In the office of Chen Dayuan, a researcher at the Institute of Zoology of the Chinese Academy of Sciences, there are photos of cows that he has successfully cloned, books and awards on cloning are displayed in the bookcase, and a big old refrigerator makes a sound from time to time. The conversation between Chen Dayuan and the reporter began with the introduction of Dolly the sheep.
In the past 10 years, although there has been no end to the moral and ethical disputes triggered by cloning, no one denies that cloning is getting closer and closer to the general public because of its wide application in fields such as agriculture and medicine.
Somatic cell cloning is a fruitful endeavor
"Before Dolly the sheep, all that was done was embryonic cell cloning. My mentor, Mr. Tong Dizhou, did embryo cloning, but it was called nuclear transplantation in China at that time. At that time, China used embryos to clone many kinds of animals such as rats, cows, sheep and pigs, and cloning was in its heyday in China at that time." Chen Dayuan recalled that Dolly the sheep was cloned from somatic cells, which are not the same as embryonic cells and are highly differentiated cells, making it difficult to return to the traits that existed during the embryonic cell period. Therefore, the appearance of Dolly the sheep shows that highly differentiated cells can return to the state of embryonic cells, a very sensational achievement in biology.
"After 10 years, the changes are there. But I personally don't think there is much improvement." Chen Dayuan told reporters this way, for a biotechnology, 10 years is actually a relatively short period of time, some major topics often need 20 to 30 years. He believes that over the past 10 years, more work has still been done to explore cloning in different species of animals.
Chen Dayuan counted most of the species that have been successfully cloned in the past 10 years for the reporter. 1998, the British PPL Medical announced the cloning of a calf; Japanese scientists announced the birth of two calves cloned from the body cells of an adult animal; scientists at the University of Hawaii, USA, have successfully bred the third generation of adult rats with the body cells of more than 50 cloned rats, which is the first time that mankind has used a cloned animal to cloning of cloned animals.
In 1999, scientists at the University of Hawaii used adult body cells to clone the first male rat; then a research team headed by Chinese-American scientist and University of Connecticut professor Xiangzhong Yang cloned a calf using cells taken from the ear of a 13-year-old cow.
In 2000, Xiangzhong Yang's research team successfully cloned six calves using cells from a bull's ear skin after a long period of in vitro cultivation; U.S. scientists announced the success of a cloned monkey, a rhesus monkey named Tetra; and Britain's PPL Medical announced that it had successfully bred five cloned pigs.
In 2002, the U.S. successfully cloned a cat; in 2003, the U.S. successfully cloned a mule, France cloned a rat, and South Korea cloned a dog; in 2004, the U.S. cloned a horse.
China's somatic cell cloning research from 1999 began to keep up, the year Yangzhou University transgenic cloning goat success; 2000, Northwest Agricultural and Forestry University cloning goat success; 2002, China's cloning of the cow has also succeeded; since then, 2003~2004, Chinese scientists have been cloning cows and goats; in 2006, the China Agricultural University and the Northeast Agricultural University cloning pigs have been were successful.
The success of somatic cell cloning of several species is seen by Li Ning, a professor at China Agricultural University, as one of the major achievements of cloning technology in the past 10 years. In an interview with Science Times, Li Ning said the cloning of most domestic animals and some pets, including mice, goats, cows, dogs, sika deer, pigs, cats and horses, has been successful. Meanwhile, somatic cell cloning technology has also saved some endangered and even extinct species, such as the New Zealand short-horned cattle, an extinct animal, which was successfully cloned by scientists using cloning technology. Similar endangered species include the Java cow and the wild Italian disk sheep.
Chen Dayuan had spent five years exploring the cloning of giant pandas, yet the experiment went to the final step when the panda's blastocyst died in the womb of a black bear. "In the end, the giant panda was not born, which is really very unfortunate." Chen Dayuan said without regret.
Li Ning believes that what is more historically significant is that cloning has allowed species that cannot reproduce to do so, such as mules, which can reproduce asexually using cloning. "The fact that both domesticated and wild animals can be cloned proves that cloning is universally relevant to the propagation of species."
