Fourth in the world! He led the team to conquer chlortetracycline and broke the US monopoly

In January 1956, the CPC Central Committee decided to hold a meeting of intellectuals. Inspired by this, Xu Changlin, a director at the Shanghai Film Studio, wanted to make a film about the friendship among intellectuals.

While collecting materials, he heard about the stories of the two scientists and was very interested. He went to the laboratory to experience their work and life. Finally, he wrote the script "Long Love and Deep Friendship" based on their stories and filmed it into a documentary. This also became the first film in New China with scientists as the protagonists.

The scene of two scientists working together on antibiotics is vividly portrayed on the screen. This scientist is one of the prototypes of the protagonist of the movie, a key figure in the development of chlortetracycline in my country, and an academician of the Chinese Academy of Sciences, Shen Shanjiong.

Academician Shen Shanjiong

Going to Science

Shen Shanjiong was born in a farmer's family in Wujiang, Jiangsu Province in 1917. Although his family was poor, his parents tried their best to give their children a good education.

Young Shen Shanjiong in 1928

In 1937, the Marco Polo Bridge Incident broke out and the country entered the stage of all-out war of resistance. It was also in this year that Shen Shanjiong was admitted to Nanjing Jinling University.

But soon after, Songhu fell and Nanjing was in danger. In mid-July 1939, Shen Shanjiong turned to Southwest Associated University. The "fortitude and perseverance" of the Associated University, who lived and died together with the country and worked hard to study and teach in order to wash away the national humiliation and revitalize China, had a profound impact on Shen Shanjiong's future study and work.

After graduation, Shen Shanjiong was assigned to the Plant Pathology Group of the Institute of Agriculture of Tsinghua University as a research assistant, working with Professor Dai Fanglan. Under the guidance of Professor Dai, he began to study the morphology and life history of ancient bottle fungi.

In 1944, a group photo with Professor Dai Fanglan and others at the Plant Physiology Group of the Institute of Agriculture of Tsinghua University (front row: Yin Xinyun and his wife, Mrs. Dai Fanglan, Mrs. Qiu Weifan; back row: Yu Dafu, Shen Shanjiong)

Later, with the recommendation of Professor Zhang Jingyue, Shen Shanjiong entered California Institute of Technology. California Institute of Technology is one of the most difficult schools to apply for in the United States. A large number of scientists such as Qian Xuesen, Zheng Zhemin, Zhuang Fenggan, and Xie Jialin graduated from here.

Before leaving, Professor Zhang Jingyue invited Shen Shanjiong to his home for dinner and solemnly said to him: "I am waiting for you and hope you will come back after completing your studies."

Homecoming Adventure

In 1950, Shen Shanjiong completed his doctoral thesis "Genetics and Biochemistry of the Relationship between Tyrosine and Cysteine ​​in Neurospora crassa". At that time, he planned to work in the United States for two years. However, with the outbreak of the Korean War, the return of Chinese students and professors in the United States was blocked, so Shen Shanjiong immediately booked a ship ticket back to China on August 31.

On September 12, Shen Shanjiong, Zhao Zhongyao, Luo Shijun and others arrived at Yokohama Port, Japan, on the President Wilson. At around 7:00, the broadcast suddenly sounded, saying that the beds in the third-class cabin would be adjusted, and Zhao Zhongyao, Luo Shijun, Bao Wenkui and Shen Shanjiong were required to take their luggage to the designated rooms. In this way, they were hurriedly taken to a guest room in the first-class cabin.

There were already guards there, and an American in military uniform claimed to be an officer of the Central Intelligence Agency (CIA) in Yokohama. They cross-examined Shen Shanjiong and others, forced them to go to the toilet and take off their clothes for a careful inspection, and opened everyone's luggage, detaining everything they thought was important, such as experimental records, some printed copies, some strains and reagents.

