MeSH I was too young to notice that mankind had finally understood how it might be that like begat like. The book had been reprinted three times. 2 May 2023. stream
262, pp. That was 1972. I wasnt concerned about the absolute rate of dissociation, because I didnt care how long the reaction took as long as nobody had to do anything. No one could recall such a process ever being tried. Mullis wrote that We got to my cabin and I started drawing little diagrams on every horizontal surface that would take pen, pencil, or crayon, until dawn.. Gene vol. The moment of truth. and transmitted securely. Thanks to its role in PCR, the enzyme was crowned "Molecule of the Year" by Science in 1989. And if we got bored of the earth, we could descend into the network of storm drains under the city. Photograph by Jim Wilson, The New York Times . Polymerase chain reaction and its uses as a diagnostic tool for cardiovascular disease. "DNA typing from single hairs." Springer Book Archive, Copyright Information: Birkhuser Boston 1994, Hardcover ISBN: 978-0-8176-3607-4Published: 01 April 1994, Softcover ISBN: 978-0-8176-3750-7Published: 01 March 1994, eBook ISBN: 978-1-4612-0257-8Published: 02 February 2012, Number of Illustrations: 85 b/w illustrations, Topics: PCR - the polymerase chain reaction - Analytical Methods (RSC 0000029326 00000 n
The site is secure. Since this method was established in 1985, significant . Watson JD, Crick FHC "A Structure for Deoxyribose Nucleic Acid", Nature vol. One such post claims: " [Dr Mullis] said that this PCR test was not made to detect any type of infectious disease. 230 pp. It would be dramatic. Gene. Verlaan-de Vries M et al. It was exactly midnight on the ninth of September. I confirmed that two to the tenth power was about a thousand and that two to the twentieth power was about a million, and that two to the thirtieth power was around a billion, close to the number of base pairs in the human genome. 34 0 obj<>
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In 1986 he became the director of molecular biology at Xytronyx, Inc. Today Mullis works in La Jolla, Calif., as a private con sultant on polymerase-chain-reaction technology and nucleic acid chemistry. From Nobel Lectures, Chemistry 1991-1995, Editor Bo G. Malmstrm, World Scientific Publishing Co., Singapore, 1997, To cite this section 2023 Apr 3;14:1038291. doi: 10.3389/fgene.2023.1038291. I was living in Columbia S.C., where no one noticed that we didnt have a copy. For more than a century, these academic institutions have worked independently to select Nobel Prize laureates. The conundrum which lingered throughout the week-end and created an unprecedented desire in me to return to work early was compelling. Cold Spring Harb. Kadowaki H, Kadowaki T, Wondisford FE, Taylor SI. Polymerase chain reaction: basic protocol plus troubleshooting and optimization strategies. I described the concept around August at an in-house seminar. Chem. We suffered no boredom and no boss. To put it lightly, Dr Mullis was considered by many in the scientific community to be a controversial and problematic figure, described as an interpersonal wrecking ball in California Magazine. Kary Mullis - The Scientist Who Invented PCR Technique We didnt need a copy. There was not a single unknown in the scheme. My girlfriend, Jennifer Barnett, was asleep. Google Scholar, The Immune Response Corporation, Carlsbad, USA, Institute for Molecular Genetics, Baylor College of Medicine, Houston, USA, 313 Marriage over, I returned to Berkeley, working for a time in a restaurant and then at the University of California at San Francisco killing rats for their brains. This also meant adding the thermally unstable polymerase after every cycle. This site needs JavaScript to work properly. What if there were deoxynucleoside triphosphates in the DNA sample, for instance? Mullis writes that the first successful attempt at PCR was on December 16, 1983. xref
Preparation of Substrates and Partial Purification of an Enzyme from Escherichia coli" J. Biol. "A dot-blot screening procedure for mutated ras oncogenes using synthetic oligodeoxynucleotides." Mullis KB et al. 0000003472 00000 n
In Berkeley it was a time of social upheaval and Joe Neilands was the perfect mentor to see his people through it with grace. We had made a number of oligonucleotides for them. %
