On July 5, 1996, a research team at the Rosslyn Institute in Edinburgh, England, used cloning technology to breed a small ewe named "Dolly". For a time, countries set off a tide of "animal cloning", and cloning technology has become a household name. But Dolly sheep is not the world's first cloned animal, as early as the early 1960s, Chinese scientists Tong Di Zhou cloned crucian carp. Unfortunately, however, very few people are aware of this scientific achievement.
From an early age, he was particularly curious
In May 1902, Tong Di zhou was born in Tong Village, Yin County, Zhejiang Province (now Yinzhou District, Ningbo City) to a poor xiucai family, a total of 8 children, he ranked 7th. A large family, relying only on a few acres of land run by my grandfather (who was still alive at the time) and my father's meager income from teaching in a private school in the countryside, lived a difficult life.
When he reached the age of school, the family could not provide for the child to attend the foreign school in the first week, so he could only follow his father to the private school to read and write. Tong Di Zhou likes to learn, memorizing ancient Chinese very hard, practicing writing is always serious, the elders in the family like him, and his father also wrote a small banner for him, which read 4 words: "Dripping water through the stone." These 4 words later became the motto of his lifelong struggle.
Young Children In Their First Week
When he was a child, Tong Di Zhou's curiosity was particularly strong, for example, he thought: How are fish born? With doubts, he used bamboo chips to cut open the belly of the fish, trying to see what was going on. He did not find the small fish in the belly of the fish, but found that there was a white air bag inside. After that, as soon as he had free time, he and his friends worked together to cut open the flower grouper, river crucian carp, etc. with bamboo pieces, and took out the air bags in the belly of the fish to play. The air sac in the belly of the fish should be particularly careful, because its epidermis is extremely thin and is connected with the liver, intestines and gallbladder, and it will puncture if it is not careful. At that time, Tong's best at the first week was to do this "operation" on the fish, so he was recommended by his friends as an autopsy hand. Now that I think about it, it was curiosity that led Tong Di Zhou to his career, and his childhood attempts cultivated a pair of dexterous hands.
When his father died, Tong was only 10 years old. Although his family was worse off, he still wanted the opportunity to further his education. At the age of 12, Tong Dizhou was arranged by the eldest brother of the head of the family to enter the Ningbo Normal Preparatory Class, which did not have to pay tuition and also managed food and accommodation. However, after just one semester of study, he proposed to take the "Practical Middle School". Xiaoshi Middle School is a first-class middle school in Ningbo, with a high reputation in the province, the school attaches great importance to the quality of teaching, and students can be guaranteed to go to university after graduation. However, Tong Di Zhou went to private school from an early age, did not learn mathematics or foreign languages, and the teaching in the effective middle school was all in English. The eldest brother asked him if he could do it? Tong Di Zhou confidently said: "I have a summer vacation time to prepare." And from the day I was ready to apply for The Practical Middle School, I began to teach myself English. ”
However, two days before the start of the school year, there was news that "Xiaoshi Middle School does not recruit new students during the year, and only recruits a small number of excellent third-grade transfer students." "Tong's first week immediately decided to try the transfer student." The result of the test was actually obtained! Tong Di Zhou became the first transfer student in the history of Xiaoshi Middle School to pass the third grade without attending middle school. However, the results were the first to last. In this regard, the students talked a lot. Tong didn't have time to pay attention to these discussions, except for class, he plunged into the library; when the lights in the classroom went out, he read under the street lamp. Finally, by the time of the final exams, his grades had changed from the first to last in the class at the beginning of the semester. Tong Di Zhou took one year to complete the three-year journey of ordinary students! Principal Chen Xiachang said with infinite emotion: "I have been the principal for many years, and I have never seen students who have improved so fast. ”
After graduating from high school, in July 1922, under the influence of his third brother who liked philosophy, Tong Dizhou was admitted to the Department of Philosophy of Fudan University to study psychology. He had hoped to become a philosopher, but he found that philosophy could not satisfy his curiosity about the mysteries of life. One day, Tong Di Zhou went to listen to the report of President Guo Renyuan of Fudan University. At that time, a kind of "animal instinct theory" was popular in the psychology community, advocating that cats and mice were cat instincts. Through experiments, Guo Renyuan rejected this theory, pointing out that cat-catching and mouse is not the "instinct" of cats born from the womb, but the result of learning. This vivid report aroused Tong's strong interest in biological science research, and he began to take biology.
