Whether the product of poor lab housekeeping, clumsy researchers, or an inexplicable urge to taste everything, there are some discoveries that would never have been made on purpose.

1. Artificial Sweeteners

Until the introduction of neotame in 2002, every common artificial sweetener had been discovered by mistake, usually by a chemist accidentally ingesting one of their compounds [1]. This trend started with saccharin in the 19th century, when Constantin Fahlbert was working in the lab of Ira Remsen.  After a long day of creating new toluene derivatives, Fahlberg left for dinner without washing his hands.  Breaking open a dinner roll, he found the bread to be unnaturally sweet, and eventually traced the cause back to a chemical residue left on his hands.   Together with Remsen he purified the residue and together they published a paper titled, “On the Oxidation of ortho-Toluenesulfonimide” (in German of course), where the effect was detailed.  Several years later Fahlberg optimized the synthesis, patented the results, and began industrial production of saccharin—all without telling Remsen.  Saccharin has had an interesting history since then, and was the first product ever sold by Monsanto.

The Remsen-Fahlberg synthesis of Saccharin.  Via wikipedia.

The Remsen-Fahlberg synthesis of Saccharin. Via wikipedia.

In almost a shot-by-shot repeat, almost ninety years later aspartame was discovered by James M. Schlatter. While synthesizing a tetrapeptide subsequence of the hormone gastrin his flask bumped, splashing aspartame (in methanol) over his hands. Unfazed, he continued lab work, until a little later he needed to pick up a piece of paper.  Licking one of his fingers, he initially thought his hand was covered in sugar, eventually tracking the taste back to his recrystallization flask.

Even among sweeteners the story of sucralose deserves special mention, as the only agent discovered accidentally-on-purpose. After hearing that his student Shashikant Phadnis had prepared the chlorinated sucrose as part of a search for new insecticides the (presumably Scottish) Leslie Hough said to “tæst it.” And so Phadnis did, dropping a small amount of the powder onto his tongue via spatula. He reported back to Hough, who was soon adding “serendipitose” to his morning coffee.

2. Polymers and other Materials

The Goodyear company does little to dispel the stove story.Polymer science also owes quite a bit to lab mishaps, starting with the (apochryphal) story of Charles Goodyear accidentally mixing rubber and sulfur on a hot stove. The saran in Saran Wrap first appeared as an off-green, impossible to remove residue on the inside of the vials and beakers at Dow Chemical, and was plucked from obscurity by Ralph Wiley, a college student hired to clean the glassware.

In another cleaning mishap, Patsy Sherman saw the promise of scotchgard when few drops of the polymer spilled onto the shoe of a research assistant. The stain on the shoe couldn’t be removed by soap or organic solvents, but also shrugged off dust and dirt. Together with Sam Smith the formulation was optimized, then marketed as a stain repellant.

Regardless of the original field of research, serendipitously discovered polymers usually have immediate applications. Such as it was for the invention of laminated (safety) glass, which almost literally fell into the lap of Edouard Benedictus.  Grabbing reagents from a high shelf via ladder, Benedictus accidentally knocked down an unrelated beaker, shattering it instantly.  Back on the ground,  he discovered the glass had largely retained it’s shape, held together by the cellulose nitrate stored inside. After a furious twenty-four hours of (rather expensive) experiments triplex was born.Triplex Aviation Glasses


Entire drug classes have grown out serendipitous side effects, with Viagra probably the best known. The list is a little too large to cover succinctly, so instead I’ll direct you to this classic paper on the subject.

Via the two Wikipedia pagesFocusing on compounds discovered through poor lab technique, in 1976 Barry Kidston was a graduate student at the University of Maryland.  Kidston had a rather unhealthy interest in narcotics, and for several months had been synthesizing the analgesic desmethylprodine (MPPP). His technique was on a slow decline during this period, until in a rush one day he accidentally overheated the final reaction step.  Elimination occurred, contaminating the MPPP with MPTP.  Unaware of his mistake and electing not to recrystallize the product, he injected the mixture.  Within three days Kidston was in the hospital with what appeared to be an acute case of Parkinson’s disease. The condition proved largely permanent, though the role of MPTP wasn’t confirmed until several years later [2].  Like a true case of Parkinson’s disease his symptoms responded to treatment with levodopa, and MPTP eventually found a role in research, inducing model Parkinson’s in primates.

On the happier side of history lies LSD-25, lysergic acid diethylamide.  With an effective dose of just twenty micrograms, it’s actually a testament to the lab skills of chemist Albert Hofmann that when the chemical was first synthesized its effects as a psychedelic went completely unnoticed. Created during a hunt for new analeptics, early research in LSD showed little biological activity, save for “marked excitation” in some lab animals. Shelved for five years, it was during the second synthesis of LSD that Hofmann was accidentally dosed. When symptoms appeared Hoffman excused himself from work for the rest of the day (it was a Friday afternoon), and went home to rest. Lying on a couch at home he then experienced the world’s first acid trip, as documented in an incident report:

Last Friday, April 16, 1943, I was forced to stop my work in the laboratory in the middle of the afternoon and to go home, as I was seized by a peculiar restlessness associated with a sensation of mild dizziness. On arriving home, I lay down and sank into a kind of drunkenness which was not unpleasant and which was characterized by extreme activity of imagination. As I lay in a dazed condition with my eyes closed (I experienced daylight as disagreeably bright) there surged upon me an uninterrupted stream of fantastic images of extraordinary plasticity and vividness and accompanied by an intense, kaleidoscope-like play of colors. This condition gradually passed off after about two hours.

By Monday morning he was fully recovered and curious to discover the root of his illness. Assuming that one of the chemicals he had been working with was responsible, he started by ingesting a miniscule 0.25 mg of LSD, not realizing the drug has an effect at a tenth that dosage. The results were “rather dramatic.”

[…]I asked my laboratory assistant to accompany me home as I believed that I should have a repetition of the disturbance of the previous Friday. While we were cycling home, however, it became clear that the symptoms were much stronger than the first time. I had great difficulty in speaking coherently, my field of vision swayed before me, and objects appeared distorted like images in curved mirrors. I had the impression of being unable to move from the spot, although my assistant told me afterwards that we had cycled at a good pace…. Once I was at home the physician was called.

This Friday will be the 70th anniversary of Hofmann’s second dose, celebrated by some as “Bicycle Day.”

LSD users make awesome pictures.

[1] Lead (II) acetate may be an exception to this, but I’m willing to bet that the Romans didn’t intentionally add crushed minerals to their food.

[2] Unfortunately, in 1982 another sloppy chemist started making MPPP, this time dealing the results to heroin addicts.  At least seven people developed severe Parkinson’s.