Stopping or Selling Human Germline Modification?

One failed experiment can crystallize a discussion. On April 18, a paper describing an attempt to use CRISPR gene-editing technology to modify a human embryo was published in Protein & Cell, an obscure Chinese journal. On April 22, Nature, which had rejected the paper on ethical grounds, published a news article about the publication, which was the first many people had heard of it. And then pretty much everyone in the biotech/bioethics world had something to say.

The pump had been primed by recent commentaries in Nature and Science that called, with significantly different emphasis, for a moratorium on human germline interventions. An earlier widely circulated article in MIT Technology Review had suggested such experiments were soon to be published.

Creating genetically modified humans has long been seen as dangerously unacceptable, and is prohibited by law in dozens of countries. Until the recent advent of new gene-editing tools, scientists had also refrained from human germline experiments.

The Center for Genetics and Society’s reasons for supporting these prohibitions are described in these press releases (1, 2) and this backgrounder. In short, CGS supports the prospect of somatic gene therapy, which if successful would help consenting patients by treating disease but would not affect their descendants; and opposes inheritable genetic modification (or germline intervention) for multiple reasons, including dire safety risks, ethical considerations and social consequences.

Most responses to the prospects of GM humans can be roughly grouped into a few categories, each of which covers a spectrum of views: opposition, either permanent or conditional; calls for dialog, with varying implications; and support, even enthusiasm. Views also vary on whether, when and under what conditions it would be appropriate or acceptable to modify the genes of human embryos for research purposes.

The lines are frequently blurry, and not everyone is convinced of the good faith of those with whom they disagree. Moreover, the discussion has so far largely been confined to professionals working in the field — researchers and bioethicists. The controversy has now reached the national and international media, and anecdotally there is growing public awareness. But we’re nowhere near the broad participation that the high stakes of this conversation demand.

What follows is by no means complete, but an attempt to lay out the current parameters of the evolving discussion. Links are included below, including to some of the most useful summaries, and readers are encouraged to follow them for further clarification.

Don’t Do It

Edward Lanphier of Sangamo BioSciences and the Alliance for Regenerative Medicine, with four co-authors, laid down an early marker on March 12, with an op-ed in Nature succinctly titled:

Don’t edit the human germ line

They opposed not only creating and bringing to term genetically modified humans but also "research involving genetic modification of human germ cells.” That is an important distinction, and controversial even among those who firmly oppose using heritable genetic modification for reproductive purposes. Those who support germline modification argue for continuing research to establish safety (if possible, which is by no means certain). Those who oppose such applications are concerned that such research "could be exploited for non-therapeutic modifications,” as Lanphier et al. wrote.

They called for a moratorium — the term “ban” is evidently considered impolitic, although many countries and international organizations have in fact banned germline intervention. Many prominent figures agreed with all or part of their approach. Broad Institute Director Eric Lander asserted that there is "no therapeutic application he could think of that would justify gene editing in human germline cells” and said:

"The call for a moratorium isn't based on a probability calculation that someone will do it. We need to truly ban this from a moral standpoint. We should forbid this for at least a while — not by law, but by agreement."

Francis Collins formally reiterated NIH policy against funding "any use of gene-editing technologies in human embryos." The Society for Developmental Biology agreed [pdf]. The International Society for Stem Cell Research called for a moratorium on clinical applications, but not research.

In addition to CGS, several activist organizations including Human Genetics Alert, the Council for Responsible Genetics and the International Center for Technology Assessment have long opposed human germline interventions. So have many religious commentators, sometimes with secular arguments such as control (referencing C. S. Lewis and The Abolition of Man). It is heartening to see that many scientists, faced with a developing technology, are willing to take a critical stance.

