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History of PCR 3
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A Short History of the Polymerase Chain Reaction
John M. S. Bartlett and David Stirling
The development of the polymerase chain reaction (PCR) has often been likened
to the development of the Internet, and although this does risk overstating the impact
of PCR outside the scientific community, the comparison works well on a number
of levels. Both inventions have emerged in the last 20 years to the point where it is
difficult to imagine life without them. Both have grown far beyond the confines of
their original simple design and have created opportunities unimaginable before their
invention. Both have also spawned a whole new vocabulary and professionals literate
in that vocabulary. It is hard to believe that the technique that formed the cornerstone of
the human genome project and is fundamental to many molecular biology laboratory
protocols was discovered only 20 years ago. For many, the history and some of the
enduring controversies are unknown yet, as with the discovery of the structure of DNA
in the 1950s, the discovery of PCR is the subject of claim and counterclaim that has
yet to be fully resolved. The key stages are reviewed here in brief for those for whom
both the history and application of science holds interest.
The origins of PCR as we know it today sprang from key research performed in
the early 1980s at Cetus Corporation in California. The story is that in the spring of
1983, Kary Mullis had the original idea for PCR while cruising in a Honda Civic on
Highway 128 from San Francisco to Mendocino. This idea claimed to be the origin
of the modern PCR technique used around the world today that forms the foundation
of the key PCR patents. The results for Mullis were no less satisfying; after an initial
$10,000 bonus from Cetus Corporation, he was awarded the 1993 Nobel Prize for
chemistry.
The original concept for PCR, like many good ideas, was an amalgamation of
several components that were already in existence: The synthesis of short lengths of
single-stranded DNA (oligonucleotides) and the use of these to direct the target-specific
synthesis of new DNA copies using DNA polymerases were already standard tools in
the repertoire of the molecular biologists of the time. The novelty in Mullis’s concept
was using the juxtaposition of two oligonucleotides, complementary to opposite strands
of the DNA, to specifically amplify the region between them and to achieve this in a
repetitive manner so that the product of one round of polymerase activity was added
to the pool of template for the next round, hence the chain reaction. In his History of
PCR (1), Paul Rabinow quotes Mullis as saying:
From: Methods in Molecular Biology, Vol. 226: PCR Protocols, Second Edition
Edited by: J. M. S. Bartlett and D. Stirling © Humana Press Inc., Totowa, NJ
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