Frances Oldham Kelsey, PhD’38, MD’50, whose refusal to approve the drug thalidomide without extensive safety testing spurred landmark reformations in the way the FDA evaluates drug safety and efficacy, passed away Aug. 7. She was 101.
Thalidomide is now known as a drug that has dramatic side effects when taken by pregnant women, including severe, debilitating birth deformities in their children. It was commonly prescribed in Europe in the late 1950s as a miracle cure for pregnancy-related morning sickness.
Kelsey had recently started her job as a reviewer for the Food and Drug Administration in late 1960, when the application for thalidomide crossed her desk. The American company William S. Merrell had just licensed and begun to distribute thalidomide. At the time, a drug could go on the market for 60 days while the FDA application was reviewed. The requirements for safety testing often relied on anecdotal evidence from doctors prescribing it to their patients—not the strict safety trials required by today’s standards.
That anecdotal evidence simply wasn’t enough for Kelsey, who was trained in both pharmacological research and medicine under Eugene MK Geiling, a noted UChicago researcher and pharmacologist. Her work with Geiling sparked an interest in a group of chemicals called teratogens, drugs that can cause birth defects.
When Kelsey rejected the application, asking for more data such as basic safety assessments of the drug’s effect in pregnant animals, the drug company put pressure on the agency to push approval through. She stood her ground. As Kelsey repeatedly rejected the application, each time requiring more safety data, the scientific community began to make the links between the increased rate of newborn children with conditions such as phocomelia, or flipper-like fins, and the prescription of thalidomide to their mothers. The drug was quickly removed from the market in 1961.
Her persistence kept the exposure of thalidomide to mothers and children in the U.S. to a minimum, but her influence extends beyond just one dangerous drug. Her story sparked a huge push in the early 1960s to reform the drug approval system and to create the modern clinical trial system. Particularly, the passing of the 1962 Kefauver Harris Amendment that required drug companies to provide definitive proof that the drug is both safe and effective before FDA approval and general distribution. She was also crucial in establishing institutional review boards, which are now a cornerstone piece in ensuring ethical practices in medical testing.
Kelsey was awarded the President’s Award for Distinguished Federal Civilian Service by President John F. Kennedy, and is remembered as the champion of modern ethical and evidence-based drug approval. She received the insignia of Member of the Order of Canada shortly before her passing. Kelsey was inducted into the National Women’s Hall of Fame in 2000 and was honored in 2010 by the FDA as the first recipient of an annual award that continues to be given in her name. She received her PhD in pharmacology at the University of Chicago in 1938, and continued on as a faculty member. She was awarded her medical degree from the institution in 1950 while investigating cures for malaria.
Kelsey is survived by her two daughters, a sister and two grandchildren.
—Note: This story first appeared on the Science Life blog.