Last month, the news broke that a research team at Sun Yat-sen University, in Guangzhou, China, succeeded in editing the genomes of live, though inviable, human embryos. Their process, a specific instance of germline modification (or germline genome modification), uses a technique called clustered regularly interspaced short palindromic repeats (CRISPR) with the Cas9 protein to cut and modify human DNA in an embryo’s nucleus. This technology is similar to that of somatic (body) cell genome editing carried out here in the U.S. in order to fix, delete or replace genes that contribute to disease in adult humans.
The Chinese researchers specifically edited the gene that contributes to the blood disorder β-thalassemia in roughly 48 percent of the experimental embryos — not quite effective enough yet for clinical use. Improvements on this yield, however, could encourage other researchers to use germline modification to combat more diseases targeted by somatic cell modification, including HIV/AIDS, assuming those researchers live in countries without bans on germline modification in research or medicine.
But while the standard somatic cell modification makes changes to a person’s genome in ways that cannot be passed down to offspring, germline modification does. And excluding issues of efficacy, therein lie the major problems that many leading bioscientists and bioethics have with pursuing germline modification as a potential new type of gene therapy. These problems include the “slippery slope” aspect of the technology when it comes to genetically engineering our children, but more importantly, germline modification also poses a threat to our conception of informed consent.
Some thinkers who have expressed concerns about the technology, including Stanford professors Paul Berg and Henry T. Greely, want to handle germline genome modification cautiously and, importantly, ethically. In a piece published in the journal Science, they propose continuing “transparent research” into the clinical applications and effects of such modification while actively and “strongly discourag[ing]” clinicians from jumping the gun and bringing the technology into medical use too soon. They propose that, before such medical use begins (if it ever does), experts, regulators and members of the public sort out the ethical issues posed by germline modification — and how both law and society will manage its use.
Others have already begun to weigh in on the ethics of the technology, specifically looking at the potential for both harmful medical outcomes and a “slippery slope” of undesirable social outcomes from allowing its use. Medically speaking, the technology works less effectively than somatic cell modification techniques — and with a seemingly higher chance of causing random, unplanned mutations in a cell’s genome that could prove harmful or even lethal. If such mutations didn’t kill an embryo in utero, they could negatively impact a person’s health or the health of their children, grandchildren, etc.; that door opens when modifying the hereditary DNA of the germline instead of the non-hereditary DNA of somatic cells. Socially speaking, they worry that the ability to edit genes that are problematic for medical reasons could help encourage such editing for genes that are “problematic” in non-medical ways; that kind of editing could include anything from engineering children to look a certain way to full-on genetic femicide.
These concerns are crucial in looking at the technology, but they only form the tip of the iceberg of problems that medical use of germline modification brings with it. More deeply embedded in that use is the issue of informed consent.
Since the release of the Belmont Report 36 years ago, the idea of informed consent has formed a cornerstone of modern medical practice and research. At its core, the concept holds that patients and research participants not only get to decide what happens or does not happen to them, but that they get to do so based on accurate and complete information about what their decision means.
Applying the doctrine of informed consent becomes tricky when children are involved, however. Legally speaking, people below the age of 18 cannot decide for themselves about their own medical care; instead, their guardians have that decision-making power. Such power, however, does not automatically extend more than one generation out; people do not have guardianship of their grandchildren, regardless of the age of their children, without a court’s intervention.
By choosing to use germline modification on their would-be children, parents would also inevitably choose to subject their grandchildren, great-grandchildren and so on to the same genetic editing. But while they may exercise their rights as parents to consent to such a treatment for their children, those rights (as they are currently constructed) do not extend any further down their bloodline. It doesn’t matter what sorts of fixes could be engineered into an embryonic genome; at a very basic level, even using germline modification solely for clinical purposes would violate the right of informed consent every future person holding those engineered genes.
Time may bring new research to light that allays the medical concerns that germline genome modification present; someday, for instance, a technique for such modification could target and correct only the disease-related gene with total efficacy. The same could happen with the “slippery slope” concerns with appropriate legal and social protections. But no matter what new advances come with germline modification, its medical use can never involve informed consent. And such nonconsensual use cannot be ethically sound.
Contact Johnathan Bowes at jbowes ‘at’ stanford.edu.