Kary Mullis

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After receiving his doctorate, Mullis briefly left science to write fiction before accepting the University of Kansas fellowship. During his postdoctoral work, he managed a bakery for two years. Mullis returned to science at the encouragement of UC Berkeley friend and colleague Thomas White, who secured Mullis's UCSF position and later helped Mullis land a position with the biotechnology company Cetus Corporation of Emeryville, California. Despite little experience in molecular biology, Mullis worked as a DNA chemist at Cetus for seven years, ultimately serving as head of the DNA synthesis lab under White, then the firm's director of molecular and biological research; it was there, in 1983, that Mullis invented the polymerase chain reaction (PCR) procedure.

Mullis acquired a reputation for erratic behavior at Cetus, once threatening to bring a gun to work; he also engaged in "public lovers' quarrels" with his then-girlfriend (a fellow chemist at the company) and "nearly came to blows with another scientist" at a staff party, according to California Magazine. White recalled: "It definitely put me in a tough spot. His behavior was so outrageous that the other scientists thought that the only reason I didn't fire him outright was that he was a friend of mine."

After resigning from Cetus in 1986, Mullis served as director of molecular biology for Xytronyx, Inc. in San Diego for two years. While inventing a UV-sensitive ink at Xytronyx, he became skeptical of the existence of the ozone hole.

Thereafter, Mullis worked intermittently as a consultant for multiple corporations and institutions on nucleic acid chemistry and as an expert witness specializing in DNA profiling. While writing a National Institutes of Health grant progress report on the development of a human immunodeficiency virus (HIV) test for Specialty Labs, he became skeptical that HIV was the cause of acquired immunodeficiency syndrome (AIDS). In 1992, Mullis founded a business to sell pieces of jewelry containing the amplified DNA of deceased famous people such as Elvis Presley and Marilyn Monroe. In the same year, he also founded Atomic Tags in La Jolla, California. The venture sought to develop technology using atomic-force microscopy and bar-coded antibodies tagged with heavy metals to create highly multiplexed, parallel immunoassays.

Mullis was a member of the USA Science and Engineering Festival's Advisory Board. In 2014, he was named a distinguished researcher at the Children's Hospital Oakland Research Institute in Oakland, California.

In 1983, Mullis was working for Cetus Corporation as a chemist. Mullis recalled that, while driving in the vicinity of his country home in Mendocino County (with his girlfriend, who also was a chemist at Cetus), he had the idea to use a pair of primers to bracket the desired DNA sequence and to copy it using DNA polymerase; a technique that would allow rapid amplification of a small stretch of DNA and become a standard procedure in molecular biology laboratories. Longtime professional benefactor and supervisor Thomas White reassigned Mullis from his usual projects to concentrate on PCR full-time after the technique was met with skepticism by their colleagues. Mullis succeeded in demonstrating PCR on December 16, 1983, but the staff remained circumspect as he continued to produce ambiguous results amid alleged methodological problems, including a perceived lack of "appropriate controls and repetition." In his Nobel Prize lecture, he remarked that the December 16 breakthrough did not make up for his girlfriend breaking up with him: "I was sagging as I walked out to my little silver Honda Civic. Neither [assistant] Fred, empty Beck's bottles, nor the sweet smell of the dawn of the age of PCR could replace Jenny. I was lonesome."

Other Cetus scientists who were regarded as "top-notch experimentalists", including Randall Saiki, Henry Erlich, and Norman Arnheim, were placed on parallel PCR projects to work on determining if PCR could amplify a specific human gene (betaglobin) from genomic DNA. Saiki generated the needed data and Erlich authored the first paper to include utilization of the technique, while Mullis was still working on the paper that would describe PCR itself. Mullis's 1985 paper with Saiki and Erlich, "Enzymatic Amplification of β-globin Genomic Sequences and Restriction Site Analysis for Diagnosis of Sickle Cell Anemia" — the polymerase chain reaction invention (PCR) — was honored by a Citation for Chemical Breakthrough Award from the Division of History of Chemistry of the American Chemical Society in 2017.

