CHAPTER 29

The Hardener’s Tale

Viagra arrived in the spring of 1998. But it didn’t truly seep into most American homes until the following winter—and not through the bedroom, but the living room. It happened on a series of successive Sundays. And before the year was out, an entire nation had collectively cringed.

By now, that deep male voice seems altogether innocuous. In the rare event of an erection lasting more than four hours, seek immediate medical help. But when those words were first uttered, they landed with the wallop of a blindside tackle. They caused many a parent (and countless children and yelping pets) to burrow into the sectional sofa.

Let’s recount the shock wave.

Our families had gathered to watch football. We were digesting, quite possibly, a holiday meal. We were settling into the ebb and flow of a close game. Then all at once the Viagra ad commandeered the screen.

It is sunset. An elderly couple in jeans and cowboy boots is doing the box step. Cut to: a handsome, bronzed pair, just entering their twilight years. They’re dancing again, comes the voice-over. Glancing again. People holding, touching, and romancing again. Next, a seated man in formal attire, possibly in a wheelchair, kisses his partner, who is perched on his lap. Viagra works by improving a man’s natural response. So with Viagra, a touch or a glance can again lead to something more. The montage continues. Couples hug and sway on a dock, on a roof deck, in the kitchen after the dishes are done. The light is enchanting, the cinematography crisp. In three of the scenes, the women are so moved that—bah-dum—they kick up their heels.

At last, the possible downsides are announced: headaches, facial flushing, visual disturbances—along with the proviso that sexual activity can be physically demanding on the heart. In these first airings, the fearsome four-hour erection is never mentioned. But soon the warning is tacked onto the commercial, phrased so ingeniously as to trigger greater appetite for the drug.

Something new was going on in this inaugural ad.

Football is family time. The TV room is family space. So talk of uncontrollable erections elicited not groans but an icy hush. And in a flash, the retaining wall had collapsed between Poppy and the grandkids, between what preteens snickered about in school and what Mom and Dad did upstairs. Here was talk of sexual congress—out in the open, over chips and guac and wings. With nowhere to slink away to, each adult viewer was forced into a quiet complicity. Yes, they had to acknowledge: we actually copulated, at some stage, to bear the children sitting nearby.

TV audiences, true enough, were not unaccustomed to commercials about sexual health. In the ’80s, as the AIDS crisis deepened, public service spots had been meant to shock so as to raise awareness and incite action. But those ads were less about sex than they were about death—and America’s silence in the face of the disease. These new commercials were instead about the quality of consensual interaction among underserved couples. And so the whiplash of the transaction—football, fornication, football—jacked up the queasy.

Private, wholesome family time could no longer charade as being either private or wholly wholesome. More and more, in the days of more and more media, domestic space had become a cul-de-sac in the public square. And sexuality’s grip on the public purse strings, through sponsored programming, ensured that such messages, even medically enlightened ones, could not be kept at bay, no matter one’s age or upbringing, no matter one’s religious belief or disbelief.

Here, then, during one of the most benign and G-rated rituals of the week—six years after Governor and Mrs. Clinton’s Super Bowl date with 60 Minutes—were the messy, miraculous, wacky facts of life, of modern science, and of commercial television.

Whence did the circuitous dance begin? How did Pfizer—the company that developed Viagra—go from creating that initial dose to that public do-si-do, giving rise to the fastest-selling prescription drug in the history of medicine?

The tale is a largely untold one. “One of the reasons you don’t read a lot about the backroom stuff on Viagra,” says David Brinkley, who headed up the team responsible for the drug’s global marketing strategy, “is because we just don’t talk about it. We have kind of—I won’t say an understanding—we just don’t talk.”

But as luck would have it, enough time has passed since. And so Brinkley, along with some of the Viagra group’s most senior scientists and consultants—all of whom have since left the company—feel comfortable opening up, for history’s sake. At one point Brinkley admits, in comments echoed by his former colleagues, “This is actually the most in-depth discussion I’ve had with anybody [about Viagra] in ten years.”

The year: 1985. The cast: four chemists and five biologists working long hours in a backwater research lab in southeastern England. The setting: farms hidden amid marshes; narrow inland wharves; hedgerows and thatched cottages; sloping hillocks with clusters of hops and, everywhere, dewdrops of grazing sheep, plump and alabaster and immobile as porcelain.

The region: time-tousled Kent, in many ways an apt breeding ground for Pfizer’s prized medicine. Up the road, the town of Canterbury, in fact, was practically the birthplace of the ribald tale. As Geoffrey Chaucer famously recounted, fourteenth-century Britons were known for trading bawdy stories on their annual pilgrimages through these parts. (“I beg you,” Chaucer writes in The Canterbury Tales, “not to consider me vulgar [as I relay these pilgrims’] exact words… no matter how crude and low.”)1 Those journeys of penance were considered by puritans of the day to be little more than church-sanctioned debauchery—the medieval equivalent of sex tourism. And nearly a century and a half later, the much-married Henry VIII would make his own pilgrimages, to nearby Hever Castle, to woo and win Anne Boleyn. (Then, of course, there is the landscape itself: Kent’s fields are veiled in layers of chalk that undergird the very ground, called the North Downs. These folds and ridges, notoriously white-flecked, imply an inherent fertility.)

