Background and development Thalidomide was first marketed in West Germany in the late 1950s as a sedative and remedy for morning sickness in pregnant women. It was promoted in several countries for its calming effects and reported low acute toxicity. By the early 1960s, reports from Europe began to link prenatal exposure to thalidomide with a striking increase in infants born with limb malformations (phocomelia) and other severe defects. The U.S. regulatory decision On February 12, 1962, the U.S. Food and Drug Administration (FDA) effectively barred widespread approval of thalidomide for general use in the United States. FDA reviewers, most notably pharmacologist Frances Kelsey, had raised concerns about the drug’s safety and the adequacy of the data provided by the manufacturer. The agency withheld approval pending more conclusive evidence, citing insufficient demonstration of safety in pregnant women and growing international reports of birth defects associated with the drug. Impact and consequences The FDA’s decision prevented the mass distribution of thalidomide in the United States and is credited with averting many cases of drug-induced congenital malformations that occurred elsewhere. The episode prompted a reevaluation of drug safety standards and accelerated reforms in U.S. drug regulation, including the passage of stricter legislation later in the 1960s that increased the burden of proof required for a drug’s safety and efficacy before approval. Scientific and regulatory legacy Thalidomide’s association with birth defects led to greater emphasis on teratology (the study of birth defects) and on rigorous clinical testing, especially for drugs intended for use during pregnancy. The case highlighted the need for careful post-marketing surveillance and for regulators to require more comprehensive clinical data. Frances Kelsey’s role in delaying approval became emblematic of cautious, evidence-based review, and influenced public trust in regulatory oversight. Nuances and later developments While thalidomide caused widespread harm when given to pregnant women in several countries, it was later found to have therapeutic value for certain conditions under tightly controlled circumstances. From the late 1990s onward, thalidomide and related compounds were approved for specific uses—such as treating multiple myeloma and complications of leprosy—under strict controls to prevent exposure during pregnancy. These later uses are subject to rigorous risk-management programs. Historical significance The FDA’s 1962 action remains a pivotal moment in pharmaceutical regulation: a cautionary episode that reshaped standards for drug testing, informed consent, and post-approval monitoring. It underscored the ethical imperative to protect vulnerable populations—particularly pregnant women and developing fetuses—when assessing new medications. Sources and verification The summary above is based on contemporary reporting and regulatory histories of the thalidomide case and the FDA’s review process. Where interpretations or emphases differ among historians and regulatory scholars, this account focuses on well-documented facts: the timing of the FDA’s refusal to approve thalidomide for general use in the United States, the role of safety concerns and international reports of birth defects, and the subsequent regulatory changes that followed.