In 1965, Chinese scientists successfully synthesized bovine insulin under the extremely difficult scientific research conditions in China at that time, which was the first synthetic protein in human history, and this synthetic bovine insulin and natural bovine insulin have the same biological activity, which can replace natural bovine insulin and control the blood sugar metabolism of diabetic patients. The research results have promoted the study of the principle of action of insulin and the structure of insulin proteins, indicating that China's research work in polypeptide and protein synthesis has entered the world's advanced ranks.
DNA is the genetic material of life, and protein is the main bearer of life activities, directly affecting the physiological functions of the human body. Proteins are so important that in the early twentieth century, academics once thought that proteins were the genetic material of living things. Famous biologists such as Arthur Kornberg and Frederick Sanger have won Nobel Prizes for their work on proteins.
When Tiselius, head of the chemistry team of the Nobel Prize Jury, visited China the following year, he spoke highly of the innovation of synthetic bovine insulin: "People can know how to build atomic bombs from textbooks, but it is never possible to learn synthetic insulin from textbooks. ”
The famous biologist Zou Chenglu is one of the heroes involved in the synthesis of bovine insulin, and before participating in the project, he has done a lot of groundbreaking work of great significance in the field of biochemistry.
Zou Chenglu
Source: Beijing News
Three academicians in one discipline
On May 17, 1923, Zou Chenglu was born in Qingdao, Shandong Province, to a family of senior railway staff. Compared to most of his peers in that barren war-torn era, he was undoubtedly lucky: he had no worries about food and clothing, his parents valued education, and his brother graduated from Tsinghua University's Department of Architecture.
In 1941, Zou Chenglu graduated from the high school of Nankai Middle School. At this time, the three famous schools of Tsinghua University, Peking University, and Nankai University had been moved to Kunming, Yunnan Province, to escape the war and merged into Southwest United University, and It was in this year that Zou Chenglu was admitted to the Chemistry Department of Southwest Union University. During his studies at Southwest Union University, he developed a strong interest in life sciences, believing that it is very meaningful to study life sciences from the perspective of chemistry, and this stage of study laid the initial foundation for his future biochemical research work.
In the following year after graduating from university, Zou Chenglu ranked first in the examination for recruiting Chinese Yinggengzi to study abroad at public expense, and was admitted to cambridge university under the supervision of professor David Keilin, a famous biochemist, engaged in respiratory chain reductase research.
(Zou Chenglu who went to the UK by boat to study Picture source: Beijing News)
When he first entered the school, his mentor Keeling did not assign him a course, but gave him three months to learn the basics of physical chemistry, and immediately after the expiration of the period, he began to study. Keeling comes to the lab on time every day to guide students, and regularly reviews students' work reports, encouraging students to think creatively and conduct independent research.
(Zou Chenglu's mentor, Professor David Keeling Source: Centenary biographical note)
Shortly after the end of World War II, Britain was starved of supplies, and Killeen's laboratory was no exception. During Zou Chenglu's doctoral studies under him, there were no cold rooms and fume hoods in the laboratory, and some experiments that required low temperature and ventilation could only be carried out on the roof in winter. But the humble environment did not affect his laboratory every year with high-level papers published, becoming one of the most famous laboratories in the world. Advanced instruments can be bought with money, but advanced innovative academic ideas cannot be bought with money.
In 1949, Zou Chenglu independently signed his first paper in the British journal Nature, and since then, he has published several high-quality papers. His academic achievements at the University of Cambridge include: the earliest international study of the relationship between protein structure and function using proteolytic enzyme partial hydrolysis; the discovery of changes in the properties of cytochrome C when it binds to mitochondria after purification; and the proof that cytochrome b is not the same substance as Succinate dehydrogenase (SDH).
(Zou Chenglu's first paper published in nature magazine Source: Nature official website)
During his studies at Cambridge University, Zou Chenglu fell in love with Li Lin, a Chinese student majoring in physics at the same school, and became married. Li Lin's father was Li Siguang, a famous geologist in China. After the founding of New China, these three outstanding scientists successively returned to China to serve the motherland, and later they were all rated as academicians of the Chinese Academy of Sciences, becoming the only "academician home" in China with three academicians.
