Kelsey, Frances Oldham
Frances Oldham Kelsey
Dr. Frances Oldham Kelsey made a name for herself as someone committed to protecting public health. She stood steadfast against granting U.S. Food and Drug Administration (FDA) approval to the drug thalidomide. She refused to cave in to pressure from the Richardson-Merrell Company, which wanted to distribute thalidomide in the United States. The drug was already in wide use in Europe and Japan during the 1950s. The company tried to cast doubt on Kelsey's professional abilities and threatened that she would lose her job. Yet she insisted on further testing to clear up questions about thalidomide effects. Soon, reports began surfacing that the drug caused birth defects overseas. Due to Kelsey's refusal to approve the drug in the United States, she single-handedly protected countless unborn American babies from developing birth defects. Ultimately, her work led to stricter laws for regulating the introduction of new drugs.
"They gave [the thalidomide application assignment] to me because they thought it would be an easy one to start on. As it turned out, it wasn't all that easy."
—Dr. Frances Oldham Kelsey.
Early education and career
Frances Kathleen Oldham was born on July 24, 1914, in Cobble Hill on Vancouver Island in British Columbia, Canada. A bright student, she received a bachelor's degree in science in 1934 and a master's degree in science in 1935 from McGill University in Montreal, Quebec, Canada. She continued her education at the University of Chicago in Illinois, earning a PhD in pharmacology in 1938 and an MD in 1950. As a pharmacologist, she would study drugs and their use in human medicine. She married fellow university faculty member Dr. Fremont Ellis Kelsey in 1943, and they eventually had two daughters. After completing an internship at Sacred Heart Hospital in Yankton, South Dakota, in 1954, Frances Kelsey became an associate professor of pharmacology at the University of South Dakota. The next year, she became a naturalized U.S. citizen. In 1957 Kelsey left her professorship to open her own private practice, which she ran until 1960 when her husband took a position that required the family to move to Washington, D.C.
Early in her career, Kelsey had investigated, with her husband, the effects of drugs on bodies at different stages of life. The couple published the results of their findings in several respected scientific journals, such as the Journal of Pharmacy and Experimental Therapy. In one study, the Kelseys discovered that the bodies of adult rabbits, pregnant rabbits, and rabbit embryos all reacted to the drug under investigation in different ways and that it proved deadly to the embryos. This research fueled her continued interest in the effect of drugs on fetuses and the safety issues involved when women take certain drugs during pregnancy.
Not long after moving to Washington, D.C., Frances Kelsey landed a job as a medical officer with the U.S. Department of Health, Education, and Welfare's Food and Drug Administration (FDA). As medical officer, she was to act as a gate-keeper between pharmaceutical companies and the public. In this job, she evaluated applications for marketing new drugs in the United States, checking to see if the new drug was proven to be safe. In September 1960, she started working on her first assignment. This work would soon bring her national attention.
One woman against an entire company
The William S. Merrell Company, a division of Richardson-Merrell of Cincinnati, Ohio, bought the rights to sell a drug called thalidomide in the United States. Developed in West Germany in the 1950s, thalidomide was marketed throughout Europe as a sleep aid. According to German manufacturer Chemie Grunenthal, thalidomide was good for aiding sleep and treating morning sickness or nausea in pregnant women. The manufacturer also claimed the drug could be given safely to those at risk of suicide because it did not absorb into the body at toxic or dangerously unhealthy levels. This meant that suicidal people, who might need sleeping pills in order to rest and relax, would not be able to kill themselves by swallowing too many of the pills. The popularity of the drug and the belief in thalidomide's safety led to its availability without prescription in Europe after 1957.
Thalidomide Still in Use
Kelsey's work to ban the distribution of thalidomide drew great public attention to the dangers of drugs created by pharmaceutical companies. But continued research into the use of thalidomide indicated that the drug did have redeeming qualities as a medication. Thalidomide proved to be beneficial in treating inflammation in leprosy patients in studies conducted in 1965. After that researchers studied thalidomide's effectiveness in treating diseases which cause tissues to swell.
By the late 1990s, thalidomide was known to provide relief to patients who suffered from arthritis, an inflammation of the joints. It also healed mouth and throat sores in people infected with Human Immunodeficiency Virus (HIV), the virus that causes Acquired Immunodeficiency Syndrome (AIDS). Some of the HIV/AIDS sufferers became thin and more vulnerable to infection because their mouth sores made eating extremely painful. In these controlled situations, thalidomide use was carefully administered and monitored. Doctors prescribing it were mindful of the irreversible nerve damage that the drug caused in the fingers and toes. They also carefully monitored women of child-bearing age, cautioning them not to become pregnant while using the drug.
