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Ethical and science conundrum: Did reporters, scientists miss nuances of embryo gene-editing story?

| April 24, 2015
embryo
CREDIT: Flickr/wellcome images
This article or excerpt is included in the GLP’s daily curated selection of ideologically diverse news, opinion and analysis of biotechnology innovation.

“To the crack of doom” ran the headline in The Economist, reporting on the now infamous research study by Chinese investigators that gene-edited human embryos.

“Critics Lash Out At Chinese Scientists Who Edited DNA In Human Embryos,” reported NPR, quoting numerous hyper critical scientists and bioethicists.

“No researcher should have the moral warrant to flout the globally widespread policy agreement against modifying the human germline,” claimed Marcy Darnovsky, a philosopher who runs the Center for Genetics and Society, a watchdog NGO that has taken a stance against embryo gene editing since the earliest days of this technology.

In the days since Nature News reported the story that Chinese researchers had, for the very first time, manipulated a human embryo and potentially impacted the germline, almost all the reporting has focused on the ‘ethical red line’ that been crossed and the potential unintended consequences of this technology.

Without a doubt, gene-editing has brought with it probably the biggest ethical question in the past decade. But it’s worth taking a step back to consider if the overheated discussion among scientists and the mass media attention is making us all look in only one direction, missing some of the genuine breakthroughs in this study and research in this area in general.

Are researchers commenting on this issue and journalists reporting them following the same thread, and in doing so potentially overstating consequences that we might face if we let research continue? Let’s review the evidence and the reporting.

Are we seeing only one side of the issue?

To be very clear, we are still quite far away from having a baby born from a genetically edited embryo, but it also seems like we are closer than ever before to having that happen. This advance is an “ethically charged first,” as Antonio Regalado, a journalist at MIT Technology Review reported. Regalado also wrote about rumors of several research groups involved in such an effort in a previous excellent feature piece for the same publication.

The current news also came in the wake of recent widespread calls for a moratorium on human germline genetic modification by pioneers in the field of gene editing and other leading researchers including Nobel laureates. It was no surprise then, that the news sent waves rippling through media (print, online and social), with every news report questioning the ethics of the research and what might happen next.

One interesting fact that is that the paper was rejected by both Nature and Science, two of the top three journals in the world, because of ethical concerns–but not on science grounds. Instead the study was published in the open access journal Protein & Cell. Rockefeller University cognitive neuroscientist John Borghi noted on Twitter that the paper was published after what apparently seems to be little more than a day of peer review, a process that normally takes weeks, months and in some cases even more than a year. In the eyes of some, this made the results of the study questionable in the first place, although others have noted that alternative explanations are possible for the contracted time span (this aspect of the study is seemingly as interesting as the main theme, with the potential to reveal what really happened with the peer-review process).

That aside, every news article on this issue has pointed out the limitations of gene editing that the study exposed (which the senior authors guiding the study, Canquan Zhou and Junjiu Huang explicitly laid out as well) – so no need to discuss that further here. Instead, let’s look at the various reactions that this study has elicited, almost all of which have expressed concern regarding the inefficacy of the technique and the ethical questions it prompts.

“This paper demonstrates the enormous safety risks that any such attempt would entail, and underlines the urgency of working to forestall other such efforts,” said CGS’ Darnovsky, who was quoted in numerous publications harshly criticizing the study and the research in general. “The social dangers of creating genetically modified human beings cannot be overstated.”

The NPR piece quoted scientists as well, including George Daley, a stem cell researcher at Harvard.

Their data reinforces the wisdom of the calls for a moratorium on any clinical practice of embryo gene editing, because current methods are too inefficient and unsafe,” he wrote in an email. “Further, there needs to be careful consideration not only of the safety but also of the social and ethical implications of applying this technology to alter our germ lines.

What was so interesting is that many reporters seemed to have interviewed only harsh critics of the procedure, including many who have signed on to statements condemning the research. For example, Nick Stockton writing in Wired, only quoted authors who have signed a widely-circulated statement demanding a moratorium on this research. Predictably, all of those interviewed rang alarms and reiterated their calls for a slow down or halt on this kind of research.

Indeed, search Google News for ‘gene editing’ and all you will find are worrying headlines. In a story that seems to have many more layers than what appears on the surface, or is being reported on by deadline challenged journalists, are we missing out details??

Nuances

At the Genetic Expert News Service (GENeS)–a new project that solicits opinion on breaking controversial genetics stories from scientists, and sends their unedited quotes directly to journalists and policy makers–we reached out to gather comments from a variety of researchers with expertise on different aspects of this issue. In the course of our outreach we were also able to collect comments from experts who had not publicly expressed their desires to halt such research (see full disclosure at end of this report). GENeS, which launched two weeks ago, discovered that that on this controversial issue, although the broad tone of the comments reflected concern, the issue seemed was much more nuanced than what most of the reporting implied.

Speaking to GENeS, Linzhao Cheng, a professor at Johns Hopkins University who had previously collaborated with one of the corresponding authors’ on a different study but was not aware of the current research, pointed out that in the larger picture this was an impressive first that has in no small way advanced biomedical research and understanding.

It’s not a trivial experiment. They are basically pioneering this technique so that we know how to do it more efficiently with human embryos (in this case tri-pronuclear embryos). I think the results are not bad at all for the first paper on this topic. People’s expectation that this can be used for treating patients is very high. In that sense, the success rate of edited embryos reported is not high enough. But I would give the authors credit for reporting what they achieved. If they had reported a higher rate I would be much more skeptical as to whether it was real.

Scientifically, I think it’s a solid paper and well worth publishing, provided they followed the proper procedures for consent for the IVF embryos to be discarded, as well as to follow the local regulations in China. Given China has a large population needing IVF, the authors took advantage of the availability of the defective embryos to be discarded and used them in the current study. I can imagine that many other IVF clinical centers in China have similar resources, and the technical capacity for a similar approach.

