Creating an organism that contains human cells and those of another species is deeply complex, with the ethical considerations as mind-boggling as the biology. A team of scientists has, however, made a major breakthrough in the field, with potentially huge ramifications for the study of human evolution, disease, drug-testing and ageing.
Researchers at the Salk Institute in San Diego injected human stem cells into non-human primate embryos, which then survived in the laboratory for up to 20 days. Not only did they survive for longer than previous experiments, but researchers identified ‘communication pathways’ that may hold clues about how human cells integrate with non-human cells in chimera organisms.
“As we are unable to conduct certain types of experiments in humans, it is essential that we have better models to more accurately study and understand human biology and disease,” said senior author Professor Juan Carlos Izpisua Belmonte, a professor in the Gene Expression Laboratory at the Salk Institute. “An important goal of experimental biology is the development of model systems that allow for the study of human diseases under in vivo conditions.”
Interspecies chimeras have been created in laboratories since the 1970s but those involving human cells have never come this far. As well as providing a tool for studying diseases and evaluating new drugs for treating them, these chimeric models could also potentially be used to grow tissue for organ transplants.
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The team at Salk created crab-eating macaque embryos outside of an animal’s body, building on work by collaborators in China. After six days, they injected 25 human stem cells into each of them. The embryos slowly died off but scientists were amazed that the percentage of human cells in the embryos remained high as they grew.
“Historically, the generation of human-animal chimeras has suffered from low efficiency and integration of human cells into the host species,” Izpisua Belmonte said. “Generation of a chimera between human and non-human primate, a species more closely related to humans along the evolutionary timeline than all previously used species, will allow us to gain better insight into whether there are evolutionarily imposed barriers to chimera generation and if there are any means by which we can overcome them.”
The breakthrough is sure to reignite debate around the ethics of creating human/non-human chimeras, a point that Izpisua Belmonte himself addressed. “It is our responsibility as scientists to conduct our research thoughtfully, following all the ethical, legal, and social guidelines in place,” he said, adding that before beginning this work, “ethical consultations and reviews were performed both at the institutional level and via outreach to non-affiliated bioethicists.”