(Li Siguang and his wife and daughter Li Lin, son-in-law Zou Chenglu Source: Sohu)
Return results
After returning to China in 1951, Zou Chenglu cooperated with biochemists Wang Yingxi and Wang Jingying to purify succinate dehydrogenase, and found that its auxiliary group was FAD covalently bound to the protein part, which was the first FAD auxiliary group to be found to covalently bind to protein. In addition, they have also studied the respiratory chain and other enzyme systems, which has laid a good foundation for the study of respiratory chain and enzymology in China.
In 1958, Zou Chenglu and a number of outstanding scientists initiated the work of artificial synthesis of bovine insulin, in which Zou Chenglu was responsible for the disassembly of insulin A and B chains. His work defined the route of total insulin synthesis and made an important contribution to the synthesis of insulin.
(The personnel of the synthetic bovine insulin research group at the beginning of the establishment, the 5th from the left in the middle row is Zou Chenglu Source: Museum of History of the Chinese Academy of Sciences)
After several years of efforts by scientists, synthetic bovine insulin was finally declared successful in 1965. Since then, Zou Chenglu's research has returned to the field of enzymatic research that he is best at. Enzyme activity inhibition is very important in the study of enzyme mechanism of action and drug design, and the enzymology works of the time generally only discuss the reversible inhibition kinetics of enzymes. In 1965, Zou Chenglu first systematically proposed the kinetic theory of the unity of reversible and irreversible inhibition of enzymology, and proposed a method for determining the rate constant of irreversible inhibition reaction. After years of theoretical development and experimental verification by him and Wang Zhixin, his theories and methods have now been widely accepted and widely adopted internationally. This work later won the second prize of the National Natural Science Award.
In addition, the chemical modification of protein side chain groups and the comparison of loss of activity are the main methods to study the functional relationship of protein structure. Zou Chenglu established the quantitative relationship formula between the chemical modification and activity loss of the essential group of the protein, as well as the mapping method for determining the number of the necessary groups, which is widely accepted and adopted internationally, and has been included in professional works, and its formula and method are called "Zou's formula" and "Zou's drawing method" respectively.
Because of his academic achievements, Zou Chenglu was recommended for the Nobel Prize in 1978 together with four other candidates. Many years later, in 2003, Zou Chenglu recalled the incident: "If a person always wants to win the Nobel Prize when doing scientific research work, I think he will never get it." Of course, you can't say you don't want to, but you can't put it first, science is the first, winning awards is the second, I think it's too much hype now. ”
In 1979, Zou Chenglu discovered that glyceraldehyde-3-phosphate dehydrogenase can form fluorescent derivatives at the active site, and the related paper was published in nature magazine, which was the first paper published by Chinese scientists in Nature after the "Cultural Revolution". This achievement won the first prize of the Science and Technology Progress Award of the Chinese Academy of Sciences.
(Zou Chenglu published a related paper in the journal Nature.)
Source: Nature's official website)
In the following ten years, Zou Chenglu's team used self-created kinetic methods to compare the relationship between conformation and activity changes of various different types of enzymes in the process of denaturation, and obtained the results of loss of activity before conformational changes, according to which the hypothesis of flexibility of enzyme active sites was proposed, and the correctness of the theory of flexibility of enzyme active sites was fully demonstrated. This is another major advance in the study of the mechanism of enzymatic action since Hermann Fischer proposed the key-lock theory of enzymatic action in the 19th century and Daniel Koshland's inductive fit theory in the 1950s, and also pushed the study of protein denaturation from a simple structural study to a new level of close binding with function. The work was published in the journal Science in 1993.
(Zou Chenglu published a related paper in the journal Science.)
Source: Science official website)
Denounc corruption
In his life as a person, Zou Chenglu was rigorous in his teachings and outspoken in righteousness, and he deeply resented all kinds of academic fraud and academic corruption, especially hated the behavior of tutors and leaders in signing papers. "Signing papers that you have not contributed to, especially using your authority to forcibly sign papers that you have not contributed, is a typical unethical act."