Finally, there is the town proper: unassuming Sandwich, where, in the 1950s, Pfizer decided to establish one of its two prime research hubs. Three decades later, quite by accident, the company’s scientists would devise a molecule that would be central to a story of chemistry and kismet. Call it The Hardener’s Tale.

That molecule: UK-92480.

Among the men most responsible for that auspicious clump of atoms is a chemist named Simon Campbell, whom many consider the godfather of Viagra. Indeed, in 2014 the queen knighted him for “services to Chemistry” (and, by extension, to the general British blood flow).

Campbell’s hair is gray now, brush-cut into a rebellious spike. His eyes are cobalt blue. His brow, knitted above a hawkish countenance, suggests intensity: Samuel Beckett by way of Ian McKellen. As he sits in his well-appointed flat in Kensington, the former president of the Royal Society of Chemistry, just entering his seventies, fixes a marksman’s glare on his guest.

“Sandwich came close to being shut a few times,” he says, revisiting Pfizer’s dire pre-Viagra days. “We were living on a knife edge. The group hadn’t been very productive in the late ’70s and mid-’80s and we were under tremendous pressure—on a precipice.” But part of the facility’s turnaround, over the course of a generation, was due to Campbell and his knack for forging consensus, along with what he calls an unwavering commitment to “scientific excellence and rigor—and deep scientific understanding of what you need in a drug.” Campbell managed and rallied the teams behind Pfizer’s new drug candidates.2 He minded the purse strings, the hiring, the construction of a massive research complex. He also played soccer in local leagues for most of those years, and became, says a close coworker, “renowned for his aggression.”

On Campbell’s watch, Sandwich rolled out the prostate drug Cardura, which brought in a billion dollars. (“I’m the sole inventor listed on the patent,” says Campbell, not one disinclined to crow.) The same with Norvasc, for angina and high blood pressure. (“Over $5 billion sales—I’m one of three inventors on that patent.”) The list winds on. By 1998, Pfizer had produced, coproduced, or acquired the rights to a portfolio of category-leading drugs such as Aricept, Celebrex, Lipitor, Trovan, and Zoloft.

But how to account for Campbell’s team and its “discovery” of Viagra, a medicine that owes a goodly share of its existence to serendipity?

Drug discovery, on the whole, is a laborious, hit-or-miss proposition. It is a process governed as much by Darwin (and the ruthless gleaning of natural selection) as by Machiavelli (the boardroom machinations, the industry hardball, the regulatory red tape). Indeed, in the pharmaceutical Ironman known as drug discovery, “only one of about seven million screened compounds,” according to Fortune magazine, “has the right stuff to make it to market.” To put it another way: it can take twelve or more years (on average)—and well north of $2 billion—to take a pill from thesis to molecule to pharmacy shelves. Given all of the biochemical, economic, and political roadblocks that await every major-market drug, it is a wonder any of them gets made, let alone one as initially miscast as Viagra.

During the mid-’80s, the question of how to erect a firm, determined penis was about the last thing on Simon Campbell’s agenda, at least while he was making the rounds in Pfizer’s labs. Instead, Campbell’s attention, for a time, was focused on coronary arteries.

In the beginning, it was merely a hunch. Campbell (then director of discovery chemistry) and Dave Roberts (a medicinal chemist) had devised a compelling hypothesis. They wondered if one could curb high blood pressure by relaxing the smooth muscle in the body’s blood vessels. Their proposed method was to introduce a compound into the bloodstream that would hike up levels of what scientists call cyclic GMP (cGMP), a natural substance in cells that, when elevated, is known to decrease tension in the heart’s arteries.

The drug they had in mind would perform a sort of vascular blockade. It would take aim at an obscure enzyme that scientists—in the alphanumeric patois of med-speak—referred to as PDE5.3 PDE5, which sounds more like the name of a cop show or a psoriasis shampoo, normally breaks down the cell substance cGMP. But the medicine that Campbell and Roberts were proposing would instead block PDE5, thereby pumping up levels of cGMP to relax smooth muscle, lower blood pressure, and increase blood flow. At the time, this was a new concept. “Little was known about the physiological role of cGMP,” Campbell reflects—and even less about PDE5.

Campbell and Roberts had uncovered evidence in research journals about a related compound called zaprinast that had actually lowered the blood pressure of anesthetized dogs. (Not that the dogs had been complaining of high blood pressure to begin with.) Intrigued, the scientists surmised that if they were to modify a zaprinast type of molecule, they might end up with a cardio drug that could zero in on spongy vascular muscle and dilate vessels in the body, including those in the heart.

They petitioned Pfizer to let one of its small units try to synthesize such a molecule. “We wrote that proposal in 1985, Dave and I,” Campbell says. “We went through all the biology, all the chemistry, all the literature, and made a cogent [argument].” Pfizer would approve their modest proposal the following year. “It wasn’t a big project. Four to six people in chemistry at the start. A dozen total. We [eventually] made two to three hundred compounds—not thousands.”