He and she are both highly talented in the study of biology
In 1926, when he graduated from college, Tong Dizhou was forced to serve in the army; soon after, he found a position in Tonglu, Zhejiang, but soon left, knowing that he was not suitable for the official environment. Just as he was in a dilemma, Ye Yufen, a girlfriend he met in college, sent a letter. Ye Yufen encouraged him not to succumb to the old forces, not to give up his profession, to go to schools, to scientific research units... These words gave Tong Di Zhou strength and inspiration.
Tong Di Zhou thought of mr. Cai Bao, a university teacher. When he was about to graduate from Fudan University, Mr. Cai had the intention to keep him as a teaching assistant, but in the end he had no power in his hands and fell short. Now that he heard that Mr. Cai had become the head of the Biology Department of Nanjing Central University, Tong Di Zhou immediately sent a letter to the teacher. Two weeks later, the reply came. Tong Di zhou was invited to Nanjing to work as a teaching assistant for Professor Cai Bao at Central University. It was the spring of 1927.
Ye Yufen was born in March 1906 to a wealthy merchant family in Zhenhai County, Zhejiang Province (present-day Zhenhai District, Ningbo), and her grandfather made a fortune in business in his early years. By her father's generation, the family had more than 200 acres of land, and there were shops in Shanghai, and the family was wealthy. After the death of her father, although the family's situation was affected, the mother still arranged for her daughter to go to school, hoping that she would have a good future. Ye Yufen was clever and clever from an early age, and she studied hard, although the road to study was not smooth, but with the support of her aunt, she still finished the Ningbo County Girls' Normal School. In 1926, introduced by the middle school teacher, Tong Di Zhou met Ye Yufen, who was still studying teacher training.
Tong Dizhou and his wife Ye Yufen discuss the results of the experiment
After graduating from normal school, Ye Yufen decided to go to Nanjing to apply for Jiangsu University. Tong Dizhou urged her to apply for Fudan University, study natural sciences, and take the road of science to save the country. After weighing it up, Ye Yufen accepted Tong Dizhou's suggestion and was finally successfully admitted to the Biology Department of Fudan University. What Ye Yufen will never forget is that Tong Di Zhou, who worked as a teaching assistant at Chuo University, covered a considerable part of her university expenses, allowing her to study at the school with peace of mind.
Since the two met, due to similar interests, the feelings have gradually deepened. Although Tong Di zhou worked at Nanjing Central University and Ye Yufen studied at Fudan University in Shanghai, the distance between the two places did not block their connection, and through letters and meetings, their feelings not only did not become cold, but quickly warmed up. Finally, the wedding ceremony was held in his hometown of Ningbo in January 1930.
One day in 1930, Tong Di Zhou told Ye Yufen that he wanted to study in Belgium, where there was a Brasher-Dak laboratory, which was the center of biology research, and Tong Di Zhou thought that he could learn there. Although Ye Yufen is pregnant, she still supports her husband to study abroad. But it is not easy to realize this ideal, and the cost of traveling far and wide will cost a lot of money. Fortunately, the third brother funded some money, and Ye Yufen sold some jewelry from her marriage, barely enough to pay for the trip to Belgium.
Indeed, getting to know Ye Yufen was something that made Tong Feel Happy for the first week. In the decades since, the Tong and His wife have fought side by side and made significant progress in cytogenetic research. For example, it is said that every Time The Wenchang fish spawning season, the couple often spends dozens of days in the laboratory day and night, observing, recording, dissecting, experimenting, accumulating data, and exploring mysteries. Most of Tong's scientific research achievements are condensed with Ye Yufen's painstaking efforts...
Thin but with a pair of dexterous hands
It is said that before going to Belgium to study, Tong Did not know French. Before leaving, Ye Yufen gave him a French reader and said worriedly: "There is French speaking there." But you haven't learned it, what to do? Tong Di Zhou replied, "Learn! I started on the road! When he was at the window of the train, waving goodbye to his loved ones, he buried his head and began to learn French. When he arrived in Brussels, Belgium, he found a low-cost rental house and lived in a province, but he did not hesitate to pay high tuition fees to teach French. After months of hard work, he was soon able to speak in French.