Zou Chenglu's insistence on the signature of the paper stems from the academic influence he received when he was studying for his doctorate. When he first submitted his article to Nature magazine, he signed the paper with the name of his mentor Keeling as a "convention", but Keeling deleted it. Killeen believes that he has not made outstanding contributions to the paper, but whether he is signed or not, he personally reviews and carefully revises each of his students' papers before agreeing to the student submission. Therefore, when Zou Chenglu became a graduate supervisor, he also objected to his students signing his name on the paper.
He said: "To solve this problem, we must first change our perceptions. Engaging in scientific research and publishing scientific research results is an honor and a responsibility. All authors of the paper must be responsible for the content, and the main author must first obtain the consent of all authors to indicate their agreement with the results of the paper and academic opinions. This is basic academic ethics, but also a rigorous scientific spirit. ”
(Work photos of Academician Zou Chenglu in his later years Source: Chinese Academy of Sciences website)
In 1981, Zou Chenglu and other academicians, who had just been elected as academicians of the Chinese Academy of Sciences, noticed the problem of academic corruption at that time, so he joined forces with Zhang Zhiyi, Hong Chaosheng, Guo Musun and several other academicians to jointly publish "Discussion on Carrying Out "Spiritual Civilization in Scientific Research Work" to oppose academic corruption. Over the next 20 years, he published articles against academic corruption and for the first time raised the issue of "scientific ethics" in the scientific community. "Scientific research must not be a little false, but some people are deceitful in pursuit of fame and fortune." It is even more intolerable that a few people even use unscrupulous means to plagiarize the results of others. ”
Because of the fight against academic corruption, Zou Chenglu also caused a lot of trouble, he once laughed at himself: "Some people I have offended, they can't do anything with me, they will sprinkle anger on my students, students are still young, they want to apply for funds and research funds, these have to be reviewed by them, at this time students often complain to me, saying that you say less, be polite, otherwise they will scatter their anger on our heads." ”
Even so, Zou Chenglu still wrote straight, and the students understood him. At the 2003 annual meeting of the China Association for Science and Technology, Zou Chenglu summed up the seven deadly sins of Chinese scientists who violate academic ethics: falsifying academic qualifications and work experience; forging or tampering with original experimental data; plagiarizing and plagiarizing the results of others; belittling the achievements of predecessors and self-exaggerating propaganda; throwing two or even multiple votes in one draft; signing papers that he has not contributed; and making unrealistic publicity for commercial advertisements.
In November 2006, Zou Chenglu completed his last article, "Academic Corruption Must Be Seriously Dealt with." 20 days after writing this article, 83-year-old Zou Chenglu passed away in his sleep. This brilliant biochemist and truth fighter in the scientific community has completed a life of hard work and a clear conscience. Just as his wife, Li Lin, asked to bury his ashes under a tree in his work unit after his death, before his death, he also asked that half of his ashes be buried in the Biochemistry Institute, half buried in the Biophysical Institute, and buried in the place where he had worked and fought.
Resources
Xiong Weimin, Zou Zongping. Zou Chenglu biography[M]. Beijing: Science Press.] 2008.
Shi Xisheng. Zou Chenglu and two academic corruption incidents 30 years ago[N]. Southern Weekend, 2006-08-24.
[3] C L Tsou，Cytochrome c Modified By Digestion with Pepsin，Nature，1949，164 ：1134.
[4] Y S Ho，C L Tsou，Formation of a New Fluorophore on Irradiation of Carboxymethylated D glyceraldehyde 3 phosphate Dehydrogenase，Nature,1979， 277：245～246.
[5] C L Tsou，Conformational Flexibility of Enzyme Active Sites，Science,1993 ，262：380～381.
Jin Zhenrong, Feng Yongfeng. Zou Chenglu: A sincere and transparent scientific life[N]. Guangming Daily, 2006-11-24.
ZHAO Ling. Zou Chenglu, a giant in China's biochemical circles: A man who tells the truth is gone[N]. Southern Weekend, 2006-11-30.
Jin Yu. Zou Chenglu: A lifelong real person[N]. The Beijing News, 2006-12-4.
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【Statement】 Life science and gene technology are developing rapidly, and for the same research topic, the research results of different teams may be different or even contradictory. In addition, due to the limitations of my knowledge structure and the accuracy of the reference materials, the content of the article is for reference only. Readers are welcome to correct errors and participate in the discussion at any time.