That task in large part fell to Nick Terrett, who would spearhead the chemical strategy for constructing molecules that might fit the bill. Terrett—whose name would be one of the three registered on the patent for Viagra—is thorough, compulsively curious, and a self-described introvert.4 In his lab-coated press pictures from those days (he was forty when the drug was finally launched) he has a cue-ball crown, salt-and-pepper beard, and dark-rimmed specs that bring to mind a young Sigmund Freud.⁵

Terrett and his colleagues were charged with constructing a single molecule, a Calderesque mobile of interlaced rings and clumps of atoms. That molecule’s properties, in theory, would fit nicely into the PDE5 enzyme, like a lock into a key—blocking it, increasing cGMP levels, and relaxing the smooth muscle of the heart’s arteries. Or at least that was the plan.

The obstacles were enormous. “The trick to inventing a drug,” insists Terrett, is to make sure the compound hits its target without causing collateral damage. “It mustn’t affect other biochemical mechanisms of the body. It must have properties that allow it to be ideally taken by mouth and get to the appropriate cells within the tissues and the appropriate biochemical target within the cells, and then be excreted or metabolized.”

To winnow down the permutations, as Terrett describes it, “there’s a very slow, methodical, interesting process. You take these compounds and you modify their structures, atom by atom or group by group, fine-tuning their properties. You have to keep an eye on [whether] the drug [will] dissolve in the stomach before it can be absorbed through the gut into the bloodstream. You have to make sure it’s going to be a nontoxic compound when it’s put into animals and, ultimately, put into man. It’s really a case of juggling twenty balls in the air at the same time.”

For centuries, healers treating tribal cultures would often use mixtures of natural substances. But contemporary drugs are different. Unlike the practice in “native, traditional medicine,” says Terrett, “[and among] shamans as well, that’s quite often a combination of different elements. In Western medicine, what we’re trying to do is find everything we need in one molecule.”

To that end, beginning in 1986, Pfizer’s chemists jiggered with a cocktail of atom bundles, swapping in various clusters. They then handed the compounds over to a cardiovascular biologist named Peter Ellis and a small squad who would test the proposed drugs on tissues—strips of aorta and other vessels from rabbits, rats, and dogs.

And for eighteen months nothing much happened. “To be absolutely fair,” Terrett says, recoiling at the memory, “for the first year or so, we thought: exactly what were we doing? There was a sense of frustration and concern.” Gill Samuels, another team member, would concur, telling the industry journal Chemistry in Britain, “There wasn’t a great deal of confidence [within] the company that we could get a really potent and selective inhibitor.”

Things looked bleak until a Pfizer biochemist named Frank Burslem joined them. Instead of dithering with vessels and tissues, Burslem went deeper. According to Jim Kling, reporting in the journal Modern Drug Discovery, Burslem used rat kidney and rabbit platelets to isolate one purified enzyme, allowing the pharmacologists to see how different drug samples would interact with it. Things quickly took a turn. The team discovered that one plucky enzyme in their experiments might be a better match for treating coronary artery disease. Suddenly, what had begun as a quest for treating high blood pressure had morphed into a medicine aimed at that condition’s most deadly consequences: angina and heart attacks.

By 1989, one molecule seemed to have real promise. The scientists code-named it UK-92480, the single standout from among the sixteen hundred substances they’d tested. In short order, Peter Ellis was conscripted to make a pitch to Pfizer’s top brass proposing that they try the drug on human beings. And—presto—the company consented, choosing the compound over twelve others (that were then being developed for various ailments by different Sandwich divisions).

To celebrate, a small party was thrown in a Pfizer conference room. “It was late afternoon,” Terrett says. “It was low-key. It had alcohol—sparkling wine, nothing special. And some appetizers.… The critical point in a discovery program is when you say, ‘This is the compound that we want to take the distance.’”

After congratulating the discovery team, Simon Campbell pulled Terrett aside. “Simon did his usual thing,” Terrett says, laughing as he remembers his boss’s sour expression. “He furrowed his brow and frowned at me, and he said, ‘D’you know, it’s a weak candidate. You’re lucky to get it nominated.’”

Poor candidate or no, UK-92480—later christened with the generic name sildenafil—would move on to the next stage: clinical trials in healthy volunteers and then, with any luck, in patients with coronary thrombosis.

Pfizer’s research facility in Sandwich is literally hidden in plain sight. One drives down Ramsgate Road through farmland and past cricket grounds. Along the lane rests an apple orchard, the Gazen Salts Nature Reserve, drowsy houseboats nestled along the river Stour. In the distance loom a half dozen silo-shaped structures along with large office buildings arranged in clusters. As Nick Terrett recalls the place in the zooming Viagra years, “We were in a very rural environment in a sleepy part of the country, which had stayed sleepy pretty much from the fifteenth century onwards.” The Pfizer campus, however, was state of the art and perpetually abuzz.

