From Patent Medicine to Federal Law
Before 1906, the American drug market was almost entirely unregulated, filled with “patent medicines” that made sweeping health claims without any requirement to prove safety, effectiveness, or even honestly disclose their ingredients. Chemist Harvey Washington Wiley, working within the Department of Agriculture’s Bureau of Chemistry, spent years documenting adulterated food and dangerous drug products, famously recruiting a group of volunteers nicknamed the “Poison Squad” to test the effects of food preservatives and additives on themselves. Wiley’s advocacy, combined with mounting public pressure, led to the Pure Food and Drug Act of 1906 — the first federal law addressing drug safety, though it primarily targeted mislabeling and adulteration rather than requiring any proof of safety before a product reached the market. The Bureau of Chemistry’s enforcement responsibilities under that law eventually evolved, through a series of reorganizations, into what was formally named the Food and Drug Administration in 1930.
The 1906 law’s gap — no requirement to prove a drug was actually safe before selling it — had catastrophic consequences three decades later. In 1937, a pharmaceutical company marketed Elixir Sulfanilamide, a liquid formulation of an antibacterial drug, using diethylene glycol as a solvent to improve its taste — a chemical now recognized as toxic, but never tested on animals or humans before the product reached patients. More than 100 people died, many of them children, before the product could be recalled. The disaster directly drove passage of the Federal Food, Drug, and Cosmetic Act of 1938, which for the first time required manufacturers to demonstrate a new drug’s safety before it could be legally marketed in the United States.
Thalidomide and the Modern Approval Process
The 1938 law still didn’t require proof that a drug actually worked — only that it was safe — and it took a second major tragedy to close that remaining gap. Thalidomide, marketed throughout Europe starting in the late 1950s as a sedative and treatment for morning sickness in pregnant women, was found by the early 1960s to cause severe birth defects in thousands of children whose mothers had taken the drug during pregnancy. The United States was largely spared the disaster’s scale because of one FDA medical reviewer, Frances Kelsey, who repeatedly refused to approve thalidomide for the American market, citing insufficient safety data despite significant pressure from the manufacturer — a decision later recognized as one of the most consequential individual judgment calls in the history of American drug regulation.
The thalidomide tragedy led directly to the Kefauver-Harris Amendment of 1962, which required manufacturers to prove not just safety but also efficacy before a new drug could be approved, and mandated that patients be informed when participating in clinical trials — establishing the modern framework of preclinical testing, phased human trials, and formal FDA review still used today. That framework has continued to evolve in the decades since, from the Orphan Drug Act of 1983, which created incentives for developing treatments for rare diseases, to modern expedited pathways designed to speed the review of drugs addressing serious unmet medical needs — each one a response, in one form or another, to the same underlying question the 1906, 1938, and 1962 laws were each built to answer: how much evidence should be required before a new drug reaches the public.
Source: National Institutes of Health (NIH) and Encyclopaedia Britannica.