# \[e-drug\] E-Drug: Dr. Francis Kelsey- the legendary figure who said "No" to Thalidomide is dead
**URL:** https://talk.edrugplus.org/t/e-drug-e-drug-dr-francis-kelsey-the-legendary-figure-who-said-no-to-thalidomide-is-dead/41966
**Category:** e-drug
**Created:** [August 8, 2015, 10:51am UTC](https://talk.edrugplus.org/t/e-drug-e-drug-dr-francis-kelsey-the-legendary-figure-who-said-no-to-thalidomide-is-dead/41966 "2015-08-08T10:51:50Z")
**Posts on this page:** 2
**Page:** 1
### Author:  [@Siyed\_Rizwanuddin\_Ah](https://talk.edrugplus.org/u/Siyed_Rizwanuddin_Ah)
#### Post date: [August 8, 2015, 10:51am UTC](https://talk.edrugplus.org/t/e-drug-e-drug-dr-francis-kelsey-the-legendary-figure-who-said-no-to-thalidomide-is-dead/41966/1 "2015-08-08T10:51:50Z")
E-Drug: Dr. Francis Kelsey- the legendary figure who said "No" to
Thalidomide is dead
-----------------------------------------------------
Dear All,
The legendary figure Dr. Francis Kelsey who kept thalidomide away from the
U.S. market is dead. We all know that it was the thalidomide tragedy that
resulted in the passage of regulations worldwide to protect people from
unsafe medicines; and the development of the field that is now known as
pharmacovigilance. I never worked with Dr. Kelsey during my 15 years at
the U.S. FDA but it was a pleasure exchanging greetings during the weekly
scientific seminars at the agency which she would never miss.
As a tribute to Dr. Kelsey may we all do our best to protect people from
unsafe medicines wherever we are.
I have copied a news article at the end of this note for e-druggers.
Best wishes,
Rizwan
Syed Rizwanuddin Ahmad, MD, MPH, FISPE, FCP
Pharmacovigilance Consultant with a Special Interest to Strengthen
National Medicines Regulatory Authorities in Resource-limited Settings
Ex-Consultant/Safety Reviewer, U.S. FDA (1998-2013)
Associate Professor (adjunct), Rutgers School of Public Health, NJ, USA
Assistant Professor (adjunct), Georgetown University School of Medicine,
Washington, DC, USA
www.drugsafetyconsultant.com
---------------------------------------------
[http://www.washingtonpost.com/national/health-science/frances-oldham-kelsey-heroine-of-thalidomide-tragedy-dies-at-101/2015/08/07/ae57335e-c5da-11df-94e1-c5afa35a9e59\_story.html?hpid=z6](http://www.washingtonpost.com/national/health-science/frances-oldham-kelsey-heroine-of-thalidomide-tragedy-dies-at-101/2015/08/07/ae57335e-c5da-11df-94e1-c5afa35a9e59_story.html?hpid=z6)
Health & Science
Frances Oldham Kelsey, FDA scientist who kept thalidomide off U.S. market,
dies at 101
By Adam Bernstein and Patricia Sullivan August 7 at 12:53 PM Washington
Post
In the annals of modern medicine, it was a horror story of international
scope: thousands of babies dead in the womb and at least 10,000 others in
46 countries born with severe deformities. Some of the children were
missing limbs. Others had arms and legs that resembled a seal’s flippers.
In many cases, eyes, ears and other organs and tissues failed to develop
properly.
The cause, scientists discovered by late 1961, was thalidomide, a drug
that, during four years of commercial sales in countries from Germany to
Australia, was marketed to pregnant women as a miracle cure for morning
sickness and insomnia.
The tragedy was largely averted in the United States, with much credit due
to Frances Oldham Kelsey, a medical officer at the Food and Drug
Administration in Washington, who raised concerns about thalidomide before
its effects were conclusively known. For a critical 19-month period, she
fastidiously blocked its approval while drug company officials maligned her
as a bureaucratic nitpicker.
