Frances Oldham Kelsey

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Frances Oldham Kelsey
Frances Oldham Kelsey.png
Born
Frances Kathleen Oldham

(1914-07-24)July 24, 1914
Cobble Hill, British Columbia, Canada
DiedAugust 7, 2015(2015-08-07) (aged 101)
London, Ontario, Canada
Alma mater Victoria College, British Columbia
McGill University
University of Chicago
OccupationPharmacologist, physician
Known forPreventing thalidomide from being marketed in the United States
Spouse(s)Fremont Ellis Kelsey (m. 1943, died 1966)
Children2

Frances Kathleen Oldham Kelsey, CM (July 24, 1914 – August 7, 2015) was a Canadian-American [1] pharmacologist and physician. As a reviewer for the U.S. Food and Drug Administration (FDA), she refused to authorize thalidomide for market because she had concerns about the drug's safety. [2] Her concerns proved to be justified when it was shown that thalidomide caused serious birth defects. Kelsey's career intersected with the passage of laws strengthening FDA oversight of pharmaceuticals. Kelsey was the second woman to be awarded the President's Award for Distinguished Federal Civilian Service by President John F. Kennedy.

Food and Drug Administration agency of the United States Department of Health and Human Services

The Food and Drug Administration is a federal agency of the United States Department of Health and Human Services, one of the United States federal executive departments. The FDA is responsible for protecting and promoting public health through the control and supervision of food safety, tobacco products, dietary supplements, prescription and over-the-counter pharmaceutical drugs (medications), vaccines, biopharmaceuticals, blood transfusions, medical devices, electromagnetic radiation emitting devices (ERED), cosmetics, animal foods & feed and veterinary products. As of 2017, 3/4th of the FDA budget is funded by the pharmaceutical companies due to the Prescription Drug User Fee Act.

Thalidomide chemical compound

Thalidomide, sold under the brand name Immunoprin, among others, is an immunomodulatory drug and the prototype of the thalidomide class of drugs. Today, thalidomide is used mainly as a treatment of certain cancers and of a complication of leprosy.

Birth defect condition present at birth regardless of cause; human disease or disorder developed prior to birth

A birth defect, also known as a congenital disorder, is a condition present at birth regardless of its cause. Birth defects may result in disabilities that may be physical, intellectual, or developmental. The disabilities can range from mild to severe. Birth defects are divided into two main types: structural disorders in which there are problems with the shape of a body part and functional disorders in which there are problems with how a body part works. Functional disorders include metabolic and degenerative disorders. Some birth defects include both structural and functional disorders.

Contents

Birth and education

Born in Shawnigan Lake, British Columbia, [3] Kelsey attended St. Margaret's School in the provincial capital, graduating at age 15. [4] From 1930-1931, she attended Victoria College (now University of Victoria). She then enrolled at McGill University, where she received both a B.Sc.(1934) and a M.Sc.(1935) in pharmacology. [3] 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". [4] Geiling, obviously unaware of spelling conventions with respect to Francis and Frances, presumed that Frances was a man and offered her the position, which she accepted, starting work in 1936. [5]

Shawnigan Lake, British Columbia Place in British Columbia, Canada

Shawnigan Lake is a village on British Columbia's Vancouver Island. The name Shawnigan is an adaptation of the Hunquminum name for the Shawnigan Lake, the lake the village is situated at, Shaanii'us. It is part of Electoral Area B in the Cowichan Valley Regional District. As of 2016, the permanent population of Shawnigan Lake is 8,558.

St. Margaret's School in Victoria, British Columbia, Canada, is an international, non-denominational private day and boarding school for girls only, with grades ranging from Junior Kindergarten to Grade 12. It is located on 22 acres (89,000 m2) of land and is the oldest, continuous independent school on Vancouver Island.

Victoria, British Columbia Provincial capital city in British Columbia, Canada

Victoria is the capital city of the Canadian province of British Columbia, located on the southern tip of Vancouver Island off Canada's Pacific coast. The city has a population of 85,792, while the metropolitan area of Greater Victoria has a population of 367,770, making it the 15th most populous Canadian metropolitan area. Victoria is the 7th most densely populated city in Canada with 4,405.8 people per square kilometre, which is a greater population density than Toronto.

During her 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. The next year, the United States Congress passed the Federal Food, Drug, and Cosmetic Act of 1938. [4] That same year she completed her studies and received a Ph.D. in pharmacology at the University of Chicago. [4] Working with Geiling led to her interest in teratogens, drugs that cause congenital malformations (birth defects). [6]

Elixir sulfanilamide

Elixir sulfanilamide was an improperly prepared sulfanilamide medicine that caused mass poisoning in the United States in 1937. It caused the deaths of more than 100 people. The public outcry caused by this incident and other similar disasters led to the passing of the 1938 Federal Food, Drug, and Cosmetic Act.

