatever they’d been handed wasn’t having any effect, though one of them thought there might be a chance she was starting to feel something.
Intrinsa and Libigel, Flibanserin, Bremelanotide, these were among the defeated drugs that had come before Lybrido and Lybridos. Intrinsa and Libigel, a patch and an ointment, delivered infusions of testosterone—and within testosterone’s failure with the FDA were lessons about how little science had managed to sort out when it came to the biochemistry of women’s lust.
Somehow, by mechanisms still just broadly understood, testosterone primes the making and messengering of dopamine, the brain’s courier of urgent wanting. This priming happens within and right near the almond-sized hypothalamus, which sits down by the brain stem and helps govern our base drives and bodily states—hunger, thirst, lust, body temperature. Intrinsa and Libigel tried to influence the dopamine circuits that are devoted to sex by sending more testosterone through the blood to the brain.
Spiking dopamine directly, instead of using testosterone, can cause trouble. The techniques aren’t refined; the results can be a brain in overall overdrive, damage to the circuitry of motor control, severe nausea, a risk of addiction if you spike too often. And, Pfaus told me, testosterone might assist desire in ways that reach beyond dopamine by tweaking other crucial neurotransmitters. Given all this, a drug supplying extra testosterone seemed a promising approach. But there were baffling complications. They were known, to some extent, even before the testosterone aphrodisiacs went into development and into trials. Whether because testosterone isn’t the main primer after all, as some scientists argue, or because there is too much other biochemistry at play, the puzzle was this: add testosterone to a woman’s bloodstream, and you wouldn’t necessarily cause a rise in desire; deplete the hormone, and you wouldn’t dependably reduce libido.
Oral contraceptives, Goldstein said, launching into a lecture on hormonal confusion, could all but eradicate a woman’s blood-borne testosterone. “Birth control pill-takers have free testosterone levels one-tenth, one-twentieth of where they would normally be.” This situation hadn’t always been so drastic. Pharmaceutical companies had lately been fabricating contraceptives that pushed testosterone lower and lower to strengthen a sales-enhancing side effect—the elimination of acne. For plenty of women, the hormonal decimation didn’t seem to make any difference to desire. For some, the pill generated drive, probably, Goldstein went on, because women without worry of pregnancy, with lighter or less frequent bleeding, were more likely to seek out sex. But for others, oral contraceptives led to a crash in libido. Why were some women harmed by the bottoming out of testosterone, others unaffected?
Menopause added to the riddles surrounding the hormone. Middle-aged women and lots of their physicians tended to blame menopause for dissipating desire. Doctors gave out testosterone as a remedy—they gave it in a way known as “off-label,” unapproved by the FDA, semilegal. And some women reported successful results. Yet despite popular belief about the time of life when the hormone dropped, menopause didn’t actually bring a decrease in testosterone at all; instead, there was a slight rebound. In truth, a steady decline had taken place long before, when a woman was in her twenties and thirties. And the depth of the decline was no worse than what went unnoticed in uncountable women who took the pill.
Was there a way to make sense of any of this? Was there a way to draw tight links between the physiological—whether something as straightforward as a hormone count or as complex as menopause—and libido? With estrogen, possibly. Around menopause, loss of estrogen led, in some women, to dryness that could undermine desire—even though, if you hooked these women to a plethysmograph and played a pornographic movie, blood raced as it did in far younger subjects. The tissues just weren’t manufacturing as much fluid anymore when the blood flowed in. So the psychological pathways of desire were intact, but the chemical reactions responsible for wetness were impaired. And the tissues themselves could thin. This could lead to obvious problems: if intercourse was uncomfortable, you weren’t likely to want it; if it was downright painful, you would probably avoid it; either way, you might quit thinking about it; desire might be destroyed. Then again, something else was obvious, too: there were any number of other ways to have sex. But a deficit—immeasurable, maybe immense—was at work. Your mind wasn’t going to be hearing the messages of your genitals as well as it once had. And the communication could be tenuous to begin with. Chivers’s experiments had shown this; her subjects could seem deaf to what their genitals were saying. Lubrication was part of the language—with that diminished, the lustful messages might be more muted, the mind less prone to the awareness of desire, the brain and body much less easily caught up in a loop of yearning.
