Before the modern era of medicine, during the first few decades of the 20th century, three of the top 10 causes of death in the United States were pneumonia, tuberculosis, and diarrhea/enteritis—all infections. Identifying drugs that could fight these infections—antibiotics—was a public health priority, worldwide.
While the safety of food and drugs, and the impact on public health, was at the core of the formation of the Food and Drug Administration, none of the legislation that created the agency in 1930 actually focused directly on a drug’s safety. Accurate labeling, yes. Prescribing limits and precise documentation of narcotics, sure. But drugs could still be sold that not only didn’t work but also simply weren’t safe, because they hadn’t been tested for safety.
That absence of a requirement to demonstrate a drug’s safety would prove to be deadly.
In 1932, a German pathologist and bacteriologist, Gerhard Domagk, discovered that a chemical called prontosil protected against bacterial infections in mice. Prontosil was converted to an active ingredient called sulfanilamide, which could fight streptococcal infections in humans (one cause of pneumonia deaths, which were actually the No. 2 cause of mortality in the early 20th century). Over the next few years, pharmaceutical companies including Merck, Squibb, and Eli Lilly started to manufacture sulfanilamide mostly as pills and tablets.
The S.E. Massengill Company of Bristol, Tennessee, had a different idea—to create a liquid form of sulfanilamide that would be easier to ingest for patients, particularly children. But sulfanilamide didn’t taste very good, so the company’s chief chemist, Harold Cole Watkins, added other substances to the solution, including raspberry extract, saccharin, caramel—and the sweet-tasting solvent diethylene glycol. More commonly known as antifreeze.
The company’s internal control lab approved the appearance, flavor, and fragrance of the concoction. But testing for toxicity wasn’t required under the Pure Food and Drug Act or its amendments. In September of 1937, 240 gallons of the liquid, called Elixir Sulfanilamide, were distributed across the country in 633 shipments. And doctors started prescribing it.
By October, six patients from Tulsa, Oklahoma, who were prescribed the antibiotic had died of kidney failure. The doctor who gave these patients sulfanilamide, A.S. Calhoun, M.D., was horrified at his unsuspecting role in the tragedy. He wrote in a letter to a colleague:
Nobody but Almighty God and I can know what I have been through these past few days. I have been familiar with death in the years since I received my M.D. from Tulane University School of Medicine with the rest of my class of 1911. Covington County has been my home. I have practiced here for years. Any doctor who has practiced more than a quarter of a century has seen his share of death.
But to realize that six human beings, all of them my patients, one of them my best friend, are dead because they took medicine that I prescribed for them innocently, and to realize that that medicine which I had used for years in such cases suddenly had become a deadly poison in its newest and most modern form, as recommended by a great and reputable pharmaceutical firm in Tennessee: well, that realization has given me such days and nights of mental and spiritual agony as I did not believe a human being could undergo and survive. I have known hours when death for me would be a welcome relief.
The American Medical Association and the FDA were notified. They asked for samples of the drug and demanded to know the composition of the compound from the Massengill Company. Before long, the antifreeze was identified as the cause of death.
Responsibility for action fell to the commissioner of the new FDA, Walter Campbell, who was first appointed by Harvey Washington Wiley as his chief inspector after passage of the 1906 act, soon after Campbell had graduated from law school. He ordered the majority of his 239 inspectors and chemists both within and outside the FDA to investigate, at Massengill headquarters and at branch offices across the country. Included among them was a young graduate student, Frances Oldham Kelsey, who would go on to become quite famous for her work with the FDA. The company had already sent telegrams to more than 1,000 salesmen, druggists, and doctors politely requesting return of the drug, but without indicating it was deadly. The FDA demanded a more pointed, second wave of messages, and a radio and newspaper campaign was initiated to warn the public about Elixir Sulfanilamide.
The next step was to try to retrieve the 240 gallons of the deadly solution that had been shipped around the country. A team of FDA inspectors scrutinized shipping records, distribution lists, and thousands of order slips; they tracked down the company’s 200 salesmen to identify the drugstores and doctor’s offices that had stocked the elixir. The team reviewed prescriptions to locate the purchasers of the drug—a particularly challenging task when some locations, like one in East St. Louis, Illinois, had filled prescriptions on which the only identification of the patient was “Mrs. Jackson” or, for a child, “Betty Jane,” with no address provided.
