As it has become easier to delete or alter defective genes in people with genetic diseases, researchers around the world are examining the ethical and technical boundaries of human gene editing research. Stanford geneticist Kelly Ormond and a team of geneticists this week published a policy statement from the American Society of Human Genetics on this practice.
Until very recently, most gene-editing research has focused on editing genes in cells such as those in the skin, the blood or the pancreas, rather than attempting to alter the genes in every cell in the body at once. The alternative, editing the human germline, had remained comparatively unexplored territory.
Germ cells, in ovaries and testes and one-cell embryos, create a continuous genetic line from one generation to the next called the germline. Editing the genes in a one-cell embryo means those genetic changes are passed on to every cell in the body, including eggs or sperm, and then to the next generation and the next.
As it happens, the debate about that kind of germline editing heated up this week, when scientists reported successfully removing a gene variant that causes a serious heart condition from the genomes of human embryos. The researchers removed the defective gene variant, which came from the father, and the embryos themselves unexpectedly replaced it with a healthy variant from the mother. None of the embryos were implanted into a woman and allowed to grow and develop.
In an interview, I asked Ormond about how she and her colleagues arrived at some very specific guidelines for this kind of work. As I summarized the statement itself:
The ASHG policy statement proposes that federal funding for germline genome editing research not be prohibited; that germline editing not be done in any human embryo that would develop inside a woman; and that future clinical germline genome editing in humans not proceed without a compelling medical rationale, evidence supporting clinical use, ethical justification, and a process incorporating input from the public, patients and their families, and other stakeholders.
For most genetic diseases, Ormond said, germline editing is not actually essential. In most situations, there are other ways of producing babies that lack a defective gene carried by one of the parents. She explained:
Germline editing doesn’t have many immediate uses. A lot of people argue that if you’re trying to prevent genetic disease (as opposed to treating it), there are many other ways to do that. We have options like prenatal testing or IVF and pre-implantation genetic testing and then selecting only those embryos that aren’t affected. For the vast majority of situations, those are feasible options for parents concerned about a genetic disease.
The number of situations where you couldn’t use pre-implantation genetic diagnosis to avoid having an affected child are so few and far between. For example, if a parent was what we call a homozygote for a dominant condition such as BRCA1 or Huntington’s disease, or if both members of the couple were affected with the same recessive condition, like cystic fibrosis or sickle cell anemia, it wouldn’t be possible to have a biologically related child that didn’t carry that gene, not unless germline editing were used.
Previously: Use caution when editing genes, new report advises, Stanford scientists describe stem-cell and gene-therapy advances in scientific symposium and A step closer to gene therapy for sickle cell disease
Image by Ernesto del Aguila III, NHGRI