© 2024 by the Chinese Academy of Sciences and published by the journal Bulletin of the Chinese Academy of Sciences.

Early on the morning of 17 September 1965, DU Yucang, a researcher at the Institute of Biochemistry of the Chinese Academy of Sciences (CAS), walked out of the laboratory holding a test tube. In his raised hand, the transparent hexagonal crystals of synthetic bovine insulin glistened in the light. “It jumped! It jumped!” All the researchers who witnessed this moment immediately hailed and jumped in raptures. This was the experimental result they had been eagerly waiting for after thousands of days and nights of work. The jumping response of the mouse, which was administered with the artificially synthesized bovine insulin, was exactly the result of an insulin overload caused by a hypoglycaemic seizure, proving that the synthetic bovine insulin has the same biological function as natural insulin (CAS Shanghai Institute of Biochemistry et al., 1966).

This moment, marking the world’s first successful synthesis of fully crystalline bovine insulin, is a historic milestone in science since the founding of the People’s Republic of China in 1949 (CAS Shanghai Institute of Biochemistry et al., 1966). From the approval of the project in December 1958 to the observation of crystallization in September 1965, this achievement took nearly seven years of dedicated efforts during a long period of complex and intense international competition.

How It Began

Not until this remarkable achievement did China unexpectedly attract the attention of international academia – the newly born nation had unfortunately been lagged behind in the two decades of rapid and vigorous progress in biochemical science worldwide.

The idea of producing synthetic bovine insulin was put forward at a symposium of leading scientists at the CAS Institute of Biochemistry in the summer of 1958. At that time, Dr. Frederick Sanger from the UK had just determined the primary sequence of insulin. Subsequently, the journal Nature predicted that the synthesis of insulin would be a distant prospect.

With the ambition to tackle challenges, a group of scientists led by Dr. WANG Yinglai, then Director of the Institute of Biochemistry, accurately assessed the frontier of biochemical research and made the crucial decision to pursue “artificial synthesis of proteins – bovine insulin”.

Bovine insulin, the world’s first synthetic protein, being assayed for its biological activity.

Graphic: CEMCS

Against All Odds

In the 1950s, China was in its early stages of development and its scientific research base was far from solid. In order to keep pace with the advances in fundamental fields, it was imperative to strengthen the capacity for scientific and technological innovation, so as to lay a solid foundation for China’s core competitiveness. The Institute of Biochemistry’s decision to explore the “no man’s land” was in line with the national strategic goals at that time.

Hexagonal crystals of synthetic bovine insulin in the lens of a microscope.

Graphic: CEMCS

Obviously, synthesizing insulin is not an easy task, and in the early stages there were even more considerable challenges. The research team faced a shortage of raw materials, namely amino acids. Undaunted, the team took the initiative to establish the Dong Feng Biochemical Reagent Factory and successfully launched the first amino acid production line in China. In addition, the team developed protocols for the separation and reconstitution of the A and B chains of natural insulin, a remarkable breakthrough that established a clear route for insulin synthesis and activity validation (CAS Shanghai Institute of Biochemistry et al., 1966).

In the early 1960s, progress on the synthetic bovine insulin project was temporarily slowed by national economic difficulties. Nevertheless, the Institute of Biochemistry continued the research with a dedicated team of professionals. In August 1963, with the encouragement of the State Science and Technology Commission and the CAS leadership, the CAS Institute of Biochemistry, the CAS Institute of Organic Chemistry and Peking University officially began their collaboration, unanimously agreeing to synthesize “bovine insulin of neither Shanghai nor Beijing, but China”. Two years later, synthetic bovine insulin was finally launched to great acclaim (CAS Shanghai Institute of Biochemistry et al., 1966).

The news of the successful synthesis of bovine insulin brought international recognition, invigorated the entire nation, and instilled pride in Chinese scientists to boost their self-confidence. “China has achieved one world scientific honor and should strive for another”, this slogan spurred the research team to embark on another ambitious project.

Mr. WANG Yinglai is working at the desk.

Graphic: CEMCS

Further Exploration

In 1968, the Institute of Biochemistry launched the project to synthesize yeast alanine transfer ribonucleic acid, which was comparable in honor to the synthesis of bovine insulin. After 13 years of perseverance and unremitting efforts in collaboration with various research institutes, this project finally succeeded and culminated in the establishment of China’s leading position in nucleic acid research (CAS Shanghai Institute of Biochemistry et al., 1982).

From the synthesis of a protein to the synthesis of a nucleic acid, these two successive and progressive achievements, like two magnificent twin blossoms, successively won the first prize of the State Natural Science in 1982 and 1987 respectively, and wrote a glorious and monumental chapter in the history of scientific and technological development of the People’s Republic of China.

The year 2025 will mark the 60th anniversary of the discovery of synthetic bovine insulin. Looking into the future, how to perpetuate the legacy of this groundbreaking discovery and inspire researchers to stay at the forefront has become a key focus for the Centre of Excellence in Molecular Cell Science of CAS, the successor to the Institute of Biochemistry.

New Journey

The Centre currently comprises a high-caliber team of 75 academic leaders, including 10 CAS Members, 29 National Outstanding Young Scholars and 4 New Cornerstone Fellows. Our mission is to conduct basic and applied research at the forefront of life sciences, focusing on the following areas: the basis and function of ribonucleic acid (RNA); the molecular basis and regulation of cell fate plasticity; and the mechanisms underlying disease development and related treatment strategies. We have made significant breakthroughs of international influence, such as revealing the important role of TET dioxygenases in mammalian epigenetic regulation, generating androgenetic haploid embryonic stem cells that can support full-term embryonic development, developing a new method of tumor immunotherapy based on the regulation of cholesterol metabolism, etc. A total of six achievements by our colleagues were selected as the Top Ten Scientific Advances in China (Shao et al., 2018; Dai et al., 2016; Yang et al., 2016; Yang et al., 2012; Gu et al., 2011; He et al., 2011; Huang et al., 2011). Notably, in the 2023 National Science and Technology Awards, the Centre harvested two second prizes for the National Natural Science Award.

On 14 December 1978, Vice Premier NIE Rongzhen received all comrades attending the insulin synthesis evaluation meeting at the Great Hall of the People in Beijing.

Graphic: CEMCS

Synthetic bovine insulin represents China’s first foray into large-scale, high-level research and is a highly successful example of the “big science” research model in the life sciences. At present, a new round of technological revolution is unfolding, with deep structural adjustment and renewal as a driving force to maintain the development momentum. However, the current institutional structure of the Centre is somewhat dispersed, which may limit our ability to pursue large-scale projects and tackle major scientific challenges, especially in the context of today’s intensifying scientific and technological competition. To address this issue, the Centre has implemented two scientific research structures from 2022 onwards, namely “Collaborative Research Group” and “Scientists Studio”, based on the individual research group leader mechanism. These approaches draw on the experience from the synthetic bovine insulin framework and are designed to enhance teamwork to solve basic and even application problems that cannot be solved by a single team.

From its establishment to the present day, the Centre of Excellence in Molecular Cell Science of CAS has undergone a series of reforms and innovations over the past 70 years. All the adjustments and renewals are aimed at development. Despite these changes, the spirit of dedication to the search for truth and unity that characterized the early days of the Centre has remained unchanged. The scientific milestones achieved by the pioneers are now being carried forward by the new generation of scientists, who are striving to build on the achievements of their predecessors.

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