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Kary B. Mullis—Nobel Laureate for Procedure to Replicate DNA

      The 1993 Nobel Prize in chemistry was awarded jointly to 2 biochemists, American Kary Banks Mullis and Canadian Michael Smith (1932-). Mullis received the award for his invention of the polymerase chain reaction (PCR), a simple technique that allows a specific stretch of DNA to be copied billions of times in a few hours. Smith developed a procedure known as site-directed mutagenesis and applied it to the study of proteins. Smith's method allows researchers to reprogram the genetic code and, consequently, to construct proteins with new properties. The 2 methods have stimulated basic biochemical research and opened the way for new applications in medicine and biotechnology.
      The second of 4 sons, Mullis was born on December 28, 1944, in Lenoir, NC, near the Blue Ridge Mountains. His father was a salesman and his mother was a real estate agent. He was reared in Columbia in west central South Carolina and developed an interest in science and technological innovations at an early age. In 1966, he received a BS degree in chemistry from the Georgia Institute of Technology in Atlanta.
      After Mullis received his baccalaureate degree, he entered the University of California at Berkeley, where he was awarded a PhD degree in biochemistry in 1972. As a student, Mullis was generally described as “very undisciplined and unruly—a free spirit.” Throughout his life, he has been known for his eccentricities. For example, after he received his doctoral degree, Mullis temporarily abandoned his scientific career and wrote fiction. Soon realizing that his writing talents were limited, he accepted a postdoctoral fellowship at the University of Kansas Medical School in Kansas City, where he worked from 1973 to 1976.
      In 1976, Mullis returned to California to begin a second fellowship, this time at the University of California in San Francisco. In 1980, he left the university to work as a biochemist at Cetus Corporation, a biotechnology firm in Emeryville (a suburb of Oakland, Calif) that hired him to synthesize oligonucleotide probes (short stretches of single- stranded DNA). In 1986, he left the Cetus Corporation to become director of molecular biology at Xytronyx, Inc, a San Diego-based biotechnology firm. In 1988, he became a freelance consultant based in La Jolla, Calif.
      Mullis began his Nobel Prize-winning research while at the Cetus Corporation. He claimed that he invented PCR by accident—the idea occurred to him while he was driving one Friday evening in April 1983 to his home in the California redwood country for the weekend. By the end of that Friday evening, he knew that if he could make his idea work in the laboratory, it would have the power to transform biological research. He described his technique for the first time in the December 20, 1985, issue of Science and received a patent in 1987.
      Polymerase chain reaction uses 4 ingredients: the double- stranded DNA segment to be copied (the template DNA), 2 oligonucleotide primers (short segments of single-stranded DNA, each of which is complementary to a short sequence on one of the strands of the template DNA), nucleotides, and polymerase enzyme that copies the template DNA by joining the free nucleotides in the correct order. When these ingredients are heated, the template DNA separates into 2 strands. The mixture is cooled, allowing the primers to attach themselves to the complementary sites on the template strands. The polymerase is then able to begin copying the template strands by adding nucleotides onto the ends of the primers, producing 2 molecules of double-stranded DNA. Repeating this cycle increases the amount of DNA exponentially. About 30 cycles, each lasting only a few minutes, will produce more than 1 billion copies of the original DNA sequence.
      Polymerase chain reaction has wide applications. In medical diagnostics, PCR makes it possible to identify the causative agent of a bacterial or viral infection directly from a very small sample of genetic material. It also is used to screen for genetic disorders, such as sickle cell anemia and Huntington chorea. Evolutionary biologists use PCR to study minute amounts of DNA extracted from fossil remains of ancient species, and forensic scientists use it to identify crime suspects or victims from traces of blood, semen, or strands of hair left at a crime scene. It is also an important tool in gene sequencing.
      Besides the Nobel Prize, Mullis has received the Preis Award (1990), the Allan Award (1990), the Gairdner Award (1991), the Koch Award (1992), the Chiron Corporation Award (1992), and the Japan Prize (1993). In2000, the Palau Islands honored him on the stamp shown above.