The Accidental Poison That Founded the Modern FDA

In 1937, the antibiotic Elixir Sulfanilamide killed more than 100 Americans. “The first time I ever had occasion to call in a doctor for [Joan] ... she was given Elixir of Sulfanilamide,” wrote the mother of one of the drug’s many young victims, in a letter imploring President Franklin Delano Roosevelt to ban the medicine. “All that is left to us is the caring for her little grave.”

At the time, taking a new drug was like playing Russian roulette. It could bring patients back from the brink, or it could push them over. A year earlier, the president’s own son, Franklin Delano Roosevelt Jr., had been saved by a related but safe antibiotic, Prontosil. Only luck spared Franklin yet condemned Joan.

The scale of the Elixir Sulfanilamide tragedy prompted American lawmakers to ask what could be done to prevent this deadly gamble from happening again. Their simple but effective answer was the Federal Food, Drug, and Cosmetic Act, or FFDCA, which FDR signed into law June 25, 1938.

Since then, mandatory safety testing of new foods and drugs has been the law of the land. Even so, drug safety isn’t guaranteed, and the FDA’s commissioner, who has had ties to the pharmaceutical industry, expressed the desire to reduce drug regulation before he took the helm at the agency.

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The story of Elixir Sulfanilamide starts with the German dye industry. Paul Ehrlich, the visionary doctor who invented the first reliable treatment of syphilis, started his career by working on how to stain cells so they show up better under a microscope. Through careful experimentation, Ehrlich found that some dye molecules, the same ones used to color garments, only stain bacteria. This led Ehrlich to a radical hypothesis: What if it were possible to dye molecules so that they would only attack bacterial cells, leaving human cells alone? A powerful antibiotic might be the result. Ehrlich spent much of his career trying to test this question. Despite his success with the arsenic-containing atoxyl, its tendency to cause vision problems in patients made doctors wary.

Still, chemists at Bayer Laboratories remained convinced that dyes would reveal the world’s first true antibiotic. Bayer and its parent company, IG Farben, were specialists in making dyes. Its chemists Josef Klarer and Fritz Mietzsch had special expertise in meticulously tuning them and changing their properties. Thousands of different dyes were made by the Bayer team and tested by Gerhard Domagk, a doctor who tried to cure bacterially infected mice with them, often without success.

In 1932, Domagk tested a red dye that caused complete recovery in the mice. That drug was Prontosil. He went on to win the 1939 Nobel Prize in Medicine for discovering this antibiotic that saved Franklin Delano Roosevelt Jr.’s life.

Further research by a team from France found that Prontosil breaks in half after patients take it, and that only one of the two pieces matters for fighting bacteria. This small fragment, called sulfanilamide, worked just as well as Prontosil for curing diseases. Even better, the patent protecting it had expired years earlier, opening the possibility for anyone to make medicines that used it. Bayer tried to sell a version of sulfanilamide after this discovery, but found that the challenges of competing with generic manufacturing companies made it unprofitable.

One of sulfanilamide’s greatest strengths, drawn from its heritage in dyes, was also one of its greatest weaknesses as an antibiotic: It wouldn’t dissolve in water. A good dye shouldn’t come out when the clothes or carpet gets cleaned, but it’s much harder to get people to eat a dry powder than a spoonful of medicinal syrup. Sulfanilamide was simply too hard to eat for it to be broadly useful in medicine, especially for children.

Samuel Evans Massengill, the head of S.E. Massengill Company, set out to solve this problem. He challenged his head chemist, Harold Watkins, to make a sweet, liquid form of sulfanilamide. After much experimentation, Watkins found that a solvent, diethylene glycol, could dissolve buckets of the stuff. Watkins added a little bit of raspberry flavoring and, satisfied with the final product, started manufacturing “Elixir Sulfanilamide.”

Problems didn’t arise until patients, many of them children like Joan, started taking Elixir Sulfanilamide. Nausea, vomiting, and abdominal pain appeared first, often followed by kidney failure, weakness, and coma for those who had consumed the mixture. For 107 of the drug’s recipients, death was the final outcome. Frances Oldham Kelsey, a steadfast FDA scientist, identified diethylene glycol as the poisonous component of the mixture—something that Watkins, Massengill’s chemist, had not known when designing the concoction. Watkins, who became increasingly overwhelmed by the climbing death toll from his creation, took his own life less than two years after devising the mixture.

Massengill was summoned to court to answer for the disaster his company had unleashed. He was unrepentant: “We have been supplying a legitimate professional demand and not once could have foreseen the unlooked-for results,” he testified. “I do not feel that there was any responsibility on our part.”

Under the laws of the era, he was right. There was no requirement for demonstrating that new medicines were safe. In fact, the only demand the FDA imposed on new medicines required that they be labeled accurately. Massengill was prosecuted to the maximum extent under this provision (he had misused the term “elixir” on his medicine; an “elixir” must use ethanol as a solvent, not diethylene glycol), and he was fined $26,000—over $400,000 today.

Though legal, the Elixir Sulfanilamide incident catalyzed public interest in drug regulations to prevent such tragedies. Royal S. Copeland, a senator from New York, responded to the outcry by introducing the FFDCA to the Senate on March 5, 1938. After two breakneck trips through both houses, the final FFDCA ended up on President Roosevelt’s desk on a hot Saturday in June, enshrining in law the right and responsibility of the FDA to demand the safety of new foods and drugs with his signature. Elixir Sulfanilamide had claimed no less than 107 innocent lives, but it protected countless more from enduring a similar tragedy.

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The FFDCA protected the public from unsafe medications, but its limitations quickly became apparent. For one part, it provided a short window for the FDA to block unsafe drugs from being sold—only 60 days. For another, it didn’t allow the FDA to ensure the quality of the medications or even to require that they worked as advertised. The Kefauver-Harris Amendments of 1962 helped address these problems. As Margaret Hamburg, the FDA commissioner from 2009 to 2015, explained, “With the passage of the amendments, FDA was no longer a helpless bystander while unproven medicines were streaming into pharmacies and onto patients’ bedside tables.”

Much like the FFDCA of 1938, the Kefauver-Harris Amendments were only passed due to a medical catastrophe—this time the horrific birth defects caused by the sedative thalidomide. While the United States was mostly spared from thalidomide by the work of Frances Oldham Kelsey—the same scientist who determined the poisonous component of Elixir Sulfanilamide—it illustrates how FDA regulations often arise in response to disasters rather than in anticipation of them.

Today, however, Scott Gottlieb, the FDA commissioner appointed by President Donald Trump, has taken an irreverent view on the safeguards that history has grudgingly established. In 2012, he wrote that the FDA has focused so much on protecting consumers that it has “sometimes subordinated and neglected its other key obligation, which is to guide new medical innovations to market.” For Gottlieb, consumer protection might be getting in the way of commercialization. “On the whole,” he wrote, “the agency’s reviewers believe it is appropriate to prioritize safety over speed.” This suggests that the FDA might be willing to loosen regulations that protect the public from the unexpected effects of insufficiently tested drugs in order to make them more immediately profitable.

It is difficult to assess Gottlieb’s impact on the FDA after less than a year in his role as its head. Even so, his views, particularly those relating to safety and consumer protections, are a departure from the norm. If the FDA does move to decrease regulation on drugs, the agency should remember conditions before the FFDCA of 1938. When Elixir Sulfanilamide claimed 107 American lives, the FDA had been powerless to stop it. A similar tragedy would only be worse if the agency has the power, as it does today, but refuses to exercise it.