Upon approaching the site, one encounters imposing fences and security gates. And today a visitor has come to call on Peter Ellis—the leader of the cardiovascular biology team that developed UK-92480—and to walk the halls where chemists first brewed that initial batch. The interloper states his name and intention into an intercom, enters the curved edifice (“Welcome to R&D HQ Europe”), and is escorted up an escalator and into an open-air atrium. It is all very Saarinenian: swooped railings, cascading glass, and amoeba-shaped swivel chairs.

One wall is etched with the names of Pfizer’s progeny: Celebrex, Lipitor, Zoloft, Zyrtec among them. Farther along is a pedestal holding a bust of Sir Alexander Fleming, the father of penicillin. (Pfizer, which dates back to 1849, mass-produced the drug during World War II.) Pfizer’s 390-acre site—upon this visit, at least—is a thriving hive. (It will be closed down, then sold off, then turned into a national “enterprise zone” in the mid-2010s.)

Peter Ellis approaches with a wide smile, friendly patter, and an armful of files. His goatee says: scholarly ’70s—as in 1870s. His grin is slightly conspiratorial, suggesting a cheeky Ricky Gervais. Ellis works as a Pfizer consultant, having left the firm the previous April. He is therefore free to divulge certain Viagra back stories that haven’t been previously shared with outsiders.

Ellis, a Yorkshire-born biologist with a pharmacology PhD, used to be a competitive rower for Scotland. He ushers his guest into a small conference suite just down the hall from the lab where UK-92480 was first brewed. He shuts the door to the Naxcel Sterile Powder room. The walls are off-Pepto pink, roughly the color of Naxcel (used in animals to treat pneumonia and foot rot). Down the hall is the Benadryl room; next door, the Listerine room. Each is painted in its medicine’s respective shade.

Ellis opens a file from his stack. In 1991, he says, Pfizer wanted to test the safety of what came to be known as sildenafil. To that end, a single modest dose was parsed out for several days to a handful of English volunteers—all of them male and seemingly free of heart disease. None had adverse reactions. Next, Ellis recalls, a second pool of healthy volunteers, this time in Wales, stayed in a medical facility for ten days and were administered the drug at various dose levels. The results—six years after Campbell and Roberts’s first conjecture—were less than encouraging.

Not only did the drug have little effect on how well the heart pumped or the blood flowed or the vessels dilated, but it also caused mild side effects—backaches, throbbing in the temples, upset stomach. “The darkness for this compound,” Ellis says, was that “the early, healthy volunteer trials showed it caused headaches and muscle aches and that when compared with nitrates”—nitroglycerin remains the drug of choice for treating angina—“[it] didn’t obviously look any better.”

Ellis, however, wasn’t ready to cave. “You feel a real sense of ownership for the compound,” he explains, “[due to] the investment in time and energy—and body and soul.… It’s like a parent defending a child.” He returned to the library, hunting down more research to support the original concept, and pressed on. “You have to have evidence. You can’t just go back to senior management and whinge. In this dark phase, I was convinced that if we stayed with this drug long enough, we’d see long-term benefits. We had faith that this compound [could] deliver—for angina.”

Then, out of nowhere, the needle moved.

The clinicians in Wales were intrigued after giving the drug to some of their volunteers. When the subjects were later asked about any side effects, Nick Terrett recollects, “They [would] say, ‘Yeah, I’ve got a headache. I feel a bit dizzy.’ What happened on this particular occasion was that many of the volunteers said, ‘I’ve got erections.’”

Mike Allen, the supervisor of the study, was similarly surprised. While he was going over test results with one of the program administrators—explains science journalist Jim Kling—the investigator “mentioned that at 50 milligrams… [there were] some reports of penile erections.” And the data suggested the arousals appeared to be delayed sometimes by a matter of days.

“None of us at Pfizer thought much of this side effect at the time,” recalled Ian Osterloh, who was working with Allen, Terrett, and Ellis. “I remember thinking that even if it did work, who would want to take a drug on a Wednesday to get an erection on a Saturday? So we pushed on with the angina studies.”

One person who wasn’t surprised was Peter Ellis. He and Terrett had had a sneaking suspicion that the enzyme-blocking technique (for which Campbell and Brown were targeting the heart) might have another application: engorging the male member. They’d written a paper in 1988 saying as much—a document Ellis plucks from his file as proof. But his colleagues, in effect, were throwing cold water on the erections. “[Scientists] are always looking for problems and for reasons why things wouldn’t work,” Terrett recalls. “People said, ‘If you are increasing blood flow through the body, why should it target the penis and not target every other tissue in the body? You won’t get selectivity in the tissues.” So the erection connection was put on the back burner. The team’s mission remained: angina or bust.

Simon Campbell remembers that the prospects seemed grim during the Wales tests. “That was the final trial where we said, ‘All right, if we don’t see anything this time, that’s the end of it.’” He admits he was skeptical. “My concerns at the [Sandwich] development stage”—as he’d warned Terrett at the launch party—“were [now being] reflected in the clinic: it didn’t have robust cardiovascular activity, in my view. At the time, we had a dozen projects going on. We all supported it, but this one was a long shot.”

