Religion & Liberty Online

The Nazi Wonder Drug and the Crisis of Regulation

Phillipa Bradbourne, a Thalidomide baby born with deformed arms. (Image credit: Associated Press)

Most people have heard of the thalidomide catastrophe: a German-manufactured drug intended to treat morning sickness caused untold numbers of birth defects worldwide. What many may not know is that the drug reached the U.S., or that the drug’s manufacturer was staffed with literal war criminals.

Read More…

The actor Hugh Laurie recently observed that “[while] you can chew all the celery you want, three-quarters of us wouldn’t be here without antibiotics.” He was getting at a basic truth. Since 1860, American life expectancy has nearly doubled, and the main reason for this is innovations coming from the pharmaceutical industry. That starts with the creation of life-saving vaccines and antibiotics. However, it isn’t only pills and shots that are permitting us to stay on the planet longer. Here’s a short list of commonplace ailments that can now be treated and ameliorated because of discoveries of U.S. pharmaceutical companies: herpes, hepatitis, hemophilia, Type II diabetes, high blood pressure, high cholesterol, dwarfism, urinary tract infections, gout, Crohn’s disease, Parkinson’s disease, multiple sclerosis, asthma, allergies, ulcerative colitis, rheumatoid arthritis, migraines, eczema, psoriasis, infertility, hyperactivity, anxiety, depression, sexual dysfunction, hair loss, anemia, epilepsy, macular degeneration, obesity, and psychosis.

Drug innovation has also made transplant surgery possible by allowing doctors to give patients medications that prevent tissue rejection, and pharma researchers have come up with cures for many forms of leukemia. On top of all that, we’re just beginning to see an emerging revolution—the introduction of new immunotherapy drugs for a wide range of cancers. A good case can be made that the U.S. drug industry has changed life more than anything since the invention of agriculture. Indeed, one might argue that the neolithic revolution should rank second to what companies like Merck and Pfizer have accomplished.

Yet because their drugs are so costly, the industry has become a favorite political target. And, of course, the history of drug manufacture isn’t composed exclusively of successes. No business has a higher rate of failure. More than 90% of the medicines that get to testing on humans—phase II trials—are never approved. However, one disastrous case of a drug that made it to market stands out: thalidomide.

That’s the subject of Jennifer Vanderbes’ exceptional new book, Wonder Drug: The Secret History of Thalidomide in America and Its Hidden Victims. Vanderbes is an acclaimed novelist, and her skill as a storyteller is much of what makes her tale so compelling. Introduced in 1957 in West Germany and marketed as a medication for anxiety and morning sickness, thalidomide became notorious. That’s because it’s toxic for fetuses growing in the womb. Standard estimates are that it led to the deaths of more than 2,000 children, and that an additional 10,000 were left with birth defects. This included thousands of cases in which children were born with partially or entirely absent limbs.

What’s new in Vanderbes’ account is the revelation that dozens of American children were harmed by the drug. That conflicts with prior versions of the story that suggested that the Food and Drug Administration (FDA) kept thalidomide out of the United States. Vanderbes shows that even though it never received FDA approval, thalidomide was quietly prescribed in the United States with many of the same terrible consequences that were seen everywhere else.

Reportedly, Vanderbes spent five years researching and writing her book, and she presents her story in a way that’s both thorough and absorbing. She’s helped not only by the inherent drama and the high stakes involved but because she has both dastardly villains and dogged heroes. Foremost among her good guys is a gal: FDA official and former University of Chicago faculty member Frances Oldham Kelsey. A native of British Columbia, Kelsey persistently refused to give thalidomide her sanction for marketing in the United States. Her concerns focused on two subjects: reports indicating that the drug caused peripheral neuritis and the lack of information provided by its would-be American manufacturer about its effect on fetuses.

As it happened, there was good reason for the want of data on how thalidomide affected pregnant women and their gestating babies. Its original producer, a start-up German pharmaceutical company called Chemie Grünenthal, hadn’t performed these tests. But, as Vanderbes reveals, that was but one of many causes for alarm. Perhaps even more worrisome were the people in charge of Grünenthal and the suspect origins of the drug.

The company’s founders were Nazis who had made extensive use of wartime slave labor, and its chief scientific officer, Heinrich Mückter, had killed hundreds of prisoners at Buchenwald by injecting them with typhus. Indeed, when he was hired by Grünenthal, he was a wanted war criminal in Poland. Moreover, he was one of many company executives who had been involved in Nazi atrocities. The company’s head of pathology, Martin Staemmler, had worked to develop Nazi population-control policies. Its chief medical officer, Heinz Baumkötter, had received sentences of 25 years to life at hard labor by a Soviet Court and then a separate if suspended eight-year sentence in West Germany; in fact, he had acknowledged in sworn statements that he was personally responsible for more than 8,000 concentration camp murders. Another executive, Dr. Ernst-Günther Schenck, had lost his medical license because he had engaged in pseudo-scientific “protein-sausage” experiments that had led to the demise of other concentration camp victims. And at least one company board member, Otto Ambros, had been convicted at the Nuremberg trials.

More remarkably, the original testing of thalidomide may have taken place in the camps, and later tests of the drug on mice raised further doubts about its safety and efficacy. It seemed that while it put humans to sleep, it was not a soporific for rodents. That brought up the question of how the drug functioned on the nervous system and how and to what extent it was being absorbed by the body. Yet, in spite of all these issues, it was approved in more than 20 countries, including Kelsey’s native Canada.