Tragedy is personal. Don Glaser, who received this Prize in physics in 1960 at age 34, would later be one of the founders of Cetus Corporation, where I was working when I invented PCR. One or two technicians were interested, and on the days when she still loved me, Jennifer, thought it might work. Nature vol. My wife of a few months went to Kansas to go to medical school and I followed her there. Dr. White denies that, saying a plan to have Dr. Mullis author the first paper describing the theory of P.C.R. Every step involved had been done already. Chien A, Edgar DB, Trela JM "Deoxyribonucleic acid polymerase from the extreme thermophile Thermus aquaticus" J. Bacteriol. To look at how Dr Kary Mullis came up with PCR, were traveling back to May 1983. Chem. RIP Kary Mullis, Father of PCR - DNA Science 0000012216 00000 n
My mother grew more cautious and often her head would appear out of an upstairs window and she would say things that were not encouraging. The reason they didnt believe this was because of the fantastic result of it. Everyone agreed that what you could do once, you could do again. As it was, I decided against using BAP, and tried to think of another way to get rid of deoxynucleoside triphosphates. An application to patent PCR was filed by Cetus in 1986, with Mullis applying for a patent in 1985. DNA chains coiled and floated. 1994;31:19-33. doi: 10.1385/0-89603-258-2:19. Accessibility Somehow, I thought, it had to be an illusion. DNA synthesis was much more fun than killing rats, and the San Francisco Bay Area was a good place to be doing it. The scientist addresses an infinitesimal audience of fellow composers. Dear Thor!, I exclaimed. Today, PCR can take minutes. National Library of Medicine 34161 (1971). Unauthorized use of these marks is strictly prohibited. If that part werent of some interest to more than a handful of people here, I would just leave it out. People dont believe things, usually, for the right reasons, Mullis said in a Google TechTalkin 2010. The polymerase chain reaction, known worldwide by the abbreviation PCR, was defined by Kary B. Mullis, the 1993 Nobel laureate, not only as a specific technique or cluster of techniques but also as a. Nobel Prize Outreach AB 2023. I wasnt sure about the law, but I was pretty happy working at Cetus and assumed innocently that if the reaction worked big time I would be amply rewarded by my employer. Saiki et al. vol. Polymerase Chain Reaction was developed in 1984 by the American biochemist, Kary Mullis. The Nobel Prize in Chemistry 1993 was awarded "for contributions to the developments of methods within DNA-based chemistry" jointly with one half to Kary B. Mullis "for his invention of the polymerase chain reaction (PCR) method" and with one half to Michael Smith "for his fundamental contributions to the establishment of oligonucleotide-based, site-directed mutagenesis and its development for . government site. After this was complete I could heat the mixture, causing the extended oligonucleotides to be removed from the target, then cool the mixture allowing new, unextended oligonucleotides to hybridize. On human DNA, it would not have worked because the oligonucleotide would not have specifically bound to a single site. Anyhow, my problems with Jennifer were not getting any better. I was thinking of DNA:DNA interactions as being reversible with all the ramifications thereof. 0000029080 00000 n
That impressed me. Clipboard, Search History, and several other advanced features are temporarily unavailable. 1636 (1986). endstream
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1995 Jul;152(1):11-6. doi: 10.1164/ajrccm.152.1.7599808. At Dreher High School, we were allowed free, unsupervised access to the chemistry lab. Through an improbable combination of coincidences, naivet and lucky mistakes, such a revelation came to me one Friday night in. Complex Thermal cyclers were constructed to perform the Klenow-based amplifications, but never marketed. Citations, 13 Careers. His colleague Fred Faloona had helped to set up the reaction. PDF THE MEDICAL ESTABLISHMENT VS. THE TRUTH By Kary Mullis Penthouse Sept. 1998 PMID: 31561703 No abstract available . It was a sophomoric astrophysical hypothesis called The Cosmological Significance of Time Reversal. I think Nature is still embarrassed about publishing it, but it was immensely useful to me when it came time for my qualifying examination. Cetus hired me in the fall of 1979. I had solved the most annoying problems in DNA chemistry in a single lightening bolt. Publication types Case Reports MeSH terms Base Composition Base Sequence Cloning, Molecular . In Berkeley it drizzles in the winter. It was about to lead me to PCR. I passed. I continued to talk about it, and by late summer had a plan to amplify a 400-bp fragment from Human Nerve Growth Factor, which Genentech had cloned and published in Nature. This