"Cloning" is not the same as "short-lived"
Li Ning, who has successfully cloned cows and pigs in China, believes that the biggest progress in cloning technology in the past 10 years is that cloning efficiency has increased from less than 1 percent in the past to an average of 5 percent which is a five- to six-fold increase, or better yet, a 10 percent success rate.
The fact that Dolly the sheep was the only individual out of 277 cells to be successfully cloned suggests that cloning was inefficient. At the time, cloning technology faced low conception rates, high abortion rates and high mortality rates, creating a sense of skepticism: can cloning technology really be developed? Even some policy makers had misconceptions of one kind or another, Chen Dayuan told reporters.
But Yang Xiangzhong's success in cloning 13-year-old cows in the United States to extend their lifespan proves that cloned animals are not short-lived. The 24 cows cloned by ACT in the U.S. have all become cow mothers, indicating that the reproductive ability of cloned animals has not diminished.In 2000, scientists at the Rockefeller University in the U.S. announced that they had found, after breeding six consecutive generations of cloned rats, that the chromosome telomeres of cloned animals are not necessarily shorter than those of normal animals, and thus may not necessarily age prematurely. This is not consistent with earlier speculation by some scientists that shortened telomeres cause premature aging.
Chen Dayuan pointed out that the premature death of Dolly the sheep is relatively special, but Dolly the sheep is only one, and had arthritis, pneumonia, there is no other control, which is a special case, is not enough to use it to show that the cloned animals are all short-lived. Some people don't pay attention to cloned animals because of their low survival rate, but these defects will gradually improve over time.
Li Ning also argued that cloning does not affect the lifespan of animals, and that the case of Dolly the sheep is special. The scientific community has also reached the ****ing understanding that cloning does not cause aging; early death is possible, but not unexplained death after a successful birth and growth. "The problem is that it's too inefficient. So scientists are still working on it."
Cloning mechanism not yet fully elucidated
"Although cloning focused on various animals has been successful over the past 10 years, the mechanism of cloning is being studied by scientists all over the world, including China, yet none of it has been clarified yet, and it won't be accomplished in a few years' time. It is possible that people have conducted separate studies from different aspects, but there is still a need for someone who can synthesize the results of all the studies, together with his own research, and finally say that the mechanism of cloning is clear." Chen Dayuan said.
In 2002, Yang Xiangzhong, known for his cloned cows, published his findings on the vulnerability of cloned cows to premature death in the journal Nature Genetics. He found that cloned cows that die early after birth have X-chromosome genes that are not properly expressed, and may be the main cause of their mortality.
In 2006, Yang Xiangzhong again published a signed article in the journal Nature Genetics, arguing that "differentiated cells can be used for animal cloning, and their efficiency can be better than that of adult stem cells," which answered the question of inefficiency in cloning, a decade-long problem that has plagued scientists worldwide. The study answers the 10-year problem of inefficient cloning that has plagued scientists all over the world. The study convincingly demonstrates that even thoroughly differentiated somatic cells, such as blood granulocytes, retain all the genetic information needed to form an individual and can support the development of an embryo into an individual.
"The scientific basis for dramatically improving the efficiency of cloning, or for having a comprehensive grasp of cloning, without understanding the mechanism is inadequate. Despite the efforts of scientists around the world to carry out exploration, but at present the cloning mechanism has hardly been completely dissected and elucidated, but only understand part of the law of cloning and a small range of mechanisms, however, this is an important progress in cloning technology in the past 10 years. The understanding of the cloning mechanism is in the period of 'blind men feeling the elephant', everyone understands part of it, but no one can see the whole picture yet. We don't have a full understanding of what kind of laws cloning actually follows. We know that causing deaths and deformities in cloned animals may be related to this or that cause, and some evidence has been found, but the complete evidence is not yet available, and the systematic laws have not yet been explored." Li Ning said.
Daoyuan Chen told reporters that their current work tends to study the reprogramming of cell nuclei, and the most important thing in this process is methylation. They found from the cloning of giant pandas and cattle stillbirths that the methylation was abnormal, while the successful cloning of cattle and sheep, the methylation was normal. Therefore, it has been proposed that the efficiency of cloning can be improved by selecting those cells with normal methylation for cloning after reprogramming the somatic cells. Chen Dayuan believes that in addition to proposing a solution from the mechanism, the efficiency problem can also be solved from the perspective of selecting the fertilized mother in the application. And to completely figure out the mechanism of cloning, Chen Dayuan believes that 10 years or eight years is not enough, and maybe it will take 30 years.
