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Saturday, August 13, 2016

History, the FDA, and Cognitive Biases

cackling villain

For reasons set forth in an earlier post, the author recently had reason to read Thomas Hager’s The Demon Under the Microscope: From Battlefield Hospitals to Nazi Labs, One Doctor's Heroic Search for the World's First Miracle Drug (2006) (Demon). Demon is a highly recommended account of an episode in history, the discovery of the first effective antibiotics, which despite its world-shaking, near-miraculous consequences to the most of the planet’s inhabitants is curiously unknown even to the educated.

Chapters 17 and 18 in Demon (p. 207-233), however, concerning the events leading to the passage of the Food, Drug, and Cosmetic Act of 1938 which for the first time empowered the FDA to control what medications Americans can make, sell, or take, is curiously unsatisfactory. This is not because the facts recounted therein are incorrect, incomplete, or biased, but because these facts are in such stark contradiction to the chapter’s tone lauding the FDA. That this contrast should have escaped the author, his editors, and presumably most readers is a prime example of certain near-universal, powerful cognitive biases.

A quick summary of the facts as recounted in Chapter 17 and 18 of Demon will give readers a chance to discover whether they share these cognitive biases. Note that every fact below comes directly from these chapters and it is stipulated that every word is accurate. None of the following comes from any other, contradictory source.

Prior to 1938, Americans were free to develop, test, market, sell, buy, and use medicines, with or without a doctor’s prescription, and with hardly any federal or state interference. While the FDA had existed for more than thirty years, it had little authority to interfere with these practices beyond dealing with mislabeled or contaminated medicines. As as consequence, there existed a large and thriving industry of patent medicine manufacturers who sold their wares by advertising either directly to consumers or to doctors and pharmacists.

This lack of regulatory power concerned the FDA and from the beginning of the New Deal, it and allied political groups sought to grant it vastly wider powers. However, these efforts faltered year after year in face of strong opposition from the patent medicine industry and general popular indifference.

In 1937, Massengill, one of the patent medicine companies, sought to enter the new, booming market for Sulfa drugs, which had recently been discovered to quickly and easily cure many types of otherwise fatal or debilitating bacterial infections. Sulfa, however, was a common chemical with little potential for profitable repackaging. To solve this problem, Massengill tried to focus on market segments which preferred its medicine in liquid rather than in pill or powder forum, such as children.

Massengill’s chief chemist, Howard Watkins, found that Sulfa would not readily dissolve in common bases for liquid medicine, like water or alcohol, but would in diethylene glycol. Not only did Sulfa dissolve well in that medium, glycol’s natural sweet taste would add additional appeal for the target demographic of children. The resulting solution of Sulfa in glycol was sold and marketed at Elixir Sulfanilamide.

What Watkins failed to realize was that glycol, while widely and safely used in medicines for external application, had recently been found to be poisonous to humans when ingested. Even small quantities of glycol, perhaps more widely known today as anti-freeze, often results in fatal kidney failure.Austrian vintners who poisoned their customers by enhancing their Rieslings with glycol in the 1980s can offer no such defense of excusable ignorance. Watkins does not appear to have conducted any human or animal tests on glycol before Massengill mass-marketed Elixir Sulfanilamide.

The consequence was equally predictable and catastrophic. Demon movingly recounts the agonies of a mother who saw her six-year-old daughter die of a medicine purchased to cure a sore throat or a doctor who killed his best friend by recommending Elixir Sulfanilamide. Equally gripping are the accounts of the doctors who first identified the common cause of their patients’s deaths and tracked down and stopped the remaining quantity of Elixir Sulfanilamide in circulation. Even so, at least seventy, and possibly as many as a hundred, Americans died of the Elixir.

The resulting popular and press outrage was sufficient to induce Congress to pass (and FDR to sign) the Food, Drug, and Cosmetic Act of 1938 which granted the FDA’s entire wish list, granting it plenary power and control over all medicine sold in the US, and rendering the sale of most medicines without prior FDA approval a crime.

The first major drug licensed under the new FDA regime was Sulfapyridine, another variation on Sulfa, but the first one to prove effective against lobar pneumonia, a mass killer:

Merck … submitted [Sulfapyridine] for approval to the newly empowered FDA in October 1938, noting a great demand for this fresh version of sulfa. But the FDA was in no hurry. The tougher approval regulations of the 1938 act were just beginning to be put into practice. Sulfapyridine was one of the first important drugs to be put through the revised system. The FDA wanted more toxicological data, more details on the metabolism of the drug, and more information on human tests before the agency would approve its use in the United States.

