Chapter 179 Dumplings dipped in vinegar


Chapter 179 Dumplings Dip in Vinegar

Princeton University, Professor Shi Yigong came to the office and saw all the letters he received yesterday piled on the table.

"Remember, President Gu from Tsinghua University said, let me read a paper! If I hadn't seen this pile of letters, I might have forgotten this!"

Shi The professor hurriedly walked to the table and found the letter from China among the many letters.

“Is the author of the paper Zhang Wei again? Is it a follow-up study on nucleoside modification? Are there follow-up results so soon? It’s really fast! As expected of a young man, he is very motivated! We work day and night on scientific research, and we can produce results in such a short time.”

Professor Shi sighed in his heart, and then began to read the content of the paper.

“AProgrammableDual-RNA-GuidedDNAEndonucleaseinAdaptiveBacterialImmunity? Not a nucleoside modification? DNA endonuclease? Is this related to gene editing? Adaptive bacterial immunity? Programmable dual RNA guidance? What is this? It has to do with gene editing Are these two things related? "

Professor Shi suddenly looked confused and couldn't figure out the title.

The gene editing technology widely used in 2005 was zinc finger nuclease technology, while transcription activator-like effector nuclease technology is being developed. Neither of these has anything to do with the title of the paper.

As an ordinary scholar, when seeing this title, the first thing they would not think of is gene editing technology. But with Professor Shi’s level, he immediately thought that this paper was related to gene editing technology.

However, adaptive bacterial immunity and programmable dual RNA guidance appeared again, two things that have nothing to do with gene editing, so Professor Shi was confused after seeing this title.

Then he started to read the introduction of the paper, which was just over 200 words long. Professor Shi finished it quickly.

“Using the CRISPR immune system of bacteria to do gene editing? How come you have such a strange idea? This thinking is too revolutionary!”

Professor Shi thought carefully for a moment and realized This idea is really feasible!

The most indispensable thing in scientific research is all kinds of weird ideas, but most of them are fantasy and cannot be realized. The ones that are truly feasible are probably not even 10% feasible.

"I heard that Zhang Wei is only twenty years old, but he can have such a transcendent thinking ability. Next time I return to China, I must see him with my own eyes."

Professor Shi continued to read the text of the paper, and followed the content As he went deeper, his expression gradually became serious.

After he read the entire paper, his expression had completely become dull, and his heart could not calm down for a long time.

"It is really a new gene editing technology! And this new technology is completely different from previous gene editing technologies in principle!" Professor Shi took a breath of air.

The development of science and technology is often accumulated step by step. Many new technologies are based on old technologies. Through continuous improvement and upgrading, they improve processes, reduce costs, and improve efficiency. Finally, new technology was formed.

The simplest example is chip manufacturing. From the era of microtubes, to the era of transistors, to the era of integrated circuits, to the current era of ultra-large integrated circuits, to put it bluntly, it is based on the original basis, regardless of improvements and improvements, and squeezed bit by bit. Toothpaste squeezed out.

Without the previous technology accumulation, it would obviously be impossible to make a chip of a few nanometers from the beginning.

Other scientific fields probably follow this development pattern.

For example, gene editing technology, the zinc finger nuclease technology that was widely used at the time, and the transcription activator-like effector nuclease technology that is being studied, both use a type of endonuclease called Fok1 The only difference is how to induce the Fok1 endonuclease.

It can be said that without the theoretical basis of the former, there would be no technological research and development of the latter.

But genetic scissors technology is completely different. This technology does not use Fok1 endonuclease to cut, but uses Cas9 protein to cut gene fragments.

These are two completely different technologies in principle. Even without zinc finger nuclease technology, the birth of genetic scissors will not be delayed.

This is probably like the difference between a gas train and a tram. Although oil trucks and trams are both cars, with four wheels pulling people around, their working principles are completely different.

Scientists in the past studied gene editing technology just like developing oil trucks, thinking about how to improve engine performance, how to save fuel, how to improve handling, how to adjust the chassis, etc. Everyone was thinking It is trying every means to get the three major parts of the oil truck done well, and people who buy cars also go for the three major parts.

Gene scissor technology is like a new energy tram. I don’t do the three big things. What I develop is battery performance and intelligent systems. Batteries need longer driving range, faster charging, and better safety, and intelligent systems must also develop in the direction of driverless driving.

Although both gasoline-powered cars and electric cars are cars, their research and development directions are completely different. It can be said that they are following two completely different tracks.

The same is true for genetic scissor technology, which is a new track.

