Practical Plan for Managing Human Germline Genetic Modification

CRISPR-Cas9 gene editing technology is a game changer on many levels both inside and soon outside the lab. There is a growing sense of urgency amongst biomedical scientists to take a proactive approach to current and future use of CRISPR technology in human germ cells and embryos.

These concerns have been heightened by rumors of multiple papers currently in various stages of peer review that will reportedly describe CRISPR-mediated gene editing of human embryos. A number of scientists and scientific organizations have recently come out with policy statements on human germline genetic modification: Lanphier, et al.Nature, Baltimore, et al. Science, and ISSCR.

I’ve outlined a proposed plan (see figure below) that I call ABCD for simplicity to try to practically manage the situation with human germline genetic modification. This plan shares a few key features with some of those already proposed by others, but in some ways it is different or more specific. This ABCD idea is just a possible plan coming from one person (me) with the intention of positively adding to the overall dialogue.

 

 

My view is that in vitro research on genetically modified human germ cells and early embryos–with appropriate training and oversight–is ethical and can in fact be of great value. Such work will provide new, valuable information about gene editing itself and early human development, fertility, and more. Therefore, such research should not be prohibited, but should only be conducted under certain conditions.

For example, the In vitro studies of genetically modified human germ cells and embryos would require appropriate approval and oversight. This is the A part of the plan. Given the urgency in terms of timing on this issue, it seems impractical to create new committees from scratch solely for this purpose. Thus, I propose that standing SCRO committees have the authority and responsibility to regulate genetically modified germ cell and embryo-related work. They already are the ones overseeing similar research now. The human germ cell and embryo CRISPR work would have to have a compelling justification to get SCRO approval.

Researchers proposing to the relevant SCRO or similar committee to conduct research related to human genetic modification of germ cells or embryos must also receivebioethics training, which is the B part of the plan. This is particularly important because of the complicated bioethical issues that this unique kind of work raises and such training would serve to provide a strong educational component. Bioethical issues to be discussed would include the human germ cell modification itself, the specific concerns over outcomes if the work were applied in vivo, and other aspects such as the sourcing of human oocytes. As to that last issue, in vitro CRISPR human genetic modification research could substantially increase the research demand for human eggs.

The C part of the plan is clarity. Both the public and scientists would greatly benefit from education and openness in this area. Transparency and outreach in lay terms is essential for public trust. Research on human germline genetic modification, including those manuscripts potentially currently in review, should be published in open access format to make the data fully available to society as a whole. No pay walls here. This area of research is too important and charged to block access.

The D part of the plan is don’t extend the work to vivo applications involving implantation of genetically modified human embryos. There should be a moratorium on this step given the major ethical and safety issues involved. Whether such a moratorium could ever be lifted is unclear and would depend on what the data that come in the next few years teaches us. Practically speaking the questions of how such a moratorium would work or be enforced are tough ones, especially if one intends to extend it internationally.

With these ABCD guidelines in place the goal would be that innovative, valuable research in this area could proceed in a responsible and ethical manner, while minimizing the risk of negative outcomes.

Within just a year or two the knowledge base regarding CRISPR-based gene editing will be vastly increased. Further, in the same timeline additional next-generation CRISPR approaches will improve accuracy and introduce further refinements in the technology. Plans for managing germline human genetic modification may need to evolve as well. The ongoing dialogue that has ramped up recently already shows signs of having very positive impact and is likely to continue to do so as it proceeds.