Manufacturing depression (30 page)

The ethical drug manufacturers were ecstatic. The new law, said Mahlon Kline, vice-president of Smith, Kline and French, would be “
the greatest instrument
for the moral uplifting of the average businessman that had ever been bestowed upon the American people.” The fact that the Bureau of Chemistry, the Agriculture Department
agency charged with enforcing the act, chose his company’s chief chemist as its new head probably figured into Kline’s enthusiasm. But even without this favor, the regulations were helpful to his industry. They would give it something that the makers of Brane-Fude and Microbe Killer couldn’t have: the legitimacy conferred by the United States government.

The bureau obliged the industry by imposing standards for drug preparations with which only a large company possessing the resources to control its supply and manufacturing process precisely could comply. Even better, while it forbade manufacturers to place on the label “
any statement…which shall be false
or misleading in any particular,” the bureau didn’t establish the method by which those statements could be verified. It was left to the drug makers to engage in a war of rhetoric in which the products backed by the most convincing experts prevailed. A company like Smith, Kline, which could muster an army of respected, science-talking doctors to attest to the truth of their labels, had a huge advantage over patent drug makers and their hucksters. Especially after
the Harrison Anti-Narcotics Law
had limited the amount of opiates allowed in medicines and the Internal Revenue Service began to impose taxes based on alcohol content, the makers of Muco-Solvent, Humbug Oil, and Swamp Root were on the run.

The situation only got better for the ethical drug industry in 1911, when the bureau tried to shut down the company that made
Dr. Johnson’s Mild Combination Treatment for Cancer
, on the grounds that it didn’t really, as the label claimed, cure cancer at home. Johnson fought the law all the way to the Supreme Court, and the law lost. Oliver Wendell Holmes—the jurist son, not the physician father—delivered the bad news to the bureau. He wrote in his majority opinion that Congress had only meant to regulate drugs “
with reference to plain matter of fact
, so that food and drugs should be what they professed to be.” That was easy enough to establish, by comparing what the label said was in the bottle with what was actually there. But drug efficacy was a different story.
Congress, Holmes said, surely did not mean “to distort the uses of its constitutional power to establishing criteria in regions where opinions are far apart.” And whether or not a drug actually did what the label said it did, whether or not Dr. Johnson’s Mild Combination Treatment actually cured people’s cancer—this, Justice Holmes said, was a matter of opinion.

The United States Congress was in a reforming mood in those days, and lawmakers were not content to leave public health to the invisible hand. They tried to give the Bureau of Chemistry the power to require that drugs be effective without running afoul of the Supreme Court, but after a few bruising floor battles, the best they could do was to
outlaw “any statement
…regarding the curative or therapeutic effect…which is false and fraudulent.” This law actually discouraged research by making ignorance a defense; falsehood is not fraud unless a company has taken the time to figure out the truth. The “greatest instrument” was only getting better for Mahlon Kline and his friends.

That may seem startlingly obtuse, but it makes sense when you remember that with a few exceptions—like Paul Ehrlich’s Salvarsan—there was no way to say with certainty why a sick person who took a particular drug got better; there was still precious little understanding of the biochemistry of disease or cure. In the absence of that knowledge, Holmes thought, a drug’s ability to cure illness was a matter for the marketplace to decide. You bought the potion, decided whether you liked it, and told your friends (and your doctor) what you thought—the same as you did with any other consumer product. The government’s role was simply to make sure that the public got what it paid for and didn’t get harmed in the process.

That turned out to be harder to accomplish than it sounds. In 1931, the Food and Drug Administration was spun off from the Bureau of Chemistry. It didn’t take long for the new agency to discover just how limited its powers were. In 1937, S. E. Massengill Company
introduced Elixir Sulfanilamide. Sulfa drugs had burst onto the medical scene in 1936, when
Franklin Roosevelt, the president’s son
, had been cured of a streptococcus infection (in those days, strep infections were potentially fatal) by a timely injection of sulfanilamide. The patent for the drug—Prontosil, derived from a dye that Paul Ehrlich had fooled around with and which was used to redden leather—had long ago expired, so drug companies sought market share by inventing new preparations. Massengill hit upon the idea of putting the antibiotic into a raspberry-flavored syrup. The problem was that the drug refused to dissolve in the syrup—until Massengill’s chemists added diethylene glycol. The company’s chemists may have been the only chemists on earth who didn’t know that this compound, used as an industrial antifreeze, was a fatal poison.