Yet there was the Australian study: on desire, new relationships trumped menopause, easily. And Goldstein spoke about how readily dryness and atrophy could be treated with estrogen supplements, with low and safe doses. Lubrication was restored, tissues regained health, but libido didn’t revive reliably. Stubbornly, the effects of hormones evaded logic. Sometimes desire seemed to hide itself from science.
He returned to talking about testosterone. He was among the thousands of doctors who provided it off-label, flouting the spirit if not the letter of the law. He didn’t hesitate to discuss this. He felt he had to do what he could for his patients. Women came to him after being dismissed by their family physicians, by other gynecologists. “If I had a nickel for every time a patient has said that her doctor told her, Just have a glass of wine.” He gave the hormone to women of all ages, though not indiscriminately—he used his own criteria, his own intuition, to try to figure out who it might benefit. He looked for low blood readings of testosterone, poorly predictive though he knew these to be. He weighed the histories he heard during his interviews, listened for the disappearance of erotic dreams. This, in his mind, was a telling sign: the evanescing of sex from the life of the unconscious. He dwelled on the clues he gathered, followed his hunches. He guessed that by proceeding in this way, he helped more than half the women he provided with the hormone. But that left a lot of his patients inexplicably unreached and a lot who didn’t qualify, by his calculus, for this treatment. And it left him reading dreams, practicing medicine by a system that was barely systematic.
This muddle, this imprecision, this inability to predict, lay within testosterone’s latest struggles with the FDA. In trials with a thousand women, a pharmaceutical company had collected data to back its product, Libigel. The product did seem to work—somewhat. On average, it made desire rise—undramatically. And yet in the trials, a fake gel, a placebo, had aided libido as much as the medicine. Self-persuasion seemed as potent as the drug.
Around the fire pit or after the school bus, the chatter about Flibanserin was light, filigreed with a joke or two, the way Wendy liked talk to be. Yet with her friends gone, after wine or coffee, she felt something insidious, a helplessness, a foreboding, a sense that she would be unable to protect—to protect what? Not her marriage, not quite that. She trusted that she and her husband would remain together. It was, she said, love that needed saving. It was—she used the simplest of words—“happiness.” She wrestled to prevent desire’s further and further withdrawal.
After college, she’d met her husband at a sports bar, laughed with him over a foosball table, laughed more later that night as he clowned, concocting his own dances. This was in New York, where she lived for a few years, intending to return home to the Midwest, to marry there, to build a life close to her family. But she found herself unguarded with him, without need of hiding, which was new. She admired “the way he could make fun without making anyone feel bad.” And there were moments almost too inconsequential to be described. They had gone to a video store one evening, stood in a crowd waiting for the clerk to set out a batch of movies—and when the film she wanted appeared, she paused before reaching, to let someone else take it. He said that he liked what she’d done, and so many years afterward she still recalled his plain and half-shy praise, the pleasure he’d taken in her gesture. Gradually, as they dated, she had grown entranced by him, thinking, when they were out with other couples, I just want to get home with him, I just want to get home with him. And then they had created a home together, inside the three-bedroom brick colonial, a life she had never regretted. It was only that she was scared.
Years ago in their house, she had seized his hand and hurried him up the stairs. Now she waited, somewhat like prey though the predator was tender, though he was cherished. “He’ll move closer to me in bed, or put his arm around me, or rub my back.” Once a week he tried to reach through the invisible barriers she built; once a week she tried not to refuse him. And like an indestructible machine, she climaxed regularly when they did make love, as she always had. But the next night she returned to being the person she’d become, the woman who willed herself to sleep or focused intently on her book as he climbed the stairs. It was impossible to understand, how those stairs had changed.
Unlike Libigel, Flibanserin tinkered directly with neurotransmitters, but its tinkering was too delicate. In trials, it didn’t do enough good to get past the FDA. Wendy and her friends had been accurate barometers. Other medications had other troubles. A few years before Wendy’s group got involved in such studies, a drug had arisen through happenstance. A team of University of Arizona researchers had been exploring a chemical as a sunless tanner, a compound that would fuel a set of pigmentation-producing cells in the skin called melanocytes. But when the scientists ran tests on a small number of men, they heard back from almost all with an unexpected response: sudden and stunningly rigid erections. And unlike the effects of Viagra, which were all about the hydraulics of the blood, the bronzer tilted the mind, left it reeling with lust. Viagra bestowed hardness where there was drive; the tanner, the researchers found, bestowed both.