item is part of a JSTOR Collection. This says something about the arbitrary way that many scientific facts get established, but for this story, its only importance is that, had I known then that BAP could be heat denatured irreversibly, I may have missed PCR. as a template for the formation on itself of a new companion chain, so that eventually we shall have two pairs of chains, where we only had one before" and, moreover, " Kary B. Mullis, Franois Ferr, Richard A. Gibbs, https://doi.org/10.1007/978-1-4612-0257-8, Preparation of Nucleic Acids for Archival Material, PCR Amplification of Viral DNA and Viral Host Cell mRNAs in Situ, Quantification of DNAs by the Polymerase Chain Reaction Using an Internal Control, Analysis of Human T-Cell Repertoires by PCR, Ultrasensitive Nonradioactive Detection of PCR Reactions: An Overview, Fluorescent Detection Methods for PCR Analysis, Application of the Hybridization Protection Assay (HPA) to PCR, Phage Promoter-Based Methods for Sequencing and Screening for Mutations, Tax calculation will be finalised during checkout, Jeffrey S. Chamberlain, Joel R. Chamberlain, Janet Embretson, Katherine Staskus, Ernest Retzel, Ashley T. Haase, Peter Bitterman, F. Ferr, A. Marchese, P. Pezzoli, S. Griffin, E. Buxton, V. Boyer, Carl T. Wittwer, Gudrun B. Reed, Kirk M. Ririe. 0000007554 00000 n
Bookshelf doi: 10.3791/3998. &|$n8N gsE#H
-] We could even buy dynamite fuse from the hardware with no questions asked. But no one had to listen. 174 pp. Ugwu CC, Hair-Bejo M, Nurulfiza MI, Omar AR, Aini I. As Kary Mullis wrote in his book, It would spread into every biology lab in the world. <>
Not so with Neilands. Would it work at all was important. Their work and discoveries range from paleogenomics and click chemistry to documenting war crimes. With two oligonucleotides, DNA polymerase, and the four nucleosidetriphosphates I could make as much of a DNA sequence as I wanted and I could make it on a fragment of a specific size that I could distinguish easily. As he drove, his brain started to get creative. I reasoned that if one of the dideoxynucleoside triphosphates in each of four aliquots of a reaction was radioactive then a analysis of the aliquots on a gel could indicate which of the dideozynucleoside triphosphates had added to the hybridized oligonucleotide and therefore which base was adjacent to the three prime end of the oligonucleotide. But my home was a few blocks away from an undeveloped wooded area with a creek, possums, racoons, poisonous snakes, dragons, and a railroad track. Kary Mullis developed a biochemical technology Called Polymerase Chain Reaction (PCR) which can be used to amplify a single copy or a few copies of a piece of DNA across several orders . I stopped the car at mile marker 46,7 on Highway 128. Maybe thats why he believed it. Saiki, R et al. We made enough money to buy new equipment. In 1985 Norm Arnheim, also a member of the development team, concluded his sabbatical at Cetus and assumed an academic position at University of Southern California. It wasn't a scientific paper. PCR can take a tiny amount of DNA that would be very difficult to study and amplify it over and over into much larger quantities, allowing it to be studied more easily. [22] Open Vet J. official website and that any information you provide is encrypted As he recounts in his book Dancing Naked in the Mind Field, Mullis was driving his silver Honda through California, heading from Berkeley to his cabin in Anderson Valley. I would be famous. Bethesda, MD 20894, Web Policies Developed in 1985 by Kary B. Mullis, PCR revolutionized the way that deoxyribonucleic acid (DNA) could be copied. Mullis KB, Ferr F, Gibbs RA "The Polymerase Chain Reaction" Birkhuser Press (1994). the polymerase chain reaction. HHS Vulnerability Disclosure, Help . Bethesda, MD 20894, Web Policies I settled on a target of more modest proportions, a short fragment from pBR322, a purified plasmid. | RSS, Conscious Activity Seen In Dying Brains May Explain Near-Death Experiences, AI Brain Activity Decoder Can Translate Thoughts Into Written Words, What Happens To Your Brain In A "Flow State", And How You Can Achieve It, People Are Just Now Learning How The "I Am Not A Robot" Captcha Test Actually Works, Men May Refuse To Quit Meat Because It Threatens Their Masculinity, Suggests Study. 0000003548 00000 n
