Manufacturing depression (27 page)

Kuhn’s affinity for Kraepelin is obvious. His theory was Kraepelinian logic on drugs. Endogenous depression was exactly the disease that imipramine cured, and the proof that you had been sick
was that imipramine cured you. Imipramine wasn’t only a cure; it was the chemical that assayed for the presence of the disease. Kuhn was pushing psychiatry closer to fulfilling Kraepelin’s promise that mental illnesses would be found in nature. After all, if a chemical could identify and fix the problem, then doesn’t it stand to reason that it was chemistry that was broken in the first place?

You would think that, especially in a permissive regulatory climate, a drug company would sit up and take notice when a doctor informs it that its new drug is a magic bullet for a widespread, if hitherto under-recognized, disease, puts that assertion on what appears to be a firm scientific footing, and then adds that “therapy must be maintained as long as the illness lasts”—which, since the problem was “endogenous,” may well be a lifetime. But Geigy was mostly unimpressed with Kuhn’s reports; the company’s marketing experts said that
depression was too small a market
to bother with. It would take thirty years before the ideas really caught fire that a disease could show up in nearly any malady and be a problem before the patient even knew it, that not feeling well enough was an illness that could be remedied by a prescription.

By then, of course, marketing experts had gotten more savvy and drug companies more determined. They wouldn’t, for instance, have let the fact that an antidepressant drug was derived from a substance called summer blue pass them by, or be dissuaded by ethical concerns about convincing people that they are sick. But that’s not to say that the first generation of antidepressants were without their hucksters. It’s just that they weren’t to be found in the Old World, but in the United States.

In 1952,
a story appeared
on the front page of the
New York Times
reporting on a drug for tuberculosis that was being tested on patients at Sea View Hospital on Staten Island. The drug—iproniazid, or as Hoffman–La Roche called it, Marsilid—was having some remarkable
effects. Not only was it healing people’s lungs, but according to doctors, it was also relieving their pain enough for them to give up narcotics and, at least sometimes, instilling in them a “euphoria” that after three or four weeks leveled off into a “normally optimistic instead of a depressed attitude.” In fact, as doctors soon discovered, the drug was capable of making patients feel better than their X-rays said they were. “This suggested,” wrote the
Times
reporter, “the use of the chemical in conditions other than tuberculosis.”

Iproniazid was invented when the stocks of hydrazine, Germany’s primary fuel for their V-1 and V-2 rockets, went to Roche at the end of World War II. There was some evidence that hydrazine could be modified into an antihistamine that might be particularly effective against tuberculosis, but once the psychological side effects made themselves known, it didn’t take a rocket scientist to figure out what to do next. It also didn’t take a drug company executive—Roche was as lukewarm as Geigy about the commercial prospects of an antidepressant. What it took was Nathan Kline, an American psychiatrist known as
“an international wheeler-dealer
, a flamboyant, buccaneering fellow [who] would try anything on his patients.” And that was according to one of his friends.

Kline was honest about his own ambitions and the love of power from which they came. “Research scientists are wide-eyed manipulators,” he once wrote.

When an observant brat
discovers for the first time that he can push buttons, turn faucets, open doors, dial phone numbers and exploit his parents, he is astonished and delighted to uncover and control the physical and social environment. Some of us never recover.

Iproniazid wasn’t the first button that Kline had put his finger on. In 1954, he’d gotten hold of reserpine, a drug that Geigy had recently synthesized. Reserpine was the active ingredient of
Rauwolfia serpentina,
or snakeroot, an herb known for centuries to India’s
ayurvedic physicians, who called it
sarpagandha,
as a cure for many complaints, and to holy men as
pagal-ki-dawa,
a remedy for insanity. Kline gave it to more than seven hundred psychiatric inpatients and found that it calmed down most of them—enough, he said, that
the glaziers at his hospital
reported that they had fewer shattered windows to replace.

