The Man Who Took LSD and Changed The World

DNA can be extracted and visualized as tangled strings, but for decades the genetic “letters” that determine traits and disease were effectively unreadable with ordinary microscopes. The breakthrough that changed that reality came from a chain of lab techniques—restriction enzymes, gel electrophoresis, and DNA probes—that could locate specific mutations—yet they were slow, inefficient, and often impractical for routine diagnosis. The turning point was Kary Mullis’s invention of polymerase chain reaction (PCR), a method that makes targeted DNA copies exponentially fast, turning a tiny genetic signal into something measurable.

In the early 1980s, Mullis worked at Cetus, one of the first biotech startups, where teams were trying to build commercial DNA tests for hospitals. A classic example was sickle cell disease: a single-letter mutation in the beta globin gene changes red blood cell shape, but that mutation is buried inside DNA sequences billions of letters long. Cetus’s approach relied on cutting DNA with restriction enzymes, separating fragments by length using gel electrophoresis, and then using synthetic DNA probes to detect whether the mutation was present. The method—known as Southern blotting—could work, but it took days or weeks and used radioactive materials, making it commercially difficult. Cetus pushed toward faster tests, but signals were often too faint to be reliable.

Mullis’s insight arrived while he was stuck doing repetitive, slow probe synthesis. With a new machine automating parts of his job, he had time to think. Driving to his cabin in 1983, he imagined not “reading” DNA like a telescope, but copying it like a photocopier. The logic hinged on DNA’s complementarity and the directional behavior of DNA polymerase: primers bind to known sequences flanking a target region, and polymerase extends them to generate copies. By repeatedly heating to unzip DNA, cooling to let primers attach, and extending with polymerase, the target region doubles each cycle. After about 30 cycles, the amount of specific DNA becomes enormous—enough to detect even from minuscule starting samples. That concept became PCR.

Convincing others at Cetus was another battle. Mullis pitched the idea aggressively, faced skepticism, and initially struggled to get PCR working on complex human DNA. A small bacterial fragment eventually produced results, but colleagues criticized the lack of controls and reproducibility. A probationary period turned into a team effort, and by spring 1985 the group achieved definitive proof that PCR could amplify DNA reliably.

The remaining obstacle was practical: each PCR cycle required heating to around 95°C, which destroyed the polymerase sourced from E. coli. The solution was already waiting in nature. Decades earlier, microbiologist Thomas Brock and student Hudson Freeze had studied heat-loving organisms from Yellowstone’s hot springs and preserved a thermostable polymerase called Taq. When Cetus adopted Taq, PCR became dramatically cleaner and easier: primers no longer needed to be cooled as far, background amplification dropped, and the process could be “set and forget,” producing billions of copies in hours.

PCR then spread rapidly across medicine and science—supporting diagnostics, forensics, cloning, vaccine development, and later COVID testing. Mullis received major recognition, including the Nobel Prize in chemistry in 1993, but his relationship with credit and credibility was contentious. His later public controversies—ranging from eccentric claims to HIV denialism—cast a complicated shadow over the man behind the method. Still, the core legacy is clear: PCR turned DNA from an unreadable artifact into a scalable tool, and it did so by combining molecular biology with automation—an approach that continues to shape modern life-saving testing.