Why did China’s synthetic bovine insulin miss the Nobel Prize in the last century?

53 years ago, on December 23, 1966, Chinese scientists used artificial methods to synthesize a biologically active protein crystalline bovine insulin for the first time in the world. This is a major scientific research result obtained by Chinese scientists after 6 years and 9 months of hard work.

Until the 20th century, humans were still completely helpless against diabetes. Once suffering from diabetes, it is tantamount to being sentenced to death, and the patient can only sit and wait for death, and there is no other way. But just as human civilization has faced troubles time after time since the ancient times and always ushered in a turn for the better, this “sweet” disease may be waiting for the emergence of people who can “enlighten” it.

Discovery of insulin

In 1889, inspired by the Russian scientist Paplov, two German scientists Merlin and Minkowski began to explore the role of the pancreas in the digestion process. They accidentally discovered that the urine of a dog whose pancreas had been removed was sugary, which meant that the dog “suffered” from diabetes. The relationship between pancreas and diabetes was confirmed.

As early as 1869, a 22-year-old German medical student, Paul Langerhans (Paul Langerhans) described in his graduation thesis that the different island cell clusters around the pancreas that can be observed under a microscope (that is, What we call “pancreatic islets” today), and speculate that these island cell clusters may secrete hormones.

Based on these two discoveries, and through the unremitting efforts of several generations of scientists, the hormone “insulin” secreted by the pancreatic islets of cattle, sheep and other animals has been gradually confirmed by the academic community for the treatment of diabetes.

By the 1920s, Eli Lilly and Co. in the United States was able to separate enough insulin from animal pancreas obtained from slaughterhouses. In 1955, St. Gerald of the United Kingdom determined the structure of insulin and completed the purification of insulin. For this reason, he won the 1958 Nobel Prize in Chemistry.

Synthetic insulin

With the increase of diabetics, the extraction of insulin from animal pancreas is far from keeping up with needs. So synthetic insulin was put on the agenda. It should be noted that the “first synthetic insulin” in a broad sense does not belong to the Chinese.

English Wikipedia only mentions two names about “first synthesis”, one is Panayotis Katsoyannis from the University of Pittsburgh, the other is Helmut Zahn from the Aachen University of Technology in Germany (West Germany). The synthesis time is in the early 1960s, and there is no China. The name of the scientist.

Other monographs are more detailed. For example, the book “Understanding Insulin Action: Principles and Molecular Mechanisms” states that insulin was first chemically synthesized in 1963, and the person who did this was Katsoyannis. The book “Insulin&Related Proteins—Structure to Function and Pharmacology” further pointed out that at the end of 1963 or early 1964, both Zahn and Katsoyannis mastered the correct synthesis strategy.

These time points are earlier than the time announced by China.

However, neither the Americans nor the Germans have obtained insulin crystals, and the products made are very low in vitality. In contrast, China’s final degree of completion is much higher.

Since 1958, the Shanghai Institute of Biochemistry of the Chinese Academy of Sciences, the Shanghai Institute of Organic Chemistry of the Chinese Academy of Sciences, and the Department of Chemistry of Peking University have joined forces, headed by Wang Yinglai, and led by Gong Yueting, Zou Chenglu, Du Yucang, Ji Aixue, Xing Qiyi, Wang You, Xu Jiecheng, etc. People formed a collaborative group. Based on previous studies of insulin structure and peptide chain synthesis methods, they began to explore chemical methods to synthesize insulin.

After careful research, they established a procedure for synthesizing bovine insulin. The synthesis work is completed in three steps:

my country’s first artificial synthesis of bovine insulin in the world

In the first step, natural insulin was split into two chains, and then they were re-synthesized into insulin. This problem was overcome in 1959. The re-synthesized insulin is a crystal with the same vitality and the same shape as the original.

In the second step, after the two chains of insulin are synthesized, the artificially synthesized B chain is connected with the natural A chain. This semi-synthesis of bovine insulin was successful in 1964.

The third step is to combine the tested semi-synthetic A chain with the B chain.

The total synthesis of crystalline bovine insulin was completed on September 17, 1965. After strict identification, its structure, biological activity, physical and chemical properties, and crystal shape are exactly the same as natural bovine insulin.

The achievement of perfect results is an advantage under the “national scientific research” system. The top scientific journal “Science” also noticed the total synthesis of insulin in Red China for the first time. In a report in 1966, it was emphasized that two Western scholars were reorganizing insulin (whether natural or The two peptide chains synthesized) encountered difficulties in restoring their biological activity. It was the Chinese who took the lead in improving the method to solve this problem.

Since China’s synthetic insulin is so perfect, why didn’t it win the Nobel Prize?

According to historical records, at the end of 1973, Yang Zhenning sent a letter to Guo Moruo, President of the Chinese Academy of Sciences, stating that he planned to nominate each of the representatives of the Institute of Biochemistry, Institute of Organic Chemistry, and Peking University to win the 1974 Nobel Prize in Chemistry. However, the Chinese Academy of Sciences and the Ministry of Foreign Affairs rejected this kind offer. There are two reasons:

First, insulin synthesis is the result of the collective efforts of scientific researchers under the leadership of the party, and it is difficult to propose a representative;

The second is that the bonus is awarded by capitalist countries, so it is better not to take it.

In 1978, Yang Zhenning once again expressed to Deng Xiaoping that he was willing to nominate the Nobel Prize for insulin synthesis. In the same year, Chinese-American logician Wang Hao made the same proposal; and the Nobel Committee of Chemistry of the Royal Swedish Academy of Sciences wrote to Wang Yinglai, director of the Institute of Biochemistry, asking him to recommend a list of Nobel candidates.

At that time, the reform and opening up had just begun, and the Chinese had already begun to attach importance to the Nobel Prize. At the end of the year, the Chinese Academy of Sciences held a special “Insulin Artificial Total Synthesis Summary Selection Meeting”. After four representatives of Niu Jingyi, Zou Chenglu, Ji Aixue, and Wang You were selected by secret ballot, considering that the number of winners for each individual award was not more than 3, Taking into account that “the Federal Republic of Germany and the United States have also achieved good results in the artificial synthesis of insulin, it is possible that this award will be jointly won by scientists from the two or three countries.” It was finally decided that Niu Jingyi would apply for the Nobel Prize on behalf of all researchers.

However, the insulin synthesis work failed in the end, but it has nothing to do with the legendary number of candidates.

Why did crystalline bovine insulin not win the Nobel Prize? Professor Zhang Peng, head of the research group of the Department of Chemistry of Peking University, who participated in this topic at the time, specifically explained this issue in an interview: China has not won the Nobel Prize for synthetic insulin. Bell Prize, but no other country has won awards for synthetic insulin.

Because the Nobel Prize has a requirement, that is, it must be completely innovative. In 1958, the British chemist Sanger won the award because his discovery was completely new and unprecedented. But why the synthesis of such a complicated thing as insulin did not win the Nobel Prize, because the methods you use are all known and no innovative methods, so you miss the Nobel Prize. China can’t get it if it wants it.

It requires completely innovative results. Because the research method of each country is the method of applying peptide synthesis, there is no innovation. The Nobel Prize must be a completely innovative result.