Given what John Gaddum and other researchers were saying about LSD and serotonin, Kline and other scientists speculated that reserpine was increasing serotonin levels in the brain. Experiments carried out at the National Institutes of Health, however, showed that reserpine
lowered
levels of serotonin in rabbits’ brains even as it made them sleepy and immobile. But the idea that a simple brain glitch was the cause of mental illness was too pleasing to be discarded because of one experiment, and soon scientists were talking about serotonin
imbalances
rather than
deficiencies;
insanity could now be a problem of excess
or
deficient serotonin.

As you’ll see in a moment, this new theory was even more wrong than the one it replaced, but before anyone knew that, Kline had already taken it a step further, using the same “naïve” reasoning that embarrassed Alan Broadhurst. If a drug could depress mental functioning—a good thing in the case of people who were agitated and hallucinating—what about a drug that did the opposite? A “psychic energizer,” as Kline named it,

would relieve simple depression
and…the sadness and inertia of melancholia…reduce the sleep requirement and delay the onset of fatigue…increase appetite and sexual desire…Motor and intellectual activity would be speeded up. It would heighten responsiveness to stimuli, both pleasant and noxious.

In 1956, Kline heard that scientists had given iproniazid along with reserpine to lab animals, which, far from being sedated, had become hyperactive. The possibility that the drug could reverse the reserpine
effect, Kline said,
“immediately led me to speculate
whether this was the psychic energizer for which we had all been looking.”

That’s how Kline told the story in 1970 anyway. Like Zarate thirty-five years later, he mostly left out the part about how the drug was already known to make people high in favor of a story about scientists reaching conclusions through sober reasoning. It’s not clear which version Kline told to the research director at Roche, but by then the company had become disenchanted with iproniazid as a tuberculosis treatment—those darned side effects!—and they remained uninterested.

“Here indeed was a fairly unique situation!”
Kline wrote years later. “A group of clinical investigators were trying to convince a pharmaceutical house that they had a valuable product rather than the other way around.” Kline was in a good position to mount his campaign for iproniazid. The drug was already on the market, and he was the director of research at New York’s Rockland State Hospital. In 1957, he put together a team that quickly launched a study of iproniazid treatment for seventeen hospitalized schizophrenics and nine of Kline’s office patients who were depressed. When the depressed patients seemed to be getting better,
Kline arranged to testify
to Congress on the subject of iproniazid and to have his work published in the
Congressional Record
—a move that at once avoided peer review and guaranteed publicity. He also used his position as the head of the American Psychiatric Association’s committee on research to secure a spot at a regional conference in Syracuse, New York, to present his findings. He parlayed this relatively obscure gig into a preconference interview with a
New York Times
correspondent, who dutifully reported that
“a side effect of an anti-tuberculosis drug
may have led the way to chemical therapy for the unreachable severely depressed mental patient.”

Kline’s showmanship paid off, at least temporarily. In the next year, Roche, which had all but abandoned iproniazid as an antitubercular, sold the drug to four hundred thousand presumably happy, or at least less unhappy, customers.

*      *      *

It is impossible to know how many of these patients would have impressed Kuhn as endogenously depressed, or, for that matter, how many American doctors rendered an official diagnosis of depression before reaching for the prescription pad. In part, that’s because diagnostic specificity and the record keeping it allows were still a thing of the future. The DSM in use in 1958 was a mere 132 pages and counted among its 125 diagnoses inadequate personality and imbecility, diseases whose eye-of-the-beholder vagueness could only support the prevailing view that, as one doctor put it in 1960,
“a disease is what the medical profession recognizes
as such.” It’s enough to make you grateful for the faux objectivity of the more recent DSMs.

But there’s another reason to wonder about what was wrong with those four hundred thousand iproniazid patients in the first place. Like imipramine, iproniazid seemed to change something underlying mood; as an anonymous “New York industrialist” told the
New York Times,
“On the antidepressant drugs,
something has happened. I just feel entirely different.” The drug, according to the
Times
, worked by bringing about a “state of well-being and happiness”—“
eudaemonia,
” the reporter called it, explaining that this was Greek for “Aristotle’s conception of a life of activity in accordance with reason as constituting human felicity.”

