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Helen Brooke Taussig: An Often Overlooked Advocate for Drug Safety

Posted 11 October 2019 | By Max Sherman  | ©

Helen Brooke Taussig: An Often Overlooked Advocate for Drug Safety

This article reviews the biography of Dr. Helen Brooke Taussig and discusses her successful efforts in the 1960s to prevent the drug “thalidomide,” the cause of wide-spread and serious birth defects in Europe, from being FDA-approved for use in the US.

Introduction

In the late 1950s and early 1960s, the drug thalidomide sent shock waves worldwide when it was proven that an allegedly harmless substance given to pregnant mothers as a sedative to combat morning sickness was the cause of debilitating birth defects. While more than 8000 children worldwide were born with such deformities, such as flipper-like arms and legs (phocomelia), the US escaped practically unscathed due to the diligence of a US Food and Drug Administration (FDA) medical reviewer, Dr. Frances Oldham Kelsey, and physician Dr. Helen Taussig. Because of their work, thalidomide was not approved for mass American distribution. While most everyone working in drug regulatory affairs may be acquainted with Kelsey since much of the credit for not approving thalidomide has been attributed to her, the work done by Taussig is equally impressive.1 Taussig’s testimony before Congress on thalidomide helped to support and augment Kelsey’s decision to deny approval.

About Dr. Kelsey

Dr. Frances Kathleen Oldham Kelsey worked at FDA for many years, retired in 2005 at age 90, and died at age 101 in London, Ontario, Canada 7 August 2015.2 Dr. Kelsey, a pharmacologist, prompted widespread and justifiable concern about the inadequacy of drug regulations in the 1960s. Dr. Kelsey's efforts in premarket review are part of the fascinating history of food and drug law and the effect individuals can have in changing it.3

About Dr. Taussig

In 1962, Dr. Taussig learned about birth defects occurring in several countries. In light of her personal concern for the welfare of children and families, she traveled to Europe to examine affected babies and learn about their medical history. Having confirmed that thalidomide was the cause, she returned to the US where she testified, lectured and wrote in opposition to the pharmaceutical industry until FDA refused to approve the drug. Without the indefatigable efforts by Drs. Kelsey and Taussig, thalidomide would likely have been approved in the US in the early 1960s. However, Taussig brilliantly summarized her findings in the New England Journal of Medicine in 1963, re-emphasizing the need to label drugs properly, record their use and to prescribe them with the greatest caution to women of child-bearing age.4

Dr. Taussig, the daughter of a Harvard professor of economics, attended Radcliffe College for two years after which she transferred to the University of California Berkeley to escape her relationship with her father. When upon graduation she told him that she wished to go into medicine, he suggested public health instead. However, the dean of Harvard’s School of Public Health politely told her that she could enroll in the four year course, but that no woman would be granted a degree.5 Refusing to be discouraged, she did obtain permission to study histology there and anatomy at Boston University, where she began investigating the heart muscle. Her advisor, the Dean of the university’s medical school encouraged her to apply to the Johns Hopkins University, where she was accepted, studied and was one of only a few women to graduate, obtaining obtained her medical degree in 1927.

 As a pediatric cardiologist, she saw many “blue babies,” their blood starved of oxygen having failed to circulate properly through the lungs. These infants gasped for breath after minimal exertion and usually died at an early age. After studying the condition, caused by a cluster of congenital heart defects, she proposed to her surgical colleague, Alfred Blalock, that it might be alleviated by diverting another artery to the lungs. They did the first Blalock-Taussig shunt in 1944 after developing the procedure in 200 surgical experiments with dogs. Although It took more than three years to develop the technique, the shunt created a life extending solution for a condition previously thought to be untreatable.

In 1954, for their work on congenital heart problems, Taussig and Blacock received the “Lasker Award,” created in 1945 by Albert and Mary Lasker to reward fundamental biological discoveries and clinical advances. The outstanding achievements in pediatric cardiac surgery were instrumental in granting her the appointment as chief of the department, a position she held until her retirement in 1963. She was the first woman to achieve the rank of full professor and the first woman to be president of the American Heart Association. In 1964, Taussig also won the “Presidential Medal of Freedom.” Many of the procedures she helped develop are still in use today. She wrote the first standard reference text for pediatric cardiology.6 Her accomplishments are all the more significant because she had to overcome learning disabilities, deafness and a medical culture not ready for women.7

Thalidomide History

Thalidomide was synthesized in West Germany in 1953 and because it had no pharmacological effect in laboratory animals, the company originally working with the drug discarded it. Subsequently, the West German firm Chemie Grunenthal undertook development of the compound, but once again thalidomide showed no effects in animals and appeared to be nontoxic. It seemed impossible to find a dose high enough to kill a rat. However, the structure of the molecule suggested it could be effective as a sedative, acting promptly to provide a deep, all night sleep without a morning “hangover.” Given the trade name “Contergan” in 1960, it became the most commonly used sleeping remedy in West Germany, available without a prescription, and was thought to be as safe for humans as it seemed for animals.8

By the early 1960s, pharmaceutical companies in countries other than West Germany began to market the drug. At the height of its demand, thalidomide was being produced by 14 firms under 15 different trade names.