During the summer breaks from Georgia Tech, Al Montgomery and I built an organic synthesis lab in an old chicken house on the edge of town where we made research chemicals to sell. Polymerase Chain Reaction (PCR) Introduction PCR (Polymerase Chain Reaction) is a revolutionary method developed by Kary Mullis in the 1980s. "It has not escaped our notice," Francis wrote, "that the specific pairing that we have postulated immediately suggests a possible copying mechanism for the genetic material." As I drove through the mountains that night, the stalks of the California buckeyes heavily in blossom leaned over into the road. Mullis K, Faloona F, Scharf S, Saiki R, Horn G, Erlich H. Specific enzymatic amplification of DNA in vitro: the polymerase chain reaction. HHS Vulnerability Disclosure, Help Basically, wherever scientists are working with DNA, there's a good chance PCR is involved. 163170 (1958). Every Cetus scientist had to give a talk twice a year. endobj
invention of the polymerase chain reaction and his current efforts: developing a chemical tool that could be used like an antibiotic for the flu. Published online 3 January . Unauthorized use of these marks is strictly prohibited. An abstract for an, The use of Taq polymerase in PCR was announced by Henry Erlich at a. What would happen? Mullis stated that he was functionally sober at this point however, his famous love for taking and making the psychedelic drug LSD gives these colorful scenes a whole other context. Neotrop Entomol. Since oligonucleotides were not that hard to make anymore, wouldnt it be simple enough to put two of them into the reaction instead of only one such that one of them would bind to the upper strand and the other to the lower strand with their three prime ends adjacent to the opposing bases of the base pair in question. The department was paying me a monthly stipend from the NIH, and eventually, Joe knew, I would have to leave. Kubista M, Andrade JM, Bengtsson M, Forootan A, Jonk J, Lind K, Sindelka R, Sjback R, Sjgreen B, Strmbom L, Sthlberg A, Zoric N. Mol Aspects Med. The site is secure. Nature vol. Biol. PCR has a huge array of applications from testing for diseases, criminal investigations, paternity tests, and even sequencing human genomes. Developed in 1985 by Kary B. Mullis, PCR revolutionized the way that deoxyribonucleic acid (DNA) could be copied. Rather than using human DNA, Mullis had settled on using a plasmid, a simpler type of bacterial DNA. I did not relish the idea of heating, cooling, adding polymerase over and over again, and held this for a last resort method of accomplishing the chain reaction. I drove on down the road. The process would end up utilizingTaq DNA polymerase, an enzyme from a bacteria found inYellowstone National Park hot springscalledThermus aquaticus. Look for popular awards and laureates in different fields, and discover the history of the Nobel Prize.
I celebrated my victory with Fred Faloona, a young mathematician and a wizard of many talents whom I had hired as a technician. vol. Book Title: The Polymerase Chain Reaction, Editors: Kary B. Mullis, Franois Ferr, Richard A. Gibbs, DOI: https://doi.org/10.1007/978-1-4612-0257-8, eBook Packages: Jennifer, wake up. Clipboard, Search History, and several other advanced features are temporarily unavailable. Mullis KB and Faloona FA "Specific Synthesis of DNA in vitro via a Polymerase-Catalyzed Chain Reaction." PDF Groundbreaking discoveries of the past and the future Kary Mullis Solid-phase reversible immobilization for the isolation of PCR products. She would later describe him as outrageous and nasty.. 8600 Rockville Pike History of polymerase chain reaction - Wikipedia Scientific American is the authority on science and technology for a general audience, with coverage that explains how research changes our understanding of the world and shapes our lives. Biology. The result would be exactly the same only the signal strength would be doubled. Semantic Scholar is a free, AI-powered research tool for scientific literature, based at the Allen Institute for AI. While the artists communication is linked forever with its original form, that of the scientist is modified, amplified, fused with the ideas and results of others, and melts into the stream of knowledge and ideas which forms our culture. 249(16), pp. Disclaimer. FOIA Nucleic Acids Res. That size would be up to me. © 2023 IFLScience. I think you can understand what it felt like to invent PCR without following the details. What I needed was PCR, but I had not considered that possibility. The famous chemist Albert Hofmann was at Rons that night. DNA-based procedures are becoming increasingly common within the analytical laboratory where the polymerase chain reaction (PCR) has become an indispensable technique. Joe was the master of microbial iron transport molecules. Diseases. Other combinations would indicate that something had gone wrong. The polymerase chain reaction (PCR) is a scientific technique in molecular biology to amplify a single or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence. By Kary Mullis Penthouse Sept. 1998 Dr. Mullis was awarded the 1993 Nobel Prize in Chemistry. If they had been used, I surely would have heard about it and so would everybody else including Jennifer, who was presently sunning herself by the pond taking no interest in the explosions that were rocking my brain. The sugar was reluctantly furnished from her own kitchen, and the potassium nitrate we purchased from the local druggist. 0000009547 00000 n
