Updated: Oct 17, 2020
Frances Kelsey and a set of scales
On Day 5 of the countdown to National Kick Butt Day (October 14), I am honoring Frances Oldham Kelsey, the scientist who prevented an untold number of congenital deformities from thalidomide. Like the other women in this series of articles, Frances was a member of the Society of Woman Geographers.
Grad School or Bread Line?
Frances graduated from college during the Depression when jobs were hard to come by. She had been hesitant to apply to graduate school because she was unsure if she was bright enough to be accepted. But the Depression left her with only two choices: graduate school or the bread line. She decided in favor of graduate work.
Frances applied to the biochemistry department at McGill University, but the master’s class was full. A professor suggested, “Why don’t you go upstairs to the pharmacology department? Dr. Raymond Stehle is working on the posterior lobe of the pituitary, and he does not like graduate students very much, but he might take you.” Frances’ philosophy was: “Trust luck, and you will get along in life,” and so she ran upstairs, and asked Dr. Stehle to supervise her graduate studies. As luck would have it, he agreed.
After Frances earned a master's degree in pharmacology, Dr. Stehle suggested that she write to Dr. Eugene Geiling at the University of Chicago about a Ph.D. She recalled:
“Postage was three cents in those days. Not much was lost, and my hopes were not very high, but to my great surprise I got back a letter Air Mail, Special Delivery, on February 15 (I remember the date).
It said: “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. Please wire immediate decision.”
But there was a hitch.
“There was just one thing that bothered me a little about that letter. It started out, ‘Dear Mr. Oldman,’ [Frances’s maiden name] and here my conscience tweaked me a bit. I knew that men were the preferred commodity in those days. Should I write and explain that Frances with an ‘e’ is female and with an ‘i’ is male?”
She asked Dr. Stehle for advice. He replied:
“Don’t be ridiculous. Accept the job, sign your name, put Miss in brackets afterward, and go!”
She moved to Chicago and started working for Dr. Geiling. She often wondered if the professor would have given her the job offer if he had realized she was a woman. Probably not: “He really did not hold too much with women as scientists. But he was very fair, and a number of women graduated from his department. I was his first Ph.D student.”
Poisoning the Children
During her second year, the Food and Drug Administration (FDA) asked Dr. Geiling for help to determine why people who took a liquid form of sulfanilamide were dying. At the time, sulfanilamide was considered a wonder drug.
“Its use spread very rapidly all over the world, so fast that no basic scientific work had really been done on this drug. But it had drawbacks, the patient had to take a large dose, the pills were pretty unpalatable and disagreeable to take, it caused gastrointestinal upsets, and so on.” To avoid these problems, the manufacturer decided to put it in a liquid solution and add some cherry flavoring and pink dye to be more attractive to children. “It sold like wildfire,” said Frances.
“Then the reports came in of fatalities.”
The FDA called Dr. Geiling and asked him to investigate the deaths. Frances helped. They discovered that the manufacturer had added diethylene glycol—antifreeze—to dissolve the chemical for more palatable ingestion. Dr. Geiling testified before Congress and told them that a toxic additive was causing the deaths. Alarmed, Congress passed the Federal Food, Drug, and Cosmetic Act of 1938, which required manufacturers to prove that a drug is safe before it goes on the market.
Which is worth more: a cow or a woman?
During World War II, Frances worked with Dr. Geiling testing out anti-malarial drugs. A veterinarian sent her a medication:
“It looked like ink and was shipped in what looked to be an ink bottle. He said he was hoping to use it to treat a plasmodium-like parasite in cattle.”
“He also said that he had just tried it on his secretary without ill effects, and he planned next to try it on cattle. It shows the relative value placed on women and cattle in Texas.”
In 1943, Frances married Fremont Ellis Kelsey, a biochemist who worked in her department. The university’s rules prohibited family members from working in the same department, and so they agreed that one of them should go to medical school. Frances volunteered, in part because, as a woman, she needed the extra credentials:
“Let us face it, I needed all the help I could get to obtain a job.”