No one was sure about everything the chemical did in the brain while it browned the body, but with each dose, the medial preoptic area of the hypothalamus, part of Pfaus’s “ground zero of desire,” sent extra dopamine coursing, for several hours, through gray matter. Not only did the appetite for sex shoot up, but the appetite for food was killed off. This fit with a known interconnection inside the subregions of the hypothalamus, with a relationship between the basic motivations: sex, food, sleep. If the desire for one gets overwhelming enough, the others stop mattering.
The company that bought the rights to the chemical believed it had something remarkable. It sculpted the compound, culling out what tanned and carving away what deadened the appeal of food, saving those effects for drugs to be developed later and concentrating first on sex. For a preliminary forecast of how well the medicine, christened Bremelanotide, might do, the company sent a box, via FedEx, to Pfaus, who sent the new molecule, via mini-skullcap, into his rats. The males sprouted erections at an extraordinary rate. This was good news for the company, given that Viagra and its chemical cousins don’t work for around one-third of impotent men. But what inspired corporate glee was the female reaction. The tallies of hops and darts, of head-pointings and prancings away, of climbing the hindside of a male and doing a demonstration hump—the utterances of I crave you in feminine rat parlance—soared.
Next the company turned to hundreds of women who lamented the state of their libidos. “I was one hundred percent into it.” They recorded their experiences in trials after absorbing Bremelanotide by way of a one-dose nasal inhaler. “I was tingling and throbbing.” “I was focused on sex; I wasn’t thinking about anything else.” “My climax was like it used to be.” “I was able to climax multiple times.” At the Maryland sex clinic where Wendy now got her EB pills, the psychologist in charge had also had high hopes for Bremelanotide. His center had taken part in those studies, and he remembered one woman inhaling the chemical, then sitting in the waiting room until she could have her vital signs checked for negative side effects. Overcome by metamorphosis in mind and genitals, she declared to everyone in earshot, “I’ve got to call my husband to make sure he’s home when I get there.”
The signs for Bremelanotide were spectacular. A major magazine put the drug on its cover with an illustrator’s vision of midtown Manhattan. Taxis had screeched to a halt. An orgy raged on hoods and windshields, on the roofs of buses, on the pavement of a traffic island.
But the snag, the Maryland psychologist recalled, was that some women weren’t celebrating in his waiting room; instead, a few were in his bathroom, vomiting in the stalls. Besides the bouts of nausea, blood pressure jumped in a small percentage of subjects. About halfway through the FDA process, with tens of millions still to spend on more trials, the company slunk away from its application, knowing it would never get approval for an aphrodisiac with those hazards. It had since moved on to studying an intravenous version, which didn’t seem to bring on queasiness or hypertension, though how many people would be willing to stab themselves with a needle for the sake of desire was a source of doubt.
And the company had always fretted about something else. In the initial phases with Bremelanotide, after seeing the randiness of the female rats, the euphoric reports pouring in from women, and the orgy on the magazine cover, company officials got frightened even as they were overjoyed. At meetings, Pfaus remembered, they anticipated that the drug might be too effective for the FDA, that the cover image of women splayed feverishly on cement, their legs hooked around strangers, would haunt the agency and scare it off. There was no telling whether the FDA would have raised the specter of sexual mayhem had the application reached a conclusive review, but the company huddled with researchers like Pfaus to ask if there were any data to suggest to the agency that the chemical’s impact would be “selective,” that Bremelanotide-sniffing wives and daughters wouldn’t “want to go off and do the football team.”
This resonated with what Goldstein recounted from his involvement with Flibanserin. In Flibanserin’s trials, he hadn’t taken his usual outsider’s role, interviewing women, dispensing medication. He’d been hired as an advisor by the corporation that owned the molecule; he’d been in on strategy sessions. “When you’re going to the FDA with this kind of drug, there’s the sense that you want your effects to be good but not too good,” he said. Too good hadn’t turned out to be Flibanserin’s problem, but, he explained, “There was a lot of discussion about it by the experts in the room, the need to show that you’re not turning women into nymphomaniacs. There’s a bias, a bias against—a fear of creating the sexually aggressive woman. There’s this idea of societal breakdown.”