Soon, Shen Shanjiong and others were escorted to the Sugamo Prison in Shimokawa, Tokyo. When he arrived at the prison and saw the room full of Japanese soldiers, Shen Shanjiong's mind immediately flashed back to the scene of his uncle being killed by the Japanese invaders during the Anti-Japanese War, and his hometown being burned and looted by the Japanese invaders. He himself was also forced to migrate and had no home. The national disaster and family feud had not been avenged, and today he fell into the hands of the enemy again. He felt great shame and resentment.

In November 1950, after being released from prison in Tokyo, they took a photo in the courtyard of the KMT delegation's residence in Azabu District, Tokyo (from left to right: Shen Shanjiong, Luo Shijun, Zhao Zhongyao)

Despite this misfortune, they never gave up the struggle. On October 31, an officer was ordered to announce the results of the investigation and they were released. On the afternoon of November 27, the President Wilson arrived in Hong Kong. The next morning, Shen Shanjiong and others took a train via Kowloon to Shenzhen. When he passed the Luohu Bridge, he was very excited - after going through hardships, he finally returned to the embrace of the motherland! At this time, he had already prepared himself mentally. As the train continued to travel on the land of China, Shen Shanjiong looked forward to his future.

In November 1950, a photo was taken on the way to Hong Kong on the President Wilson (the first on the left is Shen Shanjiong, and the others are returning overseas students)

Breaking the Monopoly

From November 20 to 24, 1952, the Chinese Academy of Sciences, the Ministry of Light Industry and the Ministry of Health jointly held a symposium on antibiotics. Among them, "vigorously expanding penicillin production" was listed as the top priority, and the production and research of chloramphenicol, streptomycin and chlortetracycline were also listed.

As the leader of the newly established Microbial Physiology Group of the Institute of Plant Physiology, Shen Shanjiong was involved in the work of chloramphenicol and streptomycin, and was responsible for researching the production of chloramphenicol and streptomycin, including the selection and fermentation of strains.

Chlortetracycline, also known as chlortetracycline, is a broad-spectrum antibacterial substance produced by fermentation of Streptomyces aureus. It is also the first broad-spectrum antibacterial drug in human history.

Because it can effectively treat 90% of bacterial infections, chlortetracycline has received considerable attention since its discovery. Its production is also regarded as high-tech. At that time, only the United States, the United Kingdom and Italy could produce it. Moreover, the production of chlortetracycline is almost completely monopolized by the American Reiter Pharmaceuticals. Even if other countries authorize the construction of factories, they must be jointly invested by the factory, the strains are exclusive, and the technology is kept confidential. The international market price is completely controlled by other countries.

There are few records about the production method of chlortetracycline in the literature of various countries. The most valuable document that can be found is the original report on the discovery of chlortetracycline. As for the method of industrial production of chlortetracycline, there are even fewer. Even the Soviet Union lacks information on the production and research of this antibiotic.

"Knowing there are tigers in the mountain, one still goes there." While Shen Shanjiong studied the few relevant papers published internationally, he went to the factory to consult experienced technicians and workers and learn from them basic operations such as fermentation, extraction and identification.

Shen Shanjiong put all his heart and soul into his work. He did not rest on Sundays. He arrived at the laboratory before 8 o'clock every day and worked until 9 o'clock in the evening. Inspired by him, other members of the research group also worked overtime every day.

In this way, after more than two years of hard work, Shen Shanjiong and his team achieved significant results and solved the key problem of chlortetracycline production. In 1954, the chlortetracycline expansion production trial undertaken by the Shanghai Industrial Experiment Institute and Shanghai Third Pharmaceutical Factory was launched.

In 1957, chlortetracycline was officially put into production at the Shanghai Third Pharmaceutical Factory. my country became the fourth country in the world to be able to produce chlortetracycline. In the year of production, the fermentation unit and product quality of chlortetracycline were close to the world's advanced level.

From May 31 to June 7, 1957, the Second All-Soviet Antibiotic Conference was held in Moscow. Shen Shanjiong gave a report entitled "The Effect of Phosphate on the Sugar Metabolism Pathway of Chlortetracycline and Its Relationship with Chlortetracycline Synthesis", which was well received by the participants. In the research of chlortetracycline, China was undoubtedly at the forefront of the participating countries.

