Frances Kathleen Oldham Kelsey: July 24, 1914 – August 7, 2015

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✪ Frances Kathleen Oldham Kelsey (née Oldham) was a Canadian-American pharmacologist and physician who served as a reviewer for the U.S. Food and Drug Administration (FDA),and refused to authorize thalidomide for market because she had concerns about the lack of evidence regarding the drug’s safety. Her concerns proved to be justified when it was shown that thalidomide caused serious birth defects.

Kelsey’s career intersected with the passage of Health laws and policies strengthening the FDA’s oversight of pharmaceuticals. In 1962, Kelsey became the second woman to receive the President’s Award for Distinguished Federal Civilian Service, awarded to her by John F. Kennedy.

Kelsey was born on July 24, 1914 in Cobble Hill, British Columbia. She attended St. Margaret’s School in the provincial capital and graduated at age 15. From 1930 to 1931, she attended Victoria College (now the University of Victoria). She then enrolled at McGill University, where she received both a Bachelor of Science degree in 1934 and an Masters in Science degree in 1935 for pharmacology. Encouraged by one of her professors, she wrote to EMK Geiling, M.D., a noted researcher who was starting up a new pharmacology department at the University of Chicago, asking for a position doing graduate work. Geiling, unaware of spelling conventions with respect to Francis and Frances, presumed Frances was a man and offered her the position. She accepted & began work in 1936.

During Kelsey’s second year, Geiling was retained by the FDA to research unusual deaths related to elixir sulfanilamide, a sulfonamide medicine. Kelsey assisted on this research project, which showed that the 107 deaths were caused by the use of diethylene glycol as a solvent. At that time, there was no law available to prosecute those who sold poisons as medicine; and Kelsey observed the need to work around incomplete regulation. 

The next year, the United States Congress passed the Federal Food, Drug, and Cosmetic Act of 1938. That same year she completed her studies and received a Ph.D. in pharmacology at the University of Chicago. Working with Geiling led to her interest in teratogens; drugs which cause congenital malformations (birth defects) learning about the mechanisms by which birth defects occur.

Upon completing her Ph.D., Oldham joined the University of Chicago faculty. In 1942, like many other pharmacologists, Oldham was looking for a synthetic cure for malaria. As a result of these studies, Oldham discovered some drugs are able to pass through the placental barrier. During this work, she also met fellow faculty member Fremont Ellis Kelsey, whom she married in 1943. The couple had two children.

While on the faculty at the University of Chicago, Kelsey was awarded her M.D. in 1950. She supplemented her teaching with work as an editorial associate for the American Medical Association Journal for two years. In 1954, Kelsey left the University of Chicago and decided to take a position teaching pharmacology at the University of South Dakota: moving to Vermillion, South Dakota with her husband and two daughters where she taught until 1957.

Kelsey became a dual citizen of Canada and the United States in the 1950s in order to continue practicing medicine in the U.S., but retained strong ties to Canada where she continued to visit her siblings regularly until late in life.

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In 1960, Kelsey was hired by the FDA in Washington, D.C. At that time, she was one of only seven full-time and four young part-time physicians reviewing drugs for the FDA. One of her first assignments at the FDA was to review an application by Richardson-Merrell for the drug thalidomide (under the tradename Kevadon) as a tranquilizer and painkiller with specific indications to prescribe the drug to pregnant women for morning sickness.

Although the drug had been previously approved in Canada and more than 20 European and African countries, Kelsey withheld approval for the drug and requested to see clinical trial information. At the time, the FDA could only withhold approval for 60 days at a time, so she continually requested further information from the company every 60 days for more than a year. Her initial reason for doing this was because the testimonials supplied by Richardson-Merrell contained no scientific methodology. She also recognized their authors as having published suspicious articles in the past. Kelsey also observed that the application said nothing about the chirality of thalidomide.

Chirality: when a molecule does not coincide with its mirror image. The property of an object that is not identical to its mirror. Meaning it cannot be perfectly superimposed on its reflection. This concept is often compared to the relationship between your hands, which are mirror images but cannot be perfectly aligned. The term comes from the Greek word for “hand.” Chirality is the most basic and universal property in nature.

In December 1960, Leslie Florence published a letter in the British Medical Journal linking thalidomide to neurological symptoms. Kelsey read this letter and added Florence’s observed symptoms to her ongoing data requests.

