What Just Happened? Looking Back at 2017’s Human Germline Editing Developments

Last January, CGS predicted that gene editing would be one of the biggest science stories of the year. This has been proven true in the numerous developments that unfolded in 2017, in areas ranging from gene drive to gene-edited animals to gene therapy. In the arena of human germline editing, also known as inheritable genetic modification, the year saw a number of important news stories in the realms of policy discussion and scientific research. Here are some of the most important, along with a brief glance into what to expect in 2018.

Policy deliberations

• In February, a committee of the National Academy of Sciences (NAS) and National Academy of Medicine (NAM) released a report, Human Genome Editing: Science, Ethics, and Governance, which recommended moving to clinical trials with human germline gene editing in certain limited circumstances. Limitations notwithstanding, this represented a radical and dangerous departure from the long-standing international consensus that interventions in the human germline should remain off limits. It also constituted a reversal of the recommendation that the NAS itself made just over a year earlier, that moving forward with this technique in humans would be irresponsible without first establishing a “broad societal consensus.” (For more information, see here.)
• In May, the Nuffield Council on Bioethics, a UK-based independent body whose examinations and reports on ethical issues in biology and medicine have a history of influencing UK policy, began circulating an online survey on the ethical implications of using gene editing for human reproduction. A number of scholars and public interest advocates disapprovingly noted what appeared to be the obvious bias in the survey that privileged individual interests over those of society, and led respondents to conclude the technique was safe and ethical. (For further critique of the survey, see here.)
• In October, the Council of Europe held a conference celebrating the 20^th anniversary of the Oviedo Convention. The 1997 Convention is a key international policy touchstone, as it includes a provision that effectively bans human germline modification for reproduction. While it was surprising that a few speakers from the UK and Poland argued in favor of an individual rights perspective and re-evaluation of the Convention’s ban on human gene editing for reproduction, it was clear that support for the ban remains strong at the Council of Europe. The conference occurred just weeks after the organization’s Parliamentary Assembly recommended that the Committee of Ministers urge member states that have not yet ratified the Oviedo Convention to do so, or at a minimum instate a national ban on establishing a pregnancy with germ cells or embryos that have undergone genome editing. (For more on the anniversary conference, see here.)
• In November, the US Senate Health, Education, Labor, and Pensions (HELP) Committee held a hearing on “Gene Editing: Innovation and Impact .” The hearing explored CRISPR gene editing technology and its potential uses, featuring testimony from three witnesses: Dr. Matthew Porteus from Stanford University, Katrine Bosley of Editas Medicine, and Dr. Jeffrey Kahn, from Johns Hopkins School of Public Health. You can read more about hearing and CGS’s written testimony to the committee here.

Scientific research

2017 saw the publication of results from four studies involving editing human embryos, bringing the total number of such publications to six.

• In March, a research team in China published an account of the first CRISPR gene-editing experiments on viable human embryos, although their work showed many problems with off-target effects and mosaicism.
• In August, Shoukrat Mitalipov and his team at Oregon Health and Sciences University were the first to edit human embryos in the US. The researchers targeted a mutation associated with hypertrophic cardiomyopathy. They claimed success with 72% of embryos exhibiting the wild-type (unaffected) allele (vs. the expected 50%), with little to no mosaicism or off-target effects. Disturbingly, in his many media interviews, Mitalipov expressed his desire to bring germline editing into fertility clinics as soon as possible. His intensive focus on clinical applications seemed to overshadow their reported discovery of a new mechanism of DNA repair in embryos, although this finding has been challenged by prominent researchers in the field. Mitalipov so far stands by the findings and has responded that it will take more research by his team and others to reproduce and confirm his findings. However, many have pointed out that this kind of research, which requires creating human embryos, would not be allowed in most US states and many countries, and the research necessary to confirm these findings could require thousands of embryos. (For more, see our press statement and analysis of questionable media coverage.)
• In September, we saw the first publication from Kathy Niakan’s group at the Francis Crick Institute in London, which received the first (and, so far, only) HFEA license to conduct human germline editing research in the UK. Niakan’s group used CRISPR to disable a gene and show that it is essential to the very early development of embryos. Niakan’s research differed from Mitalipov’s in several key ways. Niakan used existing embryos leftover from IVF treatments, whereas Mitalipov created over 100 embryos for his experiments. Niakan also focused her research on basic scientific questions, not refining gene editing techniques for use in clinical reproductive contexts.
• Also in September, we learned about an additional study from Chinese researchers led by Junjiu Huang (in fact, the same team that published the first human embryo-editing study in 2015). Their research used a new technique called “base editing” on human embryos to “correct” a genetic variant that causes beta-thalessemia. The technique allows researchers to alter a single letter in the genetic code. This study was also notable because the embryos used were created from induced pluripotent stem cells using somatic cell nuclear transfer, or cloning.

Many of these developments are unsettling, as they indicate both a clear desire among a few scientists to rush ahead into human germline modification, and the critical need for a social justice perspective in policy deliberations. The prominence of a narrow individual rights framing in policy discussions is particularly concerning. In the realm of research, it was disappointing that Mitalipov’s transgressive work was not more heavily criticized by his peers. The difference between this summer’s headlines and reactions and those that followed the first rumors of embryo editing studies in 2015 is striking. However, by year’s end, many publications seemed to be more impressed by 2017’s developments in somatic gene therapy than in germline editing.

Despite the tone of some recent policy discussions, both the Oviedo Convention and germline modification bans in dozens of countries are still in effect, and many have been reaffirmed in recent years. And although there is no such federal ban on germline editing in the US, “soft law” at the NIH and FDA prohibit federal funding and consideration of clinical trials. Public opinion shows continuing concern about germline modification, and significant figures across a range of fields have expressed opposition in response to recent events.

What developments in the arena of human germline editing will CGS be on the lookout for in the coming year? We expect to see continued policy-related discussions and publications in 2018. The Nuffield Council plans to release its report on human gene editing for reproduction this Spring; it could influence UK policy similarly to how their 2012 evaluation of 3-person IVF techniques contributed to the procedure’s legalization in the UK. According to a witness at the November Senate HELP committee hearing, the US National Academy of Sciences plans to have an international meeting on the topic in China at some point during the year.

In the area of research, we could see ongoing developments in the debate over Mitalipov’s purported findings, and perhaps additional publications from Niakan, Mitalipov, or Huang. It’s also possible that we will see a first publication from Fredrik Lanner of the Karolinska Institute in Sweden, who has been conducting embryo editing experiments, but has not published yet.

The events of 2017 and prospective developments of 2018 underscore the urgent need for broad public and civil society engagement. The stakes are too high and the potential risks too far-reaching for decisions about germline gene editing to be made by a few scientists or small panels of experts. In 2018, CGS will continue to promote engagement with diverse publics and work to bring our critical social justice framework to public and policy discussions of human genetic modification.