Kary B. Mullis

American biochemist

• Born: December 28, 1944
• Birthplace: Lenoir, North Carolina
• Died: August 7, 2019
• Place of death: Newport Beach, CA

Mullis conceived, designed, and developed the polymerase chain reaction, or PCR, which revolutionized the study of the biological and medical sciences. PCR allows for one DNA molecule to be amplified to billions of copies in a short period of time in a lab, making analysis of specific DNA targets possible. PCR is used in the diagnosis of various infectious and genetic diseases and has been widely used in forensic analysis.

Early Life

Kary B. Mullis (MUHL-lihs) was born in Lenoir, North Carolina, to Cecil Banks Mullis and Bernice Alberta Barker Mullis. His family moved to Columbia, South Carolina, when he was five years old. His interest in science, especially chemistry, was stimulated by a chemistry set he received as a Christmas present. He attended Dreher High School in Columbia, where he was vice president of the student council and a National Merit Scholar. After graduation from high school he attended the Georgia Institute of Technology (Georgia Tech), where he received a B.S. degree in chemistry in 1966. During the summers while at Georgia Tech, he broadened and increased his knowledge of chemistry while synthesizing chemicals at King’s Laboratories.

In 1966, Mullis moved to Berkeley, California, to study with Allan Wilson for a Ph.D. in biochemistry. Soon after arriving in Berkeley he started to work in the laboratory of Joseph. B. Neilands, focusing his work on schizokinen, a molecule involved with the transport of iron in bacteria. While a graduate student, he published the article “The Cosmological Significance of Time Reversal” in Nature. He received his Ph.D. in 1972, having researched and written the dissertation “Schizokinen: Structure and Synthetic Work.”

Mullis remained at Berkeley for a year as a lecturer in biochemistry, then moved to Kansas to accept a postdoctoral fellowship at the University of Kansas. At Kansas, Mullis worked in pediatric cardiology and specialized in pulmonary vascular physiology with a concentration in idiopathic respiratory distress syndrome. In 1975 he returned to Berkeley and worked in a coffee shop. In 1977 he quit this job to accept a postdoctoral fellowship in pharmaceutical chemistry at the University of California, San Francisco.

Life’s Work

Mullis accepted a position as a synthetic chemist at Cetus Corporation in California in 1979. He would specialize in the synthesis of oligonucleotides. In 1981, he was appointed head of the laboratory at Cetus that synthesizes deoxyribonucleic acid (DNA). One evening in the spring of 1983, while driving to his cottage in northern California, Mullis thought of the polymerase chain reaction (PCR). He had, for some time, been attempting to develop a technique that could efficiently amplify the beta-globin gene and screen for the presence of the sickle cell anemia mutation. Although Mullis’s initial attempts to amplify a specific target DNA failed, by June, 1984, he achieved success with both plasmid and human DNA targets. By the spring of 1985, DNA amplification by PCR had been perfected by Mullis and Cetus laboratory technicians, namely Stephen Scharf and Randall K. Saiki.

Cetus applied for a patent for the PCR procedure on March 28, 1985. Although Mullis’s name is on the patent application, all rights were held by Cetus. Mullis received a $10,000 salary bonus for his invention. The first paper which was coauthored describing the applications of PCR, “Enzymatic Amplification of Beta-Globin Genomic Sequences and Restriction Site Analysis for Diagnosis of Sickle Cell Anemia,” was published in Science on December 20. Mullis presented his concept of PCR at the May, 1986, Cold Spring Harbor Laboratory symposium on the molecular biology of Homo sapiens. Later that year, he published an elaboration of the concept of PCR and its applications in Cold Spring Harbor’s Quantitative Symposia in Molecular Biology series, and in 1987 published in Methods in Enzymology more details of PCR conditions in “Specific Synthesis of DNA in vitro via a Polymerase-Catalyzed Chain Reaction.” Cetus sold the patent rights to PCR to the pharmaceutical company F. Hoffmann-La Roche in 1992 for $300 million.

