Dr. Kelsey was the medical pharmacologist at the FDA who refused to license thalidomide for the U.S. market despite the enormous pressures put upon her by a pharmaceutical company. Her determination not to license the drug until its safety was demonstrated by evidence spared Americans from the worst pharmaceutical catastrophe in history. Furthermore, as a result of the magnitude of the averted harm, Congress enacted amendments to the Food and Drug laws requiring scientific evidence of both safety and efficacy for FDA licensure, and prohibited the distribution of an unapproved drug to physicians.
Thalidomide was first marketed in West Germany in 1957 and widely used in 46 countries under 39 different brand names (some say 51 brand names). It was prescribed as a sleeping pill and for pregnant women experiencing morning sickness. Early case reports of the drug’s serious adverse effects were dismissed by its manufacturer. During the four years in which it was widely prescribed, thalidomide caused catastrophic grotesque malformations in babies’ bodies while in their mothers’ womb. Thalidomide triggered at least 100,000 miscarriages, an untold number of infant deaths. Of the 10,000 severely deformed infants who survived, more than 50% died within a few years. Women committed suicide believing it was their fault. The thalidomide survivors suffer pain and physical deterioration beyond their years (Roger Williams. Newsweek, 2012).
In 1960, Dr. Kelsey’s first assignment at the FDA was to review the licensing application for thalidomide by its U.S. distributor was Richardson-Merrell (a subsidiary of Vick Chemical). The drug’s manufacturer was Chemie Grünenthal, a German company promoted it as a “wonder drug” for insomnia, headaches, coughs, and worst of all, it was recommended to pregnant women against morning sickness; its promotional booklet guaranteed that the drug could be “given with complete safety to pregnant women and nursing mothers without any adverse effect on mother and child.” [Recently uncovered documents during the course of litigation reveal that the company’s scientists were Nazi war criminals. See *
Dr. Kelsey was dissatisfied with the manufacturer’s evidence of thalidomide’s safety; she discovered that many of the company’s claims were not backed up with evidence. She searched the literature and read a physician’s letter in a British medical journal in which he raised concern that thalidomide might be causing peripheral neuritis — deterioration of the nerves in the feet and fingers in patients who had used thalidomide over a period of time. This was a red flag for Dr. Kelsey; she notified the company. They responded that this occurred in only one case among 300,000. But she learned the incidence was 1 in 250.
At that time, the FDA had 60 days in which to review a company’s marketing application for a new drug. If the FDA had no objections, the manufacturer was free to market the drug. During the 60 day waiting period, manufacturers sent samples of their new drugs to physicians supposedly “for research purposes.” Doctors distributed these “free samples” to their patients. While thalidomide was under review by Dr. Kelsey, Richardson-Merrell distributed the tablets to more than 1,000 doctors who gave them to about 20,000 patients.
“I had the feeling throughout the day, that they were at no time being wholly frank with me and that this attitude has obtained in all our conferences, etc., regarding this drug.” — Dr. Frances O. Kelsey said of her meetings with Merrell Drug Co.
When the 60-day deadline for FDA action drew near, Dr. Kelsey wrote the manufacturer that proof of safety had not been established. She asked that the company conduct a clinical trial; they refused. She asked that they obtain information from the physicians who were given sample tablets, but the company didn’t comply. She then asked for the names of patients who had been given the samples, but the names were not provided.
She conducted further research and discovered that some of the documents used to “prove” thalidomide’s safety were falsified. A previously hidden memorandum found in the archives of the FDA in 2010, shows that in 1956–1957, after being approached by the manufacturer of thalidomide to market the drug in the U.S., Smith Kline & French (now GSK) conducted animal tests and a trial involving 875 people in the U.S, including pregnant women. After the test results Smith Kline declined to market the drug, whereupon Richardson-Merrell was engaged. It is not known whether Dr. Kelsey was aware of those tests and their results.
What is known is that Dr. Kelsey was harassed by the company to approve the drug. She recalled how they “came in droves . . . wrote letters and telephoned as often as three times a week. . . Most of the things they called me, you wouldn’t print.” (LA Seidman and N Warren, American Biology Teacher, 2002) The Washington Post later described her ordeal under pressure: as “living the while with insinuations that she was a bureaucratic nitpicker, unreasonable — even stupid,” complained to her superior and threatened to file a lawsuit. Dr. Kelsey stood her ground and refused to back down because she was troubled by the drug’s different effect in humans compared to animals who were not made sleepy by the drug.
In April 1961, just when thalidomide was approved in Canada, reports from Germany of an unprecedented outbreak of phocomelia (Greek, meaning seal limb). An alarming number of grotesquely malformed babies were born; some with foreshortened and distorted limbs, some without both arms, or three missing limbs; others with malformed ears or eyes; and some were missing genitals or lacked openings for their ears or bowels. Less than 50% survived. Dr. Kelsey’s concerns about the drug’s safety were horribly vindicated.
In the U.S. an estimated 40 babies were severely handicapped by the “free” samples the company had provided doctors who distributed the drug to their patients.
Dr. Kelsey was publicly honored for her courage: in August, 1962, President John F. Kennedy presented her with the Distinguished Civilian Service Medal, acknowledged: “Her exceptional judgment in evaluating a new drug for safety for human use has prevented a major tragedy of birth deformities in the United States.”
Dr. Kelsey was the catalyst for a strengthening federal drug safety laws which Senator Estes Kefauver had tried for years to pass, but could not overcome industry lobbying. After The Washington Post front-page article exposed the effects of thalidomide on newborn babies to the public, industry’s opposition was overcome; the public demanded more government regulation and safer drugs.
Congress enacted the Kefauver-Harris Drug Amendments Act in 1962 to restore public confidence. It gave the FDA additional authority to demand that companies prove their drugs to be not only safe, but also effective before obtaining approval to market them in the U.S. The law mandated that drug manufacturers maintain records of adverse events linked to drugs and promptly report these to the FDA; and it required that drug advertisements include information about their side effects.
When she was 80, she was the director of the Office of Scientific Investigations for the FDA. She warned those at the agency who were about to weaken the FDA oversight, “Let’s not go backwards. We’ve seen enough tragedy.” (Saul Friedman, Gray Matters FDA’s Sad Slide: Warnings Went Unheeded, 2004)
In 2010, the FDA initiated the Dr. Frances O. Kelsey Award for Excellence and Courage in Protecting Public Health. Fittingly, it selected Kelsey — then 96 years old — as the first recipient. Unfortunately, few FDA safety officers have shown similar courage; despite those 1962 amendments, FDA is now more than ever under the influence of the pharmaceutical industry. Its undue influence is demonstrable in the number of “bad drugs” the FDA has licensed only to be withdrawn AFTER they have cut lives short.
At 100, Dr. Kelsey continues to live in her house in Chevy Chase, Maryland. She is in good health and the strongest medication she has taken in the past many years is, perhaps, an aspirin.