Sulfonamide (medicine) A molecular moiety or the drug class that uses it

Sulfonamide is a functional group that is the basis of several groups of drugs, which are called sulphonamides, sulfa drugs or sulpha drugs. The original antibacterial sulfonamides are synthetic (nonantibiotic) antimicrobial agents that contain the sulfonamide group. Some sulfonamides are also devoid of antibacterial activity, e.g., the anticonvulsant sultiame. The sulfonylureas and thiazide diuretics are newer drug groups based upon the antibacterial sulfonamides.

Diethylene glycol chemical compound

Diethylene glycol (DEG) is an organic compound with the formula (HOCH2CH2)2O. It is a colorless, practically odorless, poisonous, and hygroscopic liquid with a sweetish taste. It is miscible in water, alcohol, ether, acetone, and ethylene glycol. DEG is a widely used solvent. It can be a contaminant in consumer products; this has resulted in numerous epidemics of poisoning since the early 20th century.

Early career

Kelsey in the 1960s Frances O. Kelsey (FDA 171) (8211251003).jpg
Kelsey in the 1960s

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 learned that some drugs are able to pass through the placental barrier. [7] While at the University of Chicago, she met fellow faculty member Dr. Fremont Ellis Kelsey, whom she married in 1943. [4]

Malaria mosquito-transmitted disease

Malaria is a mosquito-borne infectious disease affecting humans and other animals caused by single-celled microorganisms belonging to the Plasmodium group. Malaria causes symptoms that typically include fever, tiredness, vomiting, and headaches. In severe cases it can cause yellow skin, seizures, coma, or death. Symptoms usually begin ten to fifteen days after being bitten by an infected mosquito. If not properly treated, people may have recurrences of the disease months later. In those who have recently survived an infection, reinfection usually causes milder symptoms. This partial resistance disappears over months to years if the person has no continuing exposure to malaria.

Placenta organ that connects the developing foetus to the uterine wall

The placenta is a temporary organ that connects the developing fetus via the umbilical cord to the uterine wall to allow nutrient uptake, thermo-regulation, waste elimination, and gas exchange via the mother's blood supply; to fight against internal infection; and to produce hormones which support pregnancy. Placentas are a defining characteristic of placental mammals, but are also found in marsupials and some non-mammals with varying levels of development.

While on the faculty at the University of Chicago, Kelsey was awarded her M.D. during 1950. [4] She supplemented her teaching with work as an editorial associate for the American Medical Association Journal for two years. Kelsey left the University of Chicago in 1954, decided to take a position teaching pharmacology at the University of South Dakota, and moved with her husband and two daughters to Vermillion, South Dakota, where she taught until 1957. [3]

American Medical Association professional association for physicians and medical students

The American Medical Association (AMA), founded in 1847 and incorporated in 1897, is the largest association of physicians—both MDs and DOs—and medical students in the United States.

<i>JAMA</i> (journal) Peer-reviewed medical journal published by the American Medical Association

JAMA: The Journal of the American Medical Association is a peer-reviewed medical journal published 48 times a year by the American Medical Association. It publishes original research, reviews, and editorials covering all aspects of the biomedical sciences. The journal was established in 1883 with Nathan Smith Davis as the founding editor. The journal's current editor-in-chief is Howard Bauchner of Boston University, who succeeded Catherine DeAngelis on July 1, 2011.

University of South Dakota public research university located in Vermillion, South Dakota

The University of South Dakota is a public coeducational research (R2) university in Vermillion, South Dakota. Established by the Dakota Territory legislature in 1862, 27 years before the establishment of the state of South Dakota, USD is the state's oldest public university.

She 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. [2]

Multiple citizenship, dual citizenship, multiple nationality or dual nationality, is a person's citizenship status, in which a person is concurrently regarded as a citizen of more than one state under the laws of those states. Conceptually, citizenship is focused on the internal political life of the state and nationality is a matter of international dealings.

