Kary Banks Mullis was born on December 28, 1944, and died on August 7, 2019. He was an American biochemist who helped create the polymerase chain reaction (PCR) technique. For this work, he shared the 1993 Nobel Prize in Chemistry with Michael Smith. He also received the Japan Prize in the same year. PCR became a key tool in biochemistry and molecular biology. The New York Times called it "highly original and significant," saying it changed biology into two time periods: before PCR and after PCR.

Mullis believed that humans had a small role in climate change. He questioned if HIV causes AIDS. He also believed in astrology and things that are not explained by science. He secretly made LSD. His statements about topics he was not an expert on, such as climate change and AIDS, were called an example of "Nobel disease" by Skeptical Inquirer.

Early life and education

Kary Mullis was born on December 28, 1944, in Lenoir, North Carolina, near the Blue Ridge Mountains. His parents were Cecil Banks Mullis and Bernice Barker Mullis. His family lived in a rural area where farming was common. As a child, Mullis enjoyed watching living things in the countryside. He and his cousins sometimes teased farm animals by feeding them through electric fences. He was especially interested in spiders that lived in his grandparents' basement. Mullis grew up in Columbia, South Carolina, and attended Dreher High School, graduating in 1962. He became interested in chemistry when he learned how to create solid fuel for rockets during high school in the 1960s.

In 1966, Mullis earned a Bachelor of Science in chemistry from the Georgia Institute of Technology in Atlanta. During this time, he married his first wife, Richards Haley, and started a business. In 1973, he completed a PhD in biochemistry at the University of California, Berkeley (UC Berkeley), in the laboratory of J. B. Neilands. His research focused on the structure and synthesis of molecules that help bacteria transport iron. Although he published a paper he wrote alone in the science journal Nature in 1968, he had difficulty passing his oral exams. A colleague later said, "He didn't get his propositions right. He didn't know general biochemistry." His PhD thesis was accepted only after friends helped remove some confusing parts, and his advisor worked to convince the committee to reconsider its decision.

Mullis's doctoral thesis studied the structure of a molecule called schizokinen, which is a type of siderophore. J. B. Neilands was known for his important research on siderophores, and Mullis contributed by describing the structure of schizokinen. After earning his PhD, Mullis completed postdoctoral research in pediatric cardiology at the University of Kansas Medical Center (1973–1977) and in pharmaceutical chemistry at the University of California, San Francisco (1977–1979).

Career

After earning his doctorate, Mullis left science briefly to write fiction before joining the University of Kansas as a fellow. During his postdoctoral work, he managed a bakery for two years. He returned to science at the suggestion of Thomas White, a friend and colleague from UC Berkeley. White helped Mullis get a job at UCSF and later helped him find a position at Cetus Corporation in California. Despite having little experience in molecular biology, Mullis worked as a DNA chemist at Cetus for seven years, eventually becoming head of the DNA synthesis lab under White, who was 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 had a reputation for acting unpredictably at Cetus. He once said he would bring a gun to work. He also had public arguments with his girlfriend, who was a fellow chemist at the company, and nearly fought with another scientist at a staff party, according to California Magazine. White said, “It definitely put me in a tough spot. His behavior was so unusual that other scientists thought I didn’t fire him because I was his friend.”

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

Later, Mullis worked as a consultant for companies and institutions on nucleic acid chemistry and as an expert in DNA profiling. In 1992, he started a business selling jewelry with amplified DNA from famous people like Elvis Presley and Marilyn Monroe. He also founded Atomic Tags in La Jolla, California, to develop technology using atomic-force microscopy and bar-coded antibodies with heavy metals to create many tests at once.

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 California.

In 1983, Mullis was a chemist at Cetus Corporation. He said he had the idea to use two primers to copy a specific DNA sequence using DNA polymerase while driving near his home in Mendocino County with his girlfriend, who was also a chemist at Cetus. Thomas White, his supervisor, let Mullis focus on PCR full-time after his colleagues were skeptical of the idea. Mullis successfully demonstrated PCR on December 16, 1983, but his results were unclear at first, and some colleagues questioned his methods. In his Nobel Prize lecture, he said, “I was sad when my girlfriend broke up with me. I felt lonely even after the PCR breakthrough.”

Other scientists at Cetus, like Randall Saiki, Henry Erlich, and Norman Arnheim, worked on separate PCR projects to see if the technique could copy a specific human gene (beta-globin) from DNA. Saiki gathered the needed data, and Erlich wrote the first paper using PCR. Mullis and others later published a paper titled “Enzymatic Amplification of β-globin Genomic Sequences and Restriction Site Analysis for Diagnosis of Sickle Cell Anemia,” which described PCR. This work was honored in 2017 with a Citation for Chemical Breakthrough Award.

A problem with PCR was that the DNA polymerase used in the reaction was destroyed by the high heat needed for each cycle and had to be replaced. In 1986, Saiki began using Taq DNA polymerase, which is heat-resistant and only needed to be added once. This change made PCR much cheaper and easier to automate. This improvement revolutionized biochemistry, molecular biology, genetics, medicine, and forensics. UC Berkeley biologist David Bilder said, “PCR changed everything. It made molecular biology much more powerful, which helped many other fields, like ecology and evolution. It’s impossible to overstate how important PCR is.” Although Mullis received a $10,000 bonus from Cetus for inventing PCR, he later criticized White and others for selling the patent to Roche Molecular Systems for $300 million.

Mullis also invented a UV-sensitive plastic that changes color when exposed to light. In 2011, he founded Altermune LLC to explore new ideas about the immune system. He described the company’s product in a TED Talk, saying the U.S. government paid $500,000 to use the technology to treat anthrax. He claimed the treatment was 100% effective, compared to the previous treatment, which was 40% effective.