Subsequently, Tong Di Zhou came to The University of Biting and met with the famous biologist Professor Brasher, hoping to study embryology under his guidance. Professor Brasher warmly welcomed Tong Tony to work in his laboratory (the Brasher-Dak Laboratory) and introduced him to his assistant Dak. Brasche's scholarship is characterized by a holistic, global, and large-scale perspective, studying the layout of individual development in the egg, rather than being confined to a particular organ or process. Maybe it's bad French, maybe it's the thin stature, and in the lab, Tong Is always alone in the corner, intently doing embryo dissection experiments alone.
At that time, most of the international students around Brasher came from top talents from various countries, and because Tong Di Zhou came from countries with backward development, he was not less discriminated against by others. These foreign students do not pay attention to this yellow-skinned Chinese classmate at all, and often ridicule him as a sick man in East Asia, believing that he is not worthy of further study in such a high-level laboratory. Although Tong Di Zhou's self-esteem was greatly hurt, this "external stimulation" strengthened his idea of trying his best to win glory for the motherland, and he worked hard to learn modern biological theories while carefully mastering advanced experimental techniques.
After Bradher fell seriously ill, Duck was promoted to professor and continued to work in Brasche-Duck's laboratory. In a classroom experiment, Professor Duck asked the frog's ovary membranes to be peeled off. Because the frog eggs are only the size of small grains of rice, smooth and round, and the eggs are breaded with three layers of soft membranes like proteins, if the egg membrane is not peeled off, many subsequent research work cannot be carried out. However, on the same day, many students' peel surgery failed, and only tong, who was usually silent, successfully completed the ovary membrane peeling.
Child week in the lab
To this end, Professor Duck arranged a observation experiment class and asked Tong to do a cell membrane peeling demonstration for his classmates in the first week. Tong Di Zhou happily agreed, and according to eyewitnesses recalled: "He came to a dissecting microscope on the test bench and sat down, operated a sharp steel tweezer, clamped a frog egg into a glass dish, and then used a tin needle to pierce a small hole in the egg cell that could not be seen with the naked eye, and the swollen egg cells immediately relaxed and became flat and round." At this time, two equally sharp steel tweezers simultaneously clamped the center of the cell, evenly tearing to both sides, and the egg membrane was stripped clean. The whole 'procedure' took less than 5 minutes. ”
Tong Di Zhou completed this perfect "operation" with dexterous and skillful movements, which stunned Professor Duck and his classmates. Later, Tong Di zhou recalled: "That incident made me believe that Chinese no more stupid than foreigners. We can still do things that foreigners think are difficult to do. ”
After this admirable thing happened, Tong Di Zhou continued to use this pair of dexterous hands to do a lot of difficult experiments and write a lot of excellent papers. In 1933, when Tong Di Zhou finally passed the graduation defense with a thesis on "positional fertilization" and obtained a doctorate in science from The University of Bikin, he was already a very well-known experimental embryologist in Europe.
In 1931, the "918" incident, which shocked China and foreign countries, occurred, and the Japanese invading army quickly occupied the three eastern provinces of our country. At this time, Tong Dizhou put down his work and organized the Chinese Student Union with international students. He drafted an open letter to Chinese students and participated in a student demonstration at the Japanese Embassy in Belgium, where he was arrested by the Belgian authorities. Later, after the struggle of progressives, Tong Di Zhou was released.
The motherland is suffering, and Tong Di Zhou cannot stand idly by! He expressed his wish to return to His country to Professor Duck. Because Tong's first week had not yet finished school, Duck did not agree. He did not disobey the teacher's kindness, and after a few more years of stay, he again made a request to return home. This time, the teacher understood his student and won him a fund to return to China. In 1934, Tong Dizhou left Brussels with superior living and scientific research conditions, and resolutely returned to China, where conditions were very difficult.
In the days of Li Zhuang
In the four years that Tong First Week studied in Belgium, Ye Yufen's life in China was very difficult. With the help of her teacher, Tsai, she found a job as a university teaching assistant. After Tong Dizhou returned to China, he took his wife Ye Yufen to work at Shandong University in Qingdao. During the War of Resistance Against Japanese Aggression, with the relocation and dissolution of Shandong University, Tong Dizhou's wife and children began a turbulent life of exile. Later, they found a position at Fudan University, and accompanied the teachers and students of the school on a arduous trek, and finally arrived in Lizhuang Town, Yibin, Sichuan in early 1941.
