Ethical Controversy Erupts Over Human-animal Embryo Research

EXECUTIVE SUMMARY

The National Institutes of Health has proposed lifting a moratorium on funding of certain controversial experiments using human stem cells to create animal embryos that are partly human. Some ethical concerns include the following:

• Once research is underway, scientists could find reasons to cross additional ethical boundaries.
• Research might not live up to the public’s expectations for curative treatments in the short term.
• The issue of making chimeras hasn’t been the focus of widespread public debate.

Do animals with partly human brains, or producing human embryos, sound like science fiction? Some worry that creating “chimeras”— embryos with cells from more than one species — opens the door to just such possibilities.

“The most basic ethical concern is whether the value of human life will be degraded by this research,” says Karey A. Harwood, PhD, associate professor of religious studies at North Carolina State University in Raleigh.

Years ago, some ethicists raised the same concern about in vitro fertilization. “They worried that turning reproduction into a process of manufacture would somehow put the product of that effort — the child — on a lesser moral plane from its parents,” says Harwood.

The issue is now being raised regarding scientific research that deliberately mixes human and animal cells. “The concern about reducing humans to their component parts, to be used instrumentally for some distant end, will very likely reawaken these same worries, perhaps for good reason,” says Harwood.

Thomas V. Cunningham, PhD, MA, MS, medical bioethics director at Kaiser Permanente West Los Angeles, says that there are both practical and theoretical issues with chimeras. An important theoretical question is their “moral status.” “Just as we might ask about the moral status of human embryos produced by fertilization in vivo or in vitro, we can now consider the same question for human-nonhuman embryos,” he says.

The National Institutes of Health (NIH) recently proposed lifting a moratorium on funding of certain controversial experiments that use human stem cells to create animal embryos that are partly human.

“Formation of these types of human-animal organisms, referred to as ‘chimeras,’ holds tremendous potential for disease modeling, drug testing, and perhaps eventual organ transplant,” NIH’s associate director for science policy and director of the Office for Science Policy, Carrie Wolinetz, PhD, recently wrote in a blog about the draft chimera policy.¹ However, multiple ethical concerns are raised by such research. NIH is establishing an internal steering committee to provide input on funding decisions for research that include the following:

• Human pluripotent cells are introduced into non-human vertebrate embryos, up through the end of gastrulation stage, with the exception of non-human primates, which would only be considered after the blastocyst stage.
• Human cells are introduced into post-gastrulation non-human mammals (excluding rodents), where there could be either a substantial contribution or a substantial functional modification to the animal brain by the human cells.

Any research falling inside this scope will trigger the review of the steering committee. “That’s not a restriction and it’s not a prohibition. It’s just another look, a careful consideration of the research, to make sure we are being thoughtful about animal welfare and ethical considerations,” Wolinetz said during a media phone call. She expects scientists to confront difficult ethical issues for years to come. “There are no hard and fast lines,” she said. “I expect this is going to be an evolving set of thinking as we understand more about the human brain.”

Where to Stop?

Once research on chimeras begins, there could always be medical or scientific reasons to push the boundary still further, experts say. “There is no obvious place to stop. For that reason, it’s an extreme step for civilization to do this,” says Stuart A. Newman, PhD, professor of cell biology and anatomy at New York Medical College in Valhalla.

If researchers start making animals that are partly human, there might be some incentive to make animals that are more human, or even mostly human. “There have been proposals to make chimeras with animal brains so that tissues can be harvested from a human body even without a human brain present,” says Newman.

Many people believe that the possibility of finding cures for diseases justifies crossing some ethical boundaries. “They might say, that to really do this work thoroughly and scientifically, they need to put a whole human brain in a sheep or pig,” Newman says. While such research might be abhorrent to many, he says, “there are always going to be people who see benefits in taking it further than most people are comfortable with.”

Down the line, researchers might contemplate doing things they previously thought were unacceptable. “People who have reservations about taking a technique further can be depicted as old-fashioned, anti-science, or just not getting with the program,” says Newman.

