Who invented PCR?

Yes, it's Kary Mullis. Although Kjell Kleppe might be the first one who brought up the concept, Mullis, together with the team of the biotech company Cetus, was the first one to make PCR a practical technology in the laboratory. However, in the first prototype PCR, it used the DNA polymerase derived from E. coli; i.e. Klenow fragment (biomedical researcher of my age should know it very well). Klenow fragment works at 37 degree C and is killed at 95 degree C when DNA is denatured. Therefore, fresh Klenow fragment needed to be added into the elongation step of the next cycle every time. Obviously, the process could not be commercialized.

Mullis and Cetus team searched literature for a DNA polymerase working at high temperature. Luckily, they found a paper published by Journal of Bacteriology in 1976, describing in detail the cloning of the DNA polymerase gene from a Thermophile bacterium, Thermus aquaticus, found in the hot spring of Yellow Stone. The enzyme worked at boiling temperature. The Cetus task force followed the methods of the paper to produce the enzyme successfully. It took only one dose of that enzyme to run all PCR cycles perfectly. In the commercialized product, the DNA polymerase was named- you bet- Taq, from the initial of the bacterium's name.

The first author of the paper and the discoverer of Taq is Jia-Yun "Alice" Chang (nee Chien). After publishing the paper, she switched to neuroscience research, received Ph.D. degree from the University of Iowa, and then returned to Taiwan to be the Professor at the National Yang-Ming University, where I went to Master Program and listened to her lecture in 1994. During my two-year graduate study there, for running PCR in my project, I learned how to transform E. coli with Taq DNA plasmid obtained from her and extract the enzyme, as it would cost much more by purchasing it from the company.

There would be no workable PCR without Dr. Chang's discovery. Taq was selected as the Molecule of the Year 1986 by Science Magazine. Later Promega used her paper to win the law suite on the patent of Taq own by Cetus in 1990. In 1994, Mullis received Nobel Prize. Dr. Chang received no attention in all these events.

I wrote this story not to feel the pity for Dr. Chang, whose achievements as a brilliant neuroscientist and a wonderful teacher has been well recognized. Instead, I want to give this as an example that scientific progress is always made by collective efforts and different fields of knowledge, including many unsung heroes.