During the war, Li Zhuang's conditions were very poor, but what made Tong Di Zhou most anxious was that the school did not even have a microscope necessary for experiments, which brought great difficulties to embryology research. One day, Tong Di zhou came home from school, found a microscope in the town's thrift store, the boss opened his mouth for 60,000 yuan, and he couldn't afford to buy it. But with this microscope, embryology experiments can be carried out smoothly. Tong Di Zhou discussed with his wife that he would buy the microscope no matter what. They had to pawn some of the clothes they had brought with them, borrow some money from acquaintances, and finally buy back the microscope.
After the microscope arrived, Tong Washu prepared to do a big job. Fortunately, around Lizhuang, there are many rice fields and ponds, and flocks of frogs are active, which provides a lot of convenience for their embryo experiments. Every spring and autumn, Tong, together with his family and students, carries large pots and small pots to the wild with great interest to catch frogs and collect frog eggs. Many years later, villagers here still remember that a couple of professors at Fudan University often wore their trouser legs and barefoot to catch frogs and eggs in rice fields and ponds.
During those war-torn years, despite the poor conditions, Tong Di Zhou still gained a lot of fun. He experimented under this microscope and, like a watchmaker, successfully peeled off the outer membrane of the frog egg. In one experiment after another, Tong Di Zhou finally achieved the world's leading research results on biological embryos.
Such a situation attracted the attention of Joseph Needham, a good friend of Tong Di Zhou, a british modern biochemist, and then the science and technology counselor of the British Embassy in China. In 1943, Needham made a special trip to Lizhuang to visit Tong Di Zhou, and the two old friends who had been separated for more than ten years met again. After talking in the yard for a long time, Needham offered to visit Tong's lab. In that humble laboratory, there were no other auxiliary instruments except for the microscope, and the indoor lighting was dim, and the research conditions were unimaginably difficult to imagine...
Although Needham was mentally prepared, he was still a little surprised and asked, "Did you use such equipment to complete such a difficult experiment?" After receiving Tong Di Zhou's affirmative answer, Needham couldn't help but be awe-inspiring and couldn't help but say: "Chinese, have ambition." "For the sake of the cause, I'd rather suffer for the rest of my life!"
A new exploration of cloned fish begins
In 1951, Tong Dizhou was appointed vice president of Shandong University, in charge of scientific research, but as an academic leader in life sciences, the busy administrative work did not make Tong Dizhou forget his beloved profession, and he began a new exploration of cloning fish. The cloning of fish used to be called nuclear transplantation of fish.
At that time, Tong Di Zhou learned in the newspaper that foreign scientists had successfully used clone experiments on amphibians such as frogs and toads. So he immediately experimented with Chinese amphibians, and the results were successful. Beginning in 1961, Tong Di Zhou took a unique path and chose goldfish as experimental material, the embryonic cells of fish are relatively small and fragile, so it is more difficult technically. In addition to being more technically challenging, the more important reason is that fish have productive value and, if the experiment is successful, can benefit humans. There was no international precedent for fish cloning at the time, so he became the first person in the world to study fish cloning techniques.
Due to the domestic and foreign environment at that time, Tong Dizhou's experiments were carried out almost in isolation from the outside world, and all the resources related to research work were extremely scarce, and the first problem he faced was the lack of experimental equipment. However, this did not deter Tong Di Zhou, who repeatedly studied the limited data and led his students to design a simple and practical experimental device. Every day, students rush to the laboratory to see the figure of Tong Di Zhou, who sits in front of the microscope and becomes a "beautiful landscape" in the laboratory. This 60-year-old man, his hands under the microscope are still dexterous, on the tiny fish eggs, accurately and skillfully operating.
In this way, after a series of arduous experiments, they transferred the nuclei of male Asian carps to the nucleated egg cells of female Asian carps, and in 1963, in tong's laboratory, they finally succeeded in producing the world's first group of cloned fish. These clones are very healthy, they complete the full ontology period, swim in the water, and eventually produce offspring. In his paper, Tong Refers to these small fish as "nuclear transplant fish." This proves that the transplantation of nuclei can also be carried out in fish.
