Aspartame

James Schlatter was not looking for sweetness—he was synthesizing a tetrapeptide to study ulcers. But when he licked his finger to turn a page in his lab notebook at G.D. Searle's research facility in Skokie, Illinois in 1965, he tasted something intensely sweet. He had accidentally contaminated his hand with an intermediate compound: a methyl ester of two common amino acids, aspartic acid and phenylalanine. Neither amino acid tastes sweet. Aspartic acid is tasteless; phenylalanine is slightly bitter. Combined in this particular configuration, they were 200 times sweeter than sugar.

The discovery was serendipitous, but the path to market was anything but. Aspartame's journey through the FDA became one of the most contentious regulatory battles in American food history, touching on brain tumor research, political appointees, and a future Secretary of Defense.

The adjacent possible for artificial sweeteners had been open since 1879, when saccharin's sweetness was discovered (also by accident, also by a chemist licking his fingers). By the 1960s, cyclamate dominated the low-calorie sweetener market until the FDA banned it in 1969 over cancer concerns. Searle saw an opportunity. Their chemists had stumbled onto a molecule that was not only intensely sweet but metabolized into ordinary amino acids—seemingly natural, seemingly safe.

The FDA first approved aspartame in 1974, then almost immediately halted the approval. An FDA scientist named Adrian Gross found serious problems in all fifteen long-term studies Searle had submitted. Internal FDA investigators documented falsified data. In December 1975, the FDA placed a stay on approval. In 1980, a Board of Inquiry composed of three independent scientists voted unanimously to withhold approval, stating they could not conclude that aspartame "did not cause brain tumors."

What happened next has fueled conspiracy theories for decades. Donald Rumsfeld had become Searle's CEO in 1977. When Ronald Reagan was elected president in 1980, Rumsfeld served on the transition team. On January 21, 1981—the day after Reagan's inauguration—Searle reapplied for approval. The newly appointed FDA commissioner, Arthur Hull Hayes Jr. (recommended by Rumsfeld's transition team), installed a sixth member on the reviewing scientific commission to break a deadlock, then cast the deciding vote himself. Aspartame was approved for dry foods in 1981 and soft drinks in 1983. Hayes left the FDA shortly after and joined Searle's public relations firm.

Monsanto purchased Searle in 1985. Aspartame, sold under brands like NutraSweet and Equal, became one of the world's most widely used artificial sweeteners, generating billions in revenue. The FDA has since called it "one of the most thoroughly tested and studied food additives" ever approved. Yet controversy persists: in 2023, the World Health Organization's cancer research arm classified aspartame as a "possible carcinogen," reigniting debates that began in Searle's original studies.

The molecule itself remains what Schlatter accidentally tasted in 1965: two amino acids joined in a configuration that happens to bind intensely to human sweet receptors. Nature did not design phenylalanine and aspartic acid to taste sweet; their combination just happens to fit a receptor shaped by evolution to detect sugars. This chemical coincidence—that ordinary amino acids could mimic sugar on the tongue—was always present in the adjacent possible. It took an accidental lick to discover it.