Tools & Techniques

Commentary: From "no" to "how"

How to build a roadmap to human gene editing

Amid the hue and cry about the perils of gene editing in human germline cells, there's a danger researchers will lose sight of the possible good this technology can do.

The scientific community is right to insist on establishing principles and protocols to avoid its misuse. But rather than framing the discussion around what to stop, the medical science community - and patients - would be better served by the creation of a path forward that defines what is safe, what is acceptable and what processes will be used to make those decisions.

The National Academy of Sciences and National Academy of Medicine have announced a meeting in the fall to discuss the scientific, ethical and policy implications of human gene editing. That could be a good first step. But given that pronouncements by NIH, the White House, and groups of prominent scientists have all focused on curtailing research and imposing moratoria, the discussion appears headed towards halting rather than enabling progress in the field.

That would be a mistake. Any technology that could eradicate some of the most severe genetic diseases should be explored, if it can be shown to be safe.

Some critics argue there are no diseases that justify using gene editing on human embryos because genetic screening combined with IVF can always solve the problem. BioCentury rejects that notion, not only because it flies in the face of scientific progress, but also because the same logic leads to the conclusion that IVF is never necessary because adoption is always an alternative.

A roadmap needs to be developed towards a system for responsible gene editing in human embryos.

This could be achieved through the creation of a dedicated committee of stakeholders for overseeing activities on viable human embryos, along with a series of guidelines for researchers to follow. These overseers should include voices from patient organizations, as well as scientists, funding agencies, industry and regulators.

If such a committee is to come out of the fall meeting, the National Academies of Science and Medicine need to include their counterparts in regions beyond the U.S. to have any impact in countries such as China that have been sources of some of the reported and rumored studies that have raised hackles.

When the committee sets to work, first and foremost, it should define "safety." What specifically must be demonstrated before we allow research on viable human embryos?

Second, the committee should define specific diseases for which gene editing can be considered, and a process for adding new diseases to that list.

Third, the committee should define how to assess efficacy, and demarcate the range of acceptable experiments once the safety criteria have been satisfied.

Finally, the committee should outline harsh punitive measures for both scientists and their institutions for deviating from the agreed-upon principles.

Off the fence

So far, the public pronouncements have all avoided the issue of what might be acceptable and when.

The White House has called human germline editing for clinical purposes "a line that should not be crossed at this time." NIH has stated it will not fund "any use" of gene-editing technologies in human embryos, but left open the door for use of the technique in human sperm and oocytes, "unless the intent is to create a human embryo for research purposes."

Moreover, as chronicled in BioCentury Innovations, one group of researchers proposes holding back from all gene editing in human germline cells, whereas another has called for ceasing studies intended to support clinical use.

The question that needs to be answered is: "At what time and under what circumstances can that line be crossed?"

Several topline safety concerns need to be satisfied first, using experiments in cell lines and animal embryos. Those include - but are not limited to - establishing that the gene-editing event occurs only at the intended site on the genome, and demonstrating that editing of the desired gene has no adverse effects on other genes or proteins either early in development or later in the animal's life.

That will involve defining parameters such as acceptable detection limits, for example for deep sequencing or other technologies, as well as outlining how many cells need to be tested and how many times experiments need to be repeated. And it means deciding what species and experiments are relevant - as is standard for any new technology or therapeutic.

The path also needs to address what should happen if the technique is proven safe in cells and animal embryos, so that the right experiments are done on human embryos to establish meaningful efficacy.

There need to be criteria for deciding which diseases could benefit most from gene editing, and which should be addressed first. Those might include monogenic diseases that are fatal in infancy or that commit patients to a lifetime of pain and their families to a lifelong burden of caring for them.

Patient voices are essential because the tolerance for risk will vary by disease, and no third party can presume to know what trade-offs people will make for themselves or their children.

Deciding on the criteria will doubtless be contentious, but we cannot turn our noses up at the chance to eradicate diseases such as Tay-Sachs disease, severe combined immunodeficiency (SCID) or neurological forms of Gaucher's disease.

Once a list of acceptable diseases is in place, there needs to be a decision process for permitting use of the technique. Until there are sufficient data to remove this requirement, gene editing should always be a last resort.

All that said, any scientist who performs research that defies the standards laid down should be ineligible for research funding from organizations that sign on to the oversight principles.

But the consequences cannot stop there: institutions must be responsible for the activities that take place inside their labs.

One option is to create a system for penalizing institutions or departments that house scientists performing experiments outside of the agreed-upon guidelines, for example by withdrawing their accreditation, agreeing not to recognize degrees or refusing to fund research from those organizations.

It is key that the oversight committee, its activities and its decisions should be transparent to the public.

Again, the National Academies forum in the fall could be the place to start this process. The backers of the meeting are well-intentioned in their desire to tackle public fears head on through an Asilomar-type forum. However, the way to allay public concerns is not to limit research, but to explain the benefits and advocate more persuasively for the potential for gene editing to eradicate some truly horrible diseases.

- Unsigned Commentary represents BioCentury's Editorial viewpoint.

Companies and Institutions Mentioned

National Academy of Sciences (NAS), Washington, D.C.

National Institutes of Health (NIH), Bethesda, Md.

References

Fishburn, C.S. "Lines in the sand." BioCentury Innovations (2015)