In 2015, the U.K. Parliament approved a controversial “three-parent” procedure to prevent mitochondrial disease. “The public was sold on that, even though it’s a very extreme procedure which created potentially harmful gene combinations that could be passed to future generations,” says Newman. “People who had reservations about it were called anti-progress.”

Newman sees a parallel in research on nuclear chain reactions which ultimately lead to the development of the atomic bomb. He points to the 70 scientists who signed a letter urging President Truman not to use the atomic bomb on Japan before that nation had been given a chance to surrender.

Newman says that similarly, today’s bioethicists need to bring to light the possible unintended consequences of chimera research.

“Unless we put on the brakes in some way and describe these things for what they really are, people are going to wake up and find out things are going on that they never would have approved of,” says Newman.

In the U.S., there are no laws prohibiting use of animal or human embryos for research. Even without NIH funding, other organizations are funding chimera research, including the Oakland-based California Institute of Regenerative Medicine.

“It really is kept off the public agenda in some ways,” says Newman. “Most people don’t have opinions about embryos, except if they are talking about abortion.” The separate issue of using embryos for research or making chimeras has, thus far, not been the focus of widespread public debate. “If the issue were truly discussed openly, I think you would have great differences of opinion,” says Newman.

The unresolved question is which ethical lines are morally acceptable to cross. Ideally, this distinction is made on the basis of careful reasoning and good evidence. Harwood says, however, “more often, it seems to be based on the evolving, arbitrary, and unpredictable comfort level of the popular majority and mainstream media.”

It’s unrealistic to assume that the purpose of chimera research is self-evident to everyone. “There is always great potential for the public to misunderstand the basic scientific facts underlying an ethical issue,” Harwood says, noting that heart transplants were originally met with strong resistance. “For this issue to get a fair hearing, the scientific community will need to educate the public.”

Cunningham expects some groups to paint chimera research as “heinous, frightening, and a slippery slope to genetic engineering and eugenics.”

When Cunningham and colleagues recently examined how policymakers and scholars talked about embryo experimentation from the 1970s through the present day, they found attitudes had changed quite a bit.

“There appears to be more support for the research by these groups than there was in the past,” he says. “Yet, there also appears to be a consensus that these practices need to be carefully regulated.”

Not All Benefits Practical

Researchers might fall short of the public’s hopes for curative treatments in the short term, and instead, simply gain knowledge. “Sometimes things we learn about now don’t pay off for many years,” says Cunningham.

If the practical payoff of chimera research is remote, that makes it difficult for the public and policymakers to understand why it’s necessary. “Unless one is quite savvy in understanding the history of scientific progress and the regulatory environment, then it is easier to see this research as superfluous and overly risky, rather than seeing it as incremental progress that may lead to a paradigm shift,” says Cunningham.

If research on chimeras is hindered by lack of funding without adequate justification, scientific and medical progress could be unnecessarily thwarted. “The worry is that if we do not allow regulated research to proceed, then we will not learn valuable information that would help us as a society,” says Cunningham.

He points to recent research showing how somatic cell nuclear transfer could be used to create embryonic stem cells in both primates and humans — procedures that, in theory, could be used to treat mitochondrial disease.²

“This team uses methods that some would find morally objectionable,” says Cunningham. “Yet others find their work extraordinarily promising.”

REFERENCES

1. National Institutes of Health Office of Science Policy. Next Steps on Research Using Animal Embryos Containing Human Cells. Aug. 4, 2016.
2. Ma H, Folmes CDL, Wu J, et al. Metabolic rescue in pluripotent cells from patients with mtDNA disease. Nature 2015;524:234-238.

SOURCES

• Thomas V. Cunningham, PhD, MA, MS, Medical Bioethics Director, Kaiser Permanente West Los Angeles. Phone: (323) 857-3431. Email: [email protected].
• Karey A. Harwood, PhD, Department of Philosophy and Religious Studies, North Carolina State University, Raleigh. Phone: (919) 515-6383. Email: [email protected].
• Stuart A. Newman, PhD, Department of Cell Biology & Anatomy, New York Medical College, Valhalla. Phone: (914) 594-4048. Fax: (914) 594-4653. Email: [email protected].