Salem Press

Great Events from History: Modern Scandals
Thalidomide Causes Birth Disorders

The widespread use of thalidomide, a drug that was prescribed to pregnant women in the 1950's as a sleep aid and as relief from morning sickness, led to birth disorders among thousands of children around the globe. Inadequate, although standard, testing for the time, along with aggressive marketing, produced an epidemic. The U.S. Food and Drug Administration, which disallowed the drug's use in the United States, would increase its regulations on drug testing and approval soon after the scandal.

Locale: Worldwide

Categories: Health and medicine; science and technology; families and children; business; women's issues

Key Figures
Frances Oldham Kelsey (b. 1914), American pharmacologist
Widukind Lenz (1919-1995), German pediatrician

Summary of Event
In the early 1950's, a Swiss pharmaceutical company had synthesized the drug thalidomide. Thalidomide was first marketed and sold under the brand name Contergan in West Germany in 1957 by the German drug company Grünenthal. The company advertised the drug as a nontoxic medication with no side effects, helpful for a variety of ailments, including sleeplessness. Soon, the drug was prescribed to pregnant women to help with morning sickness, and its use was extended to Australia, Africa, Asia, and the Americas. The drug's effect on human fetuses never was established because drug tests were not required by German law at the time.

The first so-called thalidomide baby was born in 1956, one year before the drug's initial widespread marketing. The years that followed witnessed a dramatic increase in the number of babies born with birth disorders, including deafness, cleft palate, blindness, and, characteristic of thalidomide babies, torsos without arms, legs, or both. Some babies also had "flipperlike" limbs that grew from the shoulder or hip. Eventually, physicians and researchers were able to link these birth disorders to the thalidomide taken by women while they were pregnant.

No accurate census of children that had been affected by the drug exists, but approximately five thousand thalidomide cases have been documented. It is known that thalidomide affected thousands of children worldwide. There also may have been thousands of stillborn or miscarried fetuses, and an estimated 40 percent of those born with the disorders died before their first birthday.

Grünenthal continued research and development during 1954 and for the next few years. The company marketed the drug as an anticonvulsant for epilepsy, but it was subsequently proved ineffective. However, thalidomide was found to be effective as a sedative or sleep aid. In particular, those targeted for its use were women experiencing nausea and morning sickness during pregnancy. Three years later, in October, 1957, thalidomide was marketed for morning sickness and nausea and soon became the drug of choice to help pregnant women with these symptoms. Thalidomide went into general use by 1958 and was widely prescribed around the world.

An American pharmacologist, Frances Oldham Kelsey, looked into the effects of the drug. As a U.S. Food and Drug Administration (FDA) drug evaluator, she repeatedly held off numerous efforts by a U.S.-based licensee of Grünenthal, Richardson-Merrell, to market thalidomide in the United States. Kelsey had serious doubts about the safety of the drug, even though it was being used in Europe. She also noted that the drug affected animals differently from humans and doubted the efficacy of the drug testing that had taken place. Kelsey withstood the pressure of the drug manufacturers to push through its approval.

Because thalidomide did not receive FDA approval in the United States, fewer American women gave birth to thalidomide babies. Women in the United States who were affected had obtained the drug while living abroad or had participated in earlier studies. In recognition of her critical work, Kelsey was awarded the President's Award for Distinguished Civilian Service by U.S. president John F. Kennedy in 1962.

Widukind Lenz, a German pediatrician, established a firm connection between the use of the drug by pregnant women and the birth disorders in November, 1961. He demanded that the drug be taken off the market in Germany; it was removed beginning November 27. Soon, other countries followed. Criminal indictments of nine Grünenthal employees came in 1968, and the criminal case settled two years later with a monetary settlement for those affected by the drug.

In 1972, following the criminal trial, the German government enacted a law that formed the Hilfswerk für Behinderte Kinder (disabled children's relief foundation) to support disabled children, including children born with birth disorders. Grünenthal contributed more than one hundred million marks to the fund, absolving it of further legal claims.