A drawback of the technique was that the DNA polymerase in the reaction was destroyed by the high heat used at the start of each replication cycle and had to be replaced. In 1986, Saiki started to use Thermophilus aquaticus (Taq) DNA polymerase to amplify segments of DNA. The Taq polymerase was heat resistant and only needed to be added to the reaction once, making the technique dramatically more affordable and subject to automation. This modification of Mullis's invention revolutionized biochemistry, molecular biology, genetics, medicine, and forensics. UC Berkeley biologist David Bilder said, "PCR revolutionized everything. It really superpowered molecular biology—which then transformed other fields, even distant ones like ecology and evolution. … It’s impossible to overstate PCR’s impact. The ability to generate as much DNA of a specific sequence as you want, starting from a few simple chemicals and some temperature changes—it’s just magical." Although he received a $10,000 bonus from Cetus for the invention, the company's later sale of the patent to Roche Molecular Systems for $300 million would lead Mullis to condemn White and members of the parallel team as "vultures."

Mullis also invented a UV-sensitive plastic that changes color in response to light.

He founded Altermune LLC in 2011 to pursue new ideas on the immune system. Mullis described the company's product thusly:

In a TED Talk, Mullis describes how the US Government paid $500,000 for Mullis to use this new technology against anthrax. He said the treatment was 100% effective, compared to the previous anthrax treatment which was 40% effective.

Another proof-of-principle of this technology, re-targeting pre-existing antibodies to the surface of a pathogenic strep bacterium using an alpha-gal modified aptamer ("alphamer"), was published in 2015 in collaboration with scientists at the University of California, San Diego. Mullis said he was inspired to fight this particular strep bacterium because it had killed his friend.

A concept similar to that of PCR had been described before Mullis's work. Nobel laureate H. Gobind Khorana and Kjell Kleppe, a Norwegian scientist, authored a paper 17 years earlier describing a process they termed "repair replication" in the Journal of Molecular Biology. Using repair replication, Kleppe duplicated and then quadrupled a small synthetic molecule with the help of two primers and DNA polymerase. The method developed by Mullis used repeated thermal cycling, which allowed the rapid and exponential amplification of large quantities of any desired DNA sequence from an extremely complex template. Later a heat-stable DNA polymerase was incorporated into the process.

His co-workers at Cetus, who were embittered by his abrupt departure from the company, contested that Mullis was solely responsible for the idea of using Taq polymerase in PCR. However, other scientists have written that the "full potential [of PCR] was not realized" until Mullis's work in 1983, and that Mullis's colleagues failed to see the potential of the technique when he presented it to them. As a result, some controversy surrounds the balance of credit that should be given to Mullis versus the team at Cetus. In practice, credit has accrued to both the inventor and the company (although not its individual workers) in the form of a Nobel Prize and a $10,000 Cetus bonus for Mullis and $300 million for Cetus when the company sold the patent to Roche Molecular Systems. After DuPont lost out to Roche on that sale, the company unsuccessfully disputed Mullis's patent on the alleged grounds that PCR had been previously described in 1971. Mullis and Erlich took Cetus' side in the case, and Khorana refused to testify for DuPont; the jury upheld Mullis's patent in 1991. However, in February 1999, the patent of Hoffman-La Roche (United States Patent No. 4,889,818) was found by the courts to be unenforceable, after Dr. Thomas Kunkel testified in the case Hoffman-La Roche v. Promega Corporation on behalf of the defendants (Promega Corporation) that "prior art" (i.e. articles on the subject of Taq polymerase published by other groups prior to the work of Gelfand and Stoffel, and their patent application regarding the purification of Taq polymerase) existed, in the form of two articles, published by Alice Chien et al. in 1976, and A. S. Kaledin et al. in 1980.

The anthropologist Paul Rabinow wrote a book on the history of the PCR method in 1996, in which he discusses whether Mullis "invented" PCR or merely came up with the concept of it.

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• 1990: William Allan Memorial Award of the American Society of Human Genetics, Preis Biochemische Analytik of the German Society of Clinical Chemistry and Boehringer Mannheim
• 1991: National Biotechnology Award, Gairdner Award, R&D Scientist of the Year, John Scott Award of the City Trusts of Philadelphia
• 1992: California Scientist of the Year Award
• 1992: Robert Koch Prize
• 1993: Nobel Prize in Chemistry, Japan Prize, Thomas A. Edison Award
• 1994: Honorary degree of Doctor of Science from the University of South Carolina
• 1994: Golden Plate Award of the American Academy of Achievement
• 1998: Inducted into the National Inventors Hall of Fame, Ronald H. Brown American Innovator Award
• 2004: Honorary degree in Pharmaceutical Biotechnology from the University of Bologna, Italy
• 2010: Honorary degree of Doctor honoris causa in the field of biological sciences from Masaryk University, Czech Republic