Ethical and moral controversy
"If cloning has attracted media and public attention, apart from scientific issues, there are also ethical aspects. For example, the ethical debate over human cloning, monkey cloning, and the scientists who conduct cloning research, and so on. In the field of biology, in the scientific community, there has never been any topic that has gotten so much attention as cloning." Li Ning said in an interview.
In March 2005, the 59th U.N. General Assembly approved the adoption of the U.N. Declaration on Human Cloning, urging governments to ban all forms of human cloning, including cloning of human embryos for stem cell research. The four-year-old issue*** was debated for four years, with 191 countries participating in the vote. The non-legally binding declaration was adopted by 84 votes in favor, 34 against and 37 abstentions. Countries in favor of therapeutic cloning, such as China, Britain, Belgium, Singapore, France, India and South Korea, voted against the declaration because they believe that the advanced technology of therapeutic cloning has found a hope for curing a wide range of difficult diseases, such as cancer and diabetes.
"I am against human cloning. I think the state's attitude is very correct." Chen Dayuan said all the talk of human cloning in the past should be a hoax. Human cloning is not the same as test-tube babies; cloning is asexual reproduction, which 99 percent of society should not accept. But animal cloning is available to humans.
Li Ning also thinks the legendary human cloning is not real. "There aren't many scientists around the world who have cloning technology, it's a difficult technology, and those so-called scientists are 'falling from the sky', and none of us scientists within the cloning research field know them. There have not been any scientists who have indicated a willingness to come in and do replicative cloning, that is, reproductive cloning. It's not a technical problem, reproductive cloning would be much easier than attacking therapeutic cloning, but rather that no scientist is willing to do it and take on such a responsibility." Li Ning said.
Chen Dayuan also brought up the Huang Yuxi incident, which had been a cause célèbre. After that incident, he said, some scientists studying stem cells naturally turned to the question of mechanism. This has had an impact on the world's stem cell research toward therapeutic cloning. The Huang Yuxi incident may have limited the rate of progress in stem cell research on the one hand, but on the other hand, it has also strengthened the responsibility of researchers. "When we do scientific research, we can't be half-hearted." Chen Dayuan said.
Cloned cow 'tastes great'
Japan, a country that is very conservative about genetically modified crops, is moving very fast on the road to industrializing cloning technology. Not long ago, Li Ning went to Japan to participate in the World Conference on Animal Embryo Transplantation, the first dinner used by the organizers to entertain scientists from all over the world is the meat of cloned cattle. The host said, "When you are still arguing about cloning, we have already put the cloned beef on the table, and we have been eating it for such a long time that we think it's quite good, and we also invite scientists from all over the world to taste it, and whether this cloned beef is very tasty."
Japan is the second-largest country in cloning technology, and premium beef from local river cows (Japanese cattle) has sold for hundreds of dollars a pound. Thirty-eight Japanese research institutions applied in vitro fertilized egg splitting technology to breed 578 fertilized egg cloned cows, of which 253 were put into circulation to be bought and sold, and 153 were slaughtered and marketed as vegetable cows. Li Ning told reporters that in Japan, no regulations have been introduced, and no discussion, these animals into the market. Cloned animals have been in the food chain for a long time, since the success of cloned cows in Japan in 1998, and the meat of cloned cows has been on the table in 2001.
"On that day, scientists were enthusiastically tasting the meat of cloned cows. Scientists already have the ****ing knowledge that there is no safety issue with meat from cloned animals. I personally also think there is no safety problem." Li Ning told reporters this.
Chen Dayuan agreed, saying that products such as milk and meat from cloned animals are safe and even simpler and more harmless than genetically modified plants and animals.
Early in 2007, Yang Xiangzhong published an article in Nature Biotechnology devoted to the safety of cloned animal products, in which he proved through a series of biochemical indicators that the nutritional composition of cloned beef and cloned milk is basically the same as that of ordinary beef and milk, and that some components are even better.
