Scientists announced last week that they had created the first human-animal hybrid in their lab. Like something out of a science-fiction novel, this successful experiment involved injecting human stem cells inside early-stage pig embryos. The project proves that human cells can be introduced into non-human organisms, survive, and even grow inside a host animal. The implications for developing human organs inside animals for transplant are staggering, along with the ethical ramifications.
Described as interspecies chimeras, researchers in the US implanted human cells into pig embryos that were then transferred into surrogate sows and allowed to develop until the first trimester. More than 150 of these embryos developed into chimeras- they grew precursors of organs including the heart and liver. They contained a small amount of human cells, around one in 10,000 of the hybrids’ cells were human.
This biomedical advancement has long been a dream and dilemma for scientists hoping to address a critical shortage of donor organs. Every ten minutes, another person is added to the national waiting list for organ transplants, but every day 22 people die without the organ they desperately need. Now biologists may be able to change this staggering statistic by growing custom-created organs inside a host animal.
Organ development was one of the driving motivations of the international team of researchers, led by the Salk Institute. Published in the scientific journal Cell, lead study author Jun Wu defends the controversial project. The term chimera comes from a legend in Greek mythology describing a monster who was often depicted as a lion with a goat’s head sticking from the side of its neck and a snake for a tail, but in biology, the word is defined as an organism that contains cells from two different species. But the remnants of the monster connotations still remain in society. These experiments are currently ineligible for public funding in the US, and public opinion has hampered the creation of organisms that are part human and part animal. Relying on private donors for this project, Wu and team member Juan Carlos Izpisua Belmonte (also from the Salk Institute) have shown that our stem cells can contribute to forming the tissues of a pig despite the 90 million years of evolution separating our species.
“We have shown that a precisely targeting technology can allow an organism from one species to produce a specific organ composed of cells from another species,” says Belmonte. Previously involved in other interspecies experiments, Belmonte and his team at the time were able to integrate human stem cells into mice embryos back in 2015. They manipulated the mice into growing pancreases from rat stem cells, then rat eyes and rat hearts. Interestingly enough, they were also able to grow a gallbladder inside the mice embryos using the same stem cells, which is unique because rats don’t even have gallbladders. This human-pig project built on that initial research, allowing them to discover that human cells inside the pig embryos were starting to specialize and become precursors to human tissue. These cells were living and reproducing inside the pig embryo.
Image source: Science Alert
The significance? Pigs grow large enough to develop organs that would be appropriately sized for a human. This project, although ended when the embryos were terminated after 28 days, is one large step towards the team’s true goal of growing organs inside a lab.
“Of course, the ultimate goal of chimeric research is to learn whether we can use stem-cell and gene-editing technologies to generate genetically-matched human tissues and organs, and we are very optimistic that continued work will lead to eventual success,” Belmonte said. “At this point, we wanted to know whether human cells can contribute at all,” he said in a separate statement. “Now that we know the answer is yes, our next challenge is to improve efficiency and guide the human cells into forming a particular organ in pigs.”
But a lot of people are wondering if they should. There are many critics of the research who believe that mixing humans and animals in any way crosses a line. But team member Wu has a different perspective.
“In ancient civilizations, chimeras were associated with God,” Wu says, drawing the correlation between human-bird hybrids we call angels. “Our ancestors thought the chimeric form can guard humans.” And in a sense, that’s what the team hopes human-animal hybrids will one day do. Although pigs may not be angelic in the sense of imagery we conjure with angels, they very well could be saving thousands of lives, like real guardian angels. Because the process involves a small number of human cells within an otherwise predominantly animal embryo (like a pig), the hope is that, if allowed to grow fully, the chimera embryo would develop entirely as an animal except for one harvestable organ that is human. It might even be possible for that organ to be produced from the patient’s own stem cells. It would be a perfect match, and would dramatically cut down and possibly eliminate the risk of organ rejection, and the need for the immunosuppressant drugs after transplant surgery.
Unfortunately, there’s still a long road ahead before any of that is possible. And research will still be stunted at every stage. Chimera research was banned in the US until August 2016. This study reintroduces ethical concerns which threaten to overshadow these medical breakthroughs.
One significant objection is the opportunity for viruses to more easily jump a species barrier which was previously closed to them. The risk of that pandemic is always looming when animals become carriers for sickness that can affect humans (think mad cow, avian flu, swine flu). There’s also the consideration of such an intimate mixing of human and animal tissues for medical reasons; it gives everyone pause, and some of us shudder at the thought. Animal rights advocates were quick to raise ethical questions as well. Should we allow chimeric pigs to be used as a biomedical incubator of sorts and then sacrificed to obtain a human organ? At what point is it cruelty, to raise an animal into a sentient being of sorts only to be brutally slaughtered after it has served its initial purpose? As someone who enjoys bacon pretty much every weekend, I’m not sure where I draw the line either, although I’m sure my clogged arteries would appreciate if I did sometime soon.
But there are tougher questions to answer as well. How many human cells within a chimera overall would make that chimera too close to a human being? How many human brains cells - and in particular neurons - would be too many? What would we do if a human-pig chimera accidentally ended up with an abundance of human cells in its brain? Would it have human qualities? Last I checked, almost no one wants a talking pig. And what if a human-pig chimera made human sperm or eggs? What other animals would be involved in research as it progresses? Logic dictates that perhaps monkeys or chimps would be a strong contender, but then what about species preservation efforts? What animal becomes off-limits? And should animals be used to grow multiple organs, under what classification does that fall?
Overall, though, the global shortage of organs for transplant is too urgent a problem to refuse to explore alternative and innovative solutions. Although the experiment gives me a bit of the heebie-jeebies, we should pursue more human-chimera technology. We simply need to acknowledge and address the important bioethical considerations, and what legalities need to be put into place. Scientists involved in this field need to continue to discuss and consider the far-reaching implications of their work, and ensure that it is heavily regulated. There are few legal procedures and precedent to follow in this new research and field. Researchers and biologists will need to work closely with lawyers and the government to ensure there are clear boundaries on what is acceptable and what isn’t. Chimeras are still thought of as mythological monsters; we need to make sure we don’t allow those myths to become a reality.