Biosearch and the Discovery of PCR
The roots of Biosearch Technologies can be traced back to 1978 when current President and CEO, Ron Cook, PhD founded “Biosearch” to supply research tools to the nascent Biotechnology industry. In the 1980s, Biosearch developed and manufactured automated, solid-phase DNA synthesizers, such as the SAM I, the Cyclone, Biosearch 8700 and Biosearch 8800 Prep. These instruments manufactured oligonucleotides with prodigious proficiency, catalyzing the development of revolutionary new oligo based technologies. Most notably in 1982, Kary Mullis then at Cetus Corporation, used a Biosearch Sam One DNA synthesizer to create oligos for use in his experiments, which eventually resulted in the discovery of the Polymerase Chain Reaction.

Kary Mullis and the Invention of PCR
Kary Mullis, who earned a PhD in biochemistry from University of California, Berkeley in 1973, conceived of PCR in the spring of 1983 as a means to amplify a specific locus of interest on the human genome.

After conceptualizing PCR during his famous drive to “Philo”, Kary labored for a number of months to work out experimental conditions. Since thermostable polymerases were not yet available, it was necessary to add Klenow after each thermal cycle, adding to the tedium of development. There were many failures and many reasons why PCR should not work. After all the idea was so simple, shouldn’t it have been invented before? Ignoring the doubts of many, and with encouragement from Ron Cook as well as other supporters, Kary was able to perform his first successful experiment on December 16, 1983, and the rest, as they say, is history!!! A patent for PCR was awarded to Cetus Corporation, the company who employed Kary during the time of his discovery, and was later sold to Hoffmann-La Roche for $300 million.

The discovery of PCR forever changed the molecular biology world. It is a standard, yet indispensable research technique used for numerous medical and biological applications such as DNA sequencing and genetic fingerprinting. PCR was also the lone technique that helped the synthetic oligonucleotide business become a thriving industry. Hence 25 years later, Biosearch respectfully commemorates the development of a technique that swiftly answered past DNA chemistry problems with, as Kary describes, “Abundance and distinction.”

The Evolution of PCR
As PCR introduced capabilities to identify, manipulate, and amplify DNA, research possibilities flourished. The detection of genetic mutations, the ability to detect the presence of previously unknown genetic material, as well as the ability to analyze degraded DNA, all became common practice. For example, diseases such as muscular dystrophy and HIV were detected and diagnosed with the use of PCR.

As scientists grew more familiar with the technique of PCR, they began to expand on the utility of the method. During the late 1980s PCR was used to measure the quantity of DNA present in a reaction, generating the term “quantitative PCR” or more simply, q-PCR. This technique further improved PCR by the isolation of Taq Polymerase in the early nineties. The heat stable polymerase could remain active through many cycles of heat required for amplification and created the demand for faster cycling. Russell Higuchi and associates developed a system to monitor the amplification of DNA simultaneously to the reaction. The system involved ethidium bromide, a thermal cycler to irradiate samples with UV light, and a camera to record fluorescence.

In the early 90’s, fluorogenic dual labeled probes were developed as a means to practice q-PCR. In conjunction with fluorescent probes, PCR had further evolved into a sensitive quantification tool useful for the detection of any desired genetic element. As a result, the ability to measure gene expression and practice genotyping quickly became trivial and widespread throughout the biotechnology industry. Now, with the recent development of new dyes and quenchers such as the series of Black Hole Quencher, CAL Fluor and Quasar dyes from Biosearch, the possibilities for PCR are seemingly endless.