"Jump! Jump!" All 24 teenage mice in each of the six groups twitched and jumped in shock, including Du Yucang, Gong Yueting, Shi Putao and other top biochemists in China at that time. The scene was filled with joy.

This was the early morning of September 17, 1965. Convulsion experiments showed that the biological activity of artificial insulin made by Chinese scientists reached 80% of natural insulin activity. This showed that in decades of international competition, Chinese scientists were the first to obtain artificial insulin crystals.

This is regarded as the closest Chinese to the Nobel Prize before Tu Youyou won the award for discovering artemisinin. However, this result was ultimately lost, and the reason for the missed was also as if it was marked by the mark of the times:

At the end of 1959, when we were the first to complete the disassembly and merger of insulin, in order to avoid the discovery of "imperialist" peers taking advantage of this discovery, the leaders of the Academy of Sciences and other institutions chose to "keep confidential" and did not allow the article to be published. More than a year later, American scientist Anfenson came to a similar conclusion and won the 1972 Nobel Prize.

The intermediate results were "confidential". When the Chinese finally obtained artificial insulin crystals at the end of 1965 and officially "released" this in 1978, the results were not selected due to insufficient economic practicality and low inspiration.

"Looking at the past is to know the present." When talking about this past at the Peking University Diabetes Forum, Xiong Weimin, a special professor in the Department of Science and Technology History and Science and Archaeology of China University of Science and Technology, was proud and regretful. After consulting a large number of relevant archives of the Chinese Academy of Sciences, Peking University and other units, and having a deep conversation with Zou Chenglu, Zhang Youshang, Du Yucang, Shi Putao and other parties, Xiong Weimin restored this history in more detail.

The Prime Minister stopped and kept it secret for three times.

Mistake in the Nobel Prize

The "predecessor" of the decision to synthesize insulin is to "synthemize a protein". This decision was one of the "scientific satellites" released by the Institute of Biochemistry, Chinese Academy of Sciences during the "***" movement in 1958, with the reason being that the great revolutionary instructor Engels once said: "Life is the way of protein bodies exist."

The initial goal was set to 20 years, but at the mass discussion meeting, the enthusiastic young people in the institute reduced the completion time to 5 years. Before the topic was completely determined, it was put on display at the Shanghai Science and Technology Exhibition. Mr. Xu Luoma, who was responsible for painting the exhibition board, understood synthetic protein as synthetic life, and drew the topic as a small doll standing in a triangle bottle.

At the exhibition, Prime Minister *** was attracted by the cartoon, "When will this work be completed?" the Prime Minister asked, "Is 5 years too long?"

Soon, the topic of synthesis of protein was included in the national scientific research plan (draft) in 1959, and it changed from a "scientific imagination" of the Institute of Biochemistry to a "national will". What protein was synthesized? At that time, it was determined that only one protein with a primary structure was insulin, and there was no other choice. Therefore, the Institute of Biochemistry finally determined the topic of artificial synthesis of insulin at the end of 1958, and the indicators were repeatedly advanced, from the first five years to four years, three years, and two years. Finally, everyone worked hard and decided to use this work as a gift to the tenth anniversary of the National Day in 1959.

At that time, after Vignaud, the United States and Sanger, the United Kingdom won the Nobel Prize for insulin-related research in 1955 and 1958, artificial synthesis of insulin became a popular global topic. According to foreign media reports, between 1955 and 1965, a total of 10 research groups were conducting artificial synthesis of insulin.

Based on confidentiality considerations, the "imperialist" peers were avoided from using relevant discoveries to complete the synthesis of insulin first. In June 1959, this work was awarded the unique logo of the National Confidential Research Project, codenamed "601", which means "the first key research project in 1960".

The work adopts the "five-way march" and "smart islets" scheme, which is divided into several steps: organic synthesis, natural disassembly, peptide library, enzyme activation, and peptide conversion. Without raw materials, the factory was built: Dongfeng Biochemical Reagent Factory was established at the end of 1958 to provide at least a dozen amino acids for the synthesis of insulin; if there is not enough manpower, I ask someone to help: The Party Committee of Peking University arranged the Organic Chemistry Teaching and Research Department of the Department of Chemistry, the Biochemistry Teaching and Research Department of the Department of Biology and the Institute of Biology.

The project was very difficult at the beginning. The staff had failed to completely disassemble the three disulfide bonds of insulin in seven methods. Finally, based on the new literature, Zou Chenglu, Du Yucang and others finally completely disassembled the insulin into a chain and a chain of b, and the obtained s-sulfonic acid-type a chain and b chain are very stable and can withstand repeated purification. This is a very meaningful achievement, but due to the confidentiality requirements, the researchers did not publish it immediately.

