Editing Kary Mullis (section)

=== Accreditation of the PCR technique ===

{{See also|History of polymerase chain reaction}}

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">{{Cite journal |last1=Kleppe |first1=K. |last2=Ohtsuka |first2=E. |last3=Kleppe |first3=R. |last4=Molineux |first4=I. |last5=Khorana |first5=H. G. |author-link5=Har Gobind Khorana |year=1971 |title=Studies on polynucleotides *1, *2XCVI. Repair replication of short synthetic DNA's as catalyzed by DNA polymerases |journal=Journal of Molecular Biology |volume=56 |issue=2 |pages=341–361 |doi=10.1016/0022-2836(71)90469-4 |pmid=4927950}}</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.{{Citation needed|date=December 2022}} 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">{{Cite book |last=Pon |first=Richard T. |editor-last1=Khudyakov |editor-first1=Yury E. |editor-last2=Fields |editor-first2=Howard A. |title=Artificial DNA: Methods and Applications |page=20 |isbn=978-1-4200-4016-6 |year=2002 |publisher=[[CRC Press]] |location=Boca Raton, Fla. |chapter=Chemical Synthesis of Oligonucleotides: From Dream to Automation}}</ref> and journalist [[Michael Gross (science writer)|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">{{Cite book |title=Life on the Edge: Amazing Creatures Thriving in Extreme Environments |year=2001 |isbn=978-0-7382-0445-1 |last1=Gross |first1=Michael |publisher=Basic Books |location=New York |page=103 |url=https://archive.org/details/lifeonedgeamazin0000gros_t5j2/page/103/mode/1up?view=theater |url-access=registration}}</ref>{{Synthesis inline|date=December 2022}} 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&nbsp;million for Cetus when the company sold the patent to Roche Molecular Systems. After [[DuPont (1802–2017)|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>{{Cite web |url=https://www.casemine.com/judgement/us/5914b97badd7b0493478b532 |title=Hoffmann-La Roche, Inc. v. Promega Corporation, (N.D.Cal. 2001) |publisher=Casemine |author=United States District Court, N.D. California. |date=July 26, 2001 |access-date=April 8, 2018}}</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">{{Cite journal |last1=Chien |first1=A. |last2=Edgar |first2=D.B. |last3=Trela |first3=J.M. |title=Deoxyribonucleic acid polymerase from the extreme thermophile Thermus aquaticus |journal=J. Bacteriol. |volume=127 |issue=3 |pages=1550–1557 |year=1976 |pmid=8432 |pmc=232952 |doi=10.1128/jb.127.3.1550-1557.1976}}</ref> and A. S. Kaledin et al. in 1980.<ref name="Kaledin">{{Cite journal |last1=Kaledin |first1=A.S. |last2=Sliusarenko |first2=A.G. |last3=Gorodetskii |first3=S.I. |title=Isolation and properties of DNA polymerase from extreme thermophylic bacteria Thermus aquaticus YT-1 |journal=[[Biokhimiia]] |volume=45 |issue=4 |pages=644–651 |year=1980 |pmid=7378495}}</ref>

The anthropologist [[Paul Rabinow]] wrote a book on the history of the PCR method in 1996,<ref name="Bilsker 1998">{{Cite journal |first=Richard |last=Bilsker |url=http://www.hyle.org/journal/issues/4/bilsker.htm |title=Ethnography of a Nobel Prize |journal=Hyle: International Journal for Philosophy of Chemistry |volume=4 |issue=2 |year=1998 |pages=167–169 |issn=1433-5158 |access-date=July 27, 2010}}</ref> in which he discusses whether Mullis "invented" PCR or merely came up with the concept of it.<ref name="Rabinow p4">{{cite book |last=Rabinow |first=Paul |title=Making PCR: A Story of Biotechnology |publisher=University of Chicago Press |year=1996 |pages=4–5 |isbn=0-226-70147-6 |url=https://archive.org/details/makingpcrstoryof00rabi/page/4/mode/1up?view=theater |url-access=registration}}</ref>{{Explain|date=December 2022}}