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Comprehending The Chimera: Consequences Of Genetic Interference

The conceptualization of human-animal chimeras only existed in mythical legends and fictional tales until 2003, when scientists from the Shanghai Second Medical University fused human cells with rabbit cells to form the world's first human-animal chimera.

According to Greek mythology, the term Chimera refers to a “creature with the head of a lion, the body of a goat, and the tail of a serpent”. Scientifically speaking, a chimera is fundamentally a single organism composed of cells that are derived from two (or more) genetically distinct species or organisms. It contains two different sets of DNA with the code to make two separate organisms. Human-animal chimeras are interspecific and contain cells belonging to at least two species in which one species is a human and the other a non-human animal. Such a human-animal chimera can either be an animal embryo or animal at a later stage of development containing some human cells, or a human embryo or a human at a later stage containing some animal cells. Importantly, most human-animal chimera studies to date have involved animals, oftentimes mice into which human cells have been inserted.

Rapid advances in stem-cell technology and gene-editing have widened the range of possibilities for future applications in human-animal chimera research. A scientific outlook towards the creation of such a hybrid has led to various moral, legal and technological debates and has raised questions regarding the advances in science and gene engineering. Though human-animal chimera research in small animals, such as mice, is routine, human-animal chimeric techniques are now increasingly being applied to larger animals like pigs and monkeys, with the objective of organ transplantation. Researchers hope that some human–animal hybrids would provide better models to test drugs on, and could be used to grow human organs for transplants.

In 2019, for the first time, scientists at the Kunming University of Science and Technology could grow monkey embryos in a dish for up to 20 days after fertilization. The team indicated that they did not intend to implant any hybrid embryos into monkeys. The purpose was to understand how cells of non-identical species communicate with each other during its early growth phase in the embryo. In 2017, they reported a series of other hybrids: cow embryos grown with human cells, pig embryos grown with human cells, and rat embryos grown with mouse cells. However, the latest work has divided developmental biologists. Some question the need for conducting experiments which make use of closely related primates, as these animals are not likely to be used in a way that rodents and mice are. Non-human primates are also protected by stricter research ethics rules than rodents, and they worry such work is likely to call forth public opposition.

Some are concerned about the creation and use of human-animal chimeras in general, while others are concerned about certain types of human-animal chimeras, including those that may have human cells in their reproductive system or their neural tissue. This raises concerns about human-animal chimeras obtaining humanized cognitive capacities. This would be an affront to human dignity and would violate the moral requirements that human dignity imposes. It is discernible that most or all human beings have human dignity, although definitions of dignity vary. The dignity based arguments against the creation of human-animal chimeras include disputes regarding whether the human-animal chimeras would have human dignity or not. Fusing human cells with closely related primate embryos triggers questions regarding the status and identity of the evolved hybrids. “Some people may see that you’re creating morally ambiguous entities,” says Insoo Hyun, a bioethicist at Case Western Reserve University in Ohio.

Savulescu, the director of the Oxford Uehiro Centre for Practical Ethics has argued that , “the genetically modified animal should be accorded the highest moral status consistent with its likely nature”. Thus, if we have reason to believe that a human-pig chimera has the same moral standing as any ordinary human, we should not use it as a source of donor organs and subject it only to forms of research that would be ethically acceptable to be conducted on, for example, children.

Many countries including Japan, the United Kingdom, and the United States have restricted research on human-animal chimeras at some point in time. For years, scientists have been barred from experimenting on human embryos in their labs for more than 14 days. According to the 2001 Guidelines for Handling of a Specified Embryo, human-animal chimeric embryos can only be produced for preliminary research regarding the creation of organs to be transplanted into humans. The embryos were not allowed to develop after the 14th day, and they could not be transferred into an animal/human uterus. This was declared with the aim of avoiding any ethical issues that would be raised while experimenting on living human embryos as they continue to develop. This prohibition was based on the belief that “producing a brain derived from human cells in an animal body may have an effect on animal behavior, and should be regulated even at stages before individuals are generated”.

International guidelines are leveling up to the field’s developments. The International Society for Stem Cell Research (ISSCR) released new guidelines stating that it could be permissible to study living human embryos in the lab for longer than two weeks and lifted the “14-day rule”. In March 2019, Japan lifted the ban on lab experiments with animal embryos containing human cells. The amended rules now allow the creation of chimeras with human brain cells, and the transfer of the resulting creature to a uterus where it can develop for more than 14 days until term. Despite the controversies surrounding the creation of chimeras, ISSCR applauded the revised Japanese rules permitting research on chimeric embryos and supports research creating chimeras as long as it is under appropriate ethics review and strict oversight.

Research surrounding this subject could lead to increased knowledge of human biology and further development with resultant implications that could considerably impact human health. However, creating chimeras is ethically debatable. There are various arguments, such as the human dignity dispute and the concern for animal welfare. Growing human organs within a chimera raise pressing issues on the moral status of beings that are not fully human or animal.

Physicians and scientists play a critical role in explaining the medical needs, advantages and limits of this procedure, and the ethical boundaries that must not be infringed. If these prerequisites are kept in check, acceptance of such new and borderline medical procedures may be undemanding. Development of human-animal chimeras raise necessary ethical questions about the legitimacy of creating such chimeras, and how they should be treated. Answers to these ethical questions are important to acquire for the informed development of policies directing human-animal chimera research and its applications.

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