After the bodies were counted (105), after the remaining 234 gallons of Elixir Sulfanilamide had been rounded up, and even after a government official determined that chemists at Massengill “
just throw drugs together
and if they don’t explode they are placed on sale,”
the FDA found that its only recourse
was to fine the company $26,100 for mislabeling—
elixir,
the agency said, was a term reserved for alcohol-based preparations. Inadequate as this punishment was to the scope of the tragedy, it could have been even worse.
Had Massengill named its drug
something else (Sulfa-Freeze, perhaps), the company might have been entirely beyond the reach of the law.

The Elixir Sulfanilamide debacle provoked Congress to action. In the Food, Drug and Cosmetic Act of 1938, it banned the interstate shipment of harmful substances, which in turn gave the FDA the authority to require drug companies to prove that their new products were safe before they could be brought to market. The label remained the focus of the law. It now had to disclose not only the contents of the bottle but accurate information about proper dosage and potential dangers. The law exempted some drugs from this requirement—those whose effective use and safety hinged on conditions too complex for a layman to assess. For these drugs, no label was necessary because people weren’t going to be buying them on
their own say-so, but rather only on a doctor’s orders. Along with the prescription,
doctors would dispense the information necessary
for safe use—information that they got from the drug companies, and mostly from the army of salesmen, or detailers, that the industry now began to deploy.

Like earlier pure drug laws, the 1938 version was a hit with doctors and drug companies. It gave more power to physicians and it left it up to the industry, whose in-house research staffs were still tiny, to recruit the doctors who would submit the safety information to the FDA, a cozy relationship that couldn’t hurt either party. Even more important, the law continued to steer a wide berth around the question of efficacy. That was still, as it had been in 1911, a matter of opinion, not something on which the FDA was going to weigh in.

But that didn’t mean that efficacy was off the table completely. Drug safety is generally not a straightforward question; cases of outright poisoning like Elixir Sulfanilamide are rare. More common is the problem that arose when effective drugs caused unforeseen problems as a function of, or in addition to, their therapeutic action—in other words, side effects. Sulfa drugs, for instance, could deplete white blood cells, but that risk, especially if managed by a skilled doctor, was clearly outweighed by the infection-killing benefits of the drug. Safety could only be assessed as part of a cost-benefit analysis in which efficacy had to play a part. A few articles in a journal, testifying to the effectiveness of a drug and written by doctors whose credentials as researchers weren’t necessarily sterling and whose methods were haphazard, would suffice.

The FDA did make at least one attempt to face the question squarely—with drugs that seemed to have no therapeutic effect whatsoever. These drugs were by definition unsafe because there was no benefit against which to weigh the cost. The agency focused on “glandular substances”—hormone-like remedies intended for women of a certain age that had no discernible pharmacological action—and proposed a fix: a label that acknowledged “
there is no scientific evidence
that such products…possess any therapeutic activity.”

The industry howled in protest. The FDA, a trade journal complained, was telling drug makers that they “must undertake to educate physicians”—a function they were perfectly happy to fulfill when the news was good. And when the agency declared in 1948 that it couldn’t certify the safety of such a preparation, industry hauled out the heavy guns. The FDA, it said, was interfering with the sacred doctor-patient relationship. One of Congress’s own doctors brought the warnings close to home. This edict, he told lawmakers, would make it impossible for him to offer glandular remedy to “
the wives of my Congressional group
.”

That worked. By 1950, the FDA, reminding Congress that the Supreme Court had long ago tied their hands, was officially out of the efficacy business, but it remained in the drug-certifying business. And once again, regulation uplifted the businessmen. The prescription drug industry, which already claimed science for its side, and whose products were officially only understandable by experts, could now obtain the government’s imprimatur for its products without ever proving that they worked.