Meanwhile, Ellis remained undeterred. He went so far as to recommend that his counterpart in urology, Per Andersson, inject a nip of sildenafil into an anesthetized monkey. “It was UK-92480 injected right into the penis,” Ellis recalls. “It didn’t work because the monkey was sound asleep. No sexual arousal. No drive.”

Still, Pfizer agreed to move on to more extensive trials. And since the medicine had proven relatively tolerable, a new group of volunteers—eight in all, each with a history of angina—were sequestered in a British clinic in 1992. They were administered medium doses of sildenafil intravenously.

These results were similarly underwhelming. “Patients with coronary heart disease, who had [taken] UK-92480,” says Terrett, “really showed no benefit at all—marginal benefit. The whole thing was really a disappointment.” Campbell corroborates: “We were disappointed in the cardiovascular [results] and we didn’t know what the erections meant. When we saw the erections, we didn’t know the mechanism [behind them].”

Two years of pilot studies were turning out to be a wash, and the clock started winding down. It was time, many Pfizer insiders believed, to cut their losses and move on.

Ellis, Allen, Osterloh, and a handful of others, however, were like homicide detectives with a corpse and a mound of murky evidence but no motive. They kept poring over the facts of the case. Twenty-five milligrams: nada. Higher amounts of meds: modestly better blood flow, general achiness, and some swollen boners. They just couldn’t make out the forest for the wood.

History may belong to the victors, distinguished by sword and deed and seed. But one needn’t search too far to find a counter-tale—a literature of impotence.

In the Old Testament, King David, in old age, has trouble getting it up. In Egyptian tombs, there are occasional references to a man’s fallen obelisk. Homer prescribes jimsonweed for the inoperative digit, and Shakespeare warns of alcohol’s effects on “performance” problems. Goethe, on confronting the ravages of age, observes, “Now all my members are stiff, / All except one.”

For centuries, different cultures had used a witch’s cauldron of antidotes. According to Joseph Hooper in Men’s Journal, the ancients believed sexual prowess was “best bolstered by ingesting foods that look[ed] like genitals, from phallic rhino horn to the labial oysters.” India’s Ayurvedic practitioners, some three thousand years ago, offered rare “rock salt from a mine in Sindh” for men seeking a lift. The ancient Greeks, notes Hooper, swore by “a plant called satyrion6 [that] allows a man to perform 70 consecutive acts of intercourse” (though his partner was sometimes known to complain of headaches). Journalist R. V. Scheide provides a roster of historic remedies, including “centipedes, rotten fish, [and] bear bile.” And David M. Friedman, in his seminal book on the cultural history of the penis, A Mind of Its Own, chronicles how different societies over the millennia have recommended the restorative powers that came from consuming ground-up animal testes.

For much of the last century, scientists and charlatans dipped into their kit bags to treat the unascendant appendage. Erections were held aloft—or at least promised to be—by creams, gels, lotions, under-the-tongue tablets, and liquid supplements such as ye olde Spanish fly (actually beetle extract). There were acrylic splints and implants made of animal bone or cartilage. There were hand pumps and vacuum versions and electrode-wired strap-ons. There was a type of surgery called revascularization, which could reroute the groin’s arteries in a manner akin to a coronary bypass. For one popular treatment—meant to deliver pellets to the urethra, according to Gina Kolata in the New York Times—“the patient [would] himself insert suppositories into the end of the penis with a tiny plunger.” Just so.

Then came an event, in 1983, that would set the stage for everything that followed. It happened in, of all places, Las Vegas, at a gathering of several hundred doctors at that year’s meeting of the American Urological Association.

British physiologist Giles Brindley, a fifty-seven-year-old renegade, stood onstage and addressed the assembled. Several attendees later recalled that they found it odd that Brindley was wearing sweatpants. “I have lots of slides to show, and I’m the subject in all these slides,” he began. “I’ve injected… phentolamine… into my corpus cavernosum today, and the erection that’s pushed aside by my trousers at the moment is in fact now virtually full.” After the loud chuckles and clapping subsided, Brindley discussed how he had previously injected fifteen impotent patients, eight of whom had achieved erections. “Seven of them had sexual intercourse while under cavernosal alpha blockade… most of them for the first time for years.”

Emerging from behind the speaker’s rostrum, Brindley promptly dropped trou and exposed a healthy erection. The crowd was momentarily speechless. His associates, almost exclusively male, craned their necks to see the goods. The doctor was out. And he proceeded to parade around the lecture hall, his specimen swaying slightly. So as to prove he wasn’t playing a parlor trick, as one urologist would later testify, “He walked down the aisle and let us touch it. People couldn’t believe it wasn’t an implant.”

Brindley, on that memorable Vegas stage, had instantly caught the attention of his peers in the penile colony. In short order, scientists began experimenting. Doctors began offering office booster shots. “I had patients on injection that very next week in Boston,” says Dr. Irwin Goldstein, who had sat agog that day. Soon there were anecdotal accounts of Brindley blasts being given to actors in adult films (to help them better master their parts) and to elderly L.A. moguls willing to pay top dollar (for that extra margin while squiring dewy ingénues).