Dr. Kelsey, a physician and pharmacologist later lauded as a heroine of the
federal workforce, died Aug. 7 at her daughter’s home in London, Ontario.
She was 101. Her daughter, Christine Kelsey, confirmed her death but did
not cite a specific cause.
Dr. Kelsey did not single-handedly uncover thalidomide’s hazards. Clinical
investigators and health authorities around the world played an important
role, as did several of her FDA peers. But because of her tenacity and
clinical training, she became the central figure in the thalidomide episode.
In July 1962, The Washington Post directed national attention on the matter
— and on Dr. Kelsey — with a front-page article reporting that her
“skepticism and stubbornness ... prevented what could have been an
appalling American tragedy.”
[From 1962: ‘Heroine’ of FDA keeps bad drug off the market]
The global thalidomide calamity precipitated legislation signed by
President John F. Kennedy in October 1962 that substantially strengthened
the FDA’s authority over drug testing.
The new regulations, still in force, required pharmaceutical companies to
conduct phased clinical trials, obtain informed consent from participants
in drug testing, and warn the FDA of adverse effects, and granted the FDA
with important controls over prescription-drug advertising.
As the new federal law was being hammered out, Kennedy rushed to include
Dr. Kelsey in a previously scheduled White House award ceremony honoring
influential civil servants, including an architect of NASA’s manned
spaceflight program.
“In a way, they tied her to the moonshot in showing what government
scientists were capable of,” said Stephen Fried, a journalist who
investigated the drug industry in the book “Bitter Pills.” “It was an act
of incredible daring and bravery to say we need to wait longer before we
expose the American people to this drug.”
Dr. Kelsey became, Fried said, “the most famous government regulator in
American history.”
‘I was the newest person there and pretty green’
Dr. Kelsey had landed at the FDA in August 1960, one of seven full-time
medical officers hired to review about 300 human drug applications per year.
The number of women pursuing careers in science was minuscule, but Dr.
Kelsey had long been comfortable in male-dominated environments. Growing up
in Canada, she spent part of her childhood in an otherwise all-boys private
school. She had two daughters while shouldering the demands of medical
school in the late 1940s.
In Washington, she joined a corps of reform-minded scientists who, although
not yet empowered by the 1962 law that required affirmative FDA approval of
any new drug, demanded strong evidence of effectiveness before giving their
imprimatur.
At the time, a drug could go on the market 60 days after the manufacturer
filed an application with the FDA. If the medical officer determined that
the submission was incomplete, the drug company could provide additional
information, and the clock would start anew.
Meanwhile, pharmaceutical drug companies commonly supplied doctors with new
drugs and encouraged them to test the product on patients, an uncontrolled
and dangerous practice that relied almost entirely on anecdotal evidence.
Thalidomide, which was widely marketed as a sedative as well as a treatment
for pregnancy-related nausea during the first trimester of pregnancy, had
proven wildly popular in Europe and a boon for its German manufacturer,
Chemie Grünenthal.
By the fall of 1960, a Cincinnati-based drug company, William S. Merrell,
had licensed the drug and began to distribute it under the trade name
Kevadon to 1,200 U.S. doctors in advance of what executives anticipated
would be its quick approval by the FDA.
The government later estimated that more than 2.5 million tablets were
given to about 20,000 patients, several hundred of whom were pregnant.
The Merrell application landed on Dr. Kelsey’s desk within weeks of her
arrival at the agency. “I was the newest person there and pretty green,”
she later said in an FDA oral history, “so my supervisors decided, ‘Well,
this is a very easy one. There will be no problems with sleeping pills.’ ”
Immediately the application alarmed her. Despite what she called the
company’s “quite fulsome” claims, the absorption and toxicity studies were
so incomplete as to be almost meaningless.
Dr. Kelsey rejected the application numerous times and requested more data.
Merrell representatives, who had large potential profits riding on the
application, began to complain to her bosses and show up at her office,
with respected clinical investigators in tow, to protest the hold-up.