Some of this, of course, reflects the much more lax regulatory environment of the 1950s, and the absence of well-developed testing protocols. All drugs must be judged based on their risk profile, what is in effect a cost-benefit analysis. To give a very simple example involving a common nonprescription drug: acetaminophen, the painkiller that goes by the trade name of Tylenol, is mildly hepatotoxic. This is to say that it can be damaging to the liver when combined with large amounts of alcohol. Yet it can be purchased in any drugstore because authorities believe that these risks are small when balanced against the benefits the drug provides. Society deals with a similar issue in introducing new drugs, as no level of trial research can absolutely ensure that a drug will be perfectly safe or that its mechanism of action will be precisely understood. This weighs against the enormous benefits provided by the many new drugs reaching the market. That latter fact demands that we not be overly restrictive in our testing and research requirements. A balance between undue cautiousness and too much liberality for drugmakers must be found.

The problem of poor regulation tends to arise when the commercial potential for a new drug is so great that regulators are fearful of saying no to drug manufacturers—and drug makers are criminally irresponsible in reporting their results. An example of this popped up in the 1990s with the weight loss treatment known as fen-phen (fenfluramine/phentermine). Because so many people wanted an effective obesity treatment, the executives of American Home Products, which expected giant profits from an unapproved pairing of the drugs, permitted doctors to prescribe them in combination and then failed to publicize data showing that this could cause heart damage. Compounding this problem, regulators were slow in responding to their own reports of trouble. The misuse of time-released narcotics, like Oxycontin, represents an even worse example of this sort of abuse.

A still more common difficulty arises from the question of whether whole classes of drugs, like antidepressants and statins, are being oversold.

The appeal of thalidomide grew out of the enormous success of Miltown (meprobamate), which had reached the market the year before thalidomide. Introduced by Wallace Laboratories and Wyeth Pharmaceuticals, it was one of the most successful and profitable drugs in history, and it produced a feverish search for a competing sedative. (It has since been superseded by the even less toxic class of “minor tranquilizers” known as benzodiazepines. Valium and Xanax are both in this family.) The hope of thalidomide’s U.S. distributor, Richardson-Merrell Pharmaceuticals, was that it could challenge Miltown’s huge sales. That thalidomide was mostly kept out of the U.S. market is the great achievement the FDA has long cited as justification for its extensive powers. Vanderbes chips away at this claim, showing that Richardson-Merrell had engaged in limited domestic testing of the drug. The company succeeded in keeping this secret. In part this was due to U.S. investigators’ fear of releasing the names of Americans who had been given the drug (they never did so).

Yet this does not change a basic fact: the development of new drugs is vitally important. That brings up the one criticism I have of Wonder Drug, and a broader but important point about the future of American healthcare.

Gifted storyteller that she is, Vanderbes tells her tale with the pace of a thriller. Underlying her account is an implicit thesis: we need more aggressive regulation and more government control of doctors, hospitals, and drugmakers. For that reason, Vanderbes is critical of the Kennedy administration’s response to the thalidomide crisis. Supportive of the pharmaceutical industry, it took out the language in a bill proposed by Senator Estes Kefauver that called for a requirement that newly approved drugs be better than previous ones. Vanderbes sees this as a mistake. But it may have been for the best. After all, for many categories of drugs, like antibiotics, the need is not for stronger medicines but a full arsenal of available choices. When antibiotics face drug resistance, a range of alternatives is required. Moreover, no matter the disease, a medication that works well for one patient may not for another. It is hard to say what a “better” drug is.

And this isn’t the only danger in the seemingly innocuous aim of giving government more control over healthcare. To understand this, it may be worth looking at what’s happened during recent decades in Great Britain. Ostensibly, the country has an excellent drug-development record. Indeed, two of the most successful pharma companies, AstraZeneca and GlaxoSmithKline, are headquartered there. Thus, in the midst of the COVID pandemic, working with Oxford researchers, AstraZeneca developed a vaccine.

While the company was permitted to do the initial testing of it in the U.K., that’s actually rare. AstraZeneca may have its corporate offices in Cambridge, but it actually tests its drugs elsewhere: the U.S., Brazil, Russia, India, China, or even the Caribbean—almost never in the U.K. Why? Since Britain created its National Health Service, the potential for profit no longer exists, as drug prices are fixed and kept artificially low by government officials. Those individuals gain nothing when innovation occurs, but they will be blamed if patients die during testing. The result is stasis. Nearly all the critical new medications being developed are tested outside of markets where the government has wholesale control over medical care.

Yet Britain has always had great researchers at its universities. For example, back in the 1970s, scientists at the University of Nottingham devised the initial prototypes for CAT scanners. However, the machines were produced in America, as there was no way to make any money from developing them back in the U.K. A tension exists between too much and too little government control over healthcare. This is true of both the role of regulators and the extent to which the government should run hospitals and healthcare clinics.

One more quick example: in the past few years, the FDA has cautiously approved two drugs for Alzheimer’s treatment. Neither works particularly well for most patients, and they present some real dangers. But the FDA understands that there are patients who could still benefit, that the risks to these patients can be monitored, and that approval of these drugs is a step that will provide incentives to further research and better treatments in the future.

Thalidomide is what can happen without effective regulation. The nearly comatose state of British drug testing is what happens with socialized medicine.

Jonathan Leaf

Jonathan Leaf is a playwright who writes frequently about the arts and culture.