In 1986, Mullis had joined Xytronyx, a small biotechnology company in San Diego, California, as director of molecular biology, but he left the company in 1988 to serve as a consultant for several biotechnology firms.

Mullis also developed an idea that could have significant impact in the field of immunology. He has worked on a method that uses “specific synthetic chemical linkers to divert an immune response from its nominal target” to a different target, a method called the “linker concept.” Mullis theorized that because humans are naturally immune to many antigens, a linker molecule could be synthesized to bind to the human antibody at one end and a virus at the other end. This binding could result in the inactivation of the virus. In this way antibodies that would normally bind to one antigen would, theoretically, be diverted to bind to a second antigen. The linker concept has been applied successfully to rodents. Mullis’s idea led him to a position with the Defense Advanced Research Projects Agency (DARPA), an agency of the U.S. Department of Defense that develops new technology for use by the military. To coordinate his work on immunology, Mullis formed a small company called Altermune.

Mullis served as Distinguished Researcher at Children’s Hospital Institute in Oakland, California. He was on the board of directors of several companies and organizations. In addition to his autobiography, Dancing Naked in the Mind Field (1998), Mullis’s works include several in the sciences. Along with PCR, he also developed several patents, including one for a plastic that changes color in response to ultraviolet light.

Mullis received several awards, including the Preis Biochemische Analytik of the German Society of Clinical Chemistry (1990), the William Allan Memorial Award of the American Society of Human Genetics (1990), the Gairdner Foundation International Award (1991), and the National Biotechnology Award (1991). He was named the Research and Development Scientist of the Year in 1991, received the California Scientist of the Year Award in 1992, and received the Thomas A. Edison Award and the Japan Prize in 1993.

Significance

Mullis’s development of PCR has had a profound impact on the sciences. PCR technology has been used in molecular biology, genetics, medicine, biotechnology, and forensic science. Furthermore, the use of PCR technology has accelerated the analysis of the structure and function of genes and the sequencing of several genomes, including those of humans. PCR also has been used to screen and diagnose various viral and bacterial infections, such as HIV-AIDS, tuberculosis, and staphylococcus. In addition, PCR has been used for the prenatal, neonatal, and carrier testing of numerous genetic diseases as well as for sex determination using prenatal cells. PCR also has led to the development and employment of DNA-testing methodologies for forensic applications, including human DNA profiling and identification.

For this astounding work, Mullis was awarded the Nobel Prize in Chemistry in 1993, a prize he shared with biochemist Michael Smith. In 1998, Mullis was inducted into the National Inventors Hall of Fame.

Bibliography

Batiza, Ann Finney. Bioinformatics, Genomics, and Proteomics: Getting the Big Picture. Philadelphia: Chelsea House, 2006. Foreword by Mullis. An introduction to the world of biotechnology in the twenty-first century. Good for readers with no background in biochemistry.

Mullis, Kary. Dancing Naked in the Mind Field. New York: Pantheon, 1998. Mullis’s autobiography, in which he discusses his scientific ventures and his personal life, including his three marriages, his synthesis and use of hallucinogenic and other drugs, his supposed abduction by aliens, his sexist views of women, and his belief that claims that AIDS is caused by the human immunodeficiency virus (HIV) are exaggerated.

Mullis, Kary B., François Ferré, and Richard A. Gibbs, eds. The Polymerase Chain Reaction. Boston: Birkhäuser, 1994. Articles are grouped in three sections devoted to methodology, applications, and “PCR and the world of business.” Includes a preface by Mullis and a foreword by James D. Watson. References and index.

Rabinow, Paul. Making PCR: A Story of Biotechnology. Chicago: University of Chicago Press, 1996. Rabinow, an anthropologist, challenges Mullis’s account of the PCR discovery by exploring the “culture of biotechnology” at Cetus. He interviewed several of the scientists involved in the development of PCR, and he emphasizes the social and scientific context of PCR’s discovery. No index.