She had her first child while she was in medical school. After graduation, Frances got a job as an editor for the Journal of the American Medical Association (JAMA). She continued to work part-time with Dr. Geiling.
Eventually, the Kelseys moved to South Dakota so that Fremont could serve as the head of the Pharmacology Department at the medical school in Vermillion, a small town. After eight years, they decided they preferred to live in a big city. They applied to jobs, and Frances got the first offer: medical reviewer with the FDA. She was worried about being the sole breadwinner for the family, but her anxiety was short-lived because the National Institute of Health (NIH) offered both her and her husband a job. “Things were looking up.” Frances accepted the position with the FDA.
Kelsey, Thalidomide, and Marilyn Monroe
During her first month, Frances was on a team that reviewed the sedative thalidomide. It was the second drug she reviewed as a medical officer for the agency. It was supposed to be an easy task since the drug had already been approved in Europe. She rejected thalidomide because the clinical studies were insufficient: “They were more in the nature of testimonials rather than well-designed, well-executed studies.” She asked Merrell Pharmaceuticals to submit more rigorous clinical studies.
Frances Kelsey at the FDA
While she was awaiting the new clinical studies, she happened to read an article about thalidomide that noted a side effect, nerve inflammation, which seemed unusual for a sleeping pill. She asked Merrell’s representative, Dr. Murray, a bacteriologist (not an M.D.), to look into the matter. After returning to Germany and investigating the side effect, Dr. Murray advised Frances that peripheral neuritis was not a concern. Unconvinced, Frances accused Dr. Murray of hiding the neurological toxicity of thalidomide.
From her work with Geiling, she knew that an embryo could not metabolize drugs as effectively as the mother. She worried about the effect of thalidomide on a fetus while the mother was taking the drug, perhaps for as long as the entire pregnancy. Dr. Murray claimed he did not know of any problems in pregnancy, but Frances refused to believe him. She had discovered that a patient in Europe who had taken the drug during pregnancy had delivered a deformed baby. More reports of deformed babies started to emerge—even by women who had taken just one pill during pregnancy. She continued to push Dr. Murray for answers.
Frances knew that Merrell would try to pressure her into getting the drug on the market. So, she was not surprised when Dr. Murray expressed his irritation with her continued refusal to approve thalidomide. As Christmas approached—sixteen months into the review process—he ramped up his demand that she approve the drug.
“Apparently, Christmas is the season for sedatives. It looked like a second Christmas season was coming around with no drug.”
Frances was surprised when, less than thirty days before the holidays, Dr. Murray informed her that Merrell was withdrawing the drug because it caused birth defects. He had concluded that Frances would not be bullied into approving the drug.
After Merrell withdrew the drug in Europe, Frances went to each U.S. physician who had received thalidomide as part of a clinical trial, picked up the pharmaceuticals, and inquired whether the doctor had prescribed it to pregnant women. She found ten cases of deformities in children in the United States resulting from the trial and another seven resulting from drugs purchased overseas. Children born in other countries where thalidomide had been approved were not so lucky: thousands of deformed children were born.
Concerned about the potential tragedies that would have occurred if the FDA had approved thalidomide, the FDA held hearings. The public was stunned when Dr. Lou Lasagna—who conducted a controlled trial of thalidomide for Merrell—testified before Congress:
Congress strengthened the Food, Drug and Cosmetic Act to add more exacting clinical studies. In 1962, President Kennedy awarded Frances the President’s Award for Distinguished Federal Service. She was the second woman to receive the award, and she accepted it on behalf of the team of workers at the FDA.
Frances Kelsey is Awarded the Presidential Award by President Kennedy (1962)
President Kennedy praised Frances: “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. Through high ability and steadfast confidence in her professional decision she has made an outstanding contribution to the protection of the health of the American people.” The Society of Woman Geographers also awarded Frances a gold medal.
Other Posts in this Series