On 8 September 1960, the Canadian branch of William S. Merrell Company of Cincinnati, Ohio applied to FDA for approval to sell their version of thalidomide, called “Kevadon,” in the US. The review was passed on to Dr. Kelsey, a newly hired FDA medical officer. Because the drug had already been sold to pregnant women in Europe for morning sickness, and the application seemed to be routine, it appeared to be readily approvable. Existing laws held that after an application had been submitted, the agency had 60 days in which to decide that the drug was safe for the proposed use. If FDA did not respond, the drug was automatically approved.

However, some of the drug safety data troubled Dr. Kelsey and she subsequently asked Merrell management for more information. 9

The application for “thalidomide” landed on her desk on 12 September 1960, one week after she reported to work. She was concerned that no lethal dose for rats could be found. To her, this suggested that the rats were simply not absorbing the drug. Then there was a question as to why thalidomide acted as a hypnotic in humans but did not induce sleep in animals. Dr. Kelsey waited until the 58th day after her review before declaring the application incomplete and, thus, ineligible for submission. This meant that the company had to file a new application, which provided more time for Dr. Kelsey to consider it and, potentially, reject it. The company withdrew the submission.

Considering the thalidomide tragedy in Europe, Congress reexamined the new drug approval process and passed the Kefauver Harris Amendment or the "Drug Efficacy Amendment," a 1962 amendment to the Federal Food, Drug, and Cosmetic Act. The Act introduced a requirement for drug manufacturers to provide proof of the effectiveness and safety of their drugs before approval, among other requirements.10 The amendments were the most comprehensive revision of the drug regulatory law since passage of the 1938 Federal Food, Drug, and Cosmetic Act.11

Final Thoughts

On 20 May 1986, four days before her 88th birthday, Dr. Taussig was killed in a motor vehicle collision while driving near her retirement community in Kennett Square, Pennsylvania.

Thalidomide remains newsworthy as it is currently used for several indications, but with a host of safeguards. It was initially approved in 1998 to treat a clinical form of leprosy and later for treating multiple myeloma.

References
  1. Ferry G. “A Woman’s Place.” Lancet. 2019, Vol. 394:834.
  2. McFadden RD. “Frances Oldham Kelsey: FDA Stickler who Saved US Babies From Thalidomide Dies at 101.” The New York Times. 7 August 2015.
  3. Kermode-Scott B. “Frances Kathleen Oldham Kelsey.” BMJ. 2015; 35 was F1:h4809.
  4. Taussig HB. “The Evils of Camouflage as Illustrated by Thalidomide.” NEJM. 1963; Vol. 269 (No. 2): 2-4.
  5. Nuland SB. “Helen Taussig and the Blue Baby Operation, Chapter in Doctors: the Biography of Medicine.” 1988. Alfred A. Knopf Inc., New York, 1988.
  6. Taussig H. “Congenital Malformations of the Heart.” 1947, Commonwealth Fund, New York
  7. Op cit 1.
  8. Sterling D, et al. “Thalidomide: An Amazing Recovery.” J Am Pharm Assoc. 1997; Vol NS37(3):306-13.
  9. Stephens T and Brynner R. “Dark Remedy: The Impact of Thalidomide and its Revival as a Vital Medicine. Perseus Press, Cambridge MA, 2001.
  10. Pub. L. No. 87-781, 76 Stat 780 (1962).
  11. Pub. L. No. 75-717, 52 Stat 1040 (1938), as amended 21 U.S.C. §§ 301 et seq.
About the Author

Max Sherman is a retired regulatory professional. He has contributed to Regulatory Focus for more than two decades and is the author of the book entitled "Eclectic Science and Regulatory Compliance: Stories for the Curious." The book contains 36 essays, most of which appeared in Regulatory Focus. In 2012, RAPS published "From Alzheimer's to Zebrafish: Eclectic Science and Regulatory Stories." He is also the editor of the first (2015) and second (2018) editions of "The Medical Device Validation Handbook." He may be contacted at maxsherman339@gmail.com.
 
Cite as: Sherman M. “Helen Brooke Taussig: An Often Overlooked Advocate for Drug Safety.” Regulatory Focus. October 2019. Regulatory Affairs Professionals Society.

 

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