Profiles in Character #5: Frances Oldham Kelsey Prevents the Use of Thalidomide

Frances Oldham Kelsey was not predestined to save American babies from the devastating effects of Thalidomide, but she was prepared to do so, by training and temperament.  With a master’s degree in pharmacology from McGill University, she got into the doctoral program at the University of Chicago in 1936 because the department chair thought “Frances” was a man.  With her doctorate, her ongoing research revealed that some drugs can cross the placental barrier.  This would later prove a critical insight.  After gaining her M.D. in 1950, she taught and ended up at the FDA in 1960.

With her past as preparation, in September of that year she was asked to review the application for the use of Thalidomide in the United States.  It was not by design - she just happened to be the next in line for an assignment.  The drug had already been approved for use in more than 20 nations as a sleep aide, tranquilizer and painkiller, and was also being used to treat morning sickness in pregnant women. Though reports from Europe indicated that it was effective and not dangerous, even in large doses, Kelsey was not convinced.  She was troubled by an English study that showed a nervous system side-effect.

Interviewed later, Kelsey said she was “very unimpressed” by the European studies.  She had, she said, “lived through cycles before” in which a widely touted drug’s harmful effects did not show up until a year or two of widespread use.  She was also troubled by the fact that animal studies did not show it made them sleepy, though that was one of the chief claims made for its use with humans.  So she waited, despite repeated contacts from the applicant, Richardson-Merrell.

The wait, viewed as an unreasonable delay by the applicant, provoked criticism of Kelsey.  When she did not act by the 60-day timeline after the initial application, the firm supplied more data on Thalidomide’s effectiveness, but she was still not satisfied after the next 60-day period, writing another letter – which started a new 60-day cycle.

Kelsey was not unmindful of the concerns of Richardson-Merrell, but she persisted in her determination to demand data that proved the drug was safe.  Her relations with pharmaceutical firms were “usually amiable,” she said. “We see their point, and they see ours. But the responsibility for releasing a drug is ours, not theirs."

It was not until April 1961 that reports came back from an American researcher visiting Europe of an alarming incidence of birth defects in women who had been taking Thalidomide.  Though it had been on the market in West Germany since 1958, in 1959 only 12 troublesome cases showed up, but by 1961 this had mushroomed to 302.   Babies were being born without limbs, with only flippers for limbs, with facial defects and other problems.  Still, these very troubling indications were not conclusive proof that Thalidomide was the culprit.  But they were enough for Kelsey to persist in her refusal to approve the drug.

The application for approved use in the U.S. was pending, and Kelsey continued to deny it – with the support of her superiors.  It was not until November 30, 1961, that the application was finally withdrawn. Subsequent research confirmed that Thalidomide crossed the placental barrier to impact the growing fetus.

The story of Kelsey’s work – and that of her colleagues whom she insisted should also be recognized – broke in a Washington Post story in July 1962.  By October, Congress passed legislation requiring companies to report adverse side-effects of medications and demanding that “"effectiveness [should be] required to be established prior to marketing.”

Kelsey acknowledged that, if Thalidomide had been proven effective and safe, “I would have been considered unreasonable."  Yet, she added, she would continue “playing for that 10th chance in 10 to assure safety in new drugs "to the best of my ability."

In an August 7, 1962, White House ceremony, President Kennedy gave Kelsey the very first President’s Award for Distinguished Federal Civilian Service.  In presenting the award, he said that “Through high ability and steadfast confidence in her professional decision, she made an outstanding contribution to the protection of the health of the American people.”

Kelsey would go on to lead the FDA’s drug testing program.  She would not retire until 2005 at the age of 90.

Photo Credit: U.S. Food and Drug Administration