On August 7, 2019, Nobel laureate Kary Mullis died of pneumonia at the age of 74. In 1993, he was awarded the Nobel Prize in Chemistry for developing polymerase chain reaction (PCR). The discovery not only allowed police to better use DNA evidence against criminals, but also inspired the use of fossil DNA to clone dinosaurs in the movie Jurassic Park. Today, PCR has become a core technology in biochemistry and molecular biology, and the New York Times commented: "It is highly original and significant, and almost divides biology into two eras before PCR and after PCR." ”
TED.com
After graduating with a Ph.D., he opened a bakery
Mullis was born on December 28, 1944 in Lenova, North Carolina. At the age of 7, he got a set of chemical combination toys as a Christmas present, so he mixed aluminum powder and potassium nitrate with a little other substance and heated it on an alcohol lamp. Soon, the mixture became red and hot, and eventually swelled the test tube and squirted out, while the 7-year-old Mullis was not afraid, but more excited, he wrote in his memoirs: "Of course I didn't know what happened at that time, but from then on I decided that science was full of fun." ”
This reaction releases a lot of heat. Little Mullis has not been crumbled, and has been a fortune teller, Rich And Ben Do Science/Youtube
By the time he got to high school, Mullis, like all the energetic lads, was even more restless. However, the other bear children only set off a big firework in the yard, and Mullis actually tried to build a rocket in his backyard - he really got the rocket fuel, fortunately there was no accident, so he went to Georgia Tech unscathed. In 1973, he received his Ph.D. in biochemistry from the University of California. Everyone thought he should start a scientific career, but Mullis actually left the field of science at this time, what to do? Write novels.
Mullis's novels don't make a splash, and while he did develop good writing during this time, he soon changed careers again—this time, he opened a bakery. The doctor, who was supposed to be working in the laboratory, actually began to work in the back kitchen, and it was estimated that he was almost going to go to the "Get Rich", and his waywardness could not be seen by his friend Thomas White, who could not bear to see Mullis wasting his talents, and after several persuasions, he finally pulled this unusual friend back to the scientific research community in time. Mullis later came to Cetus Biotechnology in California at White's recommendation and became a DNA chemist. It was there that he made an invention that changed the world.
When dating your girlfriend, think about how to "amplify" DNA
As we all know, DNA, as one of the most important life-based molecules, contains a large amount of information, is the ultimate source of the construction of other compounds in the cell, and is the unique identity code of organisms, which people can use for identification, archaeological detection, criminal investigation and so on. But if there are too few pieces of DNA, people can't get too much information and need to "amplify" the DNA.
How? Dr. Holana's method has been used in the industry, first doubling the DNA, and then heat treating the amplified DNA to disassemble the double helix chain of DNA; since the DNA polymerase will lose its activity after heat treatment, new enzymes will be added at this time, and then repeat the previous steps, which can amplify the DNA by another 1x.
For many years, everyone has used this troublesome and inefficient old method. Mullis was also opportunistic at first, but he encountered too many cases of only trace amounts of DNA in his work, and he was overwhelmed with it, wondering every day, is there a convenient way to quickly amplify DNA?
Mullis was fascinated by this and even thought about it when dating his girlfriend. He wanted to design a short synthetic piece of DNA to recognize a particular sequence, and then start a program that would keep the sequence self-replicating. One day in 1983, while driving his girlfriend, he suddenly had a flash of inspiration: Why not fix the dna sequence you need first, and then use DNA polymerase to replicate it? He hadn't slept for two days, had been improving his thinking, returned to the lab to do many experiments, and finally determined a new method.
Mullis had a folder on his computer dedicated to recording his brilliant ideas, and one day a new folder appeared on the desktop, which was named "polymerase chain reaction", which became the famous PCR technology.
Schematic of a polymerase chain-lock reaction. It doesn't matter if you don't understand it, there is an animated image below. 丨Enzoclop/Wikipedia
"Polymerase chain reaction" requires 4 components:
The copied double-stranded DNA fragment, called the template DNA;
Two oligonucleotide primers: short fragments of single-stranded DNA, each complementary to a short sequence on the template DNA strand;
nucleotides, which form the chemical basis of DNA;
A (heat-resistant) DNA polymerase that replicates template DNA by adding free nucleotides in the correct order (and is not inactivated by heating so that it does not have to be added repeatedly).
