Because COVID19 we hear about the PCR technique all day. I want to share with you some things about its discovery...

Kary Mullis came with the idea about how to amplify exponentially the amount of a DNA sequence in 1983. At that time he was working at Cetus Corporation (Emeryville, California).

Parenthesis 1: Cetus Corporation was one of the first biotechnology companies. At a given point the company decided to put all the eggs in a single basket: an anticancer pharmaceutical based on IL-2 (interleukin-2).

Parenthesis 2: This was not a good strategy and the company disappeared in 1991. IL-2-based drugs are actually used today as a treatment for people with advanced and metastatic melanoma.

Parenthesis 3: IL-2 is a ~16 kDa protein that regulates the activity of white blood cells. In fact...COVID-19 disease severity is characterized by increased interleukin IL-2 activity:
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30628-0/fulltext

Going back to Mullis...by the time of the discovery, he was working at Cetus developing a methodology to detect the point mutations using DNA sequencing. He came with the idea of employing DNA polymerase, an oligonucleotide primer (only 1), and ddNTPs.

He was facing a huge problem...a single primer can bind to multiple sites and the amplification is linear...he was in need of way to largely increase the concentration of DNA sequences and with high specificity.

One day he was driving (I believe back home from work) in his Honda civic...his girlfriend was sleeping next to him...

At then it happened!!...mile 46.58, California State Route 128 connecting the Mendocino coast to the Sacramento Valley (redwood forests, vineyards, apple orchards...)

he had an epiphany...he suddenly understood that by using TWO opposing primers he could amplify exponentially and with high specificity DNA sequences...

It seems that the exact words were "holy shit!!!". His girl-friend woke up, and he had to pull to the side of road: he quickly wrote his thoughts and rechecked his ideas...yes! he was right! The PCR was born!

Still, the technique had its problems...the E. coli polymerase cannot resist the denaturation step (~90C) and in each cycle he had to replenish it (imagine that)

Later in 1985, he came up with the idea of using a polymerase isolated from a extremophilic bacterium (Thermophilus aquaticus): Taq polymerase

This made the PCR technique to enter in mainstream research. We cannot imagine nowadays Biology, Medicine, Archeology, or Forensics without PCR!

Cetus gave Mullis a lousy $10K bonus...Cetus later sold the patent rights for $300M...Mullis left Cetus in 1986 and got the Nobel prize (Chemistry) in 1993. He died in August last year.

RT if you like it!