Editing Kary Mullis (section)

=== PCR (polymerase chain reaction) and other inventions ===

{{Main|Taq polymerase|History of polymerase chain reaction}}
In 1983, Mullis was working for Cetus Corporation as a chemist.<ref name="Yoffe 1994" /> Mullis recalled that, while driving in the vicinity of his country home in [[Mendocino County]] (with his girlfriend, who also was a chemist at Cetus), 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 that would allow rapid amplification of a small stretch of DNA and become a standard procedure in molecular biology laboratories.<ref name="Yoffe 1994" /> Longtime professional benefactor and supervisor Thomas White reassigned Mullis from his usual projects to concentrate on PCR full-time after the technique was met with skepticism by their colleagues.{{r|Yoffe 1994|McDonald}} Mullis succeeded in demonstrating PCR on December 16, 1983, but the staff remained circumspect as he continued to produce ambiguous results amid alleged methodological problems, including a perceived lack of "appropriate controls and repetition."{{r|Yoffe 1994|McDonald}} In his Nobel Prize lecture, he remarked that the December 16 breakthrough did not make up for his girlfriend breaking up with him: "I was sagging as I walked out to my little silver [[Honda Civic]]. Neither [assistant] Fred, empty [[Beck's Brewery|Beck's]] bottles, nor the sweet smell of the dawn of the age of PCR could replace Jenny. I was lonesome."<ref name="Yoffe 1994" />

Other Cetus scientists who were regarded as "top-notch experimentalists",<ref name="McDonald"/> including Randall Saiki, Henry Erlich, and [[Norman Arnheim]], were placed on parallel PCR projects to work on determining if PCR could amplify a specific human gene (betaglobin) from genomic DNA. Saiki generated the needed data and Erlich authored the first paper to include use of the technique,<ref name="Wade 1998" /> while Mullis was still working on the paper that would describe PCR itself.<ref name="Yoffe 1994" /> Mullis's 1985 paper with Saiki and 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.<ref name="breakthrough">{{Cite web |title=Citations for Chemical Breakthrough Awards 2017 Awardees |url=http://www.scs.illinois.edu/~mainzv/HIST/awards/CCB-2017_Awardees.php |publisher=Division of History of Chemistry of the American Chemical Society |access-date=12 March 2018}}</ref><ref>{{Cite journal |last1=Saiki |first1=R. |last2=Scharf |first2=S. |last3=Faloona |first3=F. |last4=Mullis |first4=K. |last5=Horn |first5=G. |last6=Erlich |first6=H. |last7=Arnheim |first7=N |title=Enzymatic amplification of beta-globin genomic sequences and restriction site analysis for diagnosis of sickle cell anemia |journal=Science |date=20 December 1985 |volume=230 |issue=4732 |pages=1350–1354 |doi=10.1126/science.2999980 |pmid=2999980 |bibcode=1985Sci...230.1350S}}</ref>

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."<ref name="McDonald"/> Although he received a $10,000 bonus from Cetus for the invention, the company's later sale of the patent to [[Roche Molecular Systems]] for $300&nbsp;million would lead Mullis to condemn White and members of the parallel team as "vultures."{{r|Yoffe 1994|McDonald}}

Mullis also invented a UV-sensitive plastic that changes color in response to light.<ref name=SalemBioEncyc>{{cite book |author=Vigue, C.L. |title=Salem Press Biographical Encyclopedia: Kary B. Mullis |publisher=Salem Press, a division of EBSCO |date=2021}}</ref>

He founded Altermune LLC in 2011 to pursue new ideas on the immune system.<ref name="Business Wire">{{cite press release |author1=<!--Staff writer; no byline--> |title=Loxbridge and Dr Kary Mullis Announce the Formation of Altermune Technologies with $7m Seed Investment |url=https://www.businesswire.com/news/home/20110922005770/en/Loxbridge-and-Dr-Kary-Mullis-Announce-the-Formation-of-Altermune-Technologies-with-7m-Seed-Investment |website=Business Wire |date=22 September 2011}}</ref> 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.<ref name="Nobel bio" />}}

In a [[TED Talk]], Mullis describes how the US government paid $500,000 for Mullis to use this new technology against [[anthrax]]. He said the treatment was 100% effective, compared to the previous anthrax treatment which was 40% effective.<ref name="Mullis Feb 2009">{{Cite AV media |people=Mullis, Kary |url=https://www.ted.com/talks/kary_mullis_a_next_gen_cure_for_killer_infections/transcript |title=A next-gen cure for killer infections |type=video with transcript |website=TED.com |date=February 2009 |access-date=July 27, 2010}}</ref>

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.<ref>{{Cite press release |first=Heather |last=Buschman |title=Molecular Homing Beacon Redirects Human Antibodies to Fight Pathogenic Bacteria |url=http://ucsdnews.ucsd.edu/pressrelease/molecular_homing_beacon_redirects_human_antibodies_to_fight_pathogenic_bact |publisher=[[University of California, San Diego]] |date=May 6, 2015 |access-date=July 6, 2017}}</ref><ref>{{Cite journal |pmid=25940316 |title=Retargeting pre-existing human antibodies to a bacterial pathogen with an alpha-Gal conjugated aptamer |doi=10.1007/s00109-015-1280-4 |pmc=4469262 |volume=93 |issue=6 |year=2015 |journal=J. Mol. Med. |pages=619–31 |last1=Kristian |first1=SA |last2=Hwang |first2=JH |last3=Hall |first3=B |last4=Leire |first4=E |last5=Iacomini |first5=J |last6=Old |first6=R |last7=Galili |first7=U |last8=Roberts |first8=C |last9=Mullis |first9=KB |last10=Westby |first10=M |last11=Nizet |first11=V}}</ref> Mullis said he was inspired to fight this particular strep bacterium because it had killed his friend.<ref name="Mullis Feb 2009" />