The most famous bicycle ride in the history of chemistry was not fun. On the afternoon of April 19, 1943, a 37-year-old Swiss researcher pedaled home through Basel convinced he had poisoned himself, and possibly lost his mind.
His name was Albert Hofmann, and the substance was one he had made himself five years earlier and then put on a shelf.
A compound nobody wanted
Hofmann was born in 1906 in Baden, Switzerland, took a doctorate in chemistry at the University of Zurich, and in 1929 joined Sandoz, the Basel pharmaceutical firm, in the natural products laboratory run by Arthur Stoll. His subject became ergot, a fungus that grows on rye and other grains.
Ergot had a grim reputation. In medieval Europe, bread made from infected grain caused the mass poisonings known as St. Anthony's fire. It also had a medical one: midwives had long used it to hasten childbirth. Sandoz was turning that folk knowledge into modern drugs, and Hofmann's work on ergot compounds would eventually produce useful medicines for obstetrics and for circulation.
His method was systematic. Starting from lysergic acid, the chemical core of the ergot alkaloids, he built a series of related compounds and sent each to the company's pharmacologists. In 1938 he made the twenty-fifth in the series, lysergic acid diethylamide, hoping for a stimulant for circulation and breathing. The lab code was LSD-25.
The pharmacologists were unimpressed. They noted an effect on the uterus and observed that the test animals became restless. Nothing about it looked promising, and the compound was dropped.
The Friday afternoon
Five years later Hofmann did something unusual for an industrial chemist: he went back. In his memoir he attributed the decision to a "peculiar presentiment" that the substance had more to offer than the first tests had shown. In the spring of 1943 he made a fresh batch.
On Friday, April 16, in the final stage of the work, he began to feel odd. He was restless and slightly dizzy, and he left the laboratory in the middle of the afternoon. At home he lay down and, with his eyes closed, watched a stream of fantastic images and intensely colored, shifting shapes. Then it passed.
Hofmann assumed that a trace of the compound had somehow gotten into his body, perhaps through his fingertips. If so, it had to be active in amounts far smaller than anything he knew. There was one way to find out.
The ride
On Monday, April 19, at 4:20 in the afternoon, he swallowed what he judged to be the smallest quantity that could possibly have an effect. It was a cautious guess by the standards of the day and, as it turned out, a very large underestimate of the drug's power.
Within the hour his laboratory notes trailed off into a list of symptoms: dizziness, anxiety, visual distortions, a desire to laugh. He asked his assistant to see him home. Because of wartime restrictions on cars, they went by bicycle.
Hofmann later recalled that he felt he was barely moving, though his assistant told him they had ridden quickly. At home, the furniture seemed to take on threatening forms. He asked for milk, as a general antidote to poisoning, from a neighbor who appeared to him as a malevolent witch in a colored mask. He feared he was dying or going permanently insane.
A doctor was called and found almost nothing wrong: normal pulse, normal blood pressure, normal breathing. The only abnormality was a pair of extremely dilated pupils. As the evening wore on the terror ebbed, and Hofmann began to enjoy the colors behind his eyelids. He woke the next morning clear-headed, with a sense of well-being, and walked out into a garden that seemed newly made.
What Sandoz did next
When Hofmann reported the experiment, his superiors doubted the arithmetic. "Are you certain you made no mistake in the weighing?" was the question from both Stoll and Ernst Rothlin, the company pharmacologist. Rothlin and colleagues then tried a fraction of Hofmann's amount themselves, and stopped doubting.
The first systematic human study was carried out by the psychiatrist Werner Stoll, Arthur Stoll's son, at the University of Zurich's psychiatric clinic, and published in 1947. By about 1950 Sandoz was supplying the compound to researchers and psychiatric hospitals under the trade name Delysid. It was offered as an aid in psychotherapy and as a tool for studying psychosis.
For a decade and a half it was a respectable research chemical. According to Novartis, the company that Sandoz later became, the discovery that LSD interferes with serotonin helped persuade neuroscientists that the brain runs on chemistry as well as electricity, a shift that underlies much of modern psychiatric medicine.
Then the drug left the laboratory. In the early 1960s it spread, in Hofmann's words, with epidemic speed as an intoxicant. Sandoz stopped producing and distributing it in 1965. Switzerland restricted it in 1968, and the United States outlawed it in 1970. Hofmann, who retired from Sandoz in 1971, titled his memoir "LSD: My Problem Child." He lived to see sanctioned research resume, and died in 2008 at the age of 102.
How accidental was it?
The holiday came later. In 1985, Thomas B. Roberts, a professor at Northern Illinois University, threw a party at his home in DeKalb, Illinois, and called it Bicycle Day. He had meant to mark April 16, the day of the first accidental exposure, but it fell midweek, so the 19th won.
That scheduling quirk fits the story better than it might seem, because the word "accidental" has always been slightly misleading. Hofmann himself objected to it. LSD, he insisted, came out of a planned research program; the accident arrived five years after the synthesis, and it only mattered because he was the kind of chemist who noticed a strange afternoon and then tested it on purpose.
What April 1943 really records is how thin the line is between a shelved failure and a discovery that would unsettle medicine, law and culture for the rest of the century. The compound did not change between 1938 and 1943. The only thing that changed was that someone looked again.