Dr. Kelsey’s FDA superiors backed her as she conducted her research. By
February 1961, she had found more evidence to support her suspicions,
including a letter in the British Medical Journal by an English doctor who
reported that his patients on thalidomide experienced a painful “tingling”
in the arms and feet.
Dr. Kelsey also discovered that, despite warnings of side effects printed
on British and German drug labels, Merrell had not notified the FDA of any
adverse reactions.
Another reason for her concern was that the company had apparently done no
studies on pregnant animals. At the time, a prevailing view among doctors
held that the placental barrier protected the fetus from what Dr. Kelsey
once called “the indiscretions of the mother,” such as abuse of alcohol,
tobacco or illegal drugs. Earlier in her career, however, she had
investigated the ways in which drugs did in fact pass through the placenta
from mother to baby.
While Dr. Kelsey stood her ground on Kevadon, infant deaths and deformities
were occurring at an alarming rate in places where thalidomide had been
sold. The development of seal-like flippers, a condition known as
phocomelia that previously affected an estimated 1 in 4 million infants,
began to crop up by the dozens in many countries.
Clinical investigators, because of a variety of complications including
spotty tracking systems, only belatedly made the link to thalidomide.
Grünenthal began pulling the drug from the market in Germany in late 1961.
Health authorities in other countries issued warnings. Merrell waited until
March 1962 to withdraw its U.S. application. By then, at least 17 babies
were born in the United States with thalidomide-related defects, according
to the FDA.
Influence beyond thalidomide
Dr. Kelsey might have remained an anonymous bureaucrat if not for the
front-page story in The Post. The newspaper had received a tip about her
from staffers working for Sen. Estes Kefauver, a Tennessee Democrat who had
been stalled in his years-long battle with the pharmaceutical industry to
bolster the country’s drug laws.
The coverage of Dr. Kelsey gave her — and Kefauver — a lift. As thousands
of grateful letters flowed in to Dr. Kelsey from the public, the proposed
legislation became hard to ignore or to water down. The new law was widely
known as the Kefauver-Harris Amendments.
“She had a huge effect on the regulations adopted in the 1960s to help
create the modern clinical trial system,” said Daniel Carpenter, a
professor of government at Harvard University and the author of “Reputation
and Power,” a definitive history of the FDA. “She may have had a bigger
effect after thalidomide than before.”
In 1963, Dr. Kelsey was named chief of the FDA’s investigational drug
branch. Four years later, she was named director of the new Office of
Scientific Investigations, a position she held until 1995.
She spent another decade, until her retirement at 90, working at the FDA’s
Center for Drug Evaluation and Research. In that role, she advised the
director of its compliance office on scientific and medical issues and
analyzed historical drug review issues.
According to historians of the FDA, she was instrumental in establishing
the institutional review boards — a cornerstone of modern clinical drug
development — that were created after abusive drug testing trials were
exposed in prisons, hospitals and nursing homes.
For decades, Dr. Kelsey played a critical role at the agency in enforcing
federal regulations for drug development — protocols that were credited
with forcing more rigorous standards around the world.
Name mistaken for a man’s
Frances Kathleen Oldham was born near Cobble Hill, on Vancouver Island,
British Columbia, on July 24, 1914. Her father was a retired British army
officer, and her mother came from a prosperous Scottish family.
The young “Frankie,” as she was called, grew up exploring the woods and
shorelines, sometimes bringing home frogs for dissection. At McGill
University in Montreal, she studied pharmacology — the effects of drugs on
people — and received a bachelor’s degree in 1934 and a master’s degree in
1935.
A McGill professor urged her to apply for a research assistant job at the
University of Chicago, where pharmacology professor Eugene Geiling accepted
her without an interview. Geiling, who had mistaken the names Frances for
the masculine Francis, addressed her by mail as “Mr. Oldham.”
“When a woman took a job in those days, she was made to feel as if she was
depriving a man of the ability to support his wife and child,” Dr. Kelsey
told the New York Times in 2010. “But my professor said: ‘Don’t be stupid.