With her yellow and orange scarf wrapped under her chin, Wendy told the coordinator—who was keeping information up to date after checking about the missing entries in Wendy’s EB diary—that she seldom fantasized about other men. Even passing images were rare. “I’m very attracted to my husband,” she said to me, a steely undertone just scarcely audible in her chipper voice. It was the kind of answer I’d heard from some, though far from all, of the women I’d spoken with, as if their feelings for their partners needed safeguarding, were better left unbetrayed, even in their minds. They seemed to adhere, consciously or reflexively, to timeless rules about the way women should and shouldn’t be. Did this take its toll on the sexual circuits of neurotransmitters, which, like all our circuitry, can be reinforced and augmented, or allowed to whither, throughout life? Did the narrowness of erotic thoughts attenuate the channels on which these thoughts travel within the brain, thin the ranks of neurotransmitters that flash along these paths, lead, in turn, to more constriction of thinking? Did the lessons delivered to girls about what is and isn’t natural, normal, leave these circuits less sturdy from early on? And broaden opposing tracks, channels of serotonin that rush to quell unacceptable impulse?
“I surreptitiously gaze at him from beneath my lashes as he stands in line waiting to be served. I could watch him all day. He’s tall, broad shouldered, and slim, and the way those pants hang from his hips.”
Wendy had just read Fifty Shades of Grey, the first book in the trilogy of erotica that was approaching, in America, twenty million copies sold, that was breaking records for weekly sales rates, that Wendy and so many others labeled and laughed about as “mommy porn.” It wasn’t her usual reading. She took in scenes like this as Anastasia, the heroine, recounts the beginnings of her sadomasochistic affair with Christian, his manner reticent and self-possessed, his fingers “graceful,” all of him “heart-stoppingly beautiful.”
“ ‘Does this mean you’re going to make love to me tonight, Christian?’ ”
“ ‘No, Anastasia, it doesn’t. First, I don’t make love. I fuck … hard.’ ”
And, soon, like this:
“I come instantly, again and again, falling apart beneath him as he continues to slam deliciously into me.”
And, later, like this, with Christian commanding her, “ ‘Hold out your hands in front as if you’re praying.’ … He takes a cable tie and fastens it around my wrists, tightening the plastic. ‘Hold onto the post,’ he says… . He stands behind me and grasps my hips… . He smacks me across my behind with his hand… . ‘Part your legs.’ … He reaches over me and grabs my braid near the end and winds it around his wrist to my nape, holding my head in place. Very slowly he eases into me, pulling my hair at the same time… . His other hand grabs my hip, holding tight, and then he slams into me, jolting me forward… . I grip the post harder… . He continues his merciless onslaught… . My scalp is getting sore from his tugging my hair… . I fear my orgasm… . If I come I’ll collapse… . His breathing harsh … slamming really deep … my name on his lips… . I become all body and spiraling sensation and sweet, sweet release, and then completely and utterly mindless.”
While Wendy read on her iPad, a storm knocked out power on her block for a week; this jumbled her family’s routines and left them sleeping at a neighbor’s house, so there was no telling, she said, whether the book would have accomplished what Flibanserin and her first set of EB pills didn’t, whether some of the quickening it caused would have seeped into her feelings for her husband. That week, her life was too much of a mess. She guessed that Fifty Shades would have accomplished something, if the circumstances had been different—maybe not all she hoped for from the drugs, but something.
Meana—as Christian’s self-possession gave way to “groaning,” “slamming,” and as Anastasia, bound, bent, became purely object—lay close. But I was thinking of Pfaus’s perspective. “Dopamine, dopamine, dopamine,” he said about the book’s impact. “Fifty Shades is activating the whole neurochemical soup of wanting.” For Wendy, it was like a series of injections, lasting hours, into a mind that habitually kept fantasy and its neural effects at bay.