In 2015, Mullis and scientists at the University of California, San Diego, published a study about using a special molecule to target antibodies to fight a strep bacterium that had killed his friend.

A similar idea to PCR was described earlier by Nobel laureate H. Gobind Khorana and Kjell Kleppe, who wrote about a process called “repair replication” in 1966. Their method used two primers and DNA polymerase to copy a small molecule, but it did not involve the repeated heating and cooling that made PCR so powerful.

Mullis’s colleagues at Cetus disagreed about whether he alone invented the idea of using Taq polymerase in PCR. However, biochemist Richard T. Pon said the full potential of PCR was not realized until Mullis’s work in 1983. Journalist Michael Gross noted that Mullis’s colleagues did not understand the technique’s value when he first presented it. As a result, some debate exists about how much credit Mullis and his team at Cetus deserve. Both Mullis and Cetus received recognition: Mullis got a Nobel Prize and a $10,000 bonus, and Cetus earned $300 million when it sold the patent to Roche Molecular Systems. After DuPont lost the patent sale to Roche, it tried to challenge Mullis’s patent but failed.

Views on HIV/AIDS and climate change

In his 1998 autobiography, Kary Mullis stated he did not agree with scientific evidence showing that human activities cause climate change or damage the ozone layer. He argued that theories about these issues were created by scientists and government workers working together to get money, claiming that scientists are more focused on being paid than finding true answers. The New York Times mentioned Mullis as one of several scientists who, after achieving success in their fields, made unsupported claims in other areas, especially by disagreeing with the scientific agreement on climate change and ozone depletion.

Mullis also doubted the connection between HIV and AIDS, even though he had no research experience in these areas. Seth Kalichman and Paroma Basu called him an AIDS denialist because he questioned the scientific agreement on HIV causing AIDS. He said he began to doubt the AIDS connection while preparing a report and could not find published evidence that HIV causes AIDS. In 1994, Mullis shared an alternative idea, claiming that AIDS is a diagnosis used when HIV antibodies are found in a person’s blood. Seth Kalichman, an AIDS researcher, listed Mullis among scientists who spread false ideas about AIDS. Reporters often cited Mullis as a supporter of Peter Duesberg, a biologist who also denied HIV causes AIDS. According to California Magazine, Mullis’s doubts about HIV influenced South African President Thabo Mbeki’s policies from 1999 to 2008, which may have caused up to 330,000 unnecessary deaths.

Skeptical Inquirer described Mullis’s views on HIV/AIDS and human-caused climate change as an example of "Nobel disease," a term used to describe some Nobel Prize winners who later support ideas that most scientists consider unproven and based on weak or unconfirmed evidence.

Use of hallucinogens

Mullis worked secretly in chemistry during his graduate studies, focusing on creating LSD. His friend Tom White said, "I knew he was a good chemist because he made hallucinogenic drugs at UC Berkeley." In his autobiography, Mullis wrote about his experiences making and testing different psychedelic amphetamines and a challenging experience with DET. In a Q&A interview from the September 1994 issue of California Monthly, Mullis stated, "In the 1960s and early 1970s, I used LSD often. Many people in Berkeley did this then. I found it to be a mind-opening experience. It was more important to me than any classes I took." At a symposium for Albert Hofmann, who lived to be 100, Hofmann said Mullis had told him that LSD "helped him develop the polymerase chain reaction, which helps copy specific DNA sequences."

Interest in the paranormal

Mullis was interested in unusual or supernatural events. For example, he said he saw a ghostly image of his deceased grandfather and even offered him a beer. In his autobiography, Mullis said he believed in astrology and wrote about an encounter with a fluorescent, talking raccoon that he suggested might be an alien from space.

Personal life

Mullis was a surfer and a musician who played guitar and sang. He married four times and had three children from two of his wives. At the time of his death, he had two grandchildren and was survived by his fourth wife, Nancy (whose maiden name was Cosgrove). Mullis died on August 7, 2019, at his home in Newport Beach, California, due to complications from pneumonia.

Selected publications

• Mullis, Kary (May 1968). "Cosmological Significance of Time Reversal." Published in Nature, volume 218, issue 5142, pages 663–664. Bibcode: 1968Natur.218..663M. doi: 10.1038/218663b0. ISSN 0028-0836. S2CID 4151884.
• Mullis, K.; Faloona, F.; Scharf, S.; Saiki, R.; Horn, G.; Erlich, H. (1986). "Specific Enzymatic Amplification of DNA In Vitro: The Polymerase Chain Reaction." Published in Cold Spring Harbor Symposia on Quantitative Biology, volume 51, pages 263–273. doi: 10.1101/SQB.1986.051.01.032. ISSN 0091-7451. PMID 3472723. S2CID 26180176.
• Mullis, Kary B. (April 1990). "The Unusual Origin of the Polymerase Chain Reaction." Published in Scientific American, volume 262, issue 4, pages 56–65. Bibcode: 1990SciAm.262d..56M. doi: 10.1038/scientificamerican0490-56. ISSN 0036-8733. PMID 2315679.
• Mullis, Kary B.; Ferré, François; Gibbs, Richard A., editors (1994). The Polymerase Chain Reaction. Published by Birkhäuser Boston in Boston. ISBN 978-0-8176-3750-7 – via Google Books.
• Mullis, Kary B. (1995). "A hypothetical disease of the immune system that may bear some relation to the Acquired Immune Deficiency Syndrome" (PDF). Published in Genetica, volume 95, issues 1–3, pages 195–197. doi: 10.1007/bf01435010. ISSN 0016-6707. PMID 7744261. S2CID 28158163 – via University of Michigan.

Awards and honors

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