Accept the job, sign your name and put “Miss” in brackets afterward.’ ”
In Chicago, she helped Geiling investigate the 107 deaths that occurred
nationwide in 1937 from the newly marketed liquid form of sulfanilamide, a
synthetic antibacterial drug used to treat streptococcal infections. In
tablet form, it had been heralded as a wonder-drug of the age, but it
tasted unpleasant.
Because the drug was not soluble in water or alcohol, the chief chemist of
its manufacturer, S.E. Massengill Co. of Bristol, Tenn., dissolved the
sulfanilamide with an industrial substance that was a chemical relative of
antifreeze. He then added cherry flavoring and pink coloring to remedy the
taste and appearance.
Massengill rushed the new elixir to market without adequately testing its
safety. Many who took the medicine — including a high number of children —
suffered an agonizing death.
At the time, the FDA’s chief mandate, stemming from an obsolete 1906 law,
was food safety. At the agency’s request, Geiling joined the Elixir
Sulfanilamide investigation and put Dr. Kelsey to work on animal testing of
the drug. She recalled observing rats as they “shriveled up and died.”
Amid national outrage over Elixir Sulfanilamide, Congress passed the
Federal Food, Drug and Cosmetic Act of 1938, legislation that vastly
expanded federal regulatory oversight over drugs and set a new benchmark
for drug safety before marketing.
Massengill’s owner ultimately was fined a maximum penalty of $26,000 for
mislabeling and misbranding; by technical definition, an elixir contains
alcohol.
‘We need to take precautions’
Dr. Kelsey received a doctorate from Chicago in 1938, then joined the
faculty. In 1943, she wed a pharmacology colleague, Fremont Ellis Kelsey.
After graduating from Chicago’s medical school in 1950, Frances Kelsey
taught pharmacology at the University of South Dakota medical school and
was a fill-in doctor at practices throughout the state. She also became a
U.S. citizen before arriving in Washington in 1960 when her husband was
hired by the National Institutes of Health. He died in 1966 after a heart
attack.
Survivors include their daughters, Susan Duffield of Shelton, Wash., and
Christine Kelsey of London, Ontario; a sister; and two grandchildren. Dr.
Kelsey moved to Ontario from suburban Maryland in 2014.
Babies who suffered from the effects of thalidomide and survived grew up
with a range of impairment. Some required lifelong home care. Others held
jobs and were not severely hindered by their disabilities. Many legal
settlements were reached between drug companies and the victims of
thalidomide, and new claims continue to surface. Grünenthal formally
apologized to victims of thalidomide in 2012.
The drug, however, never disappeared entirely. Researchers have
investigated thalidomide’s effects on H.I.V. and Crohn’s disease and have
conducted clinical trials for on its use for rheumatoid arthritis and
macular degeneration, a leading cause of blindness.
In 1998, the FDA approved the drug for the treatment of lesions from
leprosy. In 2006, thalidomide was cleared for use with the medicine
dexamethasone for certain cases of multiple myeloma, a cancer of the bone
marrow.
The agency enforced strict safeguards, including pregnancy testing, for
such new uses. “We need to take precautions,” Dr. Kelsey told an
interviewer in 2001, “because people forget very soon.”
---
### Author:  [@mounika\_somepalli](https://talk.edrugplus.org/u/mounika_somepalli)
#### Post date: [August 9, 2015, 4:43pm UTC](https://talk.edrugplus.org/t/e-drug-e-drug-dr-francis-kelsey-the-legendary-figure-who-said-no-to-thalidomide-is-dead/41966/2 "2015-08-09T16:43:07Z")
E-DRUG: Dr. Francis Kelsey- the legendary figure who said "No" to Thalidomide is dead (2)
----------------------------------------
That was a wonderful history to be known about Dr. Francis Kelsey. Thank
you sir for the information, I always read about the thalidomide tragedy
but knew very little of the person who was responsible for its hindrance
into the USA.
Regards,
Mounika Somepalli,
Pharm.D Intern,
Chalapathi Institute of Pharmaceutical Sciences, Guntur.
India.