After the disulfide bond is disassembled, can the a and b chains be recombined into insulin? In the past 30 years, scientists from different countries have conducted recombination experiments, and each time they get negative results. The conclusion "impossible" has been written in the literature. However, inspired by the *** situation, people did not give up. After many failures and overcoming many technical obstacles, they finally restored the overlapping vitality to 5%-10% of the original vitality before the National Day gift in 1959.

This is another major achievement, which not only guided and solved the route problem of insulin synthesis, but also experimented in advance with the last step of insulin synthesis in a sense. The Institute of Biochemistry wrote to the Party Committee of the Chinese Academy of Sciences in November 1959, requiring the publication of the results of resynthesis as soon as possible, but also because the confidentiality requirement was not agreed. A year later, Canadian scientists Dixon and Wardlow published similar results first in Nature magazine, only recovering 1%-2% of their vitality, and their results were far less than those of Zou Chenglu and others.

At the end of 1959, when we were the first to complete the disassembly and merge insulin, we found that the two chains a and b could be automatically folded into insulin according to their natural structure. The leaders of the Academy of Sciences and other institutions chose to "keep confidential" for the third time and did not allow the article to be published. This was also the closest time that a team of 50 people in the Chinese scientists at that time was close to the Nobel Prize. More than a year later, American scientist Anfenson came to a similar conclusion and later won the Nobel Prize.

The 800-man army "stripped insulin" and found almost nothing.

As a result, the leadership team for insulin synthesis was completely reorganized, and some young teachers and students who lack scientific research experience, students, Peking University's "revolutionary teachers and students" in the Department of Chemistry and a small number of "revolutionary teachers and students" in the Department of Biology of Peking University. Lu Depei, one of the main workers of insulin A-chain synthesis, later recalled in an interview: "A large number of young teachers who don't know the amino acid symbols and third, fourth and fifth grade students became the pioneers of insulin research... In their opinion, synthesizing peptides is a very simple thing: pouring two segments of peptides together is called synthesizing a new peptide - without asking whether there was a reaction, what is the specific product."

At that time, the Institute of Biochemistry, Peking University Department of Chemistry and Fudan University formed a competitive relationship. They did not separate or identify intermediate products, but just tried their best to rush to larger peptides. From April 19 to 26, 1960, at the third academic meeting of the Chinese Academy of Sciences, the "Insulin Synthesis Drama" starring three units reached its climax: they presented gifts to the academic conference and announced that they had initially synthesized artificial insulin b chain, a chain and b, a chain!

At that time, Nie Rongzhen, Guo Moruo and other leaders were extremely excited and delivered enthusiastic speeches. A grand celebration banquet was held for all relevant personnel during the famine period, leaving only Du Yucang and Zhang Youshang to conduct the final synthesis of the a- and b-chain in the laboratory. Four days later, the Institute of Biochemistry still failed to prove that artificial insulin was synthesized. At this time, Fudan University broke the good news: they obtained biologically active artificial insulin for the first time!

This news stimulated the Beijing Municipal Party Committee. They gave Peking University instructions, saying: Let’s make “Beijing brand” insulin! Peking University had to "open up a second battlefield" on May 1, 1960.

The competition from the Ministry of Higher Education stimulated the Academy of Sciences again. On May 4, 1960, Wang Zhongliang, a senior party official at the Shanghai Branch of the Chinese Academy of Sciences, decided to take charge of the order and command more than 300 people from five institutes to conduct "large-corps combat". At the "First Command Meeting" held that night, the completion time of artificial synthesis of insulin was shortened from 20 days to half a month and a week. Many people stayed asleep in the laboratory, so the leaders gave orders: "The rest and sleep of the backbone molecules must be arranged."

Unlike military struggles and industrial and agricultural production, insulin synthesis is a basic scientific research after all. The hypothesis that "a person's work of 30 days is equal to a person's work of 30 days" is not true. 70 days later, the work of the Shanghai Branch of the Chinese Academy of Sciences failed.

From June 28 to July 1, 1960, the Shanghai Science and Technology Commission convened relevant researchers from three units of Peking University, Fudan University and the Academy of Sciences to discuss the work of artificial synthesis of insulin. Representatives from the Department of Biology of Fudan University finally explained their basis for identification.

