In 2010, Frances Oldham Kelsey, then 96, was chaperoned by her two daughters as she accepted the very first Dr. Frances O. Kelsey Award for Excellence and Courage in Protecting the Public Health awarded by the Food and Drug Administration. While it was the crowning jewel of her long and remarkable career, Ms. Kelsey received multiple honors during her 101 years on earth, including the President’s Award for Distinguished Federal Civil Service from President John F. Kenneday in 1962. Shamefully, I didn’t know who this woman was.
In September 1960, Kelsey began working for the FDA as a medical officer, reviewing applications for drug approvals. Assuming the application from the William S. Merrell Co. to market thalidomide was a slam dunk, the FDA assigned it to newly hired Kelsey. And we should all be so grateful they did.
Born in 1914, she grew up on Vancouver Island, British Columbia, where a chance meeting with a vacationing teacher ignited an interest in biology. The first school she attended was Leinster Preparatory School in Shawnigan Lake, British Columbia. Theoretically an all-boys school, for several terms Kelsey was the only girl, perhaps laying the groundwork for her success in a male-centric field.
Kelsey graduated from McGill University in Montreal with a Bachelor of Science in 1934 at the age of 20. Canada had been hard hit by the Depression and there were few jobs for young university graduates, so she decided to continue her studies and pursue a Master of Science degree in biochemistry. The biochemistry course at McGill was already full, so she switched her focus to pharmacology, graduating in 1935.
Even with her master’s degree, Kelsey was unable to secure a position and stayed on at McGill as a research assistant. In February 1936, her professor heard that the University of Chicago was opening a new pharmacology department. Kelsey wrote to the chairman of the newly established department, inquiring if there may be an opening for her. Applying her three-cent stamp to the envelope and sending it off, she had no idea what lie ahead. Much to her delighted surprise, on February 15 she received a letter airmail, special delivery telling her, “If you can be in Chicago by March 1st, you may have the Research Assistantship for four months and then a scholarship to see you through a Ph.D.” She was bothered a bit that the letter started out, “Dear Mr. Oldham”. She asked her professor at McGill if she should explain to Professor Geiling the difference between Frances and Francis.
Kelsey arrived in Chicago during a national emergency. The S. E. Massengill Co.’s elixir sulfanilamide, a medicine widely prescribed for colds and other infections had been linked to a mounting nationwide death toll. Kelsey was assigned to a team assembled by Professor Geiling to identify the toxic agent. The group successfully identified the toxic agent as diethylene glycol, used as a solvent in the preparation. Today diethylene glycol is better known as the active ingredient in antifreeze. This scandal exposed the inadequacy of existing regulation.
After completing her Ph.D., University of Chicago offered her a faculty position and by 1942 she was studying drugs that would cure malaria. This was the start of Kelsey’s interest in drugs that pass from mother to fetus through the placenta.
In 1960, Professor Geiling was head of the new pharmacology center for the FDA and recruited Kelsey who would serve as a medical officer, reviewing applications for drug approvals in the U.S. Providentially, she was assigned thalidomide, a painkiller/tranquilizer used to reduce nausea. Pregnant women suffering from morning sickness were considered particularly suitable candidates for the drug.
Even without approval, in 1960 American law allowed the company to send experimental samples to doctors. Merrill sent 2.5 million tablets to over 1,000 American doctors who administered it to almost 20,000 patients, hundreds of whom were pregnant.
“The burden of proof that the drug is safe…lies with the applicant.”
Kelsey was unimpressed by Merrell’s application and refused to approve it, telling them their risk assessment was inadequate, relying on anecdotal testimony in place of clinical data. She wanted more data from controlled studies. She was extremely concerned when she realized no trials had been carried out on pregnant animals to discover if the drug could cross the placenta.
FDA drug review had to be completed within 60 days, otherwise drug approval become automatic. Merrell waged an aggressive campaign for approval, but Kelsey held firm to her scientific and ethical principles, continually blocking the approval of thalidomide and requesting additional data.
Sadly, in the late 1950s and early 1960s, about 2,000 children died and 10,000 were born malformed as a result of their mothers being given thalidomide during pregnancy. Finally in November 1961, thalidomide was withdrawn in Germany for use by pregnant women. Largely due to the heroic effort of Frances Oldham Kelsey, only 17 of these “thalidomide babies” were born in the United States.
The blocking of FDA approval of thalidomide is the best known of Kelsey’s accomplishments, but she had a long and vibrant career with the FDA. in 1963, she was appointed head of their investigational drug branch. In 1967, she become director of the office of scientific investigations, a position she held until she was 80. Even then, she continued working at the FDA as an advisor, finally retiring at age 90 in 2005.
Of all the information available online about Frances Oldham Kelsey, my favorite was her “Autobiographical Reflections.” In the opening paragraph, she talks about a letter she received in 1987 from an eighth-grade girl who was preparing a speech on Kelsey. She did ask for a couple of facts, but what got Kelsey’s attention was when she wrote: “But, most of all, perhaps you could describe how hard it was to be a woman studying science and medicine when most of your classmates were men. Perhaps you could also tell me how frustrating it must have been to find work when people thought a woman should only be a housewife.”
The last line of her Autobiographical Reflections is “It has been an interesting career.” Kelsey helped open the door for women to medical and scientific research. She was instrumental in inspiring legislation that tightened the testing parameters on experimental use of drugs and strengthened the authority of the FDA. She inspired a young girl to give a speech about her. And she did all this while marrying and having two children. A woman of consequence.