Kary Banks Mullis (born December 28, 1944) is a Nobel Prize-winning American biochemist.
In recognition of his invention of the polymerase chain reaction (PCR) technique, he shared
the 1993 Nobel Prize in Chemistry with Michael Smith and earned the Japan Prize in the same
year. The process was first described by Kjell Kleppe and 1968 Nobel laureate H. Gobind Khorana,
and allows the amplification of specific DNA sequences. The invention made by Mullis allowed
PCR to become 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 P.C.R. and after P.C.R."He has defended AIDS denialism, and climate change denial,
and has attacked sociology as a "worthless science" for not taking astrology seriously.
== Early life == Mullis was born in Lenoir, North Carolina,
near the Blue Ridge Mountains, on December 28, 1944. His family had a background in farming
in this rural area. As a child, Mullis recalls, he was interested in observing organisms in
the countryside. He grew up in Columbia, South Carolina, where he attended Dreher High School.
He has described his early interest in chemistry, and claims to have learned how to chemically
synthesize and build solid state fuel propulsion rockets as a high school student during the
1950s.Mullis earned a Bachelor of Science (BS) degree in chemistry from the Georgia
Institute of Technology in Atlanta in 1966, during which time he got married and started
a business. He then received a PhD in biochemistry from the University of California, Berkeley
in 1973; his research done in J. B. Neilands' laboratory focused on synthesis and structure
of bacterial iron transporter molecules. Following his graduation, Mullis became a postdoctoral
fellow in pediatric cardiology at the University of Kansas Medical School, going on to complete
two years of postdoctoral work in pharmaceutical chemistry at the University of California,
San Francisco.
== Career == After receiving his PhD, Mullis left science
to write fiction, but quit and became a biochemist at a medical school in Kansas City. He then
managed a bakery for two years. Mullis returned to science at the encouragement of friend
Thomas White, who later got Mullis a job with the biotechnology company Cetus Corporation
of Emeryville, California. Mullis worked as a DNA chemist at Cetus for seven years; it
was there, in 1983, that Mullis invented his prize-winning improvements to the polymerase
chain reaction. After leaving Cetus in 1986, Mullis served as director of molecular biology
for Xytronyx, Inc. in San Diego for two years. Mullis has consulted on nucleic acid chemistry
for multiple corporations.In 1992, Mullis founded a business with the intent to sell
pieces of jewelry containing the amplified DNA of deceased famous people like Elvis Presley
and Marilyn Monroe. Mullis is also a member of the USA Science and Engineering Festival's
Advisory Board. As of 2014, he is a researcher at the Children's Hospital Oakland Research
Institute in Oakland, California.
=== PCR and other inventions ===
In 1983, Mullis was working for Cetus Corp. as a chemist. That spring, according to Mullis,
he was driving his vehicle late one night with his girlfriend, who was also a chemist
at Cetus, when 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 which would allow rapid amplification of a
small strand of DNA and become a standard procedure in molecular biology labs. Cetus
took Mullis off his usual projects to concentrate on PCR full-time. Mullis succeeded in demonstrating
PCR December 16, 1983. In his Nobel Prize lecture, he remarked that the success didn't
make up for his girlfriend breaking up with him shortly before: "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."
He received a $10,000 bonus from Cetus for the invention.Other Cetus scientists, including
Randall Saiki and Henry Erlich, were placed on PCR projects to work on evaluating whether
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 a paper that would describe PCR itself.
Mullis's 1985 paper with R. K. Saiki and H. A. 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 complication at that point was that the DNA polymerase used 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 would only need to be added once, thus making
the technique dramatically more affordable and subject to automation. This has created
revolutions in biochemistry, molecular biology, genetics, medicine and forensics.
Mullis has also invented a UV-sensitive plastic that changes color in response to light, and
most recently has been working on an approach for mobilizing the immune system to neutralize
invading pathogens and toxins, leading to the formation of his current venture, Altermune
LLC, in 2011. Mullis described this idea this way:
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. The first proof-of-principle of this technology,
re-targeting pre-existing antibodies to the surface of a pathogenic strep bacteria using
an alpha-gal modified aptamer ("alphamer"), was recently published in collaboration with
scientists at UC San Diego, and is Mullis' first authorship in the scientific literature
in two decades.
