There's much ado about the gene-editing technique CRISPR/Cas9 this week, with a multinational summit in Washington, D.C. on human gene editing, plus the clock ticking down on congressional appropriations bills, one of which would prohibit the Food and Drug Administration from spending money to evaluate research on or conduct clinical trials of gene editing in human embryos. The American Journal of Bioethics, edited by David Magnus, PhD, director of the Stanford Center for Biomedical Ethics, wades into the fray with a special issue on the ethics of CRISPR.
CRISPR is an unusually precise, fast and cheap way of snipping out and replacing genes. It has implications for preventing and treating genetic diseases, engineering new versions of the plants and animals we eat, and knocking out genes in insects so they can't carry viruses that could kill us. The most controversial possibility is altering human sperm, eggs or embryos, because such germline changes would be heritable in future generations of offspring.
“The overriding question is when, if ever, we will want to use gene editing to change human inheritance," said chair David Baltimore, PhD, of Caltech in kicking off this week's summit. Ultimately, summit participants released a statement that left the door open for human germline editing, and advocated for ongoing international discussion.
Indeed, because of the low cost of CRISPR and the variability of research ethics across the globe, an international ban or moratorium would be difficult to enforce, said then-undergraduates Niklaus Evitt and Shamik Mascharak in a paper they wrote for a Stanford class co-taught by professor Russ Altman, MD, PhD. They and Altman turned it into an article for the special issue of the bioethics journal.
They propose a model regulatory framework for CRISPR human germline editing that includes vetting research for necessity and reversibility, establishing the safety and efficacy of the treatment in multigenerational animal models and conducting clinical trials over a 15-year period. "We seek concrete policies that responsibly phase in therapeutic uses of CRISPR-Cas genome editing at a pace amenable to ethical inquiry," they write.
The timing of ethical analysis during research is one of five factors the scientific community should consider in developing a framework of social responsibility, write the University of Pennsylvania's Pamela Sankar, PhD, and Stanford's Mildred Cho, PhD, in their article in the special issue.
Other factors are the basis for the research, the approach to identifying its benefits and harms, who is involved in the discussion of the research and its transparency. "Traditional, rule-based approaches to social responsibility might be insufficient as a basis for creating the more robust concept of social responsibility that recent trends in science demand," they write.
Customary approaches to federal regulation of plants and animals also are insufficient, say the University of Wisconsin's R. Alta Charo, JD, and Stanford's Hank Greely, JD, in their article in the special issue.
"CRISPR critters" — think wooly mammoths brought back to life, or unicorns created as fanciful pets — could be regulated by any of the three agencies that typically regulate biotechnology: the FDA, the Environmental Protection Agency and the United States Department of Agriculture. "This might be reassuring," the authors write, "but it also may mean there will be a morass each time a critter seems to fall between the cracks."
And not just a regulatory morass, but an ethical one, as the intense discussion this week shows. As Charo and Greely put it, "CRISPR/Cas9 and its successors appear likely to do wonderful things — and to be able to do terrible ones."
Previously: Policing the editor: Stanford scientists devise way to monitor CRISPR effectiveness, CRISPR marches forward: Stanford scientists optimize use in human blood cells and Using CRISPR to investigate pancreatic cancer
Photo by Michael Knowles