Lulu and Nana: the children who will help change our morals

I first learnt about Lulu and Nana by watching the video that Chinese scientist He Jiankiu published explaining why he had edited embryos leading to the births of the first genetically modified babies. This is strongly recommended viewing. You can read the story, as broken by the AP, here. His claims have yet to be verified.

It was anticipated that the first International Summit on Human Gene Editing, held three years ago, would result in a consensus statement calling for a moratorium on genetically modified babies. There was no call for a moratorium. Since then, others have failed to call for a moratorium. Including the US’s National Academies report (which I covered here) which instead produced a checklist for when editing could be performed (p132), and the UK’s Nuffield Council report.

He published this video on November 25th, timed just before the Second International Summit on Human Gene Editing. He referenced the NASAM report in justifying his work. (Note also that He has engaged with several bioethicists over the years.) Some, e.g. Paul Knoepfler, argue that the failure to call for a moratorium “left the door too open” for his work. The second summit also did not call for a moratorium (their consensus statement).

There has been much criticism of He, for example Oxford’s Julian Savulescu, famous for arguing that we have a moral imperative to have the best children possible, described the work as “monstrous”; Penn’s Dr Kiran Musunuru described it as “unconscionable” (link). These voices included Chinese: Qiu Renzong, bioethicist and emeritus professor at the Chinese Academy of Social Science in Beijing, stated that the work was clearly not ethical, and a fraud (link).

While most have strongly condemned He’s work, some have taken a less accusatory stance. At the summit, Dr. George Daley, dean of Harvard Medical School, characterized He’s work as a “misstep” and argues “It is time to move forward from [debates about] ethical permissibility to outline the path to clinical translation … in order to bring this technology forward.” (link). George Church states “I feel an obligation to be balanced.”, calling the criticisms of He bullying.

Should the scientific community have acted differently? David Baltimore, the convener of the Second Summit, (reported by STAT) states that “I think there has been a failure of self-regulation by the scientific community because of the lack of transparency.” Scott Gottlieb, FDA Commissioner, goes further and says that the scientific community should not have given He a platform to self promote his work. “The response from the scientific community has been far too slow and far too tepid, and the credibility of the community to self-police has already been damaged… Governments will now have to react, and that reaction may have to take consideration of the fact that the scientific community failed to convincingly assert, in this case, that certain conduct must simply be judged as over the line” (reported in BioCentury). The work would have been illegal in the US. It also likely contravened Chinese laws (link). Lawyer Glenn Cohen questions that there could be a complicit scientific community, “it seems to me that the community is acting exactly as it should when one of its members breaks the covenant” (link).

The details of the research help highlight some open ethical issues. The aim of this research was to disable the CCR5 gene, a mutation that some people (though not Han Chinese) naturally have that is protective against HIV infection. The choice seems motivated to be a CRISPR first, rather than a pressing therapeutic need. Disabling a gene is much easier than precisely tweaking a “broken” gene to be functional. The desire for fame, to have a first, was a clear motivating factor for the research: the team wrote in their submitted ethics statement “In this ever more competitive global pursuit of applications for gene editing, we hope to be a stand-out”. Potential parents were only eligible for the study if the father had HIV. Infertile women are not eligible for IVF if their partner has HIV (link). The research is thus particularly question worthy as it a) blurred the lines between research, which is supposed to recruit individuals whose main aim is to contribute to scientific knowledge, and clinical application, where direct benefit is expected, b) edited healthy embryos, rather than seeking to “fix” those who would otherwise go on to develop a serious condition, c) individuals with the introduced edit have a higher chance of infection with the West Nile virus, and a higher chance of dying from influenza; as a protective mutation, d) the edit blurs the enhancement/therapy line, e) one of the embryos was known heterozygous (and hence would not have had the protective benefits) pre-implantation; whether the prospective parents could give true informed consent has been questioned. For the very real risk of off target effects, the consent form stated that “the project team is not responsible for the risk.” The case highlights just how ambiguous language is: An item on NASAM’s checklist was that editing be done for an “unmet” medical need. As Church points out, there is no cure or vaccine for HIV. On the other hand, HIV is both preventable and treatable.

What happens next? There are decisions ahead for any editor who receives the work to review. Francis Collins, who heads the NIH, has called for a “binding international consensus”. An editorial in Nature calls for a global registry of work genetically modifying human embryos. Carl Zimmer, writing in the New York Times, draws the parallel to babies born via mitochondrial replacement therapy, and the example of how the UK has made this legal within a highly regulated environment. Throughout this debacle, two reference cases have been given. The first is to Louise Brown, the first baby born by IVF. In the years around her birth, public opinion changed from being opposed to interfering with nature in this way, to being supportive of IVF (see Table 2 here). The second is to Jesse Gelsinger, who died in 1999 after receiving an experimental gene therapy. His death seems largely creditable to hastiness around excitement of a new technology. As George Church states, it is too early to tell whether Lulu and Nana will be Louise Browns or Jesse Gelsingers. But note that, post Jesse’s death, gene therapy is once again being pursued with gusto.

Why China? While international science incentives “firsts”, this may be acutely felt in China. As Jing-Bao Nie argues, “China’s science schemes have much to do with the developing mentality that ethics is merely secondary and instrumental for cutting-edge scientific investigation and technological invention”. Additionally, Chinese society places less emphasis on the individual: As Antonio Regalado reports here, “A person who knows He said his scientific ambitions appear to be in line with prevailing social attitudes in China, including the idea that the larger communal good transcends individual ethics and even international guidelines.” Indeed, He commissioned an opinion poll that found majority support of the Chinese public for therapeutic genetic modification (this is inline with polls in the US).

I think we will see public acceptance of genetic modification of embryos, first in the therapeutic setting, and probably first in a country such as China. As we have learnt time and again from the Assisted Reproductive Technologies space, technology does change morals.

One thought on “Lulu and Nana: the children who will help change our morals

  1. Pingback: Round-up Nov 11 – Dec 21 – All The Coolest Genomics

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