A group photo of the International Antibiotic Conference held in Moscow, Soviet Union in 1957 (from left: Zhang Weishen, Shen Shanjiong, Chen Xiaoqing)

A new journey

Since the 1950s, genetics has developed very rapidly in Western countries. In 1973, Shen Shanjiong was ordered to set up a new research group to open up a new direction and engage in the research of biological nitrogen fixation.

Although they had some basic knowledge, they were basically laymen at that time. Shen Shanjiong began to spend all day in the library, and after about a year of make-up classes, he officially started his research on the genetics of biological nitrogen fixation in 1974.

Shen Shanjiong and his team selected Klebsiella pneumoniae as research material and achieved some valuable results in just three years. In December 1977, the paper "Genetic Analysis of the Nitrogen Fixation System of Klebsiella pneumoniae" was published. The international community quickly responded to this work, and many papers cited it.

In 1978, the Institute of Plant Physiology adjusted the setting of research laboratories (groups), and the Molecular Genetics Laboratory was established, with Shen Shanjiong serving as the director of the laboratory.

In 1979, all the staff of the Molecular Genetics Laboratory took a group photo (Shen Shanjiong is the eighth from the right)

At the end of 1980, Shen Shanjiong was elected as a member of the Chinese Academy of Sciences, and later elected as a standing member of the Biology Department. As a major leader in molecular genetics in China, his work was supported by the Biology Department. Shen Shanjiong lived up to expectations, and the nitrogen fixation gene expression and genetic manipulation research group he personally led made particularly rapid progress. At the 1982 Sino-US Academy of Sciences bilateral meeting on biological nitrogen fixation, it was considered to be close to the world level.

Shen Shanjiong also studied the structure and regulation of the promoter of the nif gene and reported this work at the 6th International Conference on Nitrogen Fixation in 1985, which was highly praised. The laboratory led by Shen Shanjiong is considered one of the international centers for biological nitrogen fixation research.

In the mid-1990s, the research scope of the molecular genetics research group was further developed, and the research topic was expanded to include genomic research on host plant clover and symbiotic nitrogen fixation. At this time, Shen Shanjiong was getting old, but he still insisted on going to the office to discuss with everyone.

In 1997, Shen Shanjiong entered his 80s. Although his mind was still very clear, his eyesight, hearing and energy had obviously declined. So he wrote some memoirs, leaving behind his experiences and lessons for everyone's reference as his final contribution to the motherland and the people.

Shen Shanjiong checking the experimental results in the laboratory in 1999

When he was nearly 90 years old, Shen Shanjiong would occasionally visit the laboratory. Seeing young people growing up around him and observing new phenomena, whether confirming or denying the research results of his predecessors, he was as happy as a traveler who found a source of water in the vast desert.

Photo taken on his 90th birthday in 2007 (Shen Shanjiong is the third from the left)

On March 26, 2021, Shen Shanjiong passed away in Shanghai at the age of 103. Before his death, a reporter interviewed him and asked him if he had any regrets in his life because his teachers and classmates who studied in the United States all won the Nobel Prize, but he chose to return to China despite his excellent academic performance. Shen Shanjiong said: "I have always been competitive, and I was no less outstanding than other students when I was studying there." "However, in terms of contributions to China, these cannot be compared with returning to my own country to establish laboratories, train students, and make science blossom and bear fruit in my own country."

References:

[1] Xiong Weimin. Chlortetracycline, Cowshed, Biological Nitrogen Fixation: A Biography of Shen Shanjiong [M]. Academic Growth Data Collection Project for Senior Scientists.

[2] Jiang Shiliang. Sincere words and deep patriotism: An interview with our respected Professor Shen Shanjiong [OL]. World Science, 1996.03.03

[3] Shanghai Institute of Plant Physiology. Microbial biochemistry and molecular geneticist Shen Shanjiong [J]. Science and Technology Association Forum, 1998, 13 (12): 22.