Richardson-Merrell had reportedly discovered birth defects when the drug was tested on rats but did not report this finding, Instead, Kelsey was sent misleading & partial data suggesting the product was completely safe for pregnant women. Despite the fact that thalidomide was already widely used in Europe and elsewhere, Kelsey remained suspicious and scrutinized this data with concern and skepticism; sometimes asking her husband to double check her conclusions. As 1960 turned to 1961, Kelsey’s continual requests for more information incurred the ire of her contact at Richardson-Merrell, who insisted on speeding up the approval process in an attempt to escalate the application. However, Kelsey’s superiors at the FDA stood by her.

Kelsey’s insistence the drug should be fully tested prior to approval was vindicated in November 1961 when the births of deformed infants in Europe were linked to thalidomide ingestion by their mothers during pregnancy. Researchers discovered the thalidomide crossed the placental barrier and caused serious birth defects. 

In March 1962, after distributing “experimental” tablets to tens of thousands of patients without approval (with 17 malformed births confirmed and dozens more suspected), Richardson-Merrell at finally withdrew their FDA application. Kelsey was hailed on the front page of The Washington Post as a heroine for averting a large-scale public health tragedy in the U.S. Morton Mintz, author of The Washington Post article said, “Kelsey prevented … the birth of hundreds or indeed thousands of armless and legless children.”

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The narrative of Kelsey’s persistence was used to help pass more rigorous drug approval regulations in 1962. The Kefauver Harris Amendment was passed unanimously by Congress in October 1962 to strengthen drug regulation. Companies would be required to demonstrate the efficacy of new drugs, report adverse reactions to the FDA, and request consent from patients participating in clinical studies

As a result of her blocking the American approval of thalidomide, Kelsey was awarded the President’s Award for Distinguished Federal Civilian Service by John F. Kennedy on August 7, 1962; to become only the second woman so honored. After receiving the award, Kelsey continued on in her work at the FDA. There, she played a key role in shaping and enforcing the 1962 amendments. She was named Director of the Investigational Drug Branch.

In 1966, Lyndon B. Johnson appointed James L. Goddard as Commissioner of Food and Drugs. Goddard resented the public attention Kelsey continued to receive and believed the widespread rumors spread by pharmaceutical industry executives that Kelsey had delayed the thalidomide application through pure laziness. This was precisely the opposite of the truth as most applications were automatically approved by reviewers ignoring the 60 day deadline, while Kelsey had carefully sent out data requests for over a year. Regardless, Kelsey was demoted from Director of the Investigational Drug Branch to Chief of the Division of Oncology and Radiopharmaceutical Drug Products, where she was given little work.

After Goddard’s departure, Kelsey was again appointed Director of Scientific Investigations, and continued in this position for many decades. She was involved in the contentious regulation of diethylstilbestrol, which also caused birth defects, and dimethyl sulfoxide.

In 1994, the Frances Kelsey Secondary School in Mill Bay, British Columbia, was named in her honor. She attended the opening ceremony despite having suffered broken ribs and a vertebral compression fracture on the way to the ceremony. In 1995, when she was eighty-one, the FDA’s Center for Drug Evaluation and Research created a special position for her, Deputy for Scientific and Medical Affairs in the Office of Compliance.

Kelsey retired from the FDA in 2005, at age 90, after 45 years of service. In 2010, the FDA presented Kelsey with the first Drug Safety Excellence Award and named the award after her;  announcing it would be awarded to one FDA staff member annually. In announcing the awards, Center Director Steven K. Galson said: “I am very pleased to have established the Dr. Frances O. Kelsey Drug Safety Excellence Award and to recognize the first recipients for their outstanding accomplishments in this important aspect of drug regulation.”

Kelsey turned 100 in July 2014^; and shortly thereafter, in the fall of 2014, she moved from Washington, D.C., to live with her daughter in London, Ontario.

Kelsey died in London, Ontario, on August 7, 2015, at the age of 101, less than 24 hours after Ontario’s Lieutenant-Governor, Elizabeth Dowdeswell, visited her home to personally present her with the insignia of Member of the Order of Canada.

Kelsey is interred at Cherry Hill Cemetery in Sugar Grove, Warren County, Penn. ✪