These components are heated, causing the template DNA to split into two strands. The mixture is then cooled so that the primers are attached to complementary sites on the template chain. The polymerase can then begin to replicate the template strands by adding nucleotides, producing two double-stranded DNA molecules.
Repeat this cycle, you can change 1 to 2, 2 to 4, 4 to 8... Exponentially increase the amount of DNA — if each cycle is only two minutes, the cycle can be repeated thirty times in an hour, and this can produce more than 1 billion copies of the original DNA sequence.
The first cycle of the polymerase chain-lock reaction: the two primers bind to specific sequences on the two strands of the DNA to be copied, and then the DNA polymerase begins to replicate separately 丨 gifcat
During that hectic time, Mullis's girlfriend eventually broke up with him, but the love scene was frustrated with his career — he later won the Nobel Prize.
He proposed to his son at the Nobel Dinner
In fact, after just developing pcrography technology, Mullis had a hunch that he would win the award. But the good news didn't come until 1993. The first thing Mullis did after receiving the winning call was to go out surfing. So "surfers win Nobel Prizes" became the headlines of the day.
Mullis thinks wildly, jokes, and always does amazing things, even at the Nobel Prize dinner, where he meets the king and queen, hears that their 16-year-old daughter has a rebellious personality, and he jokes about the same father: "She is a 16-year-old princess, and I believe she will grow up healthily in the future." My son is the same age as her, and I am even willing to propose to the princess on my son's behalf—as long as you are willing to give me a third of the kingdom. ”
Mullis Bonham.com with the King of Sweden
The PCR technology invented by Mullis has an extremely wide range of applications. In medical diagnostics, the technology makes it possible to identify pathogens infected by bacteria or viruses directly from small samples of genetic material; it is also used to screen patients with genetic disorders such as sickle cell anemia and Huntington's disease; evolutionary biologists can use the technology to study extracting trace amounts of DNA from fossil remains of ancient species; and forensic scientists use PCR technology to identify suspects or victims from blood, semen or hair left behind at crime scenes.
Today the technology is cheaper and more automated. This revolutionized various fields such as biochemistry, molecular biology, genetics, medicine, and forensic science, and ultimately enabled the mapping of the human genome.
Live-action version of Grandpa Rick
After winning the Nobel Prize, Mullis told The New York Times, "I was more or less dominated by my own desires, not by what others thought." I don't think I need to do something bigger or better right now. ”
Mullis was shrewd, sharp, always surprisingly frank, and often made some surprising remarks. In his 1998 autobiography Dancing Naked in the Mind Field, he made many ideas that broke the impression of scientists, such as disagreeing with the scientific evidence that supports climate change and the evidence that HIV causes AIDS, and expressing his faith in astrology.
Mullis's intellect is as famous as his eccentric nature, and his outrageous behavior, like the genius and eccentric Grandpa Rick in the anime Rick and Morty, is blunt, weird, knowledgeable, unscrupulous, full of whimsical nonsense, and tells stories that are fascinating and insightful. He was a controversial man, and as many people liked him, as many people hated him, but no one could deny his great contribution.
Mullis 丨Nobel Award official website
Mullis's death was a loss to the scientific community, but he lived a rich and interesting life with ease and excitement. This cannot but be said to be a kind of fulfillment. As he wrote in his autobiography:
"What human beings should do is feel lucky for the existence of life... Sit back and relax with a beer. That's why people have to go back to the starting point again and again before they can really learn to enjoy life.
"The sky has not fallen."
Reference Links:
https://www.dead-people.com/Kary-Mullis
https://www.nobelprize.org/prizes/chemistry/1993/mullis/biographical/
http://www.sogou.com/link?url=hedJjaC291PXp8cAo7eR0HcyUlSHJ9L62i_W2nY9bUDhk0lBNOTcV8SJAOYxbKQr50H12q7iq80.&query=Kary+B.+Mullis
https://www.thestate.com/news/state/south-carolina/article233664142.html
https://en.wikipedia.org/wiki/Kary_Mullis
Author: Wang Jiangshan
Edit: Luna
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The patent dispute behind PCR is also a good dog blood story... Are any friends interested in talking about it!
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