- Mike Martinez
Public Service Exemplars: “A Finer Spirit of Hope and Achievement”: Frances Oldham Kelsey
Frances Oldham Kelsey is discussed in a chapter of my upcoming book Public Service Exemplars: “A Finer Spirit of Hope and Achievement.” The narrative of a lone, heroic researcher laboring anonymously for years inside a laboratory only to emerge with a breakthrough discovery that revolutionizes the world of science or medicine has become a compelling myth in the twenty-first century. The collaborative, iterative nature of scientific research suggests that discoveries by lone researchers seldom occur; instead, they are the result of numerous parties working collaboratively across multiple decades in a variety of disciplines and through multiple platforms. Attributing a breakthrough to the efforts of one brilliant man or woman is usually viewed as simplistic and inaccurate.
Yet the work of Dr. Frances Oldham Kelsey can be described as the exception that proves the rule. As a reviewer for the U.S. Food & Drug Administration (FDA) during the early 1960s, Dr. Kelsey raised alarming questions about the drug thalidomide, refusing to authorize the product for sale in the United States despite unrelenting pressure from the drug’s manufacturer. Denounced as obstructionist, Dr. Kelsey refused to change her opinion despite fierce opposition. She was subsequently vindicated when studies demonstrated that thalidomide caused serious birth defects. For her stellar, courageous work, President John F. Kennedy awarded Dr. Kelsey the President’s Award for Distinguished Federal Civilian Service in 1962.
She was born Frances Kathleen Oldham in British Columbia on July 24, 1914. From an early age, she was interested in medicine. She attended Victoria College (later renamed Victoria University) before matriculating at McGill University, where she earned two degrees in pharmacology. She decided to pursue her studies in the United States, joining Dr. E.M.K. Geiling, who was commencing a pharmacology program at the University of Chicago. Oldham started working there in 1936.
Dr. Geiling began working with the FDA to research unusual deaths attributed to sulfonamide, the first broadly effective antibacterial drugs that eventually served as the basis for advances in medicine. Oldham joined him on the project, which eventually concluded that the diethylene glycol, a commonly used solvent, had contributed to 107 deaths. Oldham’s work with Dr. Geiling led her to investigate teratogens, drugs that can cause congenital malformations, or birth defects.
During the same year that she worked on the diethylene glycol project, Oldham earned a doctorate in pharmacology from the University of Chicago. She soon joined the faculty at Chicago. Like many researchers of the era, she was tasked with developing a synthetic cure for malaria. It was 1942, and American soldiers in the Pacific Theatre battled the Japanese on dozens of tropical islands. Aside from the enemy’s weapons, these soldiers faced a slew of diseases, notably malaria. A manmade cure for the disease could provide an enormous military advantage to U.S. forces.
Her time on the University of Chicago faculty was propitious. Her research led her to the realization that some drugs can pass through the placental barrier, which meant that certain drugs could adversely affect a fetus. She also married a fellow Chicago faculty member, Fremont Ellis Kelsey.
Dr. Kelsey earned a medical degree in 1950. She worked for two years as an associate editor of the American Medical Association Journal, known today as The Journal of the American Medical Association (JAMA), a prestigious peer-reviewed publication reporting on advances in medical science.
After teaching at the University of South Dakota for three years, Dr. Kelsey began reviewing drugs for the FDA in Washington, DC. She was one of only a handful of physicians employed in that capacity. Among her first assignments was an application submitted by a pharmaceutical company, Richardson-Merrell, to market a drug, Kevadon, in the United States. Kevadon was the brand name for the drug thalidomide.
FDA approval of thalidomide should have been a routine procedure. The drug was popular in Europe as a sedative as well as an antiemetic to control nausea and vomiting. Although it had not been used for pregnant women, some physicians thought that thalidomide could be effective in controlling morning sickness. Richardson-Merrell applied for approval on September 8, 1960, and sought a fast-track decision.
Only a month into her FDA career, Dr. Kelsey might easily have approved the application. Because it was already in widespread use, thalidomide appeared to be safe and effective. In fact, Richardson-Merrell was so confident of a quick approval that the company distributed 2.5 million thalidomide tablets to 1,200 American doctors while the application was pending. The goal was to ensure the drug’s availability as soon as the FDA approved its sale. Although its use was supposed to wait for approval, some 20,000 patients received the drug before the FDA rendered its decision.
Reviewing the data, Dr. Kelsey was troubled. She did not believe that the company had submitted enough controlled studies to demonstrate risk factors for thalidomide. She steadfastly refused to approve the application until she was satisfied that the drug’s safety had been demonstrated. After delving into existing studies, Dr. Kelsey learned that approximately 10,000 children around the world had been born with birth defects after their mothers used thalidomide. The drug had crossed the placental barrier and affected the fetus. In many cases, the children were born with abnormally formed arms and legs. In the United States, 17 children suffered these defects.
Richardson-Merrell executives had pressured Dr. Kelsey to approve the drug, but they could not withstand the public outcry when the studies became public. The company recalled the tablets from doctors’ offices and withdrew its FDA application. The episode became a well-known debacle that illustrated the need for stringent government regulation of medicines marketed in the United States.
The episode also transformed Dr. Frances Kelsey into a public figure. Newspapers heralded her as a heroine despite her insistence that her colleagues Oyama Jiro and Lee Geismar and her many FDA supporters deserved much credit. President John F. Kennedy awarded her the President’s Award for Distinguished Federal Civilian Service on August 7, 1962, making her only the second woman to win the award.
Congress sprang into action, enacting the Drug Efficacy Amendment—commonly called the Kefauver-Harris Amendment after the co-authors, Senator Estes Kefauver (D-TN) and Congressman Oren Harris (D-Arkansas)—a modification to a landmark 1938 statute, the Federal Food, Drug, and Cosmetic Act. The amendment required pharmaceutical companies to provide scientific studies on the safety and effectiveness of drug before the FDA will approve marketing applications. In addition, the amendment required drug advertisers to disclose information about side effects and cease selling cheaper generic drugs as the more expensive name brands without informing the public.
Dr. Kelsey might have retired from medicine to write a book and travel the lecture circuit, but she was committed to the agency’s work. She remained at the FDA for more than four decades, tirelessly reviewing applications from pharmaceutical companies and mentoring younger doctors. She eventually became the deputy for scientific research at the FDA’s Center for Drug Evaluation and Research. She retired from the FDA in 2005 at age 90 after working at the agency for 45 years.
Dr. Kelsey received numerous accolades. Schools were named in her honor. At age 87, she was inducted into the National Women’s Hall of Fame. In 2010, the FDA presented her with the inaugural Drug Safety Excellence Award. Later, the agency named the award after her. After returning to Canada to live with her daughter following her 100th birthday, Dr. Kelsey received the Order of Canada, the second highest honor for merit provided by the Canadian government.
She died on August 7, 2015, at age 101. The day before her death, Dr. Kelsey met with Elizabeth Dowdeswell, the lieutenant governor of Ontario, to receive an award, the insignia of Member of the Order of Canada, for Dr. Kelsey’s work on thalidomide. More than half a century had passed, but her work was still a potent reminder of the need for leadership from unelected public administrators.