Brindley had laid down a gauntlet. Was it now possible, experts wondered, that any guy at any age at any time could simply buy himself a swig of added manhood? The implication was that medical science might be on the road to establishing “a new masculine ideal,” in the words of author Meika Loe in her book The Rise of Viagra.

And yet doctors in the late ’80s and early ’90s were more concerned with examination-room reality. That’s because impotence—partly due to the graying of the population—was becoming a hot topic in medical and media circles. In response, a panel convened by the National Institutes of Health formally proposed rebranding the term “impotence,” instead calling it “erectile dysfunction.” “Impotence,” says urologist Goldstein, “was felt to be pejorative and discriminatory, an irrelevant term [like] another sort of nonscientific word—‘frigid.’”

Goldstein had his own role to play in the impotence tale. “The baron of boners,” in the words of a fellow Boston-trained physician, Goldstein is a colorful, charismatic doctor, who at the time was the press’s go-to guy for ED. (He is currently the director of sexual medicine at Alvarado Hospital, in San Diego.) For him, the landscape shifted one day in 1989 when a colleague, John McKinlay, walked into his Boston office one afternoon carrying a batch of books. Goldstein had been one of the coauthors of a recent article on impotence published by the New England Journal of Medicine. In it, Goldstein now says, he had bemoaned the fact that “there were no epidemiologic studies of impotence that were current and modern, and that we were really relying on [Alfred] Kinsey’s data [from] back in the 1950s.” McKinlay, however, had been engaged in studies that drew a correlation between hormonal changes and the aging process—and had the detailed statistics to show significant falloff in sexual function. “In his hands,” says Goldstein, “were three large books—on each side of his body. And he put the six books on the chair, and said, ‘Here is the epidemiology of sexual dysfunction, right on this chair.’”

That data became the basis of Goldstein’s monumental work in the field—the Massachusetts Male Aging Study (MMAS). Initially, it was an attempt to understand how testosterone and other hormones impacted aging. Soon, however, it amassed interviews with 1,290 subjects and would become a clarion call about how pervasive ED was among men of advancing years. By 1994, the National Institutes of Health would use the study’s results to boldly assert that as many as thirty million Americans over the age of forty actually experienced some degree of erectile dysfunction—roughly half of all middle-aged males.

That figure was “triple the number previously regarded as impotent,” so David Stipp and Robert Whitaker would state in Fortune. “To hear the experts tell it, E.D. was now an epidemic. A majority of men over 40 were now seen as suffering from erectile dysfunction—yet fewer than 5% were seeking treatment.” Goldstein’s findings, when later published in the Journal of Urology, literally rewrote the entire library on impotence.

Critics predictably balked. Thirty million sufferers sounded way out of line. What man over forty, at some point in his coital travails, hadn’t had a bit of funk in his wagnall? Certain foes of Big Pharma aired their own suspicions. It seemed that there might be a movement afoot to let drug companies, physicians, and health care providers have their way with the phallus, just as so many other corners of the brain and body had been overmedicated in the last two decades, largely at the behest of Baby Boomers looking for another quick fix for their afflictions. ED, never before a household term, would soon become a catchphrase—and a catchall. A man could be said to be mildly or moderately impaired, according to the NIH and Goldstein’s study (begun in 1987 and published in full in 1994), if he was not able to achieve sustained firmness that was consummate with “satisfactory sexual performance.” To many, the definition seemed to cut a pretty broad swath.7

With ED treatments on the uptick—not to mention Brindley’s show-and-tell—drug makers were beginning to take notice. Even so, Pfizer appeared to be moving toward halting the UK-92480 trials. And then, as a quiet corollary, an intriguing new thesis emerged. And it would turn all previous thinking about erections on its figurative head.

“At this same time,” Nick Terrett reflects, “there were people like Lou Ignarro and Ferid [Murad], who were looking into erectile dysfunction and beginning to realize that it was driven by a mechanism that was totally consistent with the mechanism of sildenafil. Some people were working with animals, some with isolated penile tissue, some on human volunteers, and this picture was coming together. There were a number of [articles in scientific] publications in the early ’90s, which started to gel into a theory.

“And for the first time, people began to understand how it was that sexual stimulation resulted in nervous signals to the penile tissue which then resulted in the production of cyclic GMP which we were then amplifying with our drug. And”—he hesitates as he says the phrase—“it all started to hang together.”

A Unified Erection Theory?

“Yes.” He laughs. “UET.”