Then, in the first week, they further studied the cloning between different species of fish, this time choosing goldfish and crucian carp as experimental materials. It is to take the nucleus from the goldfish eggs and then put the nucleus of the crucian carp into it. With the help of microscopes and skilled cytology techniques, Tong Di Zhou completed a difficult "operation": first the nucleus of the goldfish egg cell was taken out and thrown away, and then the nucleus of the carp embryo cell was carefully taken out to keep it intact, and then the carp embryo nucleus was injected into the goldfish egg cell that had been removed from the nucleus, so that the embryonic nucleus of the carp developed in the goldfish's egg cytoplasm.
After day after day of careful cultivation, the recombined goldfish egg cells finally developed into lively little fish, they look very strange, the corners of the mouth have the whiskers of carp, and the number of their vertebrae and lateral scales are like goldfish, for this strange fish that has never appeared on the earth, it can neither be called a carp, nor can it be called a goldfish. It is a new species created by Tong Di Zhou with excellent biological knowledge and superb transplantation skills, so scientists affectionately call it "tong fish".
Then, in cooperation with Yan Shaoyi and others, tong dizhou published a paper entitled "Nuclear Transplantation of Fish Cells" in the July 1963 issue of The Scientific Bulletin, which first reported the nuclear transplantation of fish at home and abroad.
Life has been changeable since ancient times
After the first fish research paper was published in 1963, the "Four Qing Movement" began, followed by various "movements". At first, Tong Di Zhou also wanted to direct researchers to continue their research in addition to "making a revolution". But things did not turn out as he had hoped, when the Institute of Zoology was the most active unit in the Chinese Academy of Sciences, and more than 40 people were named in the first "revolution", making the research work impossible. Not long after, a large poster was also posted on the door of Tong Di Zhou's office, and the "rebels" slandered Tong Di Zhou as a "bourgeois reactionary academic authority."
Since then, Tong Di zhou has been deprived of the right to engage in scientific research and personal freedom, and has to sweep the toilet every day under the supervision of the "revolutionary masses". For this nearly 70-year-old man, it cannot but be said that it is a cruel torture. However, Tong's first week of cleaning the toilet is also very serious, just like he is doing experiments. At the same time, he himself stipulates that every day to sweep the toilet must be completed before going to work at 8 o'clock in the morning, perhaps in his heart, after 8 o'clock should be the time to engage in scientific research, sacred and not to be desecrated; perhaps he regards the toilet sweep as a ritual before scientific research, looking forward to the new day to start cloning research, but this sweep is 5 years.
At that time, the love life of Tong Di Zhou and his wife once again underwent an unprecedented test. Someone forced Ye Yufen to expose and report Tong's first week, and Ye Yufen said coldly and categorically: "I have lived with him for decades, I know him, he is not the kind of person you say!" The other party scolded her sharply: "When is it, you still want to protect the child for the first week?" Ye Yufen calmly replied, "Say that you can protect him, I understand him, only then do I want to protect him!" ”
By 1970, with a willingness to combine research with production, Tong Washu was allowed to resume work. He sent Yan Shaoyi and Du Miao to investigate all parts of the country, and finally selected the Wuhan Institute of Aquatic Sciences of the Chinese Academy of Sciences, the Yangtze River Fisheries Research Institute of the Chinese Academy of Fisheries Sciences and the Fisheries Research Institute of Nanning Autonomous Region of Guangxi Province to form a collaborative group.
After Nixon's visit to China in 1972, the door to Sino-US exchanges was opened. In May 1973, the relevant authorities approved the joint research between The Chinese scientists Niu Manjiang and Tong Dizhou, which was called "a trump card played by Chinese leaders to promote Sino-US academic exchanges after ping-pong diplomacy." For Tong Di Zhou, he can "justifiably" carry out "cloning" research. He and Niu Manjiang put the RNA of the carp into the goldfish and found significant goldfish tail fin mutation. The October 5 People's Daily reported on the results, saying that "for the first time, animal experiments have demonstrated that the information ribonucleic acid in the cytoplasm has a significant effect on cell differentiation, ontogenesis and trait inheritance."
