EXECUTIVE SUMMARY
Stringent oversight might be necessary in order for heritable germline editing clinical trials to be conducted, according to a new report indicating use of the technique could be ethically permissible, but only for treating or preventing serious diseases.
- Moving heritable editing of DNA in the nucleus to the realm of possibility is the clearest break from prior norms.
- There is a need for encouragement of public engagement.
- The issue of human enhancement will likely be revisited as technology improves.
Clinical trials on genome editing of the human germline are within the realm of possibility — but only for serious conditions under stringent oversight, concluded a new report from the National Academies of Sciences, Engineering, and Medicine.1
“It was no longer realistic to say that it couldn’t happen. It isn’t possible now, but sometime in the not-so-distant future, it probably will be. Therefore, it’s no longer credible to say, ‘We’re never going to do it,’” says Richard O. Hynes, PhD, co-chair of the committee that produced the report.
Not surprisingly, the question of whether human germline editing should be performed at all was easily the most hotly debated aspect of the committee’s work.
“In the past, it’s always been assumed that we wouldn’t do that — that one couldn’t do that. We didn’t say it should happen now, but we didn’t say it should never happen,” says Hynes, a researcher at the Massachusetts Institute of Technology’s Koch Institute for Integrative Cancer Research in Cambridge.
Genome editing has already entered clinical trials for non-heritable applications, but should be allowed only for treating or preventing diseases or disabilities at this time, says the report. The committee decided on several criteria that should be met before allowing germline editing clinical trials to go forward.
“That was obviously the biggest serious issue,” says Hynes. “We spent a lot of time thinking about the pros and the cons, the reasons for doing it, and the reasons for not doing it.”
R. Alta Charo, JD, Warren P. Knowles professor of law and bioethics at University of Wisconsin Law School in Madison and co-chair of the committee, agrees. “Moving heritable editing of DNA in the nucleus from ‘unthinkable’ to ‘maybe, but only if,’ is the clearest break from prior norms,” she says.
Ethical Framework Needed
The following are the two biggest ethical concerns Charo sees currently:
- the risk that some basic science will be hindered by debates surrounding use of gametes and embryos in research;
- that development of somatic therapies and preventive strategies will be complicated by concerns about off-label use for so-called “enhancement.”
Hynes says that the ethics of human genome editing, while certainly complex, aren’t entirely unique. Stem cell research and in vitro fertilization pose similar ethical questions.
Hynes believes having a set of principles to guide thinking about human genome editing is very important, “not just for the U.S., but internationally,” as a framework for countries with widely varying views on the practice to consider.
Hynes notes, “Some communities, such as those facing the challenges of inheritable diseases, really think the procreation of genetically engineered children is a crucial thing to do.” Other countries take a completely contradictory view: that scientists shouldn’t interfere with natural processes.
“It has to be thought about internationally,” says Hynes. “We have to deal with the fact that the cultures are different.”
Additionally, some countries are poorly regulated. “We can’t tell another country how to run their show,” says Hynes. “But we can think about how to influence how they do it.”
The committee spent a good deal of time discussing the ethical implications of human enhancement. “The term ‘designer babies’ is often used, but means different things to different people,” says Hynes. “That’s controversial, and it should be. People should think about that very hard, although the more extreme scenarios, such as producing children with higher intelligence, are completely unrealistic at this time.”
Somatic gene editing holds promise for treating patients with a genetically inherited disease — such as sickle cell disease — by editing cells from that person and putting them back — not heritably, but just for that individual patient.
“Somatic gene editing is becoming more and more possible. New genome editing technologies are more accurate, cheaper, and easier to do,” says Hynes. “So that’s going to accelerate. Some applications are already in clinical trials, and there will be many more.”
Virtually everyone agrees that treating or preventing disease is a good thing. With a muscular dystrophy patient, for instance, the patient’s muscles could be improved using this approach. “People are working on it and it will happen,” says Hynes.
Successful use of the technique to treat diseases opens the door to the possibility of human enhancement. Similar techniques could be used to make muscles stronger in a healthy person, for instance.
“That has all sorts of societal implications that we need to think about. And we said, ‘Not now,’” says Hynes. “It’s not so clear that there are benefits to making somebody stronger than they were.” Therefore, the risk/benefit ratio would not allow enhancement to be approved by the FDA — at least not at this point.
“That could change over time. The risks will fall, and will be understood better,” says Hynes. In the near future, people may want to use gene editing to improve themselves. For instance, it could be possible to increase resistance to infectious diseases. “It’s a very difficult line to draw. Where do you say it’s OK — and where do you say it goes too far?” asks Hynes.
Gene therapy has been performed for some time, adds Hynes, “but not very effectively, because the technology wasn’t very good. It’s much better now, and it will work, for sure, for some things.” When the science improves, issues like enhancement will certainly come up, but the committee was clear that human enhancement should not happen.
Hynes acknowledges that this is a moving target. “Decades down the road, it will probably have to be looked at again,” he says.
Some ethical issues involving gene editing can be addressed with regulatory guidance. Others, like the issue of some people making themselves stronger and others unable to afford it, are broader in scope. “These are societal issues, as much as technical ones,” says Hynes.
Seventy-three percent of Americans predict gene editing will become available before it has been fully tested and understood, found a recent Pew Research survey.2 Opinions were closely divided on whether such techniques are “meddling with nature,” or no different from other ways that humans have tried to better themselves. Regarding human enhancement, 73% of respondents believe inequality will increase if brain chip implants become available, because initially they will be obtainable only by the wealthy. Most respondents felt that the downsides would outweigh the benefits for society.
“The public is diverse and comes to these things with multiple points of view,” says Hynes, adding that there is a need to foster public engagement and promote discussion. In the United Kingdom, the issue of whether to allow mitochondrial replacement therapy, a type of assisted reproduction that could allow some families to avoid passing on genetic disease, was debated in 2016. “There was a serious effort made to inform the public, then listen to what they had to say,” notes Hynes. The British government asked the public to share their thoughts; the eventual decision was made to allow the procedure. “The public basically said, ‘If kids are going to have a dreadful disease, why not fix it?” says Hynes.
The public can contribute points of view on human genome editing that a group of scientists and ethicists might not necessarily have thought about. “I think we all agree that’s something that should be part of the way we think about these things going forward,” says Hynes.
REFERENCES
- National Academies of Sciences, Engineering, and Medicine. 2017. Human genome editing: Science, ethics, and governance. Washington, DC: The National Academies Press.
- US public wary of biomedical technologies to ‘enhance’ human abilities. Pew Research Center, Washington, DC (July 26, 2016).
SOURCES
- R. Alta Charo, JD, Warren P. Knowles Professor of Law & Bioethics, University of Wisconsin Law School, Madison. Phone: (608) 262-5015. Fax: (608) 262-5485. Email: [email protected].
- Richard O. Hynes, PhD, Howard Hughes Medical Institute, Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge. Phone: (617) 253-6422. Fax: (617) 253-8357. Email: [email protected].
Stringent oversight might be necessary in order for heritable germline editing clinical trials to be conducted, according to a new report indicating use of the technique could be ethically permissible, but only for treating or preventing serious diseases.
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