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Mr. Cycle: An Automated PCR Prototype

A 1985 prototype of a semi-automated thermal cycler, hot and cold water baths not included. Credit: Courtesy of The Smithsonian Institution" />A 1985 prototype of a semi-automated thermal cycler, hot and cold water baths not included. Credit: Courtesy of The Smithsonian Institution The "aha" moment and initial experiments in 1983 through which Kary Mullis developed the idea of polymerase chain reaction (PCR) are a well trodden story.1 While Mullis says he immediately realized PCR?s pote

Terry Sharrer
Nov 30, 2006
<figcaption>A 1985 prototype of a semi-automated thermal cycler, hot and cold water baths not included. Credit: Courtesy of The Smithsonian Institution</figcaption>
A 1985 prototype of a semi-automated thermal cycler, hot and cold water baths not included. Credit: Courtesy of The Smithsonian Institution

The "aha" moment and initial experiments in 1983 through which Kary Mullis developed the idea of polymerase chain reaction (PCR) are a well trodden story.1 While Mullis says he immediately realized PCR?s potential, his employers at Cetus Corporation were wary that it didn?t fit the company?s business strategy. Still, they allowed Mullis to continue and brought others into a "PCR group" to produce results that might attract investors. By the end of 1985, the PCR group published the first paper about an application, a prenatal diagnostic test for sickle cell anemia,2 and filed the initial patent naming Mullis as the inventor.3 (For more PCR applications see p. 66 and 68) Cetus entered into a strategic partnership with PerkinElmer to develop PCR machines and reagent kits for the biomedical research market.

"Mr. Cycle," a 1985 prototype, is shown here without its accompanying hot and cold water baths (Mullis says he?s unsure who affixed the "California Dreamin" bumper sticker.) This was the first PCR device resulting from the PerkinElmer Cetus Instruments (PECI) collaboration. It was not fully automated. After each thermal cycle, an operator had to add fresh enzyme because heat damaged the polymerase. Later, Cetus scientists David Gelfand, Susanne Stoffel, Frances Lawyer, and Randall Saiki patented the heat-stable Thermus aquaticus polymerase (Taq),4 and fully automated PECI machines and "GeneAmp" reagent kits became commercially available in November 1987. PCR patent battles that ensued have been resolved only recently, nearly concurrent with the expiration of their scope in the United States.

tsharrer@the-scientist.com

References

1. K. Mullis, "The first polymerase chain reaction," The Scientist, 17(4):11, Feb. 24, 2003. 2. R. Saiki, et al., "Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia," Science, 230:1350-4, 1985. 3. US Patent 4,683,202, filed Oct. 25, 1985; issued July 28, 1987. A second patent (4,683,195, filed Feb. 7, 1986; issued July 28, 1987), with Mullis and others as inventors, further described the technique and claims. 4. US Patent 4,889,818, filed June 17, 1987; issued Dec. 26, 1989.