Dr.Frances Oldham Kelsey,BA(McGill 34) MSc( McGill 35) PhD (Pharm.Chicago 38) MD (Chicago 50) F.D.A. Stickler Who Saved U.S. Babies From Thalidomide, awarded Membership of Order of Canada at !01.
The
sedative was Kevadon, and the application to market it in America
reached the new medical officer at the Food and Drug Administration in
September 1960. The drug had already been sold to pregnant women in
Europe for morning sickness, and the application seemed routine, ready
for the rubber stamp.
But
some data on the drug’s safety troubled Dr. Frances Oldham Kelsey, a
former family doctor and teacher in South Dakota who had just taken the
F.D.A. job in Washington, reviewing requests to license new drugs. She
asked the manufacturer, the William S. Merrell Company of Cincinnati,
for more information.
Thus
began a fateful test of wills. Merrell responded. Dr. Kelsey wanted
more. Merrell complained to Dr. Kelsey’s bosses, calling her a petty
bureaucrat. She persisted. On it went. But by late 1961, the terrible
evidence was pouring in. The drug — better known by its generic name,
thalidomide — was causing thousands of babies in Europe, Britain, Canada
and the Middle East to be born with flipperlike arms and legs and other
defects.
Dr.
Kelsey, who died on Friday at the age of 101, became a 20th-century
American heroine for her role in the thalidomide case, celebrated not
only for her vigilance, which spared the United States from widespread
birth deformities, but also for giving rise to modern laws regulating
pharmaceuticals.
She
was hailed by citizens’ groups and awarded honorary degrees. Congress
bestowed on her a medal for service to humanity and passed legislation
requiring drug makers to prove that new products were safe and effective
before marketing them. President John F. Kennedy signed the landmark
law that she had inspired, and presented her with the nation’s highest
federal civilian service award.
“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,” Kennedy said at a White House ceremony.
Dr. Kelsey was appointed to the Order of Canada
last month and presented with the honor in a private ceremony the day
before her death at her daughter Christine Kelsey’s home in London,
Ontario, where Dr. Kelsey had been living, according to John Swann, a
historian at the F.D.A. and a friend of hers.
In
1962, the F.D.A. set up a branch to test and regulate new drugs, and
Dr. Kelsey was put in charge of it. Later, she became director of the
agency’s Office of Scientific Investigations, and in a distinguished
45-year career with the F.D.A. helped rewrite the nation’s
medical-testing regulations, strengthening protections for people and
against medical conflicts of interest. The rules have been adopted
worldwide.
She
was born Frances Oldham in Cobble Hill, on Vancouver Island in British
Columbia, on July 24, 1914, one of three children of Frank and Katherine
Stuart Oldham. Frances attended schools in Victoria and McGill
University in Montreal, earning a bachelor’s degree in 1934 and a
master’s in science in 1935. In 1936, she enrolled at the University of
Chicago, where she earned a doctorate in pharmacology in 1938. She
joined the faculty that year and became an assistant professor of
pharmacology.
She
and Dr. Fremont Ellis Kelsey, a professor in the university’s
pharmacology department, married in 1943. He became a special assistant
to the surgeon general in 1962 and died in 1966. The couple had two
daughters.
Besides her daughter Christine, Dr. Kelsey is survived by another daughter Susan Duffield, two grandsons and a sister.
Dr.
Kelsey received her medical degree from the University of Chicago in
1950. She was an editorial associate for the American Medical
Association Journal in Chicago for two years before the Kelseys moved to
Vermillion, S.D. He became chairman of physiology and pharmacology at
the University of South Dakota medical school. From 1954 to 1957, she
taught pharmacology there, and for the next three years was in private
medical practice. She became a naturalized American in 1956.
Her
husband’s appointment to a post at the National Institutes of Health
took the family to Washington in 1960. She accepted the F.D.A. job
evaluating applications for licenses to market new drugs. Merrell’s was
one of the first to cross her desk.
The
company made glowing claims for Kevadon’s safety and effectiveness. It
had been developed in West Germany, and since 1957 had been widely sold
in Europe and elsewhere as an excellent sedative, Merrell said, giving
prompt, deep, natural sleep without hangovers. Moreover, doctors had
recently been prescribing it to women to suppress nausea in pregnancy.
Laws
governing new drugs had been on the books for decades but were not
always rigorously enforced, and F.D.A. approval was often routine. But
Dr. Kelsey, working with a chemist and a pharmacologist, found the
evidence for Merrell’s claims about Kevadon to be insufficient. She
withheld approval and asked Merrell for more data on toxicity, strength
and purity.
Merrell stood to make millions and was anxious to get moving. It had tons of Kevadon in warehouses, ready for marketing, and 1,000 American doctors had already been given samples for “investigational” research. The company supplied more data, but also mounted a campaign to pressure Dr. Kelsey. Letters, calls and visits from Merrell executives ensued. She was called a fussy, stubborn, unreasonable bureaucrat.
But
she refused to be hurried, insisting that there was insufficient proof.
In February 1961, she read a letter in The British Medical Journal from
a doctor who suggested that thalidomide might be causing a numbing
condition in arms and legs. She notified Merrell, and the company began
its own inquiry. In May, she told Merrell that the drug might affect the
limbs of fetuses. The company called the evidence inconclusive.
“I
had the feeling,” she wrote after a meeting with company executives,
“that they were at no time being wholly frank with me, and that this
attitude has obtained in all our conferences, etc., regarding this
drug.”
Six
months later, European reports indicated that the drug was linked to an
epidemic of phocomelia, a rare but monstrous malformation of limbs in
newborns. Merrell withdrew its application as reports of the births of
“thalidomide babies” came in from many countries. Kevadon samples given
to American doctors were traced, but not all were retrieved. Seventeen
births of babies with deformities were reported in the United States,
according to the F.D.A.
Eventually
researchers learned that thalidomide crossed the placental barrier and
retarded development of the fetus, whose drug-metabolizing enzymes are
undeveloped. No one knows how many babies were affected by thalidomide,
but estimates range into the tens of thousands in Europe alone. Many
were born without arms or legs, some with no limbs or with withered
appendages protruding directly from the trunk. Some had no external ears
or deformities of the eyes, the esophagus or intestinal tracts.
After
an article in The Washington Post led to global coverage, Dr. Kelsey
was hailed as a hero. She insisted that her pharmacologist, Oyam Jiro,
and chemist, Lee Geismar, as well as her superiors share the credit. But
attention focused on her partly because the Kennedy administration and
its allies in Congress wanted to use the case to pass stronger drug
regulations. The 1962 law required tighter proof of the safety and
effectiveness of new drugs, full disclosure of side effects and generic
names, and swift removal of unsafe drugs from the market.
When
she became widely known, Dr. Kelsey, a tall, graying woman who spoke
softly and never wore cosmetics, seemed modest to the point of shyness.
But she testified in Congress, spoke to women’s groups and at college
forums and gradually became accustomed to the spotlight.
In
2000 Dr. Kelsey was inducted into the National Women’s Hall of Fame,
joining the ranks of Helen Keller, Eleanor Roosevelt, Margaret Mead and
other luminaries. She retired in 2005, and in 2010 was honored by Dr.
Margaret Hamburg, then the F.D.A. administrator, as the first recipient
of an award that continues to be given annually in her name.
