An announcement that twins modified using CRISPR genetic editing had been born unleashed an immediate wave of condemnation from scientists. With that event comes the big question – now what? Much hinges on the scientific community answer.
Megan Molteni examined questions swirling around future formal publication of these experiments on human embryos (1). One rationale to go forward with publication is utilitarian; the technical information might be useful to others in the future. However, a strong counterargument is that allowing publication in the scientific literature rewards the blatantly unethical actions of a rogue. The scientific community has grappled with the proper disposition of research results obtained through unethical practices since before the time of the Nuremberg trials. Utterly shameful doings are one thing, are scientists managing to avoid the slippery slope when violations are not so obvious?
Whataboutism and a Focus on Technical Details
An article published in The New York Times (2) pointed out how the birth of CRISPR babies is not all that ground-breaking in one sense. Genetically modified human beings, produced by different mechanisms than CRISPR, already exist. An interesting facet of this story is that one of the seminal works (2), the birth of a 3-parent baby, sparked its share of controversy (3). Stymied by F.D.A. regulations, this ambitious mitochondrial replacement therapy researcher relocated the project to a country admittedly selected because it lacked restrictive rules (3) and the results have been published in the scientific literature. Perhaps that would not have happened if the experiment had been a tragic failure. But could apparent success and the fact that genetically modified babies are technically old news make it easier to rationalize publishing the full details of the new CRISPR babies work?
No Harm, No Foul?
Unfortunately, medical research sometimes exposes human participants to hazards. Investigators are required to inform subjects of the risks and potential adverse events as fully as possible. In addition, scientists are expected to take actions to mitigate foreseeable problems. Safeguarding the health and wellbeing of the research subjects is paramount, the needs of the investigators are secondary considerations.
Meticulous preparation prior to undertaking clinical trials is no guarantee the efforts will proceed as investigators hoped. A trial of a promising drug candidate to combat Alzheimer’s disease (AD) had to be terminated after unanticipated, serious adverse events were observed (4). Once the problems were recognized, the study was ended immediately.
As far as anyone knows the CRISPR twins are fine. So, no harm, no foul? If investigators have been permitted to publish in a high-profile journal the details of a failed drug trial that seriously injured many participants (4), why are there so many questions over doing that with the CRISPR babies data? In one sense accounting for the difference in peer/community reaction is simple; the AD trial was conducted in an ethical manner and the welfare of the participants took priority over all other concerns. The contrast with the work put forth by an apparently over-ambitious and unethical rogue could not be more stark.
One general issue with the 3-parent and CRISPR babies is no one will know with certainty whether or not the manipulations produced any adverse impacts for quite some time in the future (3, 5). In the earliest public discussions of CRISPR genome editing, Nobel laureate David Baltimore suggested that a fundamental lack of knowledge regarding consequential impacts of alterations should discourage such efforts in humans for the time being (6). The true potential tragedy of the CRISPR babies is that the news reports lead us to conclude there was no compelling medical need to perform the experiment. A driven investigator may have secured his place in scientific history, but only the passage of time will reveal how much that achievement might ultimately cost the CRISPR babies.
To Expunge or Not to Expunge?
The article by Molteni (1) points out that refusing to allow the CRISPR babies study to be published poses another dilemma. She reminds us that publication serves two purposes, career building and knowledge accrual, leading to a concern that preventing the work from entering the written official record effectively throws away knowledge. The scientific community has been grappling with the holes-in-the-official-record problem posed by failed – and therefore unpublished – clinical trials funded by private corporations. Predicated on solid rationales that others might invoke as well, clinical trial data and approaches which did not achieve desired endpoints are still vitally important to future investigators because they may help prevent effort being wasted running down blind alleys that have already been traveled. There are at least two ways to look at the CRISPR data publication dilemma – the study, or at least the manuscript describing it, is being characterized as “shoddy” (1), so its absence from the scientific record may not be a huge loss. However, it might serve as an example of what not to do for future researchers, provided a person with demonstrated contempt for ethics deigns to convey his work and results truthfully. Should a manuscript of suitable quality ever be produced, perhaps this would be a moment for a publisher to accept the work with the condition that a critique will appear alongside it.
Facing the Court of Public Opinion
It is important to recognize the current rules and guidelines for research involving human subjects have been refined over a period of decades and after some hard lessons. And it seems true that now-notorious projects conducted in the past such as the Tuskegee study and Operation Sea-Spray (1) would probably never receive peer approval today. We may take some comfort in that, but the legacy of prior transgressions still hangs over us. The common thread between the work performed at Tuskegee and for Operation Sea-Spray was the deliberate use of human beings in an instrumental fashion to accomplish the goals of the scientists. To anyone who maintains those days are long gone, take another look at the CRISPR babies story.
Editing of the human germline will probably be done somewhere. However, the work can – and must – be performed transparently and ethically, which will qualify it for publication in the scientific literature. Citizens might not be interested in the deep technical details of this research, but will certainly comprehend what a mess the CRISPR babies debacle has exposed. And they will definitely understand what it means if a utilitarian rationale is employed to justify the decision to publish such derivative, thoroughly unethical and probably substandard work.
At this stage the most important audience for genome editing scientists is not their fellow research journal-reading colleagues, but the ordinary citizens who comprise the court of public opinion.
(1) Megan Molteni. How Do You Publish the Work of a Scientific Villain? Wired.com, 11 December 2018. https://www.wired.com/story/how-do-you-publish-the-work-of-a-scientific-villain/
(2) Carl Zimmer. Genetically Modified People Are Walking Among Us. The New York Times, 1 December 2018. https://www.nytimes.com/2018/12/01/sunday-review/crispr-china-babies-gene-editing.html
(3) Sara Reardon. ‘Three-Parent Baby’ Claim Raises Hopes – and Ethical Concerns. Nature, 28 September 2016. https://www.nature.com/news/three-parent-baby-claim-raises-hopes-and-ethical-concerns-1.20698
(4) Rachelle S. Doody et al. A Phase 3 Trial of Semagacestat for Treatment of Alzheimer’s disease. The New England Journal of Medicine, 25 July 2013. https://www.nejm.org/doi/full/10.1056/NEJMoa1210951
(5) David Cyranoski. Baby Gene Edits Could Affect a Range of Traits. Nature, 12 December 2018. https://www.nature.com/articles/d41586-018-07713-2
(6) Nicholas Wade. Scientists Seek Ban on Method of Editing the Human Genome. The New York Times, 19 March 2015. https://www.nytimes.com/2015/03/20/science/biologists-call-for-halt-to-gene-editing-technique-in-humans.html