This was the regulatory environment
in which the antidepressant discoveries I described in the last chapter took place. The FDA could only comment on safety, it had to take doctors’ word about efficacy, and the agency had only a short time to respond to a new drug application (sixty days, after which the drug, in the absence of a response, was automatically approved) and a small staff (1,065 in 1956, the height of the industry’s postwar boom, and only 117 more than it had ten years earlier). The FDA’s $6 million budget was dwarfed by the $140 million that the pharmaceutical companies were spending annually on research and development. A drug could make it from bench to market in just a few months.

In some respects, this laxity didn’t seem to matter. The 1950s were a time of true wonder drugs—not only the antibiotics that followed on the sulfa drugs and penicillin, but also chlorpromazine,
corticosteroids and other hormone treatments, and diuretics for high blood pressure. The results, in lives saved or transformed, seemed to speak for themselves. Armed with its government-sanctioned success, the drug industry had gained the confidence of the public as a reliable supplier of magic bullets.

The industry wasted no time in exploiting its achievements. Sometimes this was too much of a good thing, as Johns Hopkins doctor Louis Lasagna complained in 1954:

The doctor of today
is under constant bombardment with claims as to the efficacy of drugs, old and new. It is difficult, if not impossible to read a journal, attend a medical meeting, or open the morning mail without encountering a new report on the success or failure of some medication.

As if to prove Justice Holmes correct, medical journals were chock full of opinion. Doctors, it seemed, were to be guided in their prescription choices by whoever among their colleagues sounded most trustworthy to them. Or, for that matter, by the advertising in their journals:
the number of pages of
JAMA
devoted to drug company ads doubled in volume in the 1950s, even as the AMA stopped requiring advertisers to earn its Seal of Acceptance before they could hawk their wares. And if doctors were too busy to read the journals or look at the ads, there were always detail men to regale them with the latest lab results over a round of golf.

The resulting therapeutic chaos alarmed Estes Kefauver and his Anti-Trust and Monopoly Subcommittee—the same body that listened to testimony about iproniazid and other “quick pills.” A Tennessee Democrat who was Adlai E. Stevenson’s running mate in 1956, Kefauver was a liberal populist, an early champion of racial equality, a fierce opponent of Joseph McCarthy. He fought the pharmaceutical industry to the death—his own, in 1963, the fifth year of his hearings. By that time he had infuriated doctors, the drug industry, and lawmakers like Everett Dirksen with his repeated attacks on the way
that the prescription drug scheme had tilted the market toward the drug companies and turned doctors into their shills. “
He who orders
does not buy,” he said, “and he who buys does not order.” Consumers were at the mercy of drug companies; they couldn’t even evaluate advertising claims on their own because the targets of the ads, and the only people who saw them, were their doctors.

At the very least, Kefauver argued, drug companies should have to prove the merits of their drugs to the government’s satisfaction before they began their advertising onslaughts. He proposed a law giving the FDA the power to require drugs to be proven “
safe and efficacious in use
”—a question that he thought science had finally made into a plain matter of fact. Although a few renegades, like Lasagna, supported Kefauver, the AMA strongly opposed his proposed law warning that it was a step toward socialized medicine. The Judiciary Committee, to which Kefauver’s subcommittee belonged, took out the efficacy provision; the bill had been so defanged by the time it reached the Senate floor that Kefauver refused to manage it. It was headed for a quiet death in mid-1962 when lawmakers suddenly became aware of a magic bullet that had turned lethal, and that the citizens of the United States had only barely dodged.

The drug was thalidomide, and it had been invented in the late 1950s by Chemie Grünenthal, a German company that was hoping to get into the psychiatric drug business with a new tranquilizer.
The company hawked the drug
, known as Contergan and available over the counter, not only as a tranquilizer, but as a sleep aid, a flu remedy, and, at least according to a doctor on retainer to Grünenthal, a suppressor of young men’s desire to masturbate. Grünenthal also claimed, based on animal studies, that the drug was completely nontoxic, which meant that it was safe to give to pregnant women.