How to look at “Life Chimera”

  On April 15, 2021, a team of Chinese and foreign scientists from Kunming University of Science and Technology in China and the Salk Institute for Biological Research in the United States published a paper in the journal Cell, announcing the construction of the world’s first human-monkey chimera embryo, which means that it has humans at the same time. Embryos of source cells and monkey-derived cells.
  Speaking of chimeras, people might think of the Kamera in Greek mythology, which is a monster with a lion head, a sheep body, and a snake tail. However, the human-monkey chimera embryo is a life chimera combining human and animal, which is fundamentally different from Kamera. In fact, under certain conditions, many organisms, including humans, will have chimeras. For example, some fraternal twins have two different sets of DNA, which is also a kind of life mosaic.
  The Sphinx is a chimera of humans and beasts with far-reaching significance and wide-ranging influence. In Greek mythology, the Sphinx sits on a cliff near the city of Theba, stopping passers-by and asking them to guess riddles. Those who fail to guess will be eaten by it. Many people died because of incorrect answers or failure to answer, but Oedipus, the son of King Thebai, finally gave the correct answer. The Sphinx was so ashamed that he fell to his death. People have a simple motive for creating human-beast chimeras in mythology. Although humans are the most intelligent animals on the planet, compared with animals, humans have many shortcomings in form and life functions. Therefore, they must rely on the chimera with beasts to strengthen their own strength. For example, the most famous sphinx on the west side of Cairo, Egypt has this metaphor. It is believed that only by combining the power of man and lion can the pharaoh’s coffin be protected.
  Myths can be switched to reality, sometimes almost seamlessly. However, scientists create human-beast chimeras not to verify whether the myth can become a reality, but to use the power of animals to help people. Of course, this power is broad, including the use of animal tissues and organs. To be precise, it is the use of human-monkey, human-pig and other human-beast chimeras to save human lives through organ transplantation.
  According to estimates by the World Health Organization, there are about 2 million patients with severe organ failure in the world who need organ transplants each year, of which kidney transplants account for the largest number of 68.5%. There are about 1 million organ failure patients in China each year, of which 300,000 are in urgent need of organ transplantation, but only about 20,000 people can get transplantation opportunities because of the lack of donor organs. At present, the main source of donor organs is still the human body, which comes from organs donated by people in their wills. Due to too few organ donors, many patients died while waiting for their organs, leaving great regrets. In order to increase the number of donor organs to save lives, there are currently alternatives such as xenogeneic organ transplantation, organoids and 3D printing, heterogeneous chimerism (human-animal chimerism). Xeno-chimera transplantation is to allow animals to grow organs similar to humans and transplant them to patients in need of treatment. Scientists have always wanted to make breakthroughs in this field of research. Human organs are not easy to obtain. To obtain organs from animals is to draw on the power of animals.
  Although human-monkey chimera embryos are still thousands of miles away from culturing human-derived animal organs for transplantation, some significant progress has been seen. The human-monkey chimera embryos cultivated by the Chinese and foreign scientific research teams survived for 20 days, which is the maximum length of time that monkey embryos can be cultured in vitro. It also lays the foundation for the future generation of chimeric embryos and the cultivation of human-monkey animals to obtain organs for transplantation.了基。 The foundation. In addition, compared with past human-pig chimera embryos, human-monkey chimera embryos have made greater breakthroughs.
  In January 2017, Wu Jun, a researcher at the Salk Institute for Biological Research in the United States, and his team announced that they had successfully cultivated the first human-pig chimera embryo, which developed in pigs for nearly 4 weeks. However, the mosaic efficiency of these embryos is very low, and it is estimated that there may be only 1 human cell per 100,000 pig cells. Such human-pig embryos are difficult to transplant even if they are cultivated to the stage where organs can be obtained, because the rejection is very strong, and they are essentially xenogeneic organs. The purpose of constructing life chimera is to cultivate a semi-homogenous or most homogenous organs similar to humans to reduce immune rejection and ensure that they can perform normal organ functions. The chimeric efficiency of human-monkey chimeric embryos this time is about 4%, far exceeding the previous human-pig chimeric embryos. This also means that once such a human-monkey life chimera can be bred, its organs will be closer to the homology of humans, which may reduce organ rejection and save human lives.
