How one scientist averted a national health crisis - Andrea Tone

In the fall of 1960, Frances Oldham Kelsey was one of the Food and Drug Administration’s newest recruits. Before the year was out, she would begin a fight that would save thousands of lives, though no one knew it at the time. Although she was new to the FDA, Kelsey was no novice as a scientist. After graduating from high school at age 15, she enrolled at McGill University in Montreal and earned both undergraduate and master’s degrees in pharmacology. From there, she applied for a research post at the University of Chicago’s pharmacology department. Her acceptance letter was addressed to Mr. Oldham. Kelsey later joked that had her name been Elizabeth or Mary Jane, her career might have ended there. Fortunately, it didn’t. She earned her doctorate in pharmacology and accepted Chicago’s invitation to stay as faculty, where she undertook pioneering research on drugs and fetal safety. In 1950, she earned an MD, her fourth and final degree. By the time she joined the FDA, Frances Kelsey was one of the most educated, experienced scientists around. Yet, as the newest member of the team, Kelsey was assigned what everyone thought would be an easy review: an application from the US drug company Merrell to sell a drug called thalidomide. Thalidomide was a sedative developed in Germany that was already being widely used in dozens of countries to treat insomnia and workplace stress. Thalidomide’s anti-nausea properties also made it a popular remedy for pregnant women with morning sickness. Reviewing Merrell’s application, Kelsey found its data on thalidomide’s absorption and toxicity inadequate. Today, the FDA classifies drugs based on their safety for a fetus. But in 1960, many experts believed that the placental barrier shielded a fetus from harm. Kelsey’s earlier animal-based research demonstrated the opposite: drugs could pass from mother to fetus through the placenta. Like other drug companies at this time, Merrell had not tested its drug on pregnant animals. Kelsey later said Merrell’s evidence for thalidomide’s safety seemed “more like testimonials than the results of well-designed studies.” Kelsey rejected Merrell’s application and asked them to submit a second backed by better evidence. Her FDA colleagues supported this decision. Merrell had expected a quick, affirmative reply so it could launch thalidomide for the holiday season, when sedative sales soar. Instead of supplying Kelsey with the data she requested they first tried to convince her to approve the drug over a series of calls and visits. When these failed to sway her, Merrell executives complained that stubborn and nit-picking Kelsey was the problem, not thalidomide. The FDA backed Kelsey, forcing Merrell to file another application, and another, and another. As Kelsey reviewed and rejected each new application, news of thalidomide’s adverse side effects began to surface. Doctors reported cases of nerve damage in early 1961, and by fall, they’d unmasked a more horrible truth. Thalidomide, widely used by pregnant women, caused severe birth defects. Thousands of babies died in utero, and tens of thousands more were born with extra appendages, shorter limbs, or no limbs at all. In November 1961, thalidomide was pulled from the German market. Nonetheless, Merrell continued trying to get it approved in the US for several months before withdrawing their sixth and final application. While Kelsey wasn’t the only scientist to identify the risks of thalidomide, she sounded the alarm that kept it off the multi-billion-dollar American drug market. As public awareness of the thalidomide tragedy grew, the quiet scientist became a media sensation. Headlines in newspapers and magazines heralded her heroism while a smiling President John F. Kennedy presented her an award on the White House lawn. After the thalidomide scare, Congress passed laws that expanded the FDA’s authority and toughened requirements for new drug applications. Kelsey was tapped to head the agency’s drug investigation branch. Working at the FDA in different capacities into her 90s, Kelsey was able to witness the changes her actions helped inspire. Her visibility may have dimmed since, but her legacy endures. Privileging facts over opinions, and patience over shortcuts, she made evidence-based medicine the foundation of reforms that continue to protect people today.