Artificial insulin, a new era of life

   On the earth, protein is the basis of life. All discovered living organisms contain protein, and protein itself also plays a very important role. In industry, protein can decompose impurities and improve efficiency; in medicine, protein can detect diseases. , cure sickness and save lives, etc. It can be said that since humans began to synthesize proteins, the development of science has reached a new level, and it all started with the first protein synthesized by Chinese scientists - artificial insulin.

The only and correct choice

  It is hard for us to think that the time when China first synthesized protein was as early as the 1950s and 1960s, when New China was still poor. The original intention of synthesizing protein was just to "make a big project and present a gift to the tenth anniversary of the National Day". The researchers didn't know at the time what kind of problems they were facing.

  Scientists from Shanghai Institute of Biochemistry are conducting experiments.

  In any case , when scientists from Shanghai Institute of Biochemistry, Chinese Academy of Sciences proposed to use synthetic proteins as a gift to the motherland, they won unanimous approval from people with patriotic enthusiasm. Chinese scientists must first choose the synthetic object. There are so many proteins, which one to synthesize? The choice before them is actually one: insulin. Insulin was the only drug to control diabetes and the only protein with known amino acid sequence at that time. After figuring out its sequence in 1955, many scientists around the world have been trying to synthesize insulin.

Zou Chenglu

  Insulin also has the advantage of being suitable for artificial synthesis: its molecule is small, consisting of only 51 amino acids. As a result, Chinese scientists have also selected synthetic insulin as their target. The insulin molecule is so small, but scientists from all over the world have not been able to successfully synthesize it. The reason is that the 51 amino acids are divided into two chains, A and B. The A chain has 21 amino acids and the B chain has 30 amino acids. The two chains are composed of two chemical bonds. connected together, and the positions of the two keys are not determined. In this way, the structure of insulin is infinite, and it is difficult to synthesize the natural structure with activity and function.

  Chinese scientists are also facing the same difficulties. However, they have the determination to face difficulties and perseverance. No matter how many failures they experience, they will never give up. The scientific research team led by Zou Chenglu, a scientist at the Shanghai Institute of Biochemistry, is responsible for determining the positions of the chemical bonds in the A and B chains of insulin, figuring out the structure of insulin, and laying the foundation for the subsequent total synthesis.

Coincidental discovery is inevitable

  The method chosen by Zou Chenglu's group is "insulin disassembly", which is to first disassemble natural insulin into two separate A chains and B chains, and then look for conditions to recombine the separated A and B chains into natural insulin and determine which the location of chemical bonds. Easier said than done, the research team looked through all the experimental literature they could find, and they saw that many foreign scientists had tried to reconstitute insulin, but these quests had all failed without exception. Some people even believe that the method used to synthesize single-chain amino acid chains is not suitable for the synthesis of insulin.

Scientists at the Shanghai Institute of Biochemistry are conducting experiments

Crystallization of artificial insulin under high magnification microscope

  Zou Chenglu was not intimidated by the failures of his predecessors. Instead, he rose to the challenge and tried many ways to recombine the A chain and the B chain. The researchers later recalled that the chemical solvent used in the experiment was enough to fill a swimming pool. After numerous failures and restarts, after more than a year, Zou Chenglu's group finally found a way to slowly recombine insulin double chains at low temperature without using oxidants. Using this method, the A and B chains are freely recombined into a variety of "insulins" in the reaction system, of which natural insulin accounts for 10%.

  What does this mean? If there is only one A chain and one B chain in the reaction system, the structure of the formed insulin is determined, and the probability of forming natural insulin is roughly the same by repeating many sets of experiments. However, when there are thousands of A chains and B chains in the reaction system, the two chains can be combined into many kinds of "insulin" in different proportions and ways, but only one is the structure of natural insulin, so the correct combination The probability is one in infinity—about zero. However, the team of Zou Chenglu achieved the feat of recombination rate of natural insulin reaching 10%. This result implies that the natural structure of insulin is the most stable one among all its possible structures, so it has the highest content in the products formed by free recombination.

Scientists try artificial insulin in mice

Chinese scientists are conducting experiments to synthesize bovine insulin

  The experimental results of Zou Chenglu's group determined the structure of insulin, and thus began the research on artificial total synthesis of insulin. In 1964, two research groups synthesized the two chains of insulin respectively. At the same time, Zou Chenglu's group used the same method to recombine the A and B chains into natural insulin. In 1965, scientists proved that synthetic insulin does have the same activity as natural insulin through convulsion experiments in mice. After more than 6 years of hard work, Chinese scientists have synthesized crystalline bovine insulin with full biological activity by artificial methods for the first time.

Hard work pays off

  It can be seen that in the attempt to artificially synthesize insulin, Chinese scientists have invested a lot of manpower, material resources and time and energy. At that time, only in the Shanghai Branch of the Chinese Academy of Sciences, there were more than 300 scientific research teams from five research institutes. At that time, it was a difficult period for the national economy, and the synthesis work was very difficult, and it was even suspended for a time because it had no results. Fortunately, the Party Central Committee, the State Council, the Ministry of Education and other departments have all expressed support and encouragement for these work. Comrade Nie Rongzhen, then the vice premier of the State Council, stated: You do it, no matter how big the responsibility is, we will bear the responsibility, and it will take 100 years to synthesize insulin. Go on!

  We now know that this support and encouragement is of great significance to the success of the experiment and to the development of science and technology in China today. As the first basic theoretical research achievement at the world's leading level after the birth of the People's Republic of China, the synthesis of crystalline bovine insulin has caused a huge international sensation. Many well-known national media also highlighted the news, which greatly improved China's international status in the field of science and technology.

  In addition, the synthesis of artificial bovine insulin marks a key step in the journey of human beings to understand life and explore the mysteries of life, promote the development of life science, and open up the era of artificial protein synthesis; greatly promote the foundation of our country The development of research, through the artificial synthesis of insulin, the entire peptide field in China has been driven to develop; a group of scientific research talents concentrated in the research of synthetic insulin will become the backbone of my country's biochemical field in the future. Although the first synthetic insulin failed to win the Nobel Prize and did not bring actual economic benefits, its historical significance is beyond doubt.



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