Actually, it was the thesis of Dr. NO, as in nitric oxide. NO turned out to be a molecule that lines all types of blood vessels. In theory, NO, as applied to erectile function, went something like this: An erection results when the interior nerves of the penis relax enough to allow blood to course through the shaft’s two main chambers. Nitric oxide, so medical sleuths found, is a signaling substance that acts as a medium through which cells communicate, like the current in a telephone wire. In men who are unencumbered in their performance, sexual cues prompt the nerve cells of the penis to generate NO. NO, in turn, prompts enzymes to generate cGMP, letting penile vessels open up so that blood floods in. If a man remains aroused by those cues, his penis remains blood-filled. But soon after that first wave of cGMP, a second enzyme—a PDE, acting as a constrictor—starts to degrade and reduce the cGMP, “dousing” the erection.

The behavior of the newly detected nitric oxide was a revelation. Science magazine went so far as to name NO the 1992 “Molecule of the Year.” The case for NO began to build. (Indeed, before the decade was out, Robert Furchgott, Louis Ignarro, and Ferid Murad would snag a Nobel for discovering NO and its effects.) And the Pfizer team no longer seemed to be grasping at straws. They started to see how NO might be the root cause of those incidental erections in the clinic. What sildenafil might have been doing was blocking the PDE enzyme, thereby helping keep the patients otherwise engorged.

“The Eureka moment for me,” Simon Campbell affirms, came when the journal articles he was reading about NO jibed with the Wales results, which jibed with early conjectures at Pfizer by Ellis, Terrett, and Mike Allen, who’d forecast that the drug might work for impotence. “There were papers linking nitric oxide and cyclic GMP with erections. And we’re seeing erections.”

Skepticism within the Pfizer hierarchy, however, echoed a resistance in society at large. People tended to believe that the force behind a hard-on existed between the ears. “When you consider the doctors’ perspective of impotence back in the early ’90s,” Terrett reflects, “they said, ‘Well, if it’s not a patient with spinal injury or a prostatectomy due to diabetes or multiple sclerosis, it’s psychosomatic.’ And so there was a concern that if it’s a psychological problem, why would a drug actually help? It was a cultural perception.” In addition, large pharmaceutical firms at the time were dealing with the AIDS crisis by introducing antiretroviral drugs, says Terrett, and a pill designed to promote sexual activity had its share of detractors.

With UK-92480’s chances dwindling as an angina medicine, Pfizer faced new decisions—and hurdles. If the team actually changed course to test the drug as a way to treat ED, how would researchers set up a protocol for measuring their subjects’ levels of arousal? How could the clinical crew persuade their managers at decidedly conservative Pfizer that there was a market for an oral penis pill? And did men in general have the stomach—or the cojones—for a product that let their physicians, lovers, and insurance providers in on the secret that they needed a drug to perform one of the most natural and human of activities? “In the early 1990s,” Campbell says, “we were never sure impotence was a problem, that it caused a lot of tensions in families and breakdowns in relationships. People didn’t talk about it.”

Ellis and the team, cognizant of all the persuasive nitric oxide cases, made a plea to Pfizer execs to shift gears from the coronary to the urinary. “We had to present a case before the governance [board],” Ellis recalls, “to say we should take this candidate before a patient with erectile dysfunction. The senior governance body said, ‘Not looking good, guys. Why should it work in people with erectile dysfunction? It has only been shown to produce erections in healthy males.’ The jury was split.”

But after weeks of internal debate—a full year after that group of volunteers’ first stirrings—senior management came around. In late 1993, clinical trials would commence in Bristol, England, on sixteen men with ED. And overseeing the patients would not be a chemist or a biologist or a cardiologist, but a genial urologist named Clive Gingell.

It is a clear blue Friday in June, “open day” at the University of Bristol. The college green teems with parents and prospective students who enjoy picnic lunches as a band plays folk rock. Considered by many Britons to be “the birthplace of America” (because explorer John Cabot first shoved off from its banks), Bristol played a central role as the cradle for the hatchling Viagra.

In a sentimental mood, Clive Gingell (pronounced gin-gel, with two soft Gs) recounts his boyhood Fridays—born in Wales, growing up in Kettering, Northamptonshire—before his family moved to the Welsh coal-mining valley of Rhondda. “[There] was an open cattle market on a Friday,” he says, sitting in his office at the Litfield House Medical Centre, “and [as a boy] I did walks with my little dog.”

That boy, an architect’s son, is now a retired physician with a Spencer Tracy wedge of a face—expressive and handsome and topped off by a mane as white as chalk. A past president of the urology division of the Royal Society of Medicine, he is the recipient of the St. Peter’s Medal (for “notable contribution to the advancement of Urology”).

Gingell is genuinely esteemed. Whenever a peer speaks of him, it is with a warmth that has no doubt been reciprocated in kind, over years. Equally evident has been the gratitude from those in his care. “I had a very large number of patients with erectile dysfunction,” Gingell says, “[and ran] a weekly outpatient clinic. It was a topic most urologists didn’t want to get involved in. It is a very common problem. The only treatment in the early ’80s was intrapenile injections. And you had to commit yourself to teaching [men how to inject themselves].

“The problem was it worked too well in some patients, who developed prolonged and sometimes painful erections. If they didn’t have poor blood flow and it was more psychogenic, [the dose could be] too effective and they would go into a priapism.8 We had to be called in every so often to treat a four-hour erection. And you’d have to stick a rather long needle in to get the stale deoxygenated blood out, like a cramp in a muscle. You’d have to detumesce it. You had to be jolly careful.”

