Kary Mullis

Kary Banks Mullis (December 28, 1944Template:DashAugust 7, 2019) was an American biochemist. In recognition of his role in the invention of the polymerase chain reaction (PCR) technique, he shared the 1993 Nobel Prize in Chemistry with Michael Smith<ref name="Shampo 2002">Template:Cite journal</ref> and was awarded the Japan Prize in the same year. PCR became a central technique in biochemistry and molecular biology, described by The New York Times as "highly original and significant, virtually dividing biology into the two epochs of before PCR and after PCR."<ref name="Wade 1998" />

Mullis downplayed humans' role in climate change, expressed doubt that HIV is the cause of AIDS,<ref name="Pineda">Template:Cite news</ref><ref name="McClain">Template:Cite newsTemplate:Cbignore</ref><ref name="Arnaud">Template:Cite news</ref> and professed a belief in astrology and the paranormal.Template:R He also practiced clandestine chemistry by producing LSD. Mullis's unscientific statements about topics outside his area of expertise have been named by Skeptical Inquirer as an instance of "Nobel disease".Template:R

Early life and education

Mullis was born in Lenoir, North Carolina, near the Blue Ridge Mountains,<ref name="Nobel bio">Template:Cite web</ref> on December 28, 1944, to Cecil Banks Mullis and Bernice Barker Mullis.<ref>Template:Cite web</ref> His family had a background in farming in this rural area. As a child, Mullis said, he was interested in observing organisms in the countryside.<ref name="Shmaefsky 2006">Template:Cite book</ref> He and his cousins would often taunt livestock by feeding them through electric fences, and Kary was mostly interested in the spiders in his grandparents' basement.<ref>Template:Cite web</ref> He grew up in Columbia, South Carolina,<ref name="Shmaefsky 2006" /> where he attended Dreher High School,<ref name="Nobel lecture">Template:Cite web</ref> graduating in the class of 1962. He recalled his interest in chemistry beginning when he learned how to chemically synthesize and build solid fuel propulsion rockets as a high school student during the 1960s.<ref>Template:Cite AV media</ref>

He earned a Bachelor of Science in chemistry<ref name="Nobel bio" /> from the Georgia Institute of Technology in Atlanta in 1966, during which time he married his first wife, Richards Haley, and started a business.<ref name="Yoffe 1994">Template:Cite magazine</ref> He earned his PhD in 1973 in biochemistry at the University of California, Berkeley (UC Berkeley), in J. B. Neilands' laboratory, which focused on synthesis and structure of bacterial iron transporter molecules.<ref name="Mullis 1973">Template:Cite thesis</ref> Although he published a sole-author paper in Nature in the field of astrophysics in 1968,<ref name="Mullis 1968">Template:Cite journal</ref> he struggled to pass his oral exams (with a colleague recalling that "He didn’t get his propositions right. He didn’t know general biochemistry"), and his dissertation was accepted only after several friends pitched in to "cut all the whacko stuff out of it" while his advisor lobbied the committee to reconsider its initial decision.<ref name="McDonald">Template:Cite magazine</ref>

His doctoral dissertation was on the structure of the bacterial siderophore schizokinen.<ref>Template:Cite journal</ref> J. B. Neilands was known for his groundbreaking work on siderophores, and Mullis was a part of that with his characterization of schizokinen.<ref>Template:Cite web</ref> Following his graduation, Mullis completed postdoctoral fellowships in pediatric cardiology at the University of Kansas Medical Center (1973–1977) and pharmaceutical chemistry at the University of California, San Francisco (1977–1979).<ref name=":2">CV 2009 karymullis.com</ref>

Career

After receiving his doctorate, Mullis briefly left science to write fiction before accepting the University of Kansas fellowship.<ref name="Yoffe 1994" /> During his postdoctoral work, he managed a bakery for two years.<ref name="Wade 1998">Template:Cite news</ref> 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.<ref name="Shmaefsky 2006" /><ref name="Wade 1998" /> 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.<ref name="DNA's detective story">Template:Cite news</ref>

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.Template:R 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."<ref name="McDonald"/>

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.Template:Citation needed

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.<ref name=":2" /><ref name="Wade 1998" /> 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.<ref name="Gross 2001" /><ref name="Nelkin 1998">Template:Cite journal</ref> 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.<ref>Template:Cite web</ref> In 2014, he was named a distinguished researcher at the Children's Hospital Oakland Research Institute in Oakland, California.<ref name="Biography">Template:Cite web</ref>

PCR (polymerase chain reaction) and other inventions

Template:Main In 1983, Mullis was working for Cetus Corporation as a chemist.<ref name="Yoffe 1994" /> 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.<ref name="Yoffe 1994" /> 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.Template:R 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."Template:R 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."<ref name="Yoffe 1994" />

