Free Iconoclast: A Neuroscientist Reveals How to Think Differently by Gregory Berns Ph.d. Page A

efficiency mode and reconfigure its neural networks.
    One of the most important scientific discoveries in the last thirty years had its origins in exactly these types of novel circumstances. Kary Mullis came up with the basic principle of the
polymerase chain reaction
, or PCR, while driving up the northern California coast in 1983. PCR is the fundamental technology that allows any type of genetic test to be performed. PCR is used in genetic fingerprinting, crime scene investigations, paternity testing, and detection of hereditary diseases and cancer. PCR is also used widely in cloning and genetically engineered products such as vaccines. Mullis won the Nobel Prize in chemistry in 1993 for his discovery, and the circumstances of his discovery also make him an iconoclast.
    A chemist by training, Mullis had been conducting experiments on small fragments of DNA for Cetus Corporation, a biotech start-up in the Bay Area. DNA is composed of only four types of nucleotides, and theyare strung together in long double chains. These chains may contain thousands of nucleotides, and the specific sequences contain the code for producing all the proteins that make up an organism. Although the code had been cracked decades before, DNA existed in only minute quantities in the body, which made it difficult to purify and study, even in the 1980s.
    Cetus and several other biotech companies had developed technology to make short sequences of DNA, called
oligonucleotides
, but these were only ten base pairs long. Nothing close to human genome length. Conventional wisdom said there was no way to synthesize DNA strands anywhere near the length of what exists in nature. And although the machines at Cetus were efficient at cranking out oligonucleotides, they still weren’t very long and were not useful for much. With the machines making buckets of oligonucleotides, Mullis turned his attention to denaturing natural DNA. Although DNA strands will separate at 95°, they will also come together again if the temperature is dropped back down. Mullis began to play around with programming computers that could control the denaturing and annealing processes, and realized he could automate much of it.
    The breakthrough idea came to Mullis not in the Cetus laboratory, but on a spring evening while he was driving up the northern California coast.
As I drove through the mountains that night, the stalks of the California buckeyes heavily in blossom leaned over into the road. The air was moist and cool and filled with their heady aroma.
How about this, I thought? What if I mix the DNA sample with the oligonucleotides, drop in the [DNA] polymerase and wait? After this was complete I could heat the mixture, causing the extended oligonucleotides to be removed from the target, then cool the mixture allowing new, unextended oligonucleotides to hybridize.
EUREKA!!!! The result would be exactly the same only the signal strength [DNA] would be doubled.
And again, EUREKA!!!! I could do it over and over again. Every time I did it I would double the signal. For those of you who got lost, we’re back! I stopped the car at mile marker 46.7 on Highway 128. In the glove compartment I found some paper and a pen. I confirmed that two to the tenth power was about a thousand and that two to the twentieth power was about a million, and that two to the thirtieth power was around a billion, close to the number of base pairs in the human genome. 16
    Mullis realized that he could amplify a piece of DNA exponentially by simply repeating the cycle of denaturing DNA, adding an oligonucleotide to get the process started, and dumping in a bunch of naked nucleotides with some DNA polymerase. After only twenty cycles, he would have amplified a single piece of DNA a million times. Although it took him about six months of trial and error back in the laboratory, ultimately he was successful and proved wrong every other biochemist about synthesizing DNA.
    The interesting part of the story, however,