To prepare the U.S. market for the anticipated release of the drug, Richardson-Merrell distributed thalidomide samples to American doctors to give to patients, a practice that was legal in the late 1950s. With its FDA application, Richardson-Merrell provided research that suggested the relative safety of thalidomide. But Kelsey was not persuaded by the research. She wondered why the drug acted differently in animals than similar drugs. She asked for more tests and refused to let Richardson-Merrell market thalidomide until she was satisfied that the drug was safe. Richardson-Merrell submitted more research, but Kelsey rejected it. According to FDA Consumer, Kelsey said that: "The clinical reports were more on the nature of testimonials, rather than the results of well-designed, well-executed studies."
Merrell did not take kindly to Kelsey's stubborn search for proof of the drug's safety. The company exerted pressure on her to approve the drug. Representatives from the company repeatedly called and visited. Growing increasingly frustrated with Kelsey's resistance, they complained to her supervisors that she was unnecessarily delaying the release of the drug. But Kelsey took the pressure in stride, recalling to FDA Consumer: "I think I always accepted the fact that one was going to get bullied and pressured by industry. It was understandable that the companies were very anxious to get their drugs approved."
Kelsey did not give in. In February of 1961, she read a report in the British Medical Journal indicating that thalidomide caused tingling in the limbs. In November of 1961 the proof she had demanded appeared. German scientist Dr. Widukind Lenz published test results that indicated thalidomide use was the source of a German epidemic of phocomelia, a malformation of limbs in newborn babies. Richardson-Merrell asserted this report was false, arguing that the test results were inconclusive. But Kelsey stood fast. By December, the reports could no longer be denied. The German government pulled thalidomide from the market. By early 1962, Merrell withdrew its application. More than 10,000 cases of phocomelia in European children were eventually attributed to the use of thalidomide.
Protected American newborns
Once the FDA officially recognized the dangers of thalidomide, it published news releases warning of the drug's dangers. The agency sent field staff to locate the doctors who had been given thalidomide samples to urge them to contact patients who might have taken the drug. Although Richardson-Merrell had distributed more than 2.5 million thalidomide tablet samples to more than 1,000 doctors throughout the United States, only seventeen cases of birth defects have been traced to the drug within the United States. Despite the severe side effects of thalidomide use during pregnancy, as of the early 2000s the drug continued to be used to treat some diseases.
Kelsey's diligence saved countless American babies from having deformed arms and legs. In July 1962, the U.S. Senate recognized Kelsey for her "great courage and devotion to the public interest." On August 7, 1962, President John F. Kennedy (1917–1963; served 1961–63; see entry) awarded her the President's Award for Distinguished Federal Civilian Service. The award declared, as recorded in an FDA press release: "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."
Kelsey's discovery and the news about how much pressure she had endured to keep the public safe triggered renewed interest in drug safety legislation. The federal Food, Drug, and Cosmetic Act, passed in 1938, required drug manufacturers to prove that their drugs were safe. But the law President Kennedy signed on October 10, 1962—commonly called the Kefauver-Harris Amendments—required drug manufacturers to register proof with the Food and Drug Administration that new drugs were both effective and safe. The new law also provided for more rapid recall of new drugs deemed hazardous. In addition, the law required drug companies to report to the FDA any adverse reactions to a drug.
In 1963, Kelsey became chief of the Investigational Drug Branch of the FDA, the Center for Drug Evaluation and Research (CDER). The center was created to evaluate and observe clinical trials to make sure they meet new drug regulations. Kelsey continued to care for public health, serving as deputy of scientific and medical affairs in CDER's office of compliance well into her eighties. On October 7, 2000, nearly forty years after her cautious review of the thalidomide application, Frances Kelsey was inducted into the National Women's Hall of Fame in Seneca Falls, New York.
For More Information
Shearer, Benjamin F., and Barbara S. Shearer. Notable Women in the Life Sciences: A Biographical Dictionary. Westport, CT: Greenwood Press, 1996.
Grigg, W. "The Thalidomide Tragedy–25 Years Ago." FDA Consumer (February 1987): pp. 14–17.
Hunter, M. "Stiffer Drug Law Urged by Kennedy." New York Times (August 12, 1962): p. 1.
Bren, Linda. "Frances Oldham Kelsey: FDA Medical Reviewer Leaves Her Mark on History." FDA Consumer (March-April 2001). http://www.fda.gov/fdac/features/2001/201_kelsey.html (accessed August 2004).
"FDA's Dr. Frances Kelsey to be Inducted into National Women's Hall of Fame." Food and Drug Administration Press Office.http://www.fda.gov/bbs/topics/NEWS/NEW00739.html (accessed August 2004).