Kary Mullis, LSD, and the invention of PCR

Derek Muller of Veritasium tells the story of Kary Mullis, the biochemist who invented the polymerase chain reaction (PCR) and who credited his heavy LSD use with the way he thought. The video is a history of a single laboratory idea, not an argument for psychedelics. Muller and the historians he interviews are careful on both sides: they take seriously Mullis's claim that acid shaped his imagination, and they are blunt that Mullis was a difficult colleague, a sloppy experimentalist, and later a public denier of well established science. It is a useful case study for anyone interested in the history of LSD outside the clinic, because it shows how tangled the creativity claim is.

A chemist who took a lot of acid

Mullis studied biochemistry at Berkeley in the 1960s and, by the video's account, spent more time taking LSD than attending classes. His PhD committee refused to approve his dissertation until he cut what they called "all the wacko stuff" out. He drifted after graduating, wrote fiction, took a job in a bakery, and was recruited from behind the counter by Tom White of the biotech startup Cetus. White's recommendation is the sort of detail that sits oddly in a corporate hiring file: he vouched for Mullis as an excellent synthetic chemist because he had been synthesizing hallucinogenic drugs at Berkeley. The legal landscape of the era makes that line stranger still, since by then the compounds in question were criminalized.

The problem PCR solved

Cetus wanted a commercial genetic test for sickle cell disease. The available method, the Southern blot, meant cutting DNA with restriction enzymes, sorting the fragments by length in a gel, then fishing for a mutation with a radioactive probe. It took days or weeks, needed technicians handling radioactive material, and returned a signal too faint to be commercially viable. Mullis described the difficulty as reading a licence plate on Interstate 5, in the dark, from the Moon.

His own job was the dull part: synthesizing the short DNA snippets used as probes. When Cetus bought a machine that did a month of that work in a day, Mullis was left with free time, a supply of snippets, and colleagues who avoided him.

The drive to Mendocino

Driving to his cabin on a Friday night in spring 1983, Mullis stopped trying to build a better telescope and asked instead whether he could simply make more licence plates. Unzip the DNA with heat, let two designed primers bind on either side of the target, let polymerase extend them, and you have two copies. Repeat about thirty times and you have a billion. He pulled over and wrote it on the back of a gas receipt.

Muller is careful about the state Mullis was in that night. He was not tripping. The video's line is that "he wasn't on LSD, but his mind by then had learned how to get there," which is a fair description of what people often report about psychedelics and problem solving: not an answer handed over during a session, but a habit of holding a problem loosely. Mullis himself was less hedged.

"What if I had not taken LSD ever? Would I have invented PCR? I don't know. I doubt it. I seriously doubt it," Mullis wrote.

That is a personal account, not evidence. Research on psychedelics and divergent thinking is still small, mostly short term, and mixed, and a single recollection is the kind of story that gets repeated past what it can carry.

Credit, Taq, and the rest of the story

The idea was not the invention. Mullis pitched it at Cetus and people walked out of the seminar. His first year of experiments failed and he was given a probationary year with a team assigned to help. They cracked it in spring 1985. The remaining obstacle, polymerase being destroyed by each heating cycle, was solved by a heat tolerant enzyme from Thermus aquaticus, a bacterium Tom Brock and his student Hudson Freeze had pulled from a Yellowstone hot spring in the 1960s with no application in mind.

Mullis received the 1993 Nobel Prize in chemistry and, in the account of his colleagues, made PCR his story alone. He then used the fame to promote claims that were not harmless: he rejected the evidence on global warming and the ozone hole, and he denied that HIV causes AIDS, testifying in that role during South Africa's denialist period, which the video links to more than 330,000 deaths. It is a hard reminder that a mind praised for unusual associations can also be a mind that will not update, which is worth keeping in view alongside the limits of psychedelics.

Key takeaways

• ●Kary Mullis invented PCR, the technique that copies a chosen segment of DNA exponentially, making forensics, disease testing, cloning, and later COVID tests possible.
• ●He took LSD heavily as a Berkeley student in the 1960s and said publicly that he doubted he would have conceived PCR without it.
• ●The video reports he was not on LSD the night the idea arrived, only that his thinking had been shaped by prior use, a claim it presents as his own rather than as fact.
• ●Personal testimony of this kind is common in psychedelic history and remains weak evidence; research on psychedelics and creative cognition is still developing.
• ●The idea alone did not work. Two years of failed experiments and a team of colleagues at Cetus were needed to make PCR real.
• ●A separate line of curiosity driven research, Tom Brock's Yellowstone bacteria, supplied the heat tolerant enzyme that made PCR practical.
• ●Mullis later denied that HIV causes AIDS and lent his Nobel status to South Africa's denialist government, a period the video ties to hundreds of thousands of deaths.
• ●Muller's closing suggestion is that automation freeing Mullis from routine work may have mattered as much as anything else in how the idea arrived.