And Pfaus added, “Dendrites.” These are the gossamer-like tentacles that link neural fibers in our brains. Our experiences can make these tentacles grow more dense, just as plant life thickens in rich soil, and this flourishing, he explained, means “neural networks are enhanced, more sensitized, more capable of being activated.” It was possible to imagine that if, for Wendy, devouring the book led to devouring the trilogy, and if this led to more fantasy, if men on the street with fabulous shoulders and hips induced flares of lust, then, over time, “dendritic arborization” might increase and Wendy might find herself at least a bit more eager for her husband, even if his shoulders weren’t as broad and his hips weren’t as slim and his fucking wasn’t as fierce or as new as Christian’s, and her name on his lips didn’t bring on vertigo.
“Yes,” Adriaan Tuiten said, he thought often about reinforcement and neglect, about the bolstering or weakening of the circuits of desire, as he developed Lybrido and Lybridos. He was the founder of Emotional Brain. He was a Dutch researcher in his late fifties with a doctorate in psychopharmacology, whose shirt collars were skewed, whose hair was rumpled, whose dishevelment was half style and half disarray. We met periodically when he was in New York to check on the trials and to sell partnership rights and raise millions for the studies the FDA would still require. He was putting everything into getting past the American agency before its European equivalent; it was too expensive to do both at once. As we walked through Manhattan or leaned over coffee, he railed sometimes that back in the Netherlands people were rifling through his garbage. International companies, vastly larger than his own outfit of forty, were sending spies to get hold of his secrets. They were hacking into EB’s computers. Behind his chunky, tinted glasses, his eyes filled with anxiety. He seemed to be, now and then, on the edge of paranoid, crazed. But how crazy were his suspicions? So much money was at stake. And scientists like Pfaus, whose rats hadn’t been enlisted by EB, but who knew the field perhaps better than anyone—who had a small advisory role on Lybrido and Lybridos but no monetary interest in EB’s success—said that Tuiten could well be the one.
Yet when Tuiten spoke about the conception of his drugs, the germ of his ideas, a story of scientific ingenuity and monumental potential profit came down to a young man’s broken heart. It wasn’t something he wished to recollect. “What I’m working on now is functionally independent of the past,” he said. Then, slowly: “The starting point is very personal.”
Abruptly, when he was in his mid-twenties, his girlfriend, a woman he had been in love with since the age of thirteen and had lived with for years, told him she was leaving. “I was—flabbergasted. You can say that?” he asked me, making sure, in his stiffly accented, halting, but elaborate English that he was using the right word. “I was shocked. I was suffering. And she told me something at that point. She said she was so relieved by her decision that her menstruation came back.” She’d stopped using oral contraceptives two years earlier, but her period didn’t return, not until the day after she pronounced the relationship over. She believed her body was confirming that she’d made the right choice, no matter how agonizing it had been.
He felt stricken. But it wasn’t long before she asked for another chance, and he took her back. “And after a year, the same pattern repeated.” She had started taking the pill again, then quit, then went months without ovulating or menstruating; meanwhile, she realized that she really was not meant to be with this man she’d been entangled with for half her life. She let him know it was absolutely finished. And within a day or two: her period.
Battered by this cosmic verdict, he talked with the woman’s sister, who was sympathetic but informed him that yes, of course, there could be emotional causes for long stretches without menstruation, that sadly it all made sense. He wasn’t a scientist then. He was a belated university student, who’d been determined, until recently, to be a furniture builder. But he’d gravitated back to school because of books friends had given him, books that had begun to captivate him, volumes by the logician and philosopher Bertrand Russell and by Johannes Linschoten, a Dutch experimental psychologist. His mind was shifting, growing more and more avidly analytic. And it dawned on him that something was amiss. If breaking up had set his soul mate’s body free to bleed, how had this occurred within twenty-four or forty-eight hours?
How, he thought, had she skipped past ovulation and the two weeks that generally need to go by? Her uterus couldn’t have compressed into a day or two what takes half a month. True, it was conceivable that, both times, she’d resolved to end it two weeks before letting him know, but this wasn’t the story she told, and, brooding about how he’d been so blindsided, ended up so shattered, about how it could have happened twice—“I stood always under the shower, thinking and thinking”—he started to reverse his girlfriend’s logic, the logic her sister affirmed.
The reversal began as an insight, a glimmer, and slowly gained solidity as he scoured obscure journals, studying anything that might be at least tangentially related to his notion. “I’m a little bit—not insane. But. There became a need for me to understand my personal life in this way, to have a theory, an instrument, to have control.”