From May to August 1975, Niu Manjiang cooperated with Tong Dizhou and others for the second time to conduct short-term research on cells and genetics. They experimented with two different animals, salamanders (amphibians) and goldfish, injecting RNA into the fertilized eggs of goldfish with salamander cytoplasm, and found that 4 of the 382 small fish grew like small salamanders. This specific cloned fish is also praised as a "child fish". The emergence of this new "child fish" indicates that human beings will be able to breed a variety of animals that embody the advantages of their parents, and can control their own physiological aging process, and even set off a green revolution in the entire biological world.
Cloned fish are little known for their lifetime
In her old age, Ye Yufen already needed hearing aids to communicate with people, but when she worked with her husband Tong Tian Zhou, she did not need the help of hearing aids because they were so tacit. Tong Di Zhou praised his wife in this way - her work is very prominent, careful observation, statistics are also very careful, and strive for accuracy. This seems to be the highest praise that Tong Di Zhou gives to his wife. Together, they have gone through more than 40 years of ups and downs, and sixty percent of Tong's scientific research achievements in the first life were completed by the couple, and people once praised them as China's "Curie couple".
In January 1976, Ye Yufen died suddenly due to misdiagnosis of angina pectoris. In terms of seniority, she should have been rated as a professor, but until her death, her title was still associate professor. In fact, she had at least 3 opportunities to be promoted to professor, but she missed them all. Because Tong Di Zhou has always been her "top boss", whenever the personnel department reported the materials of Ye Yufen's promotion title, Tong Di Zhou always left the quota to others. After Ye Yufen's death, children often sat in a chair and fell into painful contemplation, and he once said to the children with tears: "I am sorry for her,...... She has done a great job in her life, because I have not been able to become a professor!"
After 1976, he was able to enter the laboratory again for research, but since then, the couple has only been left with the 74-year-old Tong Di Zhou. After that, before each experiment, Tong Tian Zhou had to carefully clean the utensils used by Ye Yufen in the laboratory, as if waiting for his wife to return and do the experiment together. In 1978, at the National Science Congress, Tong Dizhou was awarded the title of National Advanced Worker in Science and Technology. This time, he was unable to share it with his wife, who was struggling together.
On March 6, 1979, Tong Dizhou, as vice president of the Chinese Academy of Sciences, was invited to participate in the Zhejiang Science Conference. In his speech, he described a brilliant vision that fascinated everyone: to use biotechnology to improve human life. Just as the audience was listening intently to the lecture, Tong Di Zhou suddenly had a heart attack and fainted on the podium. People panicked and helped him down to rest, and after Tong Di Zhou eased up, he insisted on going to the podium to continue his speech. After the meeting, he returned to Beijing and was admitted to the hospital for treatment, and more than 20 days later, he died on March 30 at the age of 77. Tong Di Zhou completed his bumpy life and took away his dexterous hands.
The cloned fish first occurred in 1963, 34 years before the dolly sheep. Unfortunately, because the experimental results at that time were only published in Chinese, not even the English abstract, and the author of the alleged paper could not be named; in addition, the Lack of communication between Chinese scientists and other scientists in the world, the great scientific significance of this fish cloning research was not paid attention to and recognized by the international scientific community in time. So Dolly The Sheep became famous overnight, but the cloned fish was little known for its lifetime.
In 2002, in order to commemorate the 100th anniversary of Tong's first birth, Lu Yongxiang, president of the Chinese Academy of Sciences, wrote the four words "cloning pioneer" as an evaluation of Tong's first birthday.
Wu Zuoren's "Water Lily Goldfish Diagram"
In the 1970s, the famous painter Wu Zuoren created a "Water Lily Goldfish Picture", which depicted several small goldfish playing, but the body of the goldfish grew the tail of a crucian carp. The birth of this fish is a great empirical demonstration of biogenetics, vividly recording the miracle of life science created by Tong Di Zhou. Zhao Puchu once asked: On the painting, "Why does the xenomorph come from the beginning and the end?" Wu Zuoren laughed and replied: It is a "child fish." Therefore, this "Water Lily Goldfish Diagram" has become a precious artistic commemoration of Tong's great scientific achievements.
Source: Magazine of All Walks of Life, Issue 12, 2020
Author: Qiu Weiting