Monkey-Human Hybrid Research Offers Promise, but Sparks Ethical Debate

Embryo

For the first time ever, a team of scientists from the United States and China has successfully created monkey embryos containing human cells. But scientists not involved in this study are citing ethical concerns regarding these monkey-human hybrids, despite that the grown chimeric embryos were destroyed after 20 days.

According to the researchers, who published their findings online in Cell, certain experiments can't be conducted in humans, making nearly human hybrids a possible solution to this investigational barrier. The investigators argue that these human-animal hybrids, or chimeras, may offer deeper insights into developmental biology and improve the identification of novel cancer therapies. 

In the study, the researchers injected human stem cells into monkey embryos and waited for them to develop. The human and monkey cells began to divide and grow together in a dish, and up to three embryos survived 219 days following fertilization. 

"The overall message is that every embryo contained human cells that proliferate and differentiate to a different extent," said lead study author Juan Carlos Izpisua Belmonte, developmental biologist at the Salk Institute for Biological Studies, La Jolla, California, in an interview with Nature

Human cells were detected in 132 embryos after just one day. At 10 days, the investigators observed a total of 103 chimeric embryos still in the development process. But soon after, survival began to decline, leaving only three chimeras still alive by day 19. At this point in the study, the investigators destroyed the chimeras before they could further develop.

In 2019, members of this same research team found they could successfully grow monkey embryos for up to 20 days following fertilization. The team also reported in 2017 the successful growth of pig and cow embryos grown with human cells and rat embryos grown with mouse cells.

And while the researchers themselves suggest this work could aid biological understanding and discovery of new therapeutic agents, it has ultimately left many biologists divided in terms of the ethical concerns surrounding the work itself. 

"There are much more sensible experiments in this area of chimeras as a source of organs and tissues," said Alfonso Martinez Arias, developmental biologist at Pompeu Fabra University, Barcelona, Spain, in a recent Nature interview. Studies using livestock animals, including cows and pigs, do not pose a substantial risk to challenge ethical boundaries. "There is a whole field of organoids," he added, "which can hopefully do away with animal research."

Corresponding study author, Izpisua Belmonte, told Nature that the team has no plans to implant hybrid embryos into monkeys. Instead, the goal of any future research will be to understand how cells from different species communicate with each other in the embryo, at least during early growth phases. 

Belmonte said the work aimed at growing human-mouse hybrids is still in its preliminary stage, as these hybrids need to be healthier and more effective before they can offer valuable insights. Their evolutionary distance between the two species keeps the hybrids from thriving, making this type of investigation challenging.

"This paper is a dramatic demonstration of the ability of human pluripotent stem cells to be incorporated into the embryos of cynomolgus monkey when introduced into the monkey blastocysts," according to a statement made to Nature by Magdalena Zernicka-Goetz, developmental biologist, California Institute of Technology in Pasadena, California.

To respond to this type of research initiative, the International Society for Stem Cell Research (ISSCR) will publish revised guidelines next month for stem-cell research, which will address nonhuman-primate and human chimeras. Currently, the ISSCR guidelines prohibit investigators from mating human–animal chimeras. 

Likewise, the United States, the UK and Japan have limited chimera research involving human cells. In 2019, Japan lifted a ban on studies with animal embryos that contain human cells. The U.S. National Institutes of Health (NIH) announced in 2015 a moratorium on federal funding for work using animal embryos injected with human cells. The funding agency suggested in 2016, the ban could be lifted, but that funding ban remains in place. 

People in the scientific community are also calling for public debate regarding the implication of these human/non-human hybrids. In an interview with the BBC, director of the Progress Educational Trust, Sarah Norcross, noted there are "substantial advances" being made in both embryo and stem cell research, and these advances may offer benefits to the overall study. Despite these potential benefits, Norcross said, "there is a clear need for public discussion and debate about the ethical and regulatory challenges raised."

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