Thalidomide was produced by Grünenthal until 2003, but, according to the company, it was made for humanitarian purposes only. However, the drug remains available--made by other drug companies--in some countries, especially in the developing world, both legally and illegally. It is available in the United States to treat certain forms of leukemia.

Given the scandal of the 1950's and 1960's, the drug's continued use remains controversial. Thalidomide was approved by the FDA in 1998 for use in the United States as a treatment for leprosy, but with very strict controls. Modern research shows that it might be effective in some cases of macular degeneration, HIV-AIDS, and multiple myeloma. FDA controls on thalidomide include the following: Doctors prescribing and pharmacists dispensing thalidomide are required to participate in a program sponsored by the drug's manufacturer, and patients also must be educated about the drug's effects; women must be tested for pregnancy before beginning use of the drug and tested again after use; women who use the drug must use two forms of birth control if sexually active; men taking thalidomide also must use birth control, such as a condom, because it is not known if thalidomide can produce disorders in the children they help to conceive; and donating blood or semen, as well as breast feeding, are prohibited while taking the drug.

Impact
There are several ways to measure the impact of the thalidomide scandal. To those persons and their families directly affected by the drug, the economic and emotional effects have been severe and long lasting. Many thalidomide babies who have survived into middle age and beyond have suffered further medical problems, possibly due to initial exposure to the drug in the womb.

Even more devastating has been the knowledge that the disorders could have been prevented had the drug been tested before being placed on the market. As a consequence of the scandal, the U.S. Congress in 1962 passed the Kefauver-Harris Amendment to the Food, Drug, and Cosmetic Act of 1938, which strengthened the FDA's control of the pharmaceutical industry. Germany produced guidelines for drug testing in 1964.

Mary C. Ware

Further Reading

Hilts, Philip J. Protecting America's Health: The FDA, Business, and One Hundred Years of Regulation. New York: Alfred A. Knopf, 2003. Documents the history of the U.S. Food and Drug Administration from its establishment during Theodore Roosevelt's presidency to the beginning of the twenty-first century. Emphasizes the FDA's regulatory role and its battles against entrenched business interests.

Knightley, Phillip, et al. Suffer the Children: The Story of Thalidomide. New York: Viking Press, 1979. Dramatic and well-written account of the development of thalidomide by Grünenthal, its medical testing, and the massive international repercussions of the thalidomide controversy. Includes appendix summarizing applicable scientific research.

McCredie, Janet. Beyond Thalidomide: Birth Defects Explained. London: Royal Society of Medicine Press, 2007. Explores drug-induced birth disorders, with a focus on thalidomide use and its ramifications for pregnant women.

Pray, W. Steven. A History of Nonprescription Product Regulation. Binghamton, N.Y.: Pharmaceutical Products Press, 2003. Study of over-the-counter drug regulation in the United States. Includes a chapter on the Kefauver-Harris Amendment of 1962.

Stephens, Trent, and Rock Brynner. Dark Remedy: The Impact of Thalidomide and Its Revival as a Vital Medicine. New York: Perseus, 2001. This book was prompted by the return of the use of thalidomide in the United States. A collaboration by a scientist (Stephens) and a novelist-historian (Brynner) carefully relates the history of the drug's development, early uses, and later research and development.

Wallace, Marjorie, and Michael Robson. On Giant's Shoulders: The Story of Terry Wiles. London: Times Books, 1976. This book, later made into a film with the same title, chronicles the life of Terry Wiles, a New Zealander who was born disabled as a result of his mother taking thalidomide during pregnancy.

See also: March 21, 1928: Canada Sterilizes Thousands Deemed Genetically and Mentally Unfit; September-October, 1937: Untested Prescription Elixir Kills More than One Hundred People; Mid-1974: Dalkon Shield Contraceptive Is Removed from the Market; September 26, 1979: Love Canal Residents Sue Chemical Company; Mid-2006--March 16, 2007: China Recalls Pet Food That Has Killed Thousands of American Pets.