Calls for Dialog

Everyone says they support wide-ranging discussion of the prospect of genetically modified humans. Just how wide-ranging is a point of contention, with some scientists apparently insisting on technical expertise as a precondition for decision making, or preferring that scientists keep the conversation close and proceed with voluntary agreements or self-regulation, or assuming that “public participation” means that they will educate the public to let them do what they want.  Bioethicists and other experts naturally disagree, as do public interest advocates and everyone committed to democratic participation. 

A week after the Nature article by Lanphier et al., Science published one by Nobel laureate David Baltimore and 17 others titled:

A prudent path forward for genomic engineering and germline gene modification

This may not be quite the cynical, enabling position it seems to be at first: it likely represents a compromise among widely varying views. The Science commentary arose from a meeting organized by CRISPR expert Jennifer Doudna, who has previously expressed ethical doubts about the practice and its possible “dark side." But the co-authors also include Harvard expert George Church, who has frequently been enthusiastic about human germline interventions.

Another co-author was Stanford law professor Hank Greely, who thinks that the fuss has been overstated, because the technology will not be practical in humans "for a long time, if ever.” Nobel laureate Craig Mello seems to agree, saying "It’s not something that’s going to be easy, cost-effective or safe, given existing technology,” (Mello’s position has, however, also been characterized as, if it’s safe, go for it.) British expert Robin Lovell Badge, otherwise a strong supporter of refining techniques to create genetically modified humans, agrees that "a lot of the fuss about the possibility of germline gene editing is misplaced,” not least because PGD can be used to avoid many heritable conditions.

Advocacy

Transhumanists, including James Hughes and Zoltan Istvan, and libertarians such as Ron Bailey who have long argued in support of human germline interventions have predictably chimed in to affirm their positions. So have some philosophers associated with this view, including Julian Savulescu et al. in Nature [behind paywall and on a blog]. One of the co-authors, Chris Gyngell, wrote an op-ed in The Guardian titled “The case for genetically engineered babies,” in which he fails to mention that what he proposes is explicitly illegal in the UK, where he lives. He bases his argument on the prevention of inherited diseases, without acknowledging that this can be accomplished through already-existing embryo screening techniques. He also includes this remarkable sentence:

Genes fashionable in one generation may prove to be harmful in the next.

Many mostly rather passive supporters were quoted in this selection by the Science Media Centre, including Dusko Ilic, Ewan Birney, Darren Griffin (who mentioned a possible “moral imperative to make sure that we do it”) and Anna Smajdor, who cited the recent UK decision to allow nuclear transfer to avoid mitochondrial disease.

More worrying is the appearance of at least notional support from some self-described environmentalists, such as Amelia Urry in Grist, though that piece seems somewhat muddled on the basic distinction between somatic gene editing and germline interventions.

Summaries

Press coverage has been extensive. The following are some of the articles that include comments from scientists and others:

• Chinese scientists genetically modify human embryos, David Cyranoski and Sara Reardon, Nature, April 22, 2015
• Chinese Scientists Edit Genes of Human Embryos, Raising Concerns, Gina Kolata, The New York Times, April 23, 2015
• Critics Lash Out At Chinese Scientists Who Edited DNA In Human Embryos, Rob Stein, NPR, April 23, 2015
• Chinese scientists genetically modify human embryos for the first time, Stephen Chen, South China Morning Post, April 23, 2015
• Chinese researchers alter embryo DNA: Do results cross ethical tripwires?, Pete Spotts, The Christian Science Monitor, April 24, 2015
• Embryo editing sparks epic debate, David Cyranoski and Sara Reardon, Nature, April 29, 2015
• CRISPR germline editing reverberates through biotech community, Bioentrepreneur, Nature blogs, April 30, 2015
• DNA editing takes a serious step forward — for better or worse, Eryn Brown, Los Angeles Times, May 3, 2015
• Editing human germline cells sparks ethics debate, Tina Hesman Saey, Science News, May 6, 2015

Previously on Biopolitical Times:

• Incurious about Ethics?
• A Tipping Point on Human Germline Modification?
• With World Watching, UK Allows Experiments to Genetically Alter Babies