Zou Chenglu, Du Yucang and Zhang Youshang experimented all night and found that Fudan's test method was very irregular, which eliminated the necessary separation, purification and identification of intermediate products, and violated the requirements put forward in the "Pharmacopoeia of the People's Republic of China" - the Department of Biology of Fudan University, and has never completed the synthesis of a chain, b chain and the entire insulin.

After spending several months and paying a expensive tuition fee of tens of millions of yuan, in the second half of 1960, the "large-corps combat" of about 800 people in three units successively resigned and stopped. In addition to the Institute of Organic of the Academy of Sciences, it also left a little for continued purification and analysis, and later sorted out several papers, the research results of other units were dumped out as garbage.

After the crushing defeat of "the army attacked insulin by corps", the country also entered a period of adjustment.

The vicious competition in the "large-corps combat" caused the insulin working group in Beijing and Shanghai to be jealous. In 1963, under the support of the National Science and Technology Commission, several units decided to start collaborating. The Department of Chemistry of Peking University sent researchers to Shanghai. They learned from the previous lessons and made three decisions: unite and devote themselves to creating "Chinese" insulin.

In the early morning of September 17, 1965, Du Yucang walked out of the laboratory. From the thin tube he was holding, people looked backwards and saw the flash of crystals. After the convulsion experiment, a scene at the beginning of this article appeared.

In 1966, the results were published in Chinese and English in "Science Bulletin" and "Chinese Science" respectively. In some international conferences and academic visits, the results of Chinese artificial synthesis of insulin were recognized by Tria, an academician of the Paris Academy of Sciences in France, chairman of the Chemistry Group of the Nobel Prize Evaluation Committee of the Royal Swedish Academy of Sciences, Tislius, professor at the University of Cambridge in the UK, and Kendrew, among them, there are many opinions that believe that the achievement can win the Nobel Prize.

In 1973, Yang Zhenning wrote a letter to Guo Moruo, then president of the Chinese Academy of Sciences, saying that he was preparing to nominate China for the 1974 Nobel Prize in Chemistry, and asked Guo to provide specific candidates.

The Chinese Liaison Office in the United States responded to Yang Zhenning:

"Although if our scientific researchers win the Nobel Prize, it will play a positive role in improving our international prestige, considering that the prize is awarded by a capitalist country and that our country's insulin research results are the result of collective efforts of scientific researchers under the leadership of the Party, it is difficult to propose outstanding representative candidates, so we tend to politely decline Yang Zhenning's kindness.

When the Cultural Revolution finally passed, in 1978, Yang Zhenning once again expressed to the Chinese leaders - this time to *** - that he was willing to nominate the Nobel Prize for insulin synthesis. Later, the Nobel Prize Committee of the Royal Swedish Academy of Sciences also wrote to Wang Yinglai, director of the Institute of Biochemistry, asking him to recommend the list of candidates for Nobel Prize for Chemistry.

This time, the Chinese finally officially "relied" with artificial synthetic insulin. But in the end, they were unexpectedly defeated, shocking the Chinese.

At that time, "discrimination theory" and "time has passed" were once popular. However, in Xiong Weimin's view, although China's artificial insulin synthesis has won many important awards at home and abroad, it has improved national self-confidence to a certain extent and achieved very substantial intermediate results, but the final results may not have reached the level of winning the Nobel Prize in academic innovation, progress of tools and methods, economic benefits, etc.

Perhaps, that intermediate result of disassembling insulin was indeed the closest thing to the Nobel Prize in China's artificial insulin synthesis.

Summarize

According to Xiong Weimin's research, Kazoyanis and Chaan, who have obtained similar results as China, have "drawn" and are just two non-first-class professors from the United States and Germany. They have never obtained academic status such as academicians of the National Academy of Sciences in their later years, and have conducted research independently; while Zou Chenglu, Wang Yinglai, Wang You and others who participated in this work in my country are not only academicians, but also enjoy international reputation, and have spent millions of funds at the national level, but in the end they have a regrettable result.

Why do many outstanding scholars add together, regardless of cost, still basically tied with one or two foreign individuals who are not particularly outstanding? Xiong Weimin thought that the key is probably the system: although the planning system has the advantage of concentrating resources to overcome difficulties, in practice, this advantage is often surpassed by the disadvantages brought by bureaucracy.

Should scientific research work be "official research" or "free exploration"? Should scientific matters be decided by administrative personnel or scientists? History cannot be assumed, but in Xiong Weimin's view, these propositions are still one of the greatest value left by this history to future generations.
Chapter completed!