Last week’s report that the first gene-edited babies were born in China raised many questions about the safe and ethical use of technologies such as the CRISPR-Cas9 gene-editing tool deployed in the process. Little attention, though, was paid to the technology vendor’s responsibility to guard against misuse.
Questions of vendor ethics are similar to those raised in the contentious debate over gun sales in the US. Can a seller be held responsible for the actions of a buyer? How can a seller determine with certainty how any user will deploy a technology? What are the minimum requirements that must be met by a purchaser? Which technologies require user vetting? Does the onus of ethical behavior lie entirely with the user?
A paper published in August in the American Journal of Bioethics raised these questions, advocating ways to monitor use of genomics tools. What made the article, “Ethical Considerations in the Manufacture, Sale, and Distribution of Genome Editing Technologies,” notable was its author: the bioethics advisory panel of Merck KGaA, a German firm that became a major vendor of CRISPR-Cas9 and other genomics tools in 2015 with its acquisition of Sigma-Aldrich.
“We became the leading supplier of genome-editing technologies, and we thought it important to actively take part in the social debate,” Steven Hildemann, a physician and chief medical officer for Merck’s biopharma division, tells C&EN. Hildemann co-chairs the bioethics panel, which Merck formed in 2011.
Merck, he says, is concerned with developing a means of verifying the authenticity of its customers. The company, he says, does not condone any heritable human genome editing, “because we don’t understand the off-target effects well enough. We don’t have the full risk/benefit profile of this intervention at this time.”
Gregory Koblentz, a biodefense expert at George Mason University, agrees that providers of genome-editing tools should have “know your customer” rules and screening standards. He advocates modeling them after those adopted by the DNA synthesis industry’s International Gene Synthesis Consortium. IGSC established a common protocol whereby gene orders are screened against multiple databases, including a regulated-pathogen database, to determine potentially dangerous sequences before an order is filled. Customers get screened to verify they are engaged in legitimate research.
“At the very least, companies should know if their products are intended for use in human germline editing and, if so, has the research been approved by appropriate institutions and authorities,” Koblentz says.
While bioethicists generally agree that vendors bear responsibility for how their products are deployed, Francoise Baylis, a professor of bioethics and philosophy at Dalhousie University, is skeptical of the effectiveness of customer vetting.
“Are background checks really expected to be effective? If so, effective at what?” she asks. “Background checks might protect against incompetence, but presumably what society really wants to do is protect itself from sociopaths. This means one would need a screening tool to look at traits of character, not simply to determine whether the purchaser has a PhD in a relevant area.”
The consent document signed by the parents of the Chinese babies identifies Thermo Fisher Scientific as the supplier of the Cas9 gene editing tool and Synthego as the source of the guide RNA that directs the editing. Neither company would confirm their technology was used, though both acknowledge that it might have been. In written statements they both express commitment to fostering ethical use of the technology.
Other vendors claim to have established their own systems of checking out potential customers. For example, Addgene, a non-profit organization that supplies genes deposited by university researchers, investigates every application to assure genes will be used in legitimate research, according to Executive Director Joanne Kamens.
“We make sure every person who makes an account is a scientist with an accredited research institution,” she says, adding that Addgene only ships to accredited labs. The group is able to determine with a high level of certainty that customers are on the level, she says, validating requests with information that can be gleaned online. When necessary, it contacts the lab. “We have 30 PhDs working at Addgene,” she says. “It’s pretty easy for them to tell.”
The company ships anywhere in the world other than to countries that the US government doesn’t allow exports to. “The only places we don’t ship to are the ones UPS doesn’t ship to,” she says.
Addgene supplies many customers in China, where bioethicists agree the potential for rogue science is high due to relatively relaxed regulation compared to the US and Europe. “There is a lot of great science going on there at very legitimate research organizations,” Kamens says. “It doesn’t really matter what we are shipping out there, because they can easily recreate any of the things they see in the literature in a matter of days.”
Kamens concedes that misuse can’t be prevented once genes are shipped. “Of course there are rogue scientists,” she says. “The researchers who deposit genes with us want their materials to go to actual researchers who are doing legitimate research. We take that responsibility seriously and are very careful about it.”
And that responsibility is formidable, Merck’s Hildemann says. “We are talking about gene editing now, not new software or the next iPhone,” he says. “We are talking about intervention into the genome and potentially the human germline.”
With additional reporting from Ryan Cross.