Human-animal Chimeras: who knows where embryo manipulation will stop?


Scientists have now created mixed human/animal embryo chimeras reports the American journal Cell. Their stated objective is to be able to grow human organs inside animals for organ transplants.

The technique uses totipotent human stem cells (from human embryos or reprogrammed somatic cells): master cells which can produce any kind of tissue or organ. These are combined with host animal embryos, such as pigs in this case to create hybrids.

These human cells were implanted in animal embryos, thus producing 2000 “chimerical” or hybrid embryos which contain both human and animal cells. More than 150 embryos were allowed to continue their development and were then implanted in the surrogate pig mother’s uterus.

These pig-human embryos were allowed to develop for 28 days, (corresponding to the first trimester for a pig’s pregnancy) before scientists stopped the experiment and removed the embryos. If they had allowed the pregnancy to continue until its term, it would have resulted in the birth of “partially-human” piglets. The study demonstrated signs that human cells had started to be transformed into muscle cells.

The group led by Izpisua Belmonte discovered that human stem cells need to be injected at exactly the right stage in their own development for them to survive and become part of the growing animal.  Another challenge is that the pig pregnancy lasts about 112 days, compared to nine months in humans, meaning that the embryonic cells are developing at completely different rates.

Similar studies had previously been carried out with mice, but « This is the first time we have observed human cells growing inside a larger host animal” declared Professor, Juan Carlos Izpisua Belmonte at the Salk Institute. Several different goals were stated for their research study. For instance: to incubate human organs, genetically-matched to a transplant patient, to test new therapeutic drugs, and also to study certain diseases, better understand embryonic growth or the differences in the development of certain organs.

Professor Juan Carlos Izpisua Belmonte, at the Salk Institute for Biological Studies in La Jolla, California and senior author of the paper said: “This is a real breakthrough. The ultimate goal is to grow functional and transplantable tissue or organs (pancreas, liver, heart…) in animal hosts, but we are far away from that. This is an important first step.”

To overcome immunological compatibility issues, DNA modification may also be at stake. To create piglets with a human pancreas, the scientists used the gene-editing technique, CRISPR-Cas9, to turn off the gene that makes the pancreas. Thus, the human pancreas created by the human-pig chimera could be used to treat severe diabetes cases. And if human induced pluripotent stem cells (iPS) come from the patient himself, such transplants would no longer entail life-long immunosuppressive therapy.

These experiments raise numerous ethical concerns. The US National Health Institute (NIH) imposed a moratorium on funding for the controversial experiments research last year while these risks were considered.

Dr. Daniel Garry, a cardiologist who leads a different chimera project at the University of Minnesota states that the chimera research “had prompted a range of troubling questions, including whether the progeny would look more human or more pig, which would happen if a chimera had human thought, and whether it was possible for the human cells to cannibalize the pig embryo, resulting in a mostly-human, slightly-pig offspring”.

Professor John De Vos, from the Department of Cell and Tissue Engineering at Saint-Éloi hospital (Montpellier, France) states: “Limits for the acceptable percentage of human brains in animals need to be established, and strictly regulated, limiting the percentage of human neurons to 1% for example”.  

He adds that certain boundaries should not be crossed. “The first is the transfer of human cells into animal brains, since it raises the specter of intelligent animals with humanized brains”. Different means have been conceived to avoid this risk, for instance, a gene responsible for central nervous system development could be deactivated in the iPS cells prior to injection into animal embryos. Another solution might involve programming iPS cells to only produce digestive system or cardiovascular cells, and in no case whatsoever, produce neurons. The scientist adds: “There is another red line not to be crossed: never produce human gametes via the reproductive organs from human-animal chimeras”. Finally, any animals with a human resemblance such as a porcine embryo with hands or feet resembling that of humans should be sacrificed before birth.

Will humankind’s identity be blurred by such research which clouds the differentiation between humans and animals? Who knows where embryo manipulation will stop?



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