"Although the mechanism is not clear, but did not affect cloning in the industrialization of this road 'Mercedes-Benz', many companies and scientists in the government support are stepping up industrialization, step up the application of this technology." This is another important development according to Li Ning.
Particularly prominent is the United States, which is not only the world's No. 1 cloning country, where a lot of animals have been cloned first; but they have also been the most aggressive on the road to industrialization. They cloned a large number of cows; through cloning technology also get a large number of genetically modified animals, through these genetically modified animals - especially goats - the production of drugs, the first drug has been approved on August 2, 2006 on the market. According to Li Ning, this is an important milestone, breaking the boundaries between animal husbandry and pharmaceuticals, between agricultural production and industrial production, turning agricultural production into industrial engineering, and turning pharmaceuticals, which is a difficult technology, into an animal husbandry process, and its cost is reduced to 1/100th of the original way.
On the other hand, the United States has realized in the case of dairy cows and breeding bulls the industrialization of cloning. For two consecutive years, in the auction of dairy cows, the top ten most popular are cloned cows. Meanwhile, the U.S. announced in October 2006 that it was going to let products such as meat, hides, and milk from cloned animals enter the market in February 2007, arguing that they are safe and are not subject to labeling and evaluation. "They think cloning is just a way of reproduction, just like embryo transfer and in vitro fertilization in the past, nothing new." Li Ning said.
Will China fall behind?
Li Ning told reporters that China has gradually become a cloning power, although compared with the United States and Japan there is still a gap, the overall strength is still not enough, but a certain number of subject groups are still relatively strong, has been in the world's first-class level. The difference is that there are too few excellent teams in China. "The United States and Japan respectively have more than 30 groups that can successfully clone cattle at the same time, while China currently has just six or seven such groups. Cloning is a very important technology for China, because although the United States and Japan are now moving faster, but after all, they have not fully industrialized, which creates a good opportunity for China. Today in cloning, the most cutting-edge technology, our country is not far away from them, I think, seize this opportunity to catch up in the most cutting-edge technology, will greatly shorten the distance with these developed countries, may make our country's entire science and technology and its industrialization strength to compete with the developed countries." Li Ning said with emotion.
"However, China has invested very limited funds in cloning technology." Li Ning said that at the beginning of the "Eleventh Five-Year Plan", the world's funding for cloning is on the rise, and China's funding for all kinds of research is also on the rise, but no further support has been given to the research of cloning technology itself. "There are some excellent cloning groups in China that now lack the funds to keep going. These scientists treat cloning technology as a lifelong endeavor, and this spirit is really admirable to me."
Chen Dayuan also told reporters that in the 11th Five-Year Plan, there are no more big projects on cloning, only small ones. "This has more or less affected the development of cloning technology in China, but now the country attaches great importance to research on therapeutic cloning and mammary bioreactors, that is, research that emphasizes the combination of cloning technology with other technologies." However, governments and companies in developed countries pay more attention to the research and development of cloning technology, Chen Dayuan said, which is mainly reflected in three aspects: therapeutic cloning combined with medical treatment; genetic breeding with clones; and pharmaceuticals with mammary gland bioreactors. Chen Dayuan, in cooperation with the Linyi Shengneng Group in Shandong Province, is working to build a research and development base in the area, which will mainly be engaged in breeding and mammary gland bioreactor research.
Discipline crossing to expand the new world of cloning
Chen Dayuan believes that, on the whole, there are certain shortcomings in cloning technology itself, but they can be solved gradually. In the process of solving the problem, the characteristics of cloning technology can be brought into play, and other technologies can be combined to play a great role. Without cloning, many other technologies could not be developed rapidly.
Chen Dayuan said the combination of cloning technology with transgenic technology is an important development direction. Transfer the human target gene to the cow's body cells, and then clone the cow, the calf grows up, the target gene will produce milk protein, the milk has the composition of human milk, so that it can be made into functional milk. This functional milk can also be used as a raw material for pharmaceuticals, this technology is called "mammary bioreactor", is through cloning, so that the mammary glands of cows and goats as a bioreactor, to secrete the milk that people need, to be used for direct consumption or extraction of pharmaceuticals.