Professor Shi, a senior molecular biologist, certainly knows what it means to have a brand new gene editing technology. After a brief shock, he fell into deep thought again.

“This CRISPR-Cas9 is indeed a new technology, but compared with the old technology, who will have more advantages? Can it replace the original old technology?”

Professor Shi first thought of the zinc finger nuclease technology that was widely used at the time, and then began to compare it with genetic scissors.

Let’s not discuss work efficiency. In terms of cost alone, genetic scissors can completely defeat zinc finger nuclease technology.

The synthesis of zinc finger nuclease is difficult and expensive. The minimum cost of an experiment is US$5,000. Using zinc finger nuclease technology for gene editing is a waste of money!

As for the CRISPR-Cas9 used by the genetic scissors, it is originally the immune system of bacteria. All kinds of bacteria can produce it. Even if you go to the toilet and rub some E. coli, you can produce CRISPR- The protein Cas9.

In terms of cost, this is the sky and the earth, there is no comparison at all.

Even if the genetic scissors are less efficient, I can’t stand being cheap!

For the money you spend on one experiment using zinc finger nuclease, Gene Scissors can do a hundred experiments, and the final success rate will be dozens of times higher.

But at this point, zinc finger nuclease technology will definitely be eliminated!

Thinking of this, a ray of joy suddenly appeared on Professor Shi's face. If a new technology can eliminate the existing technology, it is already a success!

Then Professor Shi remembered the transcription activator-like effector nuclease technology being developed by major scientific research institutes.

The transcription activator was discovered in Xanthomonas, which is also a very common pathogenic bacteria. It can be found on the yellow grass in roadside green belts, so the cost is also very low. , can also use zinc finger nuclease technology.

In terms of cost, genetic scissors technology has no advantage.

Since the costs are almost the same, we can only compare efficiency.

In principle, the transcription activator-like effector nuclease technology is actually the same as zinc finger nuclease, but the cost is lower. In terms of efficiency, the gap is not very big.

So Professor Shi directly compared the efficiency of genetic scissors and zinc finger nuclease technology.

“Regardless of off-target factors, zinc finger nuclease technology can have a target every at least 500 bases! How many CRISPR-Cas9s are there?”

Professor Shi read the paper again and saw the content about PAM cutting points.

“An arbitrary nucleotide plus two guanines? Don’t have too many such structures in the gene sequence! As long as you are not too lucky, there will be several such cutting points in 500 bases. Let’s go!”

More cutting points naturally means higher efficiency.

"Cheaper and more efficient, this is a revolutionary technology! The entire field of molecular biology is about to change!" Thinking of this, Professor Shi's hands holding the paper began to tremble.

The next second, he suddenly realized that this revolutionary achievement was actually made by Chinese scientists from Tsinghua University!

“Change lanes and overtake!”

These four words flashed through Professor Shi’s mind!

There is a saying called "overtaking in corners". This situation is very common on the racing track. Almost all overtaking on the track occurs in corners.

In economics, this term also applies to all fields related to development, including technological development, and refers to catching up from behind.

However, genetic scissors technology has a completely different theoretical basis from previous gene editing technologies. This is equivalent to two different tracks, and it is inappropriate to describe overtaking in corners. It can only be said to be changing lanes to overtake!

......

Director Wang from Sinopharm Group came to Tsinghua University again with three academicians.

Sitting in the business car, Director Wang was the first to ask: "In such a short period of time, Tsingta University has developed a new gene editing technology. Three academicians, how much do you think it contains?"

Director Wang did not ask "Is there any moisture?" but asked "How much moisture is there?" He made it clear that Tsinghua University's gene editing technology had been falsely reported.

The three academicians looked at each other, and Academician Zhang was the first to speak: "I have known President Gu for many years, and I still trust his credibility. I think that if Tsinghua University dares to invite us here, it must have produced certain results. "

Academician Li also said: "The time is a bit fast, but maybe Tsinghua University has a relatively rich research accumulation in this area, and with another funding, it will be able to produce results. Here we come.”

The two academicians spoke one after another, but Academician Qian lowered his head and remained silent.

"Old Qian, please say something!" Academician Li poked Academician Qian with his finger.

Academician Qian sighed and said: "To be honest, I am not optimistic about the scientific research results of Tsinghua University. After I went back last time, I checked a lot of foreign literature and talked with well-known foreign universities. Scholars consulted.

According to my understanding, foreign research institutions have not been successful in developing transcription activator-like effectors. The mechanism for binding transcription activator-like effectors to DNA has not yet been found.

