On September 5th, the authoritative organization of artificial insemination and embryology (HFEA) in the UK approved in principle an experiment of mixed embryos of human and animals, which was actually a response to the research application put forward by research institutions such as Newcastle University and King's College in the UK one or two years ago.
The government will examine the research applications of scientists one by one. This means that British scientists can finally formally carry out this kind of hybrid embryo research.
It is a kind of research, because the experiment of heterogeneous mixed embryos actually has three levels:
The first is to combine the sperm of one animal with the egg of another animal to form a fertilized egg. This kind of research is the most ethical, and there are many technical obstacles.
The second type is called "chimera", that is, the embryonic stem cells of one animal are injected into the embryos of another developing animal, so that they can develop into embryos with mixed cells of two animals. Its ultimate goal is to provide spare parts for the repair of human organs. The British side did not give a "green light" to this experiment.
The third kind of experiment approved this time is to inject the nucleus of an animal into enucleated oocytes of cattle, rabbits and sheep by somatic cell nuclear transfer technology, culture early embryos (blastocysts) and extract embryonic stem cells from them.
The first institution to publish a paper
"We have been doing experiments on heterogeneous mixed embryos and are the first research institution in the world to officially publish papers." Chen Jinxue said proudly.
Chen is the director of the Developmental Biology Research Center of Xinhua Hospital affiliated to Shanghai Jiaotong University School of Medicine. By "we", he means the research team led by Sheng. At that time, Chen was her deputy. This research institute occupies a white five-story building in an obscure alley next to Xinhua Hospital. "The British actually want to repeat our work." Chen said to:
From 65438 to 0999, Sheng left the National Institutes of Health (NIH) and returned to China as the director of the Developmental Biology Research Center of Shanghai Second Medical University at that time, and then undertook the 973 "Basic Research and Clinical Application Project of Stem Cells". In 2002, Nature magazine introduced the work of China scientists such as Sheng et al. on the topic of "Stem Cell Research Rising in the East". Now this article is still posted on the first floor of the Developmental Biology Research Center, but Sheng has left this research team and went to the United States to continue his research work.
In 2003, Sheng became a scientist who attracted the attention of domestic and foreign media and scientific circles. In August of that year, the research team led by her used cloning technology to extract cells from skin tissue discarded by surgery, and fused these cells into enucleated oocytes of New Zealand rabbits, and successfully obtained hundreds of fused embryos, of which 100 developed into blastocysts and extracted embryonic stem cells. This paper was published in Cell Research, the most influential international academic journal in China. Nature, The Wall Street Journal and Washington post all commented on the same day and the next day, because this is the first report on the successful fusion of human-animal embryos in the world.
Chen said: "Last year, Britain held a hearing to study human and animal embryos and invited three international experts. Teacher Sheng is one of them, which also shows her academic position in this field. "
have no other choice but
The fusion of human and animal cells is actually a necessity for scientists.
Human somatic cells, such as skin cells, are specialized cells and have long lost the ability to develop into embryos. However, stem cell research has found that if the nucleus of oocytes is removed and replaced with adult nucleus, it is possible to regenerate somatic cells.
Oocytes are like magical magicians. They contain cytoplasmic substances, which awaken the hidden ability in somatic nuclei and enable them to develop into blastocysts. In this way, scientists can extract embryonic stem cells from them-these stem cells have the possibility of developing into various cells and implant them into injured spinal cord, cornea and brain regions of some patients. These cells may play the role of repairers and help treat some diseases that were once considered hopeless. This is called "therapeutic cloning". In addition, if the patient's own somatic cells are used, the problem of immune rejection can be eliminated.
Unfortunately, this technology is not mature, the success rate is very low, and a large number of oocytes are needed. However, it is illegal to obtain oocytes directly from women. Chen said, "We can only cooperate with the institutions that carry out IVF projects and get some extra discarded eggs with the consent." In the case of no choice, scientists had to settle for the second best and ask animals for oocytes. Fortunately, animal oocytes can also "stimulate" human somatic cells.
However, if this technology is applied to people, it must be tested by ethics. Although DNA is mainly in the nucleus, there is also a small amount of genetic material in the cytoplasm, namely mitochondria. Responsible for coding 13 gene, whose main function is to provide energy for life activities. Although these 13 mitochondrial genes are only a few "impurities" compared with thousands of human genes in the nucleus, people are worried that if someone develops these mixed embryos into individuals, these guys will bring great problems to ethics.
However, in the eyes of scientists, this kind of worry is just unfounded. It is found that in most cases, animal mitochondria in cells will be gradually lost with the development of embryos. Moreover, mitochondria are only energy supply units and do not encode any protein related to the characteristics of "human". But the most crucial point is that there is an ethical bottom line in embryonic stem cell research, that is, human and animal embryos are never allowed to be implanted into the uterus and must be destroyed before the embryos develop to 14 days. "These embryos will terminate in 14 days at most, and they are not allowed to be transplanted into the uterus of people or animals, so it is impossible to reproduce. Defining these boundaries may eliminate more than half of the concerns. " Shen Mingxian, director of the Ethics Department of the Southern Research Center of the National Human Genome, said, "China has no restrictions on basic research in this field." It was Shen Mingxian's department that conducted ethical review of Sheng's thesis that year, and their conclusion was that "it should be supported, but it cannot be applied to clinic."