Store by store, druggist by druggist, and prescription by prescription, the FDA team worked to find every patient who still had a bottle of the elixir and to confiscate the remaining medicine. Inspectors went to extraordinary lengths in some instances to find discarded bottles: One inspector, hearing about a bottle tossed out of a patient’s window, was able to track down the remaining ounce or two among the detritus of an alley.
Another learned of a patient who had died from the tainted antibiotic and heard that the custom in one small South Carolina community was to leave leftover medicines in the dirt over a person’s grave. The inspector went over to the cemetery where this patient was buried, found his grave, and spied the sulfanilamide bottle, rising from the soil like an unholy crocus in early spring. Through their dogged efforts, the FDA’s inspectors managed to recover 234 gallons and 1 pint of the original 240 gallons that had been shipped. The remainder had been consumed.
All told, 71 adults and 34 children died as a result of taking the liquid antibiotic that was tainted with poison, as far east as Virginia, and as far west as California. Many had the same symptoms that had affected the first six victims from Oklahoma, including kidney failure, severe abdominal pain, nausea and vomiting, and convulsions that are now recognized consequences of ingesting antifreeze. In a heart-wrenching letter to President Franklin Roosevelt, one mother of a girl who died wrote:
The first time I ever had occasion to call in a doctor for [Joan] and she was given Elixir of Sulfanilamide. All that is left to us is the caring for her little grave. Even the memory of her is mixed with sorrow for we can see her little body tossing to and fro and hear that little voice screaming with pain and it seems as though it would drive me insane. … It is my plea that you will take steps to prevent such sales of drugs that will take little lives and leave such suffering behind and such a bleak outlook on the future as I have tonight.
The owner of the manufacturing company. Samuel Evans Massengill, was far less emotional, declaring sanctimoniously:
My chemists and I deeply regret the fatal results, but there was no error in the manufacture of the product. We have been supplying a legitimate professional demand and not once could have foreseen the unlooked-for results. I do not feel that there was any responsibility on our part.
His chief chemist did not agree. Horrified at the deaths his recipe had caused, on Jan. 17, 1939, Harold Watkins died by suicide, using a gun to shoot himself in the heart.
A 16-page report to Congress from Secretary of Agriculture Henry Agard Wallace (a future vice president under Franklin Roosevelt) was full of condemnation for the S.E. Massengill Company. Wallace lambasted an inadequate federal law that could not be invoked to head off more deaths. In fact, the only way the FDA could hold the company accountable for the disaster was by challenging the label’s use of the word elixir, which implied that the solution contained alcohol, which it didn’t.
Had the manufacturer called its medicine “Sulfanilamide Solution,” the FDA could not have held it responsible for the deaths at all and would have had no legal authority to recover the medicine. The report further stated that “before the elixir was put on the market, it was tested for flavor but not for its effect on human life.” A few simple experiments would have averted the tragedy. Wallace cited other drugs that had injured patients, including dinitrophenol, used for weight loss, which had caused blindness and death in a few, and cinchophen, a drug used for rheumatism, which had caused liver damage. Wallace implored Congress to regulate the distribution of highly potent drugs through an adequate federal food and drug law.
Public outrage in response to the tragedy reached a crescendo, and Congress finally acted. Royal S. Copeland, M.D., a physician and three-term senator from New York, became the principal author of what would become the Federal Food, Drug, and Cosmetic Act. It passed both the House and the Senate, and President Franklin Roosevelt signed it into law on June 25, 1938.
Drugs and the FDA: Safety, Efficacy, and the Public’s Trust
By Mikkael A. Sekeres. MIT Press.
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In an article written for the Journal of the American Medical Association in 1939, Theodore Klumpp, M.D., who at the time was chief of the Drug Division at the FDA, predicted that the new law would lead to a lower incidence of poisoning, to more intelligent purchasing and use of drugs by the public, and, for the first time, to a doctor’s implicit trust in the strength, quality, purity, and safety of the medications that would be prescribed to patients.
All the things we take for granted nowadays when recommending and taking drugs.
Excerpted from Drugs and the FDA: Safety, Efficacy, and the Public’s Trust. Copyright © 2022 by Mikkael A. Sekeres. Used with permission of the publisher, MIT Press.