Meanwhile, cloning technology applied to stem cell research is also an important area. Li Ning told reporters that therapeutic cloning with stem cells is avidly supported and invested in by governments and companies around the world. The same goes for the Chinese government, which has deployed a lot of funds into stem cell research in the "863" program, the major research areas of the National Medium and Long-Term Plan and the "973" program, as well as the National Natural Science Foundation of China (NSFC), making it almost the hottest field. Optimistic people think that after 10 years, conservative people think that after 20 years, cloning will become the most important means of medical treatment. Now medical treatment with chemical drugs, relying on chemical small molecules, proteins, the next generation of treatment may use the cell, directly replace the cell with a cell, instead of repairing, adjusting and killing this cell. "Stem cell and cloning research in the past 10 years, there are six times to become the hot spot of scientific research in the year, that is, Nature, Science magazine rated as the hottest research areas of the year." Li Ning said. However, Chen Dayuan said there has not been a single successful clinical case of therapeutic cloning with embryonic stem cells, and whether the use of stem cells in clinical treatment of human diseases is free of defects and produces cancerous cells is an issue to be seriously studied.
On the other hand, Chen Dayuan believes that cloning technology can also play a role in breeding. Not only can it be used to clone domestic animals and shorten the breeding time of good breeds, but it can also be used to clone endangered animals. Chen Dayuan emphasized, "It is not about denying natural instinctive interbreeding, but about finding and providing a method of reproduction that extends life and prolongs the existence of a species. Cloning is a technology that can provide that help." Chen Dayuan has done research on sexual reproduction of giant pandas for 16 years, and it is for this reason that he came up with the idea of using cloning to breed pandas.
Future unlimited
After 10 years, cloning technology seems to have just finished its first few steps as it tentatively keeps moving forward. So where does cloning go from here?
Li Ning is optimistic that the future of cloning technology will allow all ordinary people to feel the important role it plays in improving their own quality of life and in promoting the development of the country's national economy. "In the future, many people may not be able to live without products related to cloning technology, treatments and technologies linked to cloning technology, and the progress it will bring to human civilization cannot be underestimated, and it is incalculable from now on. It is conceivable that after the success rate of cloning technology increases, if you need a high-quality animal product, you can copy it with cloning technology and anyone can eat it; the wide application of therapeutic cloning technology in clinic will also greatly improve the health of human beings."
Yang Xiangzhong said in an interview with Science Times, "In the future, the application of cloning in agriculture is not to produce large quantities of meat and milk (which are expensive because of their high cost), but to clone the world's best breeds of livestock in order to supply developing countries that have only inferior breeds to develop their animal husbandry. This technology could allow China to improve its dairy breeds and milk production levels for 30 to 50 years; currently, our milk production is 3.5 tons per cow per year, which is lower than the 5-ton level in the United States 50 years ago, which now produces 10 tons of milk per cow per year."
This view is also supported by Chen Dayuan, who said that the significance of cloning itself lies not in cloning one or several animals, but in breeding breeds with excellent traits, because cross-breeding is difficult with traditional methods and often can't be done well for 10 or 8 years, while it can be obtained quickly with cloning. Chinese cows can only produce 2 tons of milk a year, while foreign imports of cows can produce 10 tons of milk a year, if you use cloning technology, spend 1 to 3 years to get the offspring, greatly reducing the time of genetic breeding.
Yang Xiangzhong told reporters that the cloning technology in the dairy industry in the application of not only the efficiency is still relatively low, and high cost. Therefore, scientists have yet to address issues including: why cloning is so inefficient and how to improve the situation; and whether cloning technology can be used for medical treatment, i.e., the use of therapeutic clones (not reproductive clones) to produce medicines to cure some currently incurable diseases, such as spinal cord injuries, cardiovascular diseases, Parkinson's syndrome, diabetes and cancers, etc. "The application of cloning technology in the field of cellular reprogramming for pharmaceuticals has the potential to cause a revolution in the pharmaceutical world of 'curing incurable diseases'. Therapeutic cloning technology will cure incurable diseases such as cell or organ mutations and play an immeasurable role in human health and longevity." Yang Xiangzhong said.