=== Accreditation of the PCR technique === A concept similar to that of PCR had been
described before Mullis' work. Nobel Prize laureate H. Gobind Khorana and Kjell Kleppe,
a Norwegian scientist, authored a paper seventeen 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. The suggestion that Mullis was solely responsible
for the idea of using Taq polymerase in the PCR process has been contested by his co-workers
at the time, who were embittered by his abrupt departure from Cetus. However, other scientists
have written that "the full potential [of PCR] was not realized" until Mullis' work
in 1983, and that Mullis' 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
later, 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 (entitled Making PCR) in which he
discussed whether or not Mullis "invented" PCR or "merely" came up with the concept of
it. Rabinow, a Foucault scholar interested in issues of the production of knowledge,
used the topic to argue against the idea that scientific discovery is the product of individual
work, writing, "Committees and science journalists like the idea of associating a unique idea
with a unique person, the lone genius. PCR is thought by some to be an example of teamwork,
but by others as the genius of one who was smart enough to put things together which
were present to all, but overlooked. For Mullis, the light bulb went off, but for others it
did not. This is consistent with the idea, that the prepared (educated) mind who is careful
to observe and not overlook, is what separates the genius scientist from his many also smart
scientists. The proof is in the fact that the person who has the light bulb go off never
forgets the Ah experience, while the others never had this photochemical reaction go off
in their brains."
== Personal views ==
Mullis has said that the never-ending quest for more grants and staying with established
dogmas has hurt science. He believes that "science is being practiced by people who
are dependent on being paid for what they are going to find out," not for what they
actually produce. Mullis has been described as an "impatient and impulsive researcher"
who finds routine lab work boring and instead thinks about his research while driving and
surfing. He came up with the polymerase chain reaction while driving along a highway.In
his 1998 autobiography, Mullis expressed disagreement with the scientific evidence supporting climate
change and ozone depletion, the evidence that HIV causes AIDS, and asserted his belief in
astrology. Mullis claims climate change and the HIV/AIDS connection are due to a conspiracy
of environmentalists, government agencies and scientists attempting to preserve their
careers and earn money, rather than scientific evidence. Mullis has been criticized for his
association with AIDS denialist Peter Duesberg, claiming that AIDS is an arbitrary diagnosis
only used when HIV antibodies are found in a patient's blood. The medical and scientific
consensus is that Duesberg's hypothesis is pseudoscience, HIV having been conclusively
proven to be the cause of AIDS and that global warming is occurring because of human activities.
Seth Kalichman, AIDS researcher and author of Denying AIDS, "[admits] that it seems odd
to include a Nobel Laureate among the who's who of AIDS pseudoscientists". Mullis also
wrote the foreword to the book What If Everything You Thought You Knew About AIDS Was Wrong?
by Christine Maggiore, an HIV-positive AIDS denialist who, along with her daughter, died
of an AIDS-related illness. A New York Times article 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. An article in the Skeptical Inquirer described Mullis as an
"AIDS denialist with scientific credentials [who] has never done any scientific research
on HIV or AIDS."
== Use of LSD == Mullis details his experiences synthesizing
and testing various psychedelic amphetamines and a difficult trip on DET in his autobiography.
In a Q&A interview published in the September 1994 issue of California Monthly, Mullis said,
"Back in the 1960s and early '70s 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 revealed that he was told by Nobel-prize-winning chemist Kary
Mullis that LSD had helped him develop the polymerase chain reaction that helps amplify
specific DNA sequences."
== Personal life == Mullis enjoys surfing. He has been married
four times. He has three children by two ex-wives. Mullis reported an encounter with a "glowing
green raccoon" at his cabin in the woods of northern California around midnight one night
in 1985; he denies having been on LSD or any other drug at the time.
== Publications and books == K.F. Mullis, F. Faloona, S. Scharf, R. Saiki,
G. Horn and H. Erlich, 1986, Specific enzymatic amplification of DNA in vitro: The polymerase
chain reaction. Cold Spring Harbor Symposium in Quantitative Biology, 51:263–273.
K. Mullis, 1990, The unusual origin of the polymerase chain reaction. Scientific American,
April 56–65. The Polymerase Chain Reaction, 1994, co-edited
Francious Ferre and Richard A. Gibbs (Basel: Birkhauser) ISBN 0817637508 ISBN 978-0817637507
Dancing Naked in the Mind Field. 1998, Vintage Books.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.
== Awards and honors == 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 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
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, ItalyMullis also received the John Scott Award
in 1991, given by the City Trusts of Philadelphia to others including Thomas Edison and the
Wright Brothers.
== See also == Nobel Prize controversies
The Other Side of AIDS House of Numbers
== References ==
== Further reading == Paul Rabinow, Making PCR: a story of biotechnology
(University of Chicago Press, 1996). ISBN 0-226-70147-6
Anthony Liversidge, "Kary Mullis, the great gene machine" at the Wayback Machine (archived
January 21, 2001), Omni magazine (April 1992). Kary Mullis, Dancing Naked in the Mind Field.
Vintage Books (1998). ISBN 0-679-44255-3.
== External links == Kary Mullis (personal webpage).
Patent portfolio, Directory inventor, archived from the original on January 10, 2013.
=== Interviews === Interview, Nobel Prize committee, 2005.
Klipfel, Sarah (1998), Interview, archived from the original on July 6, 2005 regarding
his views on HIV/AIDS.