It is the late 1950s and a new “wonder drug” is going on the market. First debuted in West Germany by a pharmaceutical company called Chemie Grünenthal, you see this new sedative and tranquilizer become an international superstar. Therapeutic Advances in Hematology recalls that researchers assure that testing on rodents shows no amount of this drug results in a fatal dose. Advertisements market thalidomide as completely safe for human use—anyone can take it. Soon enough it is 1960 and thalidomide is popularly prescribed to pregnant women because its antiemetic effects can help with morning sickness. Birth Defects Research shares that doctors receive samples of this drug to freely distribute to their patients; its lack of federal approval is not a big deal.
It is a few years later and the “wonder drug” has become what Birth Defects Research describes to be the “largest man-made medical disaster.” It turns out thalidomide is safe for anyone except pregnant women, because it causes birth defects—the early research from the 1950s and 1960s had not accounted for pregnant subjects in testing for the safety of thalidomide consumption. According to the Science Museum Group, at the time scientists also thought that the placenta was a durable barrier between the fetus and the mother, not allowing any drug the mother ingested to penetrate into the womb. We now know that this is not the case.
When thalidomide reaches a fetus, it causes a wide range of damage. Scientists do not fully understand the mechanisms of its harm on the fetus, but they found that thalidomide has antiangiogenic properties. When exposed to thalidomide in the embryonic stage (from fertilization to eight weeks of gestation), the drug targets blood vessel formation in the embryo. These disruptions in blood vessel development manifest in birth defects, such as shortened limbs (phocomelia) and extra digits in the hands or feet (polydactyly). Other effects include ear malformations, internal organ damage and neural damage. Babies born with these conditions were coined “thalidomide babies.”
The thalidomide tragedy changed the way drugs are tested and regulated. Thalidomide had never actually been approved in the United States during the period of 1957 to 1962. Toxicologic Pathology credits Dr. Frances Kelsey as the physician and pharmacologist in the Food and Drug Administration (FDA) who pushed back against pressures to approve the drug because she saw insufficient safety testing and data on thalidomide. After the impacts of thalidomide were finally illuminated, the United States refurbished its drug regulations. Birth Defects Research discusses that in drug testing, there was more awareness of species differences in drug responses. Mice, the species used to test thalidomide, happened to be less responsive to thalidomide. The Science Museum Group recounts that animal testing was no longer enough for drug approval. Therapeutic Advances in Hematology further explains that the FDA also began enforcing stricter guidelines for clinical trials and company transparency about the product. Packaging labels were revamped to include information on contra-indications of the drug and specifications on safety of its consumption for pregnant women.
Thalidomide was banned in the United States during the 1960s, but scientists had not totally abandoned this drug and its potential. After researchers uncovered uses of its antiangiogenic and anti-inflammatory properties, the FDA allowed restricted use of thalidomide. According to the National Library of Medicine, this drug can treat patients with plasma cell myeloma, which is cancer in the bone marrow, by preventing tumor growth, increased concentration of blood vessels attached to the tumor (hypervascularity) and the spread of cancer (metastasis).
Microbes and Infection describes how thalidomide can also treat leprosy, which is a skin disease caused by infection of a bacteria called Mycobacterium leprae (M. leprae). Leprosy patients may sustain nerve damage and skin lesions. While thalidomide does not have an antimicrobial effect on M. leprae, it has been shown to inhibit the production of a pro-inflammatory protein involved in reactions to leprosy, called Tumor Necrosis Factor Alpha (TNF-α). Thalidomide’s anti-inflammatory property comes from its ability to degrade the messenger RNA (mRNA) that codes for this specific inflammatory protein.
According to Therapeutic Advances in Hematology, even as the FDA approved thalidomide in the United States in 1998 to treat leprosy and in 2006 for myeloma, memories of the “thalidomide babies” linger. Toxicological Sciences refers to the FDA enforcing the System for Thalidomide Education and Prescribing Safety (STEPS)—a program directing doctors to educate all patients on the effects, both positive and negative, of thalidomide. It also requires doctors to provide contraceptive counseling and reproductive oversight and receive informed consent from patients to participate in follow-up surveys before prescribing the drug. This program serves as a safeguard to disallow thalidomide access to pregnant women.
Thalidomide is inextricably linked to tragedy, understandably so, given that it was a preventable man-made medical disaster with far-reaching consequences. The lack of strict regulations allowed the pharmaceutical industry to deem the drug safe, even for pregnant women, which gave rise to birth defects in the babies born from mothers who were prescribed thalidomide. These consequences warrant caution, but that is the crux.
Despite its history, thalidomide has useful applications, like for cancer treatment, and it need not be demonized for its past. People, from both the scientific and political realms, are responsible for how thalidomide reaches and interacts with society—the problem is not the drug itself. Researchers excluded pregnant women from thalidomide’s safety concerns and the politicians failed to uphold protective regulations. Thalidomide cannot be disentangled from the people in white coats or expensive suits making the decisions, but it also can not be frozen in a state of scientific disaster.