Everyone studying in the lab every day, it must be boring! Today, I will be willful again with Xiaobian! Listen to Xiaobian to tell you stories. Attention, the friends are sitting on the bench and sitting down! Xiaobian wants to start talking!

The story has to start from the PCR we are familiar with~~~

PCR (Polymerase Chain Reaction), polymerase chain reaction, the famous method "nuclear fission chain reaction". First, the DNA template to be amplified is degenerated and melted by melting; when cooled to a certain temperature, the primer is annealed to the template sequence to be amplified; and then the temperature is raised to extend the annealing primer under the action of DNA polymerase. The meaning of "chain" is that the template used in the next reaction cycle is the product in the previous cycle, so the DNA fragment to be amplified grows in a geometrical order of 2^n in the chain reaction.

Although the basic principle of PCR is very simple, it hides a lot of interesting stories. Let's start with the history of PCR invention, talk about the PCR we are most familiar with and the most unfamiliar! Which big professor invented PCR? Correct! It was this handsome guy at the time, Dr. Kelly Mullis!

KBMullis was born in 1944. In his childhood, Mullis and his brothers and sisters were naughty on the farm. At this time, Mullis' life and natural sciences have not been related to each other. His childhood was not like other big scientists, and he was very interested in the natural phenomena around him. In 1953, when the theoretical basis of PCR technology, the DNA double helix model, was proposed, Mullis and his friends were still playing happily in the country. In the middle school era, Mullis came to Columbia, the capital of South Carolina, and started a little science-related activities, which was actually a rocket. Using the sugar from the mother's kitchen, the potassium nitrate from the local pharmacy, and the explosives that I don't know where to get it, Mullis and the friends designed the rocket in their yard. After repeated experiments, their rocket size became bigger and bigger, and finally the frog would have been launched and flew for more than a mile!

At the graduate level, Mullis came to UC Berkeley to pursue a Ph.D. in biochemistry, and the genetic code was just cracked. But Mullis still doesn't catch a cold on DNA. Instead, he was immersed in the course of astrophysics. In 1968, he even published a paper on nature to explain his hypothesis, The Cosmological Significance of Time Reversal. It is this article that helped him “smoothly” pass the assessment. (This kind of experience is estimated to be placed in the current domestic university, and it is certainly not known how many times the boss is looking for a conversation!)

After graduation, Mullis moved around several cities and changed a few different jobs (writing science fiction, killing mice...). In 1979, he found a fixed job, working on DNA synthesis at Cetus Biotech, and providing DNA segments of about 20 nt in length for research in other parts of the company. At this time, he is already 35 years old (it seems that all are late!), Mullis has contact with DNA.

Because his work was relatively quiet, he began to help people in the next-door lab to think about how to detect single-base mutations in the genome. For this subject, Mullis has proposed a method called "oligomer restriction", which is very similar to the principle of Sanger sequencing: a short DNA fragment is bound upstream of the base to be tested, followed by radiolabeled dideoxyribonucleoside triphosphate (ddNTP) is used as a raw material for DNA replication in vitro. Due to the nature of ddNTP, DNA replication will stop at the ddNTP binding site. Next, it is only necessary to radiolabel four ddNTPs in turn, and then by running the glue to observe what the base of the site to be tested is. Mullis' thinking about this issue is "great thinking," because the idea evolved into PCR technology, and it was similar to the 1980 Nobel Prize-winning Sanger sequencing.