Why can't it be used in clinic? Shen Mingxian explained that scientists don't know whether animal mitochondria will interact with human mitochondria or other components because there are still risks. The bigger risk is the virus. "Some viruses are harmful to people, but harmless to animals." Therefore, research in this field must be "cautious, scientific and ethical".
"Our accumulation is broken."
However, after the completion of the 973 project, Sheng was no longer re-employed by Jiaotong University Medical College. She left the team and mainly engaged in research work in the United States. Regarding Sheng's departure, "the reasons are very complicated." Chen said to:
"There are still technical problems." Chen admitted. The article in 2003 was almost published in the Proceedings of the National Academy of Sciences, and even made into sample printing. However, some experts in the United States disagreed, because the experimental demonstration of "blastocyst can separate embryonic stem cells" was controversial, so it had to be published in the domestic Cell Research. Later, "some work in this field was done one after another, focusing on the research mechanism, but the repeatability of the experiment was not good and the success rate was not high." Chen said to:
It is very difficult to study human and animal embryos. Apart from Sheng's work, there are no officially published papers in the world. Chen believes that the research team has done a good job and published many articles in the field of stem cells, which is in a leading position at home and abroad, but "the state and Shanghai are not prepared to support it any more."
Shen Mingxian believes that due to some ethical disputes, it is not easy to formally publish the research on human and animal embryos. "There are international support and opposition", which is "part of the reason" for Sheng's resignation. But there must be other factors. "There are many reasons." As an expert who did ethical verification for Sheng's work in those years, Shen Mingxian was familiar with Sheng, but "as an outsider, I can't say many questions." "Teacher Sheng is disappointed." Li Feng thinks. Li Feng is a postdoctoral fellow recruited by Sheng himself. After sheng left, he has been working in this institute. That "Mr. Sheng is not satisfied with the surrounding environment. If she chooses to stay, she will definitely get the project funds. "
But Sheng still chose to leave. Due to Sheng's departure, the institute has received almost no funding now. "Cooperation with the Chinese Academy of Sciences stopped and some instruments were taken back. We borrowed the rest until the end of the year, and now we mainly rely on the project funds I applied for. " Chen said, "but it's hard."
There used to be forty or fifty students in this five-story building, but now there are only a dozen students left, and the building looks empty. Chen explained: "Because most experiments are conducted at night. We are now mainly doing experiments on cloning pigs, taking fresh oocytes from slaughterhouses and killing pigs at night. " Cloning pigs is his current research topic, which is a cooperative project between Chen and the Agriculture Committee.
We are still doing the continuation project left by Sheng. We are cooperating with Chen Dayuan's research group of Institute of Zoology, Chinese Academy of Sciences to do genetic analysis of "human bovine embryos". The Institute of Zoology fused human somatic cells with bovine oocytes and developed them into embryos. "We have blastocysts, so let's make an analysis." Li Feng said, "That's what Teacher Sheng meant. She wants to prove her results in multiple species, because different animals have different oocyte reprogramming ability. It is possible that cattle are more likely to succeed. " But now they can only achieve blastocysts, "they can't continue to separate embryonic stem cells from blastocysts" because "the problem has passed and there is no financial support".
Chen said: "Many students go abroad after graduation, and it is difficult to retain outstanding students in China. After completing the postdoctoral program, Li Feng will go abroad. But scientific research needs to be accumulated and cannot be broken. If we don't do a lot of work, we will lose opportunities. " "After Teacher Sheng left, our accumulation here was broken." Chen is a little sad.
There should be continuity in research.
In addition to the formal publication of papers, there are many attempts to clone human beings and animals in the world. From 65438 to 0998, a private American "Advanced Cell Company" injected human buccal nucleus into enucleated bovine oocytes and cloned embryonic stem cells. Chen said, "All countries are doing it now" because the prospects in this field are very good. If therapeutic cloning technology can be broken, the methods of treating major diseases such as Parkinson's disease and Alzheimer's disease may be broken.
There are also many studies on the "chimera" of man and beast. In March this year, Professor Ismail Zangani of the University of Nevada in the United States bred sheep with 15% human cells. This work is to inject human embryonic stem cells into fetal sheep, so that sheep embryos can grow together with human embryonic stem cells during development, and finally adult sheep and human cells are mixed. The report of this "human-sheep chimera" has caused great repercussions at home and abroad.
In fact, there are similar studies in China. Huang Shuzhen and Ceng Fanyi of Shanghai Jiao Tong University School of Medicine developed the world's first "human-goat chimera". Related papers published in the Proceedings of the National Academy of Sciences last May proved that human stem cells can survive in goats. The significance of this kind of research is that it is possible for human beings to obtain organs such as liver, kidney and heart with some human cells from animals for human organ transplantation.
On June 6th this year, three research groups from the United States and Japan respectively genetically modified normal mouse cells and successfully produced "embryonic stem cells". Related research results are published on the websites of Cell Stem Cells and Nature. This study directly transforms somatic cells into embryonic stem cells. If it can be successfully tested in human body, it will avoid the long-standing ethical debate around the use of human embryos and is considered as a major breakthrough in the field of stem cell research.
Chen said, "If this work is successful, there will be no need for therapeutic cloning", but he believes that "research is continuous, and only by constantly trying can there be a major breakthrough."