  Another technological advancement of human-monkey chimera embryos is that researchers injected human expanded pluripotent stem cells (human EPS cells) into the early blastocysts of more than 150 cynomolgus monkeys, and found the longest surviving ( The 3 chimeric embryos of 20 days) have entered the stage of gastrulation development, that is, the blastocyst has begun to differentiate into ectoderm, mesoderm and endoderm. In the outer, middle and inner germ layers, the researchers observed mosaicism. Since a high proportion of human cells are maintained in the embryo, and these human cells have begun to differentiate into different cell types, it also means that they can further develop into different organs. Therefore, human-animal chimeras may eventually be cultivated successfully. In addition, this progress also provides experience and clues for the cultivation of human-pig chimera. By analyzing and summarizing the cell signaling pathways and molecular mechanisms related to the embryonic development process, it can be used for reference and applied to increase the chimerism between humans and other distant species embryos and improve the survival rate.
  In fact, the organs of human-pig chimera animals are more suitable for humans, because humans and pigs are similar in weight, size, and organ size. Monkeys are small in size. The adult body length of cynomolgus monkeys is about 40-47 cm, males weigh 5-7 kilograms, and females weigh about 3 kilograms. Their organs are not in the same order of magnitude as human organs. Even if the immune rejection reaction of its organs is small, the organs are too small to replace the original organs after transplantation, so the practicality is not strong.
  After human-monkey chimera or human-pig chimera grows up, the use of organs also faces many risks and difficulties. The biggest technical difficulty is whether immune rejection can be avoided. Even if human organ transplantation (allotransplantation) is adopted, the matching problem must be considered. Before organ transplantation, it is necessary to check whether the human leukocyte surface antigen (HLA) of the donor and the recipient are compatible, and if they match, the transplantation can be performed. After the human-animal chimera grows up, if organs are to be harvested for transplantation, antigen matching tests must also be performed. This matching is obviously more difficult than that of allogeneic human organs. In the future, with the progress of research, such technical problems may be solved.
  The most difficult thing to solve is the ethical problem in cultivating human-animal chimeras and using the organs of such species. The researches published in academic journals have been approved by the relevant ethics committees, and these studies have not transplanted human-animal chimeras into the uterus for development, and have not produced human-animal species, so the controversy is still not big. However, with the deepening of research, whether it is possible to approve the transplantation of human-animal chimera embryos into animals, and finally develop into a certain organism and give birth, is facing huge ethical controversy. Furthermore, if human-monkey or human-pig chimera animals are produced, can their organs be approved for transplantation into patients? Will the organs of human-animal chimeras cause new diseases, and can they cause DNA exchanges between humans and animals and cause genetic problems, thereby affecting human reproduction and fertility? Robert Striver, a bioethics and philosopher at the University of Wisconsin-Madison, said: “The worst-case scenario is that people can imagine a person who has the same ethical status as you and me, but is used for research and is subject to Animal-like treatment.”
  The ending of the Sphinx myth may be a flattery to people and the world. If the answer is regarded as the bottom line between humans and animals, surpassing this bottom line may lead to the result of the debunking of the mystery, either the death of the Sphinx or the death of Oedipus. The same is true for the use of human-beast chimera organs. Once the ethical bottom line and social control are exceeded, it will either be human damage, including the aggravation or death of the recipient of the organ, and the wrong path of human evolution, or it will be for human needs. Fall into the “miserable world”. The success of the first human-monkey chimera embryo is gratifying as a technological advancement, but at the same time it is also issuing a warning-in the era of rapid technological development, human ethics and laws are facing unprecedented severe tests.