How Pcr Changed Genetic Science

A strip of PCR tubes.

Image: Madeleine Price Ball

Biochemist Kary Mullis was imagining red and blue molecules floating above a dark highway one night in 1983 when he had a jolt that changed the world, and has made billions of dollars.

As Mullis tells it, the moon was out, and his headlights were catching the edges of the trees and the white line of the highway as he headed for Mendocino, California. Mullis, then 39, was passing the time visualizing interactions of chemical reactions when suddenly DNA chains coiling and uncoiling configured into a pattern of reactions that solved a crucial dilemma in bio-science: how to rapidly copy, or clone molecules such as DNA. 

Feeling giddy, Mullis pulled over and jotted down notes on a scrap of paper. He woke up his girlfriend asleep in the seat next to him, telling her he was going to be famous and win a Nobel Prize. She told him to keep driving and dozed off again.

To understand the import of Mullis's epiphany, imagine a world without copy machines and printers, where every paper, report, and book had to be typed out or printed by hand. In biology, the equivalent was researchers and companies having to work with the miniscule quantities of DNA and proteins naturally produced by plants, animals, and people.

Mullis's process of polymerase chain reaction—PCR—is a crucial element in everything from blockbuster biologic drugs to new agrifuels, and from diagnoses for diseases and criminal forensics to identifying deadly new pathogens such as SARS.

Every bio-research lab in the world uses this inexpensive technology, with units costing as little as a few hundred dollars. Even so, the PCR industry generates billions of dollars a year in revenues.

The recipe behind PCR is remarkably simple. Take a string of DNA you want copied and heat it up until its double helix separates. Then add small pieces of DNA—primers—which attach to the target and activate biochemical processes that cause it "to reproduce the hell out of itself," Mullis wrote in his autobiography, Dancing Naked in the Mind Field.

Mullis made his discovery while working for Cetus Corporation, an early biotech company based in the San Francisco Bay area. PCR was patented by Cetus, which paid Mullis only a $10,000 bonus. In 1992, Cetus sold the PCR patent to Hoffmann La Roche for $300 million.

I called Roche and asked if they knew how many devices using PCR technology had been sold since they first went on sale, and if anyone had ever calculated a total sales figure. A spokewoman made a few calls and told me that somewhere within Roche there must be someone who knew, but she'd been unable to find that person. (I didn't give her much time right before a holiday weekend.) Later, she called back to tell me that the diagnostics market alone is worth $2 billion.

In 1993, Mullis won the Nobel Prize for discovering PCR, and quickly became one of the most colorful and controversial of Nobel Laureates. He is a surfer who talks about using LSD, and about being abducted by extraterrestrials. He has said that HIV does not cause AIDS, and is a skeptic that human activity causes global warming.

Critics also have claimed that he takes more credit than he is due for the PCR, saying the invention was more of a collaborative effort by scientists at Cetus than a one-man discovery.

In 2005, the core patents for PCR ended for Roche, though they and others continue to sell billions of dollars worth of machines with multiple patents covering specific uses, such as diagnostics and drug development.

Mullis himself has continued to invent things, including a UV-sensitive plastic that changes color in response to light—when he's not surfing, that is.