If one were made longer than the other then their single base extension products could be separated on a gel from each other and one could act as a control for the other. This site needs JavaScript to work properly. Sexing of cattle embryos using RNA-sequencing data or polymerase chain reaction based on a complete sequence of cattle chromosome Y. TaqMan probe-based qPCR method for specific detection and quantification of fowl adenovirus 8b challenge from chickens inoculated with live attenuated or inactivated virus. Someone else would have done it and I would surely have heard of it. An application to patent PCR was filed by Cetus in 1986, with Mullis applying for a patent in 1985. Request Permissions. However, scientists at Cetus persisted for months alongside Mullis to create a proper experimental system to make it work. Because DNA polymerase can add a nucleotide only onto a preexisting 3'-OH group, it needs a primer to which it can add the . This one could wait till morning. ~&5z3^ !S e i& 0 jN*
Kubista M, Andrade JM, Bengtsson M, Forootan A, Jonk J, Lind K, Sindelka R, Sjback R, Sjgreen B, Strmbom L, Sthlberg A, Zoric N. Mol Aspects Med. I started studying DNA synthesis in the library. 0000002859 00000 n
In the spring of 1985 John Sninsky at Cetus began to use PCR for the difficult task of measuring the amount of HIV circulating in blood. Both patents were granted in 1987. 61(5) pp. Henry Rapaport, who discovered psoralens would be the scientific advisor to my department at Cetus, and would co-author two patents with me. When I first heard in 1984 that Luc Montagnier of France's Pasteur Institute and Robert Gallo of America's National Institutes of Health By afternoon it was clear. It was not a perfect control, but it would not require a lot of effort. In 1986 Edward Blake, a forensics scientist working in the Cetus building, collaborated with Henry Erlich a researcher at Cetus, to apply PCR to the analysis of criminal evidence. People Are Not Happy After Learning How Parmesan Cheese Is Made, Netflix Finally Says When It Will Stop Password Sharing Around The World, This Small, Vibrating Bracelet Might Change Your Life, Don't Travel Without These CES-Featured Translation Earbuds, Stay Warm in a Blackout with this CES-Featured Power Station, From Dragons To Mythic Locations, These Are The Biggest Mistakes In Ancient Maps, The Ancient Persians Built Windmills Over 1,000 Years Ago That Still Work Today, A Day In The Life Of An Ancient Egyptian Doctor. Cold Spring Harbor Symposia On Quantitative Biology. Methods in Enzymology vol. Okay, Doc, if you say so. He knew I was more concerned with my life than with those cute little purple-topped tubes. For those of you who got lost, were back! Scientific American. EUREKA!!!! Blake and Erlich's group used the technique almost immediately in "Pennsylvania v. Pestinikas",[28] the first use of PCR in a criminal case. Saiki RK et al. Francis Crick and I came to write the first Nature paper describing the double helical structure of the DNA molecule, Francis had wanted to include a lengthy discussion of the genetic implications of a molecule whose struc ture we had divined from a minimum of experimental data and . The result on paper was so obviously fantastic, that even I had little irrational lapses of faith that it would really work in a tube, and most everyone who could take a moment to talk about it with me, felt compelled to come up with some reason why it wouldnt work. Perhaps I should have followed his advice, but then things would have worked out differently and I probably wouldnt be here on the beach in La Jolla writing this, which I enjoy. and transmitted securely. 324 (6093) pp. What if I leave out the radioactive dideoxynucleoside triphosphates, mix the DNA sample with the oligonucleotides, drop in the polymerase and wait? 332(6164) pp. Sanger F, Nicklen S, Coulson AR "DNA sequencing with chain-terminating inhibitors" Proc Natl Acad Sci vol. The archives of Scientific American include articles penned by Albert Einstein, Thomas Edison, Jonas Salk, Marie Curie, Stephen Hawking, Franklin D. Roosevelt, Stephen Jay Gould, Bill Gates, and more. Quant. 