Gingell’s role in the Viagra saga began in 1993 when two doctors from Pfizer’s clinical research came calling. Mike Allen and Mitra Boolell—both of whom had been acquainted with the urologist’s work from their days as med students at Bristol—traveled from Sandwich to see if he’d agree to coordinate the trials for Pfizer’s new drug. Allen and Boolell, recalls Gingell, began by describing the unaccountable erections they had seen in Wales. “Mitra said, ‘We want to start by treating people who have no obvious cause for their problem—people with nonorganic ED. Meaning: largely psychologically based.” The candidates would need to be relatively young and fit.

And how would they go about taking the measure of these men in full? They would need a RigiScan. The device, perfected in the mid-’80s, was the size of an electric razor and resembled a large computer mouse coupled with a tricked-out calculator. A tiny triumph of sex-research engineering, the RigiScan—available in mah-jongg tile ivory—was meant to mechanically quantify an erotic process that hitherto had been understood by its qualitative facets. Here was a contraption that could actually measure an erection’s firmness, circumference, and duration; in short, a peter meter.

Two white loops, like small lassos, extended from the RigiScan console. They would be slid in ring-toss fashion down the length of the penis—one around the base of the shaft, the other around the tip. As arousal commenced and fresh blood flowed into the pubic area, a mini-motor inside the control unit would subtly tighten the wires around the patient’s own unit until there was a degree of resistance. “The device was set to measure the circumference (tumescence) and rigidity (hardness) continually throughout the experimental period,” Ellis explains. “The data was then expressed primarily as duration of rigidity greater than 60 percent, representing the minimum for penetrative intercourse, and 80 percent to represent a full erection.”9

The Bristol volunteers would be wired up and then shown to their rooms for some private time. “At Pfizer, we thought you needed arousal [to activate the drug],” Ellis says. “And they came up with RigiScan-plus-pornography as the answer—the enabling methodology.”

Yes, porn. The scientists had determined that to get any observable results, tolerable doses of triple-X fare had to be administered along with the drug. But who had a viable stash (at a time when hardcore hadn’t gone mainstream)? “U.K. law,” says Ellis, “specifically excluded use of erotic material of a strong sexual nature. Thou shalt not show an erection or a couple engaged in coitus.”

Clive Gingell’s grin widens as he remembers. “Mitra and Mike Allen [asked and] I said, ‘Yes, we’ve got a RigiScan. Yes, we’ve got [hardcore] videos.’” Gingell stops and laughs. “You want to ask me where we got them? Amsterdam and Hamburg. They were brought in”—he reaches over and picks up a briefcase, to illustrate—“by hand luggage. And we had some top-flight magazines as well. They [were leftovers that] had been used for other cases such as patients with prostate cancer.… So we had to have a choice of offerings—all types, a variety of what’s going on between people. Some [sexual activities] that some would find arousing, others wouldn’t. We’d come back from conferences in Europe—and have them.”

Gingell had the patient pool, the expertise, the staff, and the compassion required for treating men with ED. He also had the RigiScans and a lending library of porn tapes and stroke books. He readily agreed to wrangle the patients and administer Pfizer’s studies. And in late 1993, Gingell reconfigured a ward in the style of a sleep lab, working with research registrar Ken Desai and an exactingly precise doctor named Sam Gepi-Attee. “I had to do this in a private setting on evenings and weekends,” Gingell remembers, discussing the need for patient confidentiality and the sensitivity of bringing lewd movies and magazines onto public hospital grounds.

Three times a day, for seven days, sixteen ED outpatients would go about their daily business, ingesting a pill containing either a placebo or a small 25-milligram dose of sildenafil. They would be asked to maintain a journal, dutifully marking down the number of erections they maintained, how hard each hard-on seemed, and the probable cause. At the end of the week, they would be admitted to the ward, rigged up with RigiScans, and sequestered in their rooms. Then they would settle in with fresh batches of porn and for two hours research aides would monitor the subjects’ firmness, width, frequency, and duration—either reviewing the results later (as downloaded data) or in real time in an adjoining room (as graphs on printout paper).

Since 25 milligrams was a minimal dose, Gingell and his partners back in Sandwich were keeping their power dry. Pills of much higher potency had been required to get an appreciable rise in Wales. But, lo and behold, the men’s journals and their printouts proved promising: those taking the placebo reported little change; those taking sildenafil occasionally reported a new spunk in their junk.

Underwhelmed but not discouraged, Pfizer recommended that Gingell run another pilot study, this time with a dozen men taking tablets of differing strengths, from 10 to 25 to 50 milligrams—but only a single dose a day. By day three or four, some of the subjects at the higher levels actually remarked that they were getting “spontaneous erections”—this among some men who had been troubled by impotence for years.

Then, at the tail end of that second study, in 1994, the chief aide on the Bristol trial called Pfizer’s Ian Osterloh in Sandwich. He had, he said, some stunning news.