Other Cetus scientists who were regarded as "top-notch experimentalists",<ref name="McDonald"/> 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 use of the technique,<ref name="Wade 1998" /> while Mullis was still working on the paper that would describe PCR itself.<ref name="Yoffe 1994" /> 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.<ref name="breakthrough">Template:Cite web</ref><ref>Template:Cite journal</ref>

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 needed to be added to the reaction only 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."<ref name="McDonald"/> 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."Template:R

Mullis also invented a UV-sensitive plastic that changes color in response to light.<ref name=SalemBioEncyc>Template:Cite book</ref>

He founded Altermune LLC in 2011 to pursue new ideas on the immune system.<ref name="Business Wire">Template:Cite press release</ref> Mullis described the company's product thusly: Template:Blockquote

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.<ref name="Mullis Feb 2009">Template:Cite AV media</ref>

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.<ref>Template:Cite press release</ref><ref>Template:Cite journal</ref> Mullis said he was inspired to fight this particular strep bacterium because it had killed his friend.<ref name="Mullis Feb 2009" />

Accreditation of the PCR technique

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.<ref name=":0">Template:Cite journal</ref> 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 contested the notion that Mullis was solely responsible for the idea of using Taq polymerase in PCR.Template:Citation needed However, biochemist Richard T. Pon has written that the "full potential [of PCR] was not realized" until Mullis's work in 1983,<ref name="Pon 2002">Template:Cite book</ref> and journalist Michael Gross states that Mullis's colleagues failed to see the potential of the technique when he presented it to them.<ref name="Gross 2001">Template:Cite book</ref>Template:Synthesis inline As a result, some controversy surrounds the balance of credit that should be given to Mullis versus the team at Cetus.<ref name="Wade 1998" /> 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.<ref name="Yoffe 1994" /> Mullis and Erlich took Cetus' side in the case, and Khorana refused to testify for DuPont; the jury upheld Mullis's patent in 1991.<ref name="Yoffe 1994" /> 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<ref name=Roche_v_Promega>Template:Cite web</ref> 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 covering the purification of Taq polymerase) existed, in the form of two articles, published by Alice Chien et al. in 1976,<ref name="Chien">Template:Cite journal</ref> and A. S. Kaledin et al. in 1980.<ref name="Kaledin">Template:Cite journal</ref>

The anthropologist Paul Rabinow wrote a book on the history of the PCR method in 1996,<ref name="Bilsker 1998">Template:Cite journal</ref> in which he discusses whether Mullis "invented" PCR or merely came up with the concept of it.<ref name="Rabinow p4">Template:Cite book</ref>Template:Explain

Views on HIV/AIDS and climate change

In his 1998 autobiography, Mullis expressed disagreement with the scientific evidence for humans' role in climate change and ozone depletion.<ref name="Carlson 1998">Template:Cite news</ref><ref name="Capricorn">Template:Cite book</ref> Mullis claimed that scientific theories about ozone depletion and climate change were the product of scientists and government bureaucrats conspiring to secure funding,Template:R saying that "science is being practiced by people who are dependent on being paid for what they are going to find out" instead of searching for the truth.<ref name="Yoffe 1994" /> The New York Times listed Mullis as one of several scientists who, after success in their area of research, go on to make unfounded, sometimes bizarre statements in other areas, especially in regard to contradicting the scientific consensus on climate change and ozone depletion.<ref name="Johnson Oct 2007">Template:Cite news</ref>

Mullis also questioned the scientific validity of the link between HIV and AIDS, despite never having done any scientific research on either subject,<ref name="Nattrass 2009">Template:Cite book</ref><ref name="SI">Template:Cite magazine</ref><ref name="Winter 2011">Template:Cite web</ref> leading Seth Kalichman and Paroma Basu<ref>Paroma-Basu, semanticscholar.org</ref> to call him an AIDS denialist.<ref name="Kalichman 2009a">Template:Cite magazine</ref><ref name="Basu">Template:Cite journal</ref> He wrote that he began to question the AIDS consensus while compiling a report for a project's sponsor and being unable to find a published reference for HIV being the cause of AIDS.Template:RTemplate:Third-party inline Mullis published an alternative hypothesis for AIDS in 1994,<ref>Template:Cite journal</ref> claiming that AIDS is an arbitrary diagnosis used when HIV antibodies are found in a patient's blood.<ref name="Youson">Template:Cite news</ref> Seth Kalichman, AIDS researcher and author of Denying AIDS, names Mullis "among the who's who of AIDS pseudoscientists".<ref name="Kalichman 2009b">Template:Cite book</ref> Mullis was often cited in the press as a supporter of molecular biologist and AIDS denialist Peter Duesberg.<ref name="Cohen 1994">Template:Cite journal</ref> According to California Magazine, Mullis's HIV skepticism influenced Thabo Mbeki's denialist policymaking throughout his tenure as president of South Africa from 1999 to 2008, contributing to as many as 330,000 unnecessary deaths.<ref name="McDonald"/>