1990 Scientific American, a division of Nature America, Inc. I found one at the medical school working with two pediatric cardiologists and a pathologist. This brainwave wasnt left in the drivers seat of his car. S ometimes a good idea comes to you when you are not looking for it. Maybe I would be rich in Tahiti. I was working on the enkephalins. However, shocking to me, not one of my friends or colleagues would get excited over the potential for such a process. It was an inspiration to the first of the molecular biologists, and has been, along with Delbrck himself, credited for directing the research during the next decade that solved the mystery of how like begat like.. 2019 Sep;67(9):96. Biochemist and PCR test creator Kary Mullis died in 2019, months before the . Part of Springer Nature. But then there was a seminar describing the synthesis and cloning of a gene for somatostatin. The air was moist and cool and filled with their heady aroma. Abundance and distinction. I decided to become a neurochemist. The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). What I would hope to see is that one of them would pick up one radioactive nucleotide and the other would pick up its complement. Before 2007 Jun;8(4):234-51. doi: 10.2174/138920207781386960. Wed all heard about, but not read, the classic papers. There were no government regulators to stifle our fledgling efforts, and it was a golden age, but we didnt notice it. However, to look at how he came up with PCR, were traveling back to May 1983. One of the most heralded developments in basic science to reach clinical application in recent years has been the polymerase chain reaction (PCR). 0000001158 00000 n
Abstract. Please enable it to take advantage of the complete set of features! The product sold because people were of the impression that you could not irreversibly denature BAP. The scientist has in common with the artist only this: that he can find no better retreat from the world than his work and also no stronger link with his world than his work.. In 1953, when Jim Watson and Francis Crick published the structure of DNA, Schroedingers little book and I were eight years old. In another, we inadvertently frightened an airline pilot, who was preparing to land a DC-3 at Columbia airport. Encouraged by my progress on the thought experiment I continued to think about it and about things that could possibly go wrong. Kary Mullis - Wikipedia This would mean that after the area of interest was marked by the oligonucleotides, the natural tendency of DNA to replicate itself could be harnessed to reproduce this area of interest over and over and over and over. In 1987 Russ Higuchi succeeded in amplifying DNA from a human hair. 239 pp. This article is excerpted from his forthcoming book, Dancing Naked in the Mind Field, to be published by Pantheon. Methods Mol Biol. 8600 Rockville Pike But by the 1980s, scientific magazines . H|SM0+T;cY EKnUd+HV!G`^Q1J B#b32;e4V\Hro/:y:[-0y!QGi#a,HQ^!{06Y. Samuel Becketts contributions in literature, being honored at the same time, seemed to Max somehow universally accessible to anyone. Clipboard, Search History, and several other advanced features are temporarily unavailable. FOIA This technique of DNA amplification, which has already had an enormous effect on the way in which molecular biology research is done (and whose inventor, Kary Mullis, was awarded the Nobel Prize in . It wasnt done like that in most labs, where the head of the lab would prefer that you help advance his career by elaborating on some of his work. vol. 251(3) pp. I boiled for a few minutes, cooled, added about 10 units of DNA polymerase, closed the tube and left it at 37. This Technical Brief covers the basics of PCR and some of its variations. But it WAS different. Soc. On the increasingly numerous days when she hated me, my ideas and I suffered her scorn together. As he had learned all the biochemistry he knew directly from me he wasnt certain whether or not to believe me when I informed him that we had just changed the rules in molecular biology. For two years I did medical research, learned how to appreciate Old World values from two Italians and a New York Jew, and learned human biology for the first time. PDF Polymerase Chain Reaction: Methods, Principles and Application I could have waited another hundred years as I had no idea what the absolute rates might be.
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