Кари Маллис: Путь от фермерского детства к биохимии.

American biochemist (1944–2019)

Mullis was born in Lenoir, North Carolina, near the Blue Ridge Mountains, on December 28, 1944, to Cecil Banks Mullis and Bernice Barker Mullis. 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. 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. He grew up in Columbia, South Carolina, 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. He earned a Bachelor of Science in chemistry 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. Although he published a sole author paper in Nature in the field of astrophysics in 1968, 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. His doctoral dissertation was on the structure of the bacterial siderophore schizokinen. J. B. Neilands was known for his groundbreaking work on siderophores, and Mullis was a part of that with his characterization of schizokinen. 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).

After receiving his doctorate, Mullis briefly left science to write fiction before accepting the University of Kansas fellowship. 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. 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." 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. 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." He founded Altermune LLC in 2011 to pursue new ideas on the immune system. Mullis described the company's product thusly:
Blockquote |style=font size:100% |It is a method using specific synthetic chemical linkers to divert an immune response from its nominal target to something completely different which you would right now like to be temporarily immune to. Let's say you just got exposed to a new strain of the flu. You’re already immune to alpha 1,3 galactosyl galactose bonds. All humans are. Why not divert a fraction of those antibodies to the influenza strain you just picked up. A chemical linker synthesized with an alpha 1,3 gal gal bond on one end and a DNA aptamer devised to bind specifically to the strain of influenza you have on the other end, will link anti alpha Gal antibodies to the influenza virus and presto, you have fooled your immune system into attacking the new virus. 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. 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. However, biochemist Richard T. Pon has written that the "full potential [of PCR] was not realized" until Mullis's work in 1983, and journalist Michael Gross states 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. 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, 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.

In his 1998 autobiography, Mullis expressed disagreement with the scientific evidence for humans' role in climate change and ozone depletion. Mullis claimed that scientific theories about ozone depletion and climate change were the product of scientists and government bureaucrats conspiring to secure funding, 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. Mullis also questioned the scientific validity of the link between HIV and AIDS, despite never having done any scientific research on either subject, leading Seth Kalichman and Paroma Basu to call him an AIDS denialist. 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. Mullis published an alternative hypothesis for AIDS in 1994, claiming that AIDS is an arbitrary diagnosis used when HIV antibodies are found in a patient's blood. Seth Kalichman, AIDS researcher and author of Denying AIDS, names Mullis "among the who's who of AIDS pseudoscientists". Mullis was often cited in the press as a supporter of molecular biologist and AIDS denialist Peter Duesberg. 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.

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." 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." 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".

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. 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.

Mullis was a surfer as well as a musician,). Mullis died on August 7, 2019, at his home in Newport Beach, California, from complications of pneumonia.

The Polymerase Chain Reaction, 1994, co edited with Francious Ferre and Richard A. Gibbs (Basel: Birkhauser)
Mullis's 1998 autobiography Dancing Naked in the Mind Field 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.

.