His girlfriend was a runner, a vegetarian, a dieter. This was a recipe for amenorrhea, the ceasing of the menstrual cycle—a recipe that was little researched in those days. Her regimen had inflicted havoc on her hormonal system and delayed the renewal of her period after she gave up the pill, he felt sure as he read what he could find. It had also reconfigured “her affective life,” he said while we talked in a café, the remote and professional word “affective” at odds with his expression, his voice. Thirty years afterward, he was wistful, bereft. For a long while, with her amenorrhea ravaging her hormones and her brain’s biochemistry, she’d lost desire for him. And with desire, her love, too, had flattened. But eventually, with the pill out of the picture and probably with a slight, unnoted easing of her running, her diet, hormones had revived, ovulation had resumed. In the brain, the molecules of eros had resurged. This didn’t restore her emotions for him, though. Instead, her reawakened sex drive seemed to flee straight from him toward the wish for other men. “The biological changed her affective feelings for me,” he used the word again, scientific, crushed. She decided to cut the bond, to wrest herself free. The sudden switch in her molecular state had cost him the love of his life.
Both times, coincidentally, it had taken her about two weeks to make the decision. His girlfriend and her sister had got it wrong, he thought. The psychological hadn’t dictated the hormonal. Rather, biochemistry had determined the trajectory of lust and love; it had destroyed everything.
Tuiten’s reasoning had led to his writing and publishing his first scientific paper while he was still working toward his master’s (the article was about discerning causality, he said, but “nothing about my suffering”), to his seeking his PhD, to his researching a biochemical vortex that can suck girls into anorexia, to his studying sex. Throughout it all, there were themes, threads that converged in his current inventing. One was the reign of the chemical within the psychological; another was timing. There was the molecular narrative, the biochemical chronology, behind his own tragedy. There was his resequencing of the forces that pull girls into anorexia. There was, after an experience with another girlfriend, his scrutiny of the molecular relationships that plunge certain women into severe premenstrual syndrome, with deprivations of serotonin and, for some, lowered inhibition and crests of lust. There was, much later, his investigation of the exact delay between doses of testosterone and the spurring of desire in women who respond to infusions of the hormone. There were his ruminations on the timing of serotonin pulses and on the timing of compounds that temporarily suppress this neurotransmitter.
Why were some women more prone than others to have desire plummet for their long-term partners, as habit and entrenched commitment robbed spark from stimuli? Why were some less or better able to feel a moderate flame? Why were a few capable of decades and decades of combustion, thrall? Baseline measures of blood-borne hormone weren’t much of a predictor, but Tuiten and his EB experts examined how efficiently a woman’s brain cells guided the testosterone molecule through cell interiors, so the hormone could do its transformative work, setting off the chemical changes that prime the erotic. Cells that do this guiding in a begrudging way—with molecular receptors that are resistant—might make a plentiful amount of free-floating testosterone partially irrelevant. Welcoming receptors could help a woman do a lot with a minimal quantity. One strand in the weblike thinking behind Tuiten’s drugs was spun from genetic coding that hinted at the character of those receptors. Blood could be read for that coding; the personality of the receptors could be deduced. This was one element in EB’s effort to peer into the molecular components of the sexual psyches of individual women. It was one reason why Goldstein saw the company’s work as a breakthrough and as a possible answer to his testosterone riddles.
Another angle on the testosterone system, on its capacity to incite dopamine, relied on something more crude than genetic coding. It involved measuring the second and fourth fingers of a woman’s right and left hands, and calculating the relationship between the index and ring digits. Wendy and all the other EB subjects, when they’d first been interviewed for the trials, had been asked to put their hands on a computer scanner. These images had been sent off to the company. Tuiten was building on emerging evidence, from humans and from rats, that the difference in length between the two fingers was another reflection of how receptive a person’s cells were to testosterone in both brain and bones.
Then there was the serotonin network, headquartered toward the front of the brain, a network that can override dopamine, that filters out stimuli and subdues urges, that is responsible for keeping us calm, rational, organized. For a glimpse of serotonin’s wiring, Tuiten gazed at another genetic script, illumined by using a fluorescent dye, an electrified gel.