But, he also noted that the study comes at a very unique time when we are grappling with larger questions about the risks and rewards of gene editing,

The paper has been published in the center of a perfect storm. There are many societal issues associated with the applications of the powerful CRISPR technology. The paper itself is not controversial, due to the fact the research is on ‘tri-pronuclear’ embryos that cannot fully develop beyond the blastocyst stage.

I don’t think anyone knows whether the same results would be seen in viable embryos. This is a typical Catch-22 situation. Many people are concerned that we shouldn’t be doing this, even in abnormal embryos that would arrested at the blastocyst stage and otherwise would be discarded. If many people have deep concerns about doing it even in non-viable embryos then how will we ever find out whether using a normal embryo would be better or worse?

Similarly, comments collected from UK researchers by the Science Media Centre (SMC) in the UK (whose basic model GENeS emulates) revealed some largely unreported nuances as well. Robin Lovell-Badge, Head of the Division of Stem Cell Biology and Developmental Genetics at the MRC National Institute for Medical Research in London echoed some of the thoughts of Linzhao Cheng and emphasized the importance of such research to not only generate promising therapies but also advance understanding of basic biology,

The possibility of using such methods to genetically modify human embryos, and therefore humans, has been on the cards since these methods were first described, and recently these prospects have been brought to the attention of the public through several commentaries made by senior scientists and commentators, some of whom have called for a moratorium to halt any attempts.

I disagree with a moratorium, which is in any case unlikely to work well, indeed I am fully supportive of research being carried out on early human embryos in vitro [in culture/in the lab], especially on embryos that are not required for reproduction and would otherwise be discarded. If the techniques work, there are many interesting questions that could be asked about the role of specific genes in early human embryo development, especially as there is accumulating evidence that equivalent stages of embryos from other mammals, notably the mouse from which most of our understanding has come, may rely on the activity of different genes.

Importantly, he also provided alternative scientific hypotheses as to why there might have been signicant off-target effects which has been a thorny issue in the discussion surrounding this study,

The authors used abnormally fertilised embryos, presumably because they did not want to be accused of using embryos that could undergo development to term if implanted. However, it is possible that the DNA repair mechanisms that are more likely to lead to errors have been activated in such abnormal embryos, as these struggle to cope with an abnormal genetic complement (they are triploid rather than diploid), and are destined to block early in development. Secondly, it would have made sense to test out the techniques and reagents (notably the “guide RNA”) using human embryonic stem cells, which would be more similar to human embryos than the somatic cell line they used. They also chose a gene target that might itself be problematic, given that it is part of a closely linked family of globin genes with highly related sequences, making it hard to target one without affecting the others.

Lovell-Badge also noted the fact that the paper was first rejected on ethical grounds and this overreaction might have been circumvented had the experiment been done under the regulatory framework present in the UK. While making it exceedingly clear that “it would be illegal to implant any such manipulated embryo into a woman for further development,”

[…]  it is clear that if the work had been done in the UK, with the excellent regulatory system we have provided by the HFEA (Human Fertilisation and Embryology Authority), any ethical concerns would have had to have been solved before the work could have been started, as it would require a licence from the HFEA. Indeed, with a licence, research of this sort could be conducted in the UK, and, with justification, it would be possible to use normally fertilised embryos.

Indeed, a lot of the fuss about the possibility of germline gene editing is misplaced, because there are very few instances where it would be necessary to correct a gene defect (which was the ultimate aim of the work reported here), because alternative techniques, notably pre-implantation genetic diagnosis (PGD), can be used to choose embryos for implantation that would not develop diseases such as beta-thalassaemia.”

Carl Zimmer did better than most journalists in putting this in perspective, comparing this research to the early days of cloning, pointing out that while cloning is a well established technology now that is used under regulation, at one time it was pretty unpredictable and open, until there were broadly agreed upon terms for safe use of the technology. And then he makes this elegant point on the future of gene editing in humans,

We still don’t clone people, though–not because we can’t, but because we choose not to. We may need to make the same choice about editing embryos before too long.

But the choice about gene editing is going to be much harder than cloning, simply because of the therapeutic promise it holds for all of humanity. And this issue is by no means as simple as the news suggests. The fact is that scientists are pioneers and explorers, and the hope of discovering new lands is what drives them (and our society) in the first place to push the envelope. So, it isn’t unreasonable to think that this study could spur other researchers to experiment with (non-viable?) human embryos in order to improve its efficacy even though it might test the limits of the ethical conundrum that is geome editing technology.

Let’s also remember that efforts that challenge our moral compass have always existed and will continue to do so. But this is a good time as any to ask: Will the Chinese study be the final straw that broke the camel’s back, forcing a moratorium? Is this the ‘Asilomar moment’? Is it time for something more than a moratorium even? We don’t know yet, but we should, very soon.

No matter what happens, it’s just getting started, so buckle up and keep up with the news because this is going to affect all of us.

Arvind Suresh is a science media liaison at the Genetic Expert News Service. He is also a science communicator and a former laboratory biologist. Follow him @suresh_arvind.

Additional Resources

Disclosure: I’m a member of the staff at GENeS which provides rapid access to scientific expertise and opinion on the latest genetics and biotechnology news. GENeS is an independent project affiliated with the World Food Center Institute for Food and Agricultural Literacy at University of California, Davis and funded in part by the Genetic Literacy Project. For more information see our website.

 

The GLP featured this article to reflect the diversity of news, opinion and analysis. The viewpoint is the author’s own. The GLP’s goal is to stimulate constructive discourse on challenging science issues.

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