Work at the FDA and thalidomide

Kelsey received the President's Award for Distinguished Federal Civilian Service from President John F. Kennedy, 1962 Frances Oldham Kelsey and John F. Kennedy.jpg
Kelsey received the President's Award for Distinguished Federal Civilian Service from President John F. Kennedy, 1962

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" [4] 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. Even though it had already been approved in Canada and more than 20 European and African countries, [8] she withheld approval for the drug and requested further studies. [3] Despite pressure from thalidomide's manufacturer, Kelsey persisted in requesting additional information to explain an English study that documented a nervous system side effect. [4]

Kelsey's insistence that the drug should be fully tested prior to approval was vindicated when the births of deformed infants in Europe were linked to thalidomide ingestion by their mothers during pregnancy. [9] Researchers discovered that the thalidomide crossed the placental barrier and caused serious birth defects. [7] She was hailed on the front page of The Washington Post as a heroine [10] for averting a similar tragedy in the U.S. [11] Morton Mintz, author of The Washington Post article, said "[Kelsey] prevented… the birth of hundreds or indeed thousands of armless and legless children." [10] Kelsey insisted that her assistants, Oyam Jiro and Lee Geismar, as well as her FDA superiors who backed her strong stance, deserved credit as well. The narrative of Dr. Kelsey's persistence, however, was used to help pass rigorous drug approval regulation in 1962. [1]

After Morton Mintz broke the story in July 1962, there was a substantial public outcry. The Kefauver Harris Amendment was passed unanimously by Congress in October 1962 to strengthen drug regulation. [9] Companies were required to demonstrate the efficacy of new drugs, report adverse reactions to the FDA, and request consent from patients participating in clinical studies. [12] The drug testing reforms required "stricter limits on the testing and distribution of new drugs" [7] to avoid similar problems. The amendments, for the first time, also recognized that "effectiveness [should be] required to be established prior to marketing." [9]

As a result of her blocking American approval of thalidomide, Kelsey was awarded the President's Award for Distinguished Federal Civilian Service by John F. Kennedy, [13] becoming the second woman so honoured. [14] After receiving the award, Kelsey continued her work at the FDA. There she played a key role in shaping and enforcing the 1962 amendments. [11] She also became responsible for directing the surveillance of drug testing at the FDA. [3]

Kelsey retired from the FDA in 2005, at age 90, after 45 years of service. [8] In 2010 the FDA established the Kelsey Award, to be awarded annually to an employee. [15]

Later life and death

Kelsey (age 87) at the FDA Reception commemorating her induction into the National Women's Hall of Fame Frances O. Kelsey 2001.png
Kelsey (age 87) at the FDA Reception commemorating her induction into the National Women's Hall of Fame

Kelsey continued to work for the FDA while being recognised for her earlier work. She was still working at the FDA's Center for Drug Evaluation and Research in 1995 and was appointed deputy for scientific and medical affairs. In 1994, the Frances Kelsey Secondary School in Mill Bay, British Columbia was named in her honour. [16] She retired in 2005. [17]

In 2010, the FDA presented Kelsey with the first Drug Safety Excellence Award and named the annual award after her, [18] announcing that it would be given to one FDA staff member annually. [19] 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." [20]

Kelsey turned 100 in July 2014, [21] and shortly thereafter, in the fall of 2014, she moved from Washington, D.C., to live with her daughter in London, Ontario. [22] In June 2015, when she was named to the Order of Canada, Mercédes Benegbi, a thalidomide victim and the head of the Thalidomide Victims Association of Canada, praised Dr. Kelsey for showing strength and courage by refusing to bend to pressure from drug company officials, and said "To us, she was always our heroine, even if what she did was in another country." [22]

Kelsey died in London, Ontario, on August 7, 2015 at the age of 101, [23] less than 24 hours after Ontario's Lieutenant-Governor, Elizabeth Dowdeswell, visited her home to present her with the insignia of Member of the Order of Canada for her role against thalidomide. [24]

Legacy and awards

The "Drug Detective" Frances O. Kelsey (FDA 113) (8205474573).jpg
The "Drug Detective"

