First came the prospect of pigs incubating human organs. Now a medical ethicist is raising new moral questions by suggesting scientists create human-animal chimeras to produce human eggs.
While the goal, for now, would be to create a ready supply of eggs purely for biomedical research purposes, should the hybrid human eggs turn out to be as good as ones produced by humans, “I do not see any reason for not using them for treating human infertility,” said César Palacios-González, of the Centre of Medical Law and Ethics at King’s College London.
In a commentary in Reproductive BioMedicine Online, Palacios-González tests arguments against creating chimeras for human gamete production, and finds all of them wanting.
“Despite ongoing research and scientific and ethical discussions about the development of chimeras capable of producing solid organs such as kidneys and hearts for transplantation purposes,” he writes, “no wide discussion of the possibility of creating chimeras-IHGP (intended for human gamete production) has taken place.” If anything, scientists have fallen over themselves to reassure the public steps will be taken to avoid creating such creatures.
A leading Canadian reproductive biologist called the paper “deeply thought provoking” and says the idea isn’t outside the realm of possibility.
“Humans are mammals and there is really nothing intrinsically different about the process of reproduction between humans and every other mammal,” said Roger Pierson, a world expert on ovarian physiology at the University of Saskatchewan.
There is really nothing intrinsically different about the process of reproduction between humans and every other mammal
“We’re talking here not about what the combination of mammalian gametes might become, but we’re talking about the actual biological processes of passing our DNA from one generation to the next,” he said.
“The biology that comes out of this analysis is questioning some of the tenets of our assumptions about reproduction.”
In theory, the process could involve “interspecies blastocyst complementation” — the same technique researchers are exploring to create pigs capable of generating human organs for transplant.
A blastocyst — an early embryo — is taken from an animal and genes crucial for the development of a particular cell line or organ edited out. “In this case you would aim at the reproductive system,” Palacios-González said in an interview.
Next, human pluripotent stem cells (cells that have the potential to develop into any type of tissue in the body) taken from a donor’s skin are injected into the blastocyst to “compensate for the existing niche,” he said. “In this case human stem cells would complete the reproductive system, which would then create gametes.”
What conceivably could result is the ovary of a sow (or cow or other animal) that produces human eggs.
In January, Salk Institute scientists reported in the journal Cell they had succeeded in creating the first human-pig chimera embryos. None were allowed to grow beyond four weeks and half were abnormally small. But in others, the human stem cells survived and turned into progenitors for different tissues and organs.
The achievement was hailed a scientific “tour de force.” It also rattled ethicists, who warned of the remote but not impossible risk human stem cells intended to morph into a new liver, pancreas or heart could wend their up to the animal’s brain, raising the prospect of a chimera with human consciousness.
Others worried about transplanted human stem cells generating reproductive tissues. “Few people want to see what might result from the union between a pig with human sperm and a sow with human eggs,” the New York Times warned.
Palacios-González said that as far as he is aware, no one is actively pursuing creating chimeras capable of producing human sperm or eggs. “But maybe I am wrong, the world is just too big.” (The research that comes closest, he said, was published in 2014, when stem cells were taken from a skin sample from a man who produced no sperm and transplanted into the testicles of a mouse, where they became immature sperm.)
However, Palacios-González argues that claims that the creation of chimeras violates human dignity are “just false.”
Most don’t consider lab mice grafted with human cells such a violation, he writes in Reproductive BioMedicine. “Neither do we consider that human dignity is violated when someone receives a pig heart valve, which effectively turns them into a chimera.”
If human dignity is tied to “the possession of certain higher mental capacities,” he added, gene-editing tools like CRISPR could be used to avoid generating brain tissue, thereby reducing “the possibility of accidentally creating a chimera with human brain cells.”
Fears a human egg-producing chimera could become pregnant is a practical issue that could easily be avoided by, for example, creating only female chimeras, he writes. “This would be the most sensible thing to do given that there is no shortage of human sperm for research purposes.”
Even if it should one day become desirable to create chimeras capable of producing both eggs and sperm, “we could just take the appropriate measures for (the chimeras) to be segregated by sex.”
He also argues that — whether generated by humans or chimeras — human gametes “do not possess intrinsic worth capable of being debased” and that the eggs incubated by chimeras could go toward research “capable of saving people’s lives.”
Pierson said that, with focused work and funding, “this kind of work could be done in probably a year or less. This is not far fetched.”
“This is not about having a male mouse that’s ejaculating human sperm, coupled with a female mouse that’s ovulating human eggs and creating a human embryo in the mouse,” Pierson said.
Rather, among research questions, “It’s about understanding what our reproductive processes are — and what they could become,” he said. “We need to lay down the ethical principles for exploring these new types of ideas.”
Pierson said it could be the next step toward the completely lab-based generation of sperm and eggs. In vitro gametogenesis, or IVG, a technique still in its infancy, is aimed at creating functional sperm and eggs from induced stem cells. Last year, researchers in Japan reported in the journal Nature they had created mouse pups born from eggs created in a petri dish.
Pierson said any eggs generated from a nonperson chimera would likely come from a cow, and not a mouse, noting cows and humans share similar ovarian function.
NYU School of Medicine bioethicist Arthur Caplan said the technology is “a decade or more away and would need safety testing in animals for another few years, if it even worked.”
“Safety issues are huge for chimeras, just huge,” he added, including unknown mutations, subtle chemical differences in the derived eggs and the risk of communicating animal viruses.