But that was all to do with the inborn. He incorporated, too, as best he could, the learned. He knew that the social impact on the skeins of serotonin and dopamine, on their relative health, on the way they collaborated or competed, was crucial. Serotonin could either add the right drop of coherence to the sexual brain or it could interfere, inhibit, shut eros down. He knew that what the culture repressed or rewarded molded these networks. To gauge this, he used a series of questions, dealing with arousal and orgasm and frequency of masturbation. In combination, the answers spoke—imperfectly, tellingly—to inhibition’s intensity. He placed a woman’s replies, as well as her genetic coding and finger ratios, into an equation, an algorithm. The equation used eleven elements in all. In this way, he pieced together a vision of a woman’s erotic neurology.
This could sound like lunacy. But it was the most detailed attempt at comprehension by any drug company so far. It fed into the composition of his two medicines and into EB’s sorting of which women should take which one. The drugs were to be taken a few hours before a woman wanted to feel overwhelmed by eros. Each drug consisted of two parts: a peppermint-flavored coating of testosterone melted in the mouth; an inner pill was swallowed when the peppermint faded away.
In Lybrido, the pill was a cousin of Viagra. In Lybridos, it was a compound called buspirone. And here Tuiten’s long obsession with timing was at work. He’d realized that he could arrange a meeting, so that testosterone’s peak hours of sexual priming would coincide with the aid many women would need from the other two chemicals. This help, in the case of the Viagra-like chemical, was a heightening of genital swelling, which ramped up sensation and triggered the brain to produce more dopamine. In the case of buspirone, it was a squelching of serotonin. In their different ways, both Lybrido and Lybridos altered the interplay between serotonin and dopamine.
Lybridos was perhaps the more intriguing invention, the clearer example of Tuiten’s fixation on timing. Buspirone is an antidepressant. And like all antidepressants, it elevates serotonin. But there is a distinction. Unlike the most popular compounds for depression, the selective serotonin reuptake inhibitors, the SSRIs, buspirone causes, at first, a brief slow-down in the release of the neurotransmitter. And if buspirone isn’t taken every day, the gradual rise in serotonin won’t occur. The critical effect is serotonin’s very short-term suppression. Put this together with testosterone’s key hours of stoking dopamine and, even if that stoking was half-crippled by begrudging receptors, Tuiten might provoke an interval of lust; he might provide a replica of what had been felt long ago, when none of this manipulation had been necessary—when the newness of a lover had sent the biochemicals of desire into a frenzy.
It seemed that Tuiten, disheveled and eternally heartbroken, was about to be astonishingly rich. A minor yet enormous reason was this: over fifteen million American women, and countless more around the world, depend on SSRIs to battle their melancholy. Some would be enrolled in an upcoming phase of the trials. With the boosting of serotonin brought about by SSRIs, there is, for most, an inevitable flight of eros. Desire can become dim, imperceptible. And this can be worsened by the fact that excesses of serotonin disrupt the physical mechanics of orgasm, impeding contractions, so that climax feels farther and farther off, until it is unattainable. For women on SSRIs, each tablet of Lybridos, with its temporary blocking of serotonin, would grant eros a reprieve.
But above all, if Tuiten’s thinking was right, if the data he already held, from small sets of women in provisional studies, were borne out in his larger trials, then he had conjured a pair of drugs that were an antidote to monogamy. His medicine promised to rescind years.
Lust, in its most powerful moments, can propel us outside ourselves, outside the world, outside time. We are offered this oblivion. How wonderful the trance is—or was, if such moments have been sacrificed, lost in the quest for another kind of escape: for safety, for constancy, for a fortification against growing old alone, against enduring the terrors of time by ourselves. Could Tuiten’s pills perform a type of magic, allowing the trance to coexist with the comfort? Permitting both kinds of escape? Could Tuiten’s chemicals execute that trick?
Wendy prayed that her first round of EB tablets had been placebos. But if, for her, Tuiten’s drugs didn’t succeed, she said, “There’s got to be something else. They’ve got all these meds for all these other psychiatric issues. Something’s got to pop up that can help with this. Right? Right? Right?”
All she was asking was that the round of pills she was now bringing home would stop and reverse what she called “the dwindling.” All she was asking was that the medicine would drive her to take her husband’s hand at the base of the stairs and draw them together to the top. All she wanted was this: to leave time inconsequential, to turn time into nothing at all.