See also

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References

  1. 1 2 McFadden, Robert (August 7, 2015), Frances Oldham Kelsey, F.D.A. Stickler Who Saved U.S. Babies From Thalidomide, Dies at 101, The New York Times .
  2. 1 2 Peritz, Ingrid (November 24, 2014), Canadian doctor averted disaster by keeping thalidomide out of the U.S., The Globe and Mail , retrieved August 7, 2015.
  3. 1 2 3 4 5 "Frances Kelsey", Canada Heirloom Series, Heirloom Publishing Inc., 986, retrieved August 15, 2009.
  4. 1 2 3 4 5 6 7 8 Bren, Linda (March–April 2001), "Frances Oldham Kelsey: FDA Medical Reviewer Leaves Her Mark on History", FDA Consumer, archived from the original on October 20, 2006, retrieved August 15, 2009.
  5. "When Kelsey read Geiling's letter offering her a research assistantship and scholarship in the PhD program at Chicago, she was delighted. But there was one slight problem — one that 'tweaked her conscience a bit.' The letter began 'Dear Mr. Oldham,' Oldham being her maiden name. Kelsey asked her professor at McGill if she should wire back and explain that Frances with an 'e' is female. 'Don't be ridiculous,' he said. 'Accept the job, sign your name, put 'Miss' in brackets afterwards, and go!'" Bren (2001).
  6. Spiegel, Rachel, Research in the News: Thalidomide, archived from the original on August 22, 2007, retrieved August 15, 2009.
  7. 1 2 3 Simpson, Joanne Cavanaugh (September 2001), "Pregnant Pause", Johns Hopkins Magazine, 53 (4), retrieved April 30, 2006.
  8. 1 2 3 Rouhi, Maureen (June 20, 2005), "Top Pharmaceuticals: Thalidomide", Chemical & Engineering News, 83 (25), retrieved April 30, 2006.
  9. 1 2 3 "The Story Of The Laws Behind The Labels", FDA Consumer, June 1981, retrieved August 15, 2009.
  10. 1 2 Mintz, Morton (July 15, 1962), 'Heroine' of FDA Keeps Bad Drug Off of Market, The Washington Post, p. Front Page. See also Mintz's comments from 2005 on Kelsey.
  11. 1 2 Dr. Frances Kathleen Oldham Kelsey, National Library of Medicine, retrieved April 30, 2006.
  12. Frances Oldham Kelsey, Chemical Heritage Foundation, archived from the original on July 12, 2016, retrieved March 23, 2014
  13. Kennedy, John F. (1962), Remarks Upon Presenting the President's Awards for Distinguished Federal Civilian Service , retrieved May 1, 2006.
  14. 1 2 Women of the Hall – Frances Kathleen Oldham Kelsey, Ph.D., M.D., National Women's Hall of Fame, 2000, retrieved May 1, 2006.
  15. Lyndsey Layton (September 13, 2010), "Physician to be honored for historic decision on thalidomide", The Washington Post.
  16. FKSS History, Frances Kelsey Secondary School, archived from the original on October 19, 2012, retrieved December 26, 2014.
  17. "Frances Kelsey, scientist - obituary". The Telegraph. August 11, 2015. Retrieved 11 August 2015.
  18. Harris, Gardiner (September 13, 2010), "The Public's Quiet Savior From Harmful Medicines", The New York Times , retrieved January 4, 2011.
  19. Margaret A. Hamburg, M.D., Commissioner of Food and Drugs – Remarks at the Award Ceremony for Dr. Frances Kelsey .
  20. Barber, Jackie (November 10, 2005), "Center ceremony honors 107 individuals, 47 groups: Spring event inaugurates Frances Kelsey Drug Safety Award", News Along the Pike, archived from the original on June 15, 2007, retrieved August 15, 2009.
  21. McElroy, Justin (July 24, 2014), Canadian scientist Frances Kelsey, who spurred FDA reforms, turns 100, Global News , retrieved July 24, 2014.
  22. 1 2 3 Ingrid Peritz (July 1, 2015), "Doctor who opposed thalidomide in U.S. named to Order of Canada", The Globe and Mail , retrieved July 1, 2015.
  23. Bernstein, Adam; Sullivan, Patricia (August 7, 2015), Frances Oldham Kelsey, FDA scientist who kept thalidomide off U.S. market, dies at 101, The Washington Post , retrieved August 7, 2015.
  24. Ingrid Peritz (August 7, 2015), "Canadian doctor who kept thalidomide out of U.S. dies", The Globe and Mail , retrieved August 7, 2015.
  25. Gold Key Award Recipients, The University of Chicago The Medical & Biological Sciences Alumni Association, retrieved August 14, 2006.
  26. Geraghty, Karen (July 2001), "Profile of a Role Model – Frances Oldham Kelsey, MD, PhD", Virtual Mentor – American Medical Association Journal of Ethics, 7 (7), archived from the original on September 29, 2007, retrieved August 15, 2009.
  27. 2006 Foremothers Awards Luncheon, National Research Center for Women & Families, archived from the original on May 14, 2011, retrieved August 15, 2009.
  28. "FDA honors one of its own". CNN blog. September 16, 2010. Retrieved August 9, 2015.
  29. "Honorary doctor of science degree from Vancouver Island University", Nanaimo News Bulletin, Black Press, Inc., 2012-06-06.

Further reading