According to Skeptical Inquirer, Mullis's statements on HIV/AIDS and human-caused climate change are an instance of "Nobel disease", i.e. the tendency of some Nobel laureates to go on to embrace ideas that are scientifically implausible, rejected by most scientific experts, and based mostly on anecdotal or uncorroborated evidence.<ref name="Basterfield 2020">Template:Cite magazine</ref>

Use of hallucinogens

Mullis practiced clandestine chemistry throughout his graduate studies, specializing in the synthesis of LSD; according to his friend Tom White, "I knew he was a good chemist because he'd been synthesizing hallucinogenic drugs at UC Berkeley."<ref name="McDonald"/> He detailed his experiences synthesizing and testing various psychedelic amphetamines and a difficult trip on DET in his autobiography.<ref name="Mullis 1998">Template:Cite book</ref>Template:Rp In a Q&A interview published in the September 1994 issue of California Monthly, Mullis said, "Back in the 1960s and early 1970s I took plenty of LSD. A lot of people were doing that in Berkeley back then. And I found it to be a mind-opening experience. It was certainly much more important than any courses I ever took."<ref name="Schoch">Template:Cite magazine</ref>Template:Vn During a symposium held for centenarian Albert Hofmann, Hofmann said Mullis had told him that LSD had "helped him develop the polymerase chain reaction that helps amplify specific DNA sequences".<ref>Template:Cite news</ref>

Interest in the supernatural

Mullis expressed interest in the paranormal. For example, he said that he had witnessed the "non-substantial form" of his deceased grandfather, even offering it a beer.<ref name="Jarry 2019">Template:Cite web</ref> In his autobiography, Mullis professed a belief in astrology and wrote about an encounter with a fluorescent, talking raccoon that he suggested might have been an extraterrestrial alien.Template:R

Personal life

Mullis was a surfer as well as a musician,Template:R<ref name="Golden 2000">Template:Cite magazine</ref><ref name="Yoffe 1994" /> being both a guitarist and vocalist. He married four times,<ref name="Yoffe 1994" /> and he had three children by two of his wives. At the time of his death, he had two grandchildren and was survived by his fourth wife, Nancy (née Cosgrove<ref name="Times Oct 2019">Template:Cite news</ref><ref name="Thompson">Template:Cite news</ref>). Mullis died on August 7, 2019, at his home in Newport Beach, California,Template:R<ref name="Clark">Template:Cite news</ref> from complications of pneumonia.Template:R<ref name="MyNewsLA">Template:Cite news</ref>

Selected publications

• Template:Cite journal
• Template:Cite journal
• Template:Cite journal
• Template:Cite book
• Template:Cite journal
• Template:Cite book
  • Mullis's autobiography gives his account of the commercial development of PCR, as well as providing insights into his opinions and experiences. In the book, Mullis chronicles his romantic relationships, use of LSD, synthesis and self-testing of novel psychoactive substances, belief in astrology and an encounter with an extraterrestrial in the form of a fluorescent raccoon.Template:R

Awards and honors

• 1990: William Allan Memorial Award of the American Society of Human Genetics,<ref>Template:Cite web</ref> Preis Biochemische Analytik of the German Society of Clinical Chemistry and Boehringer Mannheim<ref>Template:Cite web</ref>
• 1991: National Biotechnology Award,<ref name="Newton p163">Template:Cite book</ref> Gairdner Award,<ref name="Newton p163" /> R&D Scientist of the Year,<ref name="Newton p163" /> John Scott Award of the City Trusts of Philadelphia<ref>Template:Cite web</ref>
• 1992: California Scientist of the Year Award<ref name="Newton p163" />
• 1992: Robert Koch Prize<ref>Template:Cite web</ref>
• 1993: Nobel Prize in Chemistry, Japan Prize,<ref name="Laureates" /> Thomas A. Edison Award<ref name="Newton p163" />
• 1994: Honorary degree of Doctor of Science from the University of South Carolina<ref name="Biography" />
• 1994: Golden Plate Award of the American Academy of Achievement<ref>Template:Cite web</ref>
• 1998: Inducted into the National Inventors Hall of Fame,<ref>Template:Citation</ref> Ronald H. Brown American Innovator Award<ref>Template:Citation</ref>
• 2004: Honorary degree in Pharmaceutical Biotechnology from the University of Bologna, Italy<ref>Template:Cite web</ref>
• 2010: Honorary degree of Doctor honoris causa in the field of biological sciences from Masaryk University, Czech Republic<ref>Template:Cite web</ref>

See also

• Template:Slink
• History of the polymerase chain reaction method
• List of National Inventors Hall of Fame inductees
• List of Nobel laureates in Chemistry
• Nobel Prize controversies
  • Luc Montagnier, Nobel laureate who has promoted controversial and unverified health claims

Further reading

• Template:Cite magazine

External links

• Template:Official
• Template:Cite web.
• Template:Nobelprize
• Template:Cite AV media

Interviews

• Template:Citation.