We haven’t even found the mechanism, let alone developed gene editing technology. The technology in Europe and the United States is much more advanced than ours. Why can we come up with technologies that have not been developed by developed countries in Europe and the United States? "

Academician Qian's words immediately caused the other two academicians to fall into silence. This was not about emphasizing other people's ambitions and destroying one's own prestige, nor was it about worshiping foreign countries and fawning over foreign countries. The moon was all foreign round, but the reality at that time. situation.

Compared with developed countries in Europe and the United States, the level of domestic scientific research is indeed far behind, especially in the field of basic science. The gap is even greater when it comes to technologies that have not been developed in developed countries. He couldn't figure it out. He was really stating a sad fact.

Seeing the three academicians fall silent at the same time, Director Wang had already made a judgment in his mind. He became more and more convinced that Tsinghua University was falsely reporting scientific research. How to trick yourself into investing in the research and development of mRNA vaccines

At this time, the car had arrived in front of the Tsinghua University office building, and Principal Gu was already waiting at the door.

"Director Wang, three academicians, please come in." Principal Gu invited a few people to the conference room and began the reporting work.

On the PPT, Zhang Wei took his time and began to show the scientific research results of genetic scissors to everyone.

"Director Wang, three academicians, this is the new gene editing technology I have developed over several months! I call it genetic scissors!"

" Genetic scissors, the name is quite fancy!" Director Wang thought to himself.

At this time, the subtitle has appeared on the PPT: Programmable dual RNA-guided DNA endonuclease in adaptive bacterial immunity.

"Bacterial immunity? Programmable dual RNA? Isn't this transcription activator-like effector nuclease technology?" Academician Qian said immediately.

“No, this is a new technology!” Zhang Wei said.

“Didn’t you say when we last met that we were going to develop transcription activator-like effector nuclease technology? We all heard it!” Academician Qian continued to ask.

“Last time you took the initiative to bring up this technology, so I just followed your words and answered a few words. At that time, I just said that we would develop new gene editing technology, but I didn’t explicitly say that we would do it. What kind of technology!" Zhang Wei said cheerfully.

Academician Qian was immediately speechless and thought to himself: "Would you like to play word games with me? I want to see what new things you can come up with!"

Zhang Wei continued to report, in fact, he was going to Revise and summarize his paper.

When they heard that Zhang Wei was going to use the bacterial CRISPR system for gene editing, the expressions of the three academicians became solemn at the same time.

Obviously, this research and development idea has surprised them! They never thought that CRISPR could be used for gene editing.

Zhang Wei did not give them time to think. In this report, he had to let the three academicians follow their own ideas.

As Zhang Wei continued to display the contents of the PPT, the expressions of the three academicians changed from solemn to horrified!

They never expected that Zhang Wei had really developed a new gene editing technology, and it was a gene editing technology that overturned past theories and formed its own system!

At the end of the PPT, Zhang Wei also added a segment of genetic scissor technology to compare the advantages of zinc finger nuclease technology. Let the three academicians understand more intuitively the advantages of genetic scissors.

Such content is about exalting oneself and belittling others, and it is definitely inappropriate to appear in the paper. Saying that there is nothing wrong with oneself, but belittling others is against academic ethics.

When reporting results, there is no problem in doing so. Just like bringing goods, you can brag about yourself.

"That's it for my report. I would like to ask the three academicians to provide more comments and suggestions. Thank you all!"

Zhang Wei bowed slightly to the three of them and walked off the podium.

But the three academicians stared there with big eyes and didn't speak for a long time. They have been shocked by the genetic scissors technology.

In the end, Director Wang could not bear it anymore and asked: "Three academicians, what do you think of the gene editing technology of Tsinghua University? This gene editing technology can lead to the development of mRNA vaccines. How much help can you give me?"

Academician Qian reacted first. He sighed and said, "The dumplings are dipped in vinegar!"

"Dumplings dipped in vinegar? Do you want to eat dumplings?" Director Wang was startled, thinking, "Didn't you eat in the morning?" Even if you haven’t eaten, there’s no need to come and order food!

Even asked for dumplings! Is the Chinese Academy of Sciences missing this bite of dumplings?

You are a dignified academician, and you came to Tsinghua University to eat dumplings. When word spread, your character collapsed!

Principal Gu replied smoothly: "If you want to eat dumplings, it's easy! I'll ask the cafeteria to make them for you. What kind of filling do you want to eat?"

"Eat dumplings? What to eat? Dumplings! Who wants to eat dumplings?" Academician Qian slammed the table: "I mean you made a special plate of dumplings to dip this dish in vinegar!"

(End of this chapter)

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