The 1938 act required that new-drug applications be approved or rejected by the agency within six months, a deadline fast approaching in March 1939 when the FDA finally gave its stamp of approval to the drug—as long as it was carefully labeled and administered “under close, continuous observation of a qualified practitioner of medicine.”

Demon at p. 240-41. Sulfapyridine proved a great success. Within a few years, sulfapyridine was saving the lives of more than thirty-three thousand pneumonia patients each year in the United States alone. Demon at p. 242.

So much for the summary. Let’s set aside a few minor eye-catching wrinkles in the account, such as that the hero of effort—Senator Royal S. Copeland who pushed through the ’38 Act—was by profession a doctor of homeopathy, a branch of ineffective fringe medicine which by depriving patients of genuine medicine has doubtlessly killed far more than the patent medicine industry did and which yet curiously escaped regulation both in ’38 and today thanks to Copeland’s modern-day epigones and fellow peddlers of quack cures such as the former Senator Tom Harkin.

Can the gentle reader spot the flaw in this narrative of progressive, life-saving regulation?

The availability of Sulfapyridine saved the lives of 33,000 Americans every year. The empowering of the FDA delayed the introduction by six months (a much, much shorter period than any modern medicine can expect under modern, even stricter FDA regulation). Hence, a straightforward estimate of the number of innocent, sick Americans killed by that delay is 16,500.

This is only a rough estimate. Even without the ’38 Act, Sulfapyridine might not have become as widely used in the winter of ’38/39 and hence fewer lives may have been lost. Conversely, the FDA prevented the use of Sulfapyridine during exactly the winter months when pneumonia peaks. Hence, the number of cases and hence lives lost was likely larger than a mere halving of the annual figure would suggest.

In other words, in one of the industry’s worst, most headline-grabbing abuses, a patent medicine company kills 100 innocent Americans. This results in an outrage so great that, contrary to long-standing tradition, the FDA is granted near-total power over pharmaceuticals. In one of its first exercises of that power, the FDA kills more than a hundred times as many people as the original outrage. Yet, this is near-universally accepted as an example of life-saving progress.Hager, to his credit, quotes a doctor who expresses concern that the present lack of a drug for seriously ill patients is not worse than operating under the old Food and Drug Act, Demon at p. 241, but neither follows up, nor endorses, this near-obvious truth.

Why do intelligent, educated people reading the above passages or otherwise confronted with these or related facts not immediately reach the same conclusion? Why will most people, even when these facts are demonstrated, still firmly cling to the belief that central controls are both good and necessary, even if they increase the net amount of suffering and death?

Modern social psychologists such as Jonathan HaidtProf. Haidt is the author of , author of The Righteous Mind: Why Good People Are Divided by Politics and Religion (2013), which is recommended but not entirely endorsed here. might offer one potential answer:

There you go again with your numbers and probabilities, Type A and Type B errors, and all that technocratic gobbledygook. But normal, moral people are not your dessicated type of rationalistic utility (or life) maximizers. They have moral sentiments which are profoundly outraged by the thought of selfish and greedy merchants rubbing their hands and counting their coins as they laugh over the corpses of dead children they leave in their wake. They are profoundly grateful that wise, kind, and selfless doctors at the FDA are working hard every day to protect them from this sort of moral violation. Which system actually kills more people is neither here nor there.

This may very well be an accurate description of the way most people feel, even after being exposed to the facts. Nonetheless, the underlying preconceptions are self-gratifying myth.

The cackling villain of this piece was not Watkins, the Massengill Chemist who created Elixir Sulfanilamide. He sincerely believed he was doing good and, when informed of the problem, was so confident in the innocuousness of glycol that he demonstrated drinking large doses himself (and of course fell seriously ill of it). Later, when the fullness of the disaster he had wrought became clear to him, he killed himself. He was reckless and incompetent. But he did not consciously choose the death of countless innocents to gratify his own desires.

Rather, this description far better fits those who will in order to gratify their own moral sense gladly sacrifice the lives of countless innocent sufferers. They, rather than any hobgoblin spooking their minds, are the selfish villains they purport to hate so much.