Where Roland Kuhn had been careful to tie imipramine to a disease—albeit a disease that seemed tailor-made to the drug—Kline showed no such restraint. Neither was he interested in turning over the
“moral and social implications”
of a drug that altered people so deeply to philosophers and clergy, as Kuhn had suggested. Instead, by the end of 1957 Kline was urging doctors to move ahead with a project to determine whether drugs like iproniazid
“could improve ordinary performance.”

You could scour the medical journals from 1957 and 1958 (or you could let me do it for you) and you would find virtually no indication
that the new antidepressant drugs were being used for anything other than the “severely depressed mental patient.” But then again, you could also take a quick look at the
New York Times
from April 1958, just a year after Kline first reported his findings about iproniazid, and conclude that Kline’s experiment was under way, courtesy of those four hundred thousand patients—and with some untoward results.

The problems began in April 1958, when Frances Simpson, a fifty-five-year-old San Franciscan, met an untimely demise, which the coroner blamed on liver failure due to iproniazid use. Her doctor claimed that Mrs. Simpson had a
“persistent moderate depression,” but the
Times
had a different diagnosis, rendered as a headline: “
DEATH OF WOMAN LAID TO ‘PEP PILLS
.’” By the next day, Roche’s public relations department had kicked into gear, telling the paper that Mrs. Simpson was taking the 150-milligram
dose intended for “severe depression,”
that in this role it “had repeatedly proved to be a life-saving drug,” that there was no such thing as a “completely safe drug,” and, perhaps most important, that while iproniazid may be an energizing drug, the “very opposite of a tranquillizer, it is not…a so-called ‘pep pill.’ Such pills give a quick lift. Iproniazid’s action is slow and cumulative.”

The good news for the company was that these denials, unlike the original headline, were printed on the paper’s front page. The bad news, however, was that the new article—“
CITY RESTRICTS SALE OF ENERGIZING DRUGS
”—was mostly about the forty health-department agents who were at that very moment fanning out across the city to impound supplies of iproniazid. And three days later, after the inspectors had seized 2,671 bottles containing nearly 324,000 tablets, the city medical examiner, under the headline “
DRUG INVESTIGATED IN 2 DEATHS IN CITY
” disclosed that two recent deaths had a “suggestive relationship” to the drug.

Within a few years,
reports of jaundice
and other liver-related ailments in iproniazid users began to pour in. In 1960, a doctor—and not Nate Kline this time—testified to Congress (“
PHYSICIAN
WARNS ON WONDER DRUGS
”) about the dangers of the drugs. Despite a spirited defense by Senator Everett Dirksen, who accused his colleague Estes Kefauver of
“headline hunting”
when he convened hearings on these questions, Roche voluntarily withdrew iproniazid from the market in 1961, the pharmaceutical house by then no doubt ruing the day that it had listened to the likes of Nate Kline.

Iproniazid succumbed to liver problems, but plenty of drugs before and since have been a lot worse for their patients and still stayed alive in the marketplace. One clue about what turned a little jaundice into a terminal condition for Roche can be found in those headlines, in their pep-pill innuendo, their implication that doctors and patients and pharmaceutical firms were up to something not quite savory with these mind-altering drugs. Another can be found in
the roster of “wonder drugs”
hauled before Kefauver’s committee in 1960: iproniazid, chlorpromazine (Thorazine), norethandrolone (Nilevar, an early anabolic steroid), and Diabenes, an anti-diabetes compound. Can it be a coincidence that three of these drugs are for conditions that, especially in 1960, were not considered strictly medical, and that two of them were mind-altering substances?

Kline’s proposal to use drugs merely to “improve ordinary performance” may simply have come too early, before Americans were willing to wring their hands about this idea, rather than simply rejecting it outright. But the blitheness with which he tossed it off indicates an ignorance—perhaps willful—of a deep confusion in the American character on the subject of using drugs simply to make life easier.