The biggest ethical worry about human gene editing is that it will be used to make long-lasting, heritable changes at the embryo stage or on germ (sperm or egg) cells. Posts earlier this year have asked whether we should envision a scenario in which human germline gene editing is accepted in a limited number of cases, with the treatment of sickle cell anemia being proposed as a case in point.
Last weekend, at the annual meeting of the American Society of Hematology, I was reminded that ethical problems often can be avoided by finding a more acceptable alternative approach. In this case, the alternative was somatic stem cell editing of the sickle hemoglobin gene. Briefly, a speaker in one symposium described work in which an infant with the disease would have his or her blood stem cells, which are destined to form blood cells, edited to repair the hemoglobin gene, which is mutated in sickle cell anemia. (A further reminder: there are several techniques for gene editing, all similar in mechanism, not just the CRISPR/Cas9 approach that has drawn the most attention this year.)
Some key points from the presentation, which summarized the current state of work that has been in progress for over a decade:
- The idea would be to harvest the blood stems from the diseased infant, editing them outside the body with a normal DNA sequence, then return them to the patient in a bone marrow transplant procedure similar to current treatment. The advantage is that one would not need to find a marrow donor, who would have to be biologically matched to the patient.
- Refinements in selecting donor (normal) DNA sequences for the editing are increasing its efficiency.
- To prevent the disease, it might not be necessary to replace all of an affected person’s abnormal red blood cells. A fraction of about 70% normal cells, keeping the number of abnormal red blood cells less than 30%, might be sufficient.
- Normal, non-sickling red blood cells are hardier than their diseased counterparts, and would tend to take over within a person’s body if there is a mixture.
- Hence, one might need to edit only 5% or so of the patient’s harvested blood stem cells to have a viable cure for the disease.
It’s still heavy therapy, but without the concern that one is changing genes that are passed on from generation to generation. Would the latter be preferred—edit out the offending gene once and for all and be done with it? Surely some will argue that. But the less adventurous approach I heard described seems to me preferable on ethical grounds.
Finally, the speaker I heard did say that there is still a lot of work to bring this approach safely to the clinic. To begin with, one has to demonstrate to regulators and ethics boards that the gene-edited blood stem cells are safe, and there is no lab test or animal model to predict that. Also, every step of the process and every device used in it has to be brought into line with “Good Manufacturing Practice,” the set of standards that regulators worldwide use to ensure that drugs are made safely, to a defined standard of purity, the same way, every time. And that’s not a trivial task. Those concerns would be magnified many-fold for a germline gene editing project.