Interview: Carrie D. Wolinetz of the NIH on gene editing

Xavier Symons
and Carrie D. Wolinetz
February 23, 2016
Reproduced with Permission

New gene editing technologies like the CRISPR-Cas9 technique hold great promise for medicine and the biological sciences. Some researchers say we may soon be able to eradicate infectious diseases like malaria, and edit HIV out of the genome of AIDS sufferers. Others believe we can use gene editing techniques to make animal organs suitable for human transplants.

Yet there are many ethical questions attentant to research in the area, and ethicists are struggling to catch up with scientists eagerly refining the new gene editing techiques. Recently I spoke with Dr. Carrie D. Wolinetz, assistant director for Science Policy at the National Institutes of Health, about various concerns raised by bioethicists about gene editing.

Dr. Wolinetz worked on biomedical research policy issues as the Deputy Director for Federal Affairs at the Association of American Universities (AAU) and the Director of Scientific Affairs and Public Relations at the Federation of American Societies for Experimental Biology (FASEB). She also served as the President of United for Medical Research, a leading NIH advocacy coalition. Outside of NIH, Dr. Wolinetz teaches as an Adjunct Assistant Professor at Georgetown University in the School of Foreign Service's program on Science, Technology & International Affairs.

Xavier Symons: The NIH is funding research into gene editing, but has stopped short of assisting projects involving human embryos. Why?

Carrie D. Wolinetz: On April 29, 2015, the NIH Director, Dr. Collins, issued a statement that "NIH will not fund any use of gene-editing technologies in human embryos." In this statement, the Director noted the great potential that genomic editing technologies have for advancing the understanding of gene function and for non-heritable, therapeutic applications, including several human gene therapy trials studying the use of gene editing in somatic cells for HIV-1, β thalassemia, and hemophilia.

However, the use of these technologies to modify the human germline raises complex issues, and while recent technological advances such as CRISPR-Cas9 have increased the technical feasibility, safety and ethical concerns have yet to be allayed. Moreover, as referenced in the statement cited above, there are some relevant prohibitions, including a prohibition against federal funds being used for the creation of human embryos for research purposes or for research in which human embryos are destroyed, a prohibition on FDA review of research in which a human embryos is created or modified to include a heritable genetic modification, and policy that the NIH Recombinant DNA Advisory Committee will not consider germline alteration proposals.

Across the Atlantic, in the United Kingdom, leading researchers are broadly in favor of editing the human genome, as long as it is done prudently. Won't the United States get left behind?

International competitiveness is only one consideration in thinking about whether NIH should fund human germline editing. Unlike non-heritable human gene editing, which the NIH continues to support, editing of embryos raises many scientific, safety, ethical, societal, and policy issues that need to be sufficiently considered and addressed. This is a topic of great international discussion.

For instance, last May, the US National Academies of Science and Medicine, the Royal Society, and Chinese Academy of Science initiated a study to guide decision making about human gene editing and, in December, they convened an international summit to explore associated scientific, ethical, and governance issues. Findings from these proceedings are expected in late spring.

In a recent NIH statement Dr. Francis Collins alluded to "serious and unquantifiable safety issues" involved in research on human embryos. What are they?

A major concern with the genetic editing techniques is off-target effects of double stranded breaks that could inactivate essential genes, activate oncogenes, or cause chromosomal rearrangements. For work with embryos, there is also the risk of mosaicism if the alterations do not end up in all the cells of the organism. There are likely to be unknown risks associated with the rapidly dividing and differentiating cells of the embryo. In the first report of gene editing in non-viable embryos (Liang, P., et al., (2015) CRISPR/Cas9-mediated gene editing in human tripronuclear zygotes. Protein & Cell 6:363-372.), the efficiency of the targeted gene repair was low, off-target cleavage occurred and the edited embryos were genetic mosaics.

Some scientists complain that restricting research into reproductive applications because it is premature and dangerous will ensure that it remains forever premature and dangerous. How would you respond?

The NIH has supported and will continue to support, research on genetic editing technologies, approaches to improve the safety and efficacy of these technologies, basic research into gene functions, development of disease models, and clinical research on somatic gene therapy applications. Progress is likely to be made through such research while the scientific community, regulators, ethicists, and the public grapple with the issues that should be resolved before reproductive applications.

Dr. Collins has also discussed the "ethical issues presented by altering the germline in a way that affects the next generation without their consent". What is wrong with seeking proxy consent for these embryos from parents?

The question of whether it is appropriate for parents to give consent on behalf of future children for embryonic modifications is a highly discussed issue. Dr. Collins has expressed concerns about the lack of consent from not only the child but all subsequent generations for an intervention with great uncertainty about the risks of harms that may not be detected until birth, adulthood, or later generations.

CRISPR obviously makes "designer babies" possible. Do you think that this will eventually become legal in the United States?

Genomic editing is a promising tool for the gene therapy field, which is in the early phase of attempting to correct single gene mutations. More complex interventions would require editing many genes simultaneously, and the effort would be obviously fraught with numerous technological, safety, ethical, and societal concerns. In addition to the increased safety challenges, there is still the need for greater understanding of which genes are involved in specific traits, their complex interactions, and the role of the environment.

CRISPR is a cheaper, quicker, more accurate and more accessible way to edit genetic code -- which means that eventually hobbyists could set up labs in their garages. Do you foresee dangers with the "democratization" of genetic engineering?

The US Government has already considered some of the implications of the growing accessibility of life sciences technologies to practitioners working outside of traditional institutional environments (so called DIY biologists) and, in fact, issued a report in 2011 that highlighted the importance of outreach and education to the amateur biologist community to promote responsible research from both the biosafety and biosecurity perspective.

The hobbyist community is still relatively small, and while the field of amateur biology is in its formative stages, we have a unique opportunity to foster education that includes biosafety and biosecurity content and lays the groundwork for developing a culture of responsible use of life science technologies.

Does the world need an international agreement on a bright ethical line on genome editing?

While it may be difficult to identify a bright line for many of the ethical concerns, the organizing committee at the International Summit did begin to address these issues in its statement. The organizing committee concluded that basic and preclinical research could proceed - subject to appropriate oversight - but noted that "if early human embryos or germline cells underdo gene editing, the modified cells should not be used to establish a pregnancy." Regarding the clinical use of human gene editing, the organizing committee supported gene therapy applications involving somatic cells; however, they concluded that at this time, "it would be irresponsible to proceed with any clinical use germline editing."

Another area of great agreement the need for an international forum for these issues. At the International Summit, the organizing committee recommended that the U.S. National Academy of Sciences and U.S. National Academy of Medicine; the Royal Society; and the Chinese Academy of Sciences create "an ongoing international forum to discuss potential clinical uses of gene editing; help inform decisions by national policymakers and others; formulate recommendations and guidelines; and promote coordination among nations.

The forum should be inclusive among nations and engage a wide range of perspectives and expertise - including from biomedical scientists, social scientists, ethicists, health care providers, patients and their families, people with disabilities, policymakers, regulators, research funders, faith leaders, public interest advocates, industry representatives, and members of the general public."

This type of engagement should be very useful as the field moves forward with the many exciting applications that now seem possible.