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An ISCT Ethics of Cell & Gene Therapy Committee Write-Up on Roundtable Session: "Is Germline Editing Feasible and Should it be Permissible?"

At the ISCT 2025 Annual Meeting in New Orleans the Ethics of Cell and Gene Therapy Committee (ECGT) held a roundtable titled “Is Germline Editing Feasible and Should it be Permissible?” Co-chaired by Bruce L. Levine (Chair of ISCT ECGT Committee) and Miguel Forte (ISCT President), the panel featured expert insights from Kiran Musunuru (University of Pennsylvania), Fyodor D. Urnov (University of California, Berkeley), and Bambi J. Grilley (ISCT Chief Regulatory Officer).

Context and Rationale Behind this Roundtable Discussion

Bruce L. Levine opened the discussion by referencing the 2018 controversy when a Chinese scientist created gene-edited babies, a tragic and pivotal moment that sparked urgent ethical questions worldwide. Levine explained how ISCT, alongside the American Society for Cell and Gene Therapy and the Alliance for Regenerative Medicine, are closely monitoring this topic — not because it’s currently urgent, but because it could become urgent very quickly.
He also clarified terminology: the term “Germline Editing” has been reframed as “Heritable Human Genome Editing” (HHGE) to better convey its meaning.
A key ethical question raised was on consent — while parents can consent on behalf of the embryos, future generations affected by the HHGE cannot. 

Constant Dialogue is Important

Miguel Forte emphasized that, although HHGE isn’t an immediate concern, continuous conversations across scientific and clinical communities are essential. He highlighted that the topic HHGE is at the top of the ISCT ECGT Committees agenda and remains under constant review.

Defining the Scientific and Regulatory Challenges

After brief introductions from each panellist, Bruce L. Levine posed 3 key questions:

1. What is the “drug product” in HHGE?
2. What preclinical steps are needed?
3. What would be needed to make this happen clinically if there was broad societal and scientific consensus to proceed?

Bambi J. Grilley responded by clarifying that, in this context, the embryo itself would be considered the product, and such a product currently falls outside the scope of existing regulations within the United States. She noted that implementing a regulatory framework for this would require a fundamental overhaul of the current system. Even if we wanted to do this, Grilley acknowledged that it would likely take 4 to 7 generations of animal testing to demonstrate that there are no untoward effects and estimated that it would take approximately 30 years of safety and efficacy testing.

The Scientific Reality Check: Insights from Kiran Musunuru

Kiran Musunuru expressed his opinion on the scientific untenability of HHGE. Musunuru explained that there is no way of non-invasively sequencing the cell and that the only way of doing this is by destroying the cell. Preimplantation genetic diagnosis is limited to sampling a small number of cells. One would have to do a lot of this to analyse the gene edits. When using CRISPR in high concentrations the zygote divides, and there would be increased risk of mosaicism. Even in the remote scenario of perfect gene editing it cannot be assumed that the edits will have uniform effect uniformly and there won’t be off target edits.
 
Musunuru explained that in the 2018 Chinese gene-edited babies- rampant mosaicism was observed in the embryos and placenta thus highlighting the risks. He said if HHGE is to go forward the absence of significant off-target effects would need to be demonstrated - something that cannot be demonstrated in the foreseeable future.

Musunuru also cautioned against viewing HHGE as a tool for enhancement purposes, instead proposing it might only be justifiable for correcting severe disease variants. Even then, he noted embryo selection techniques could negate the need for HHGE.

Offering hope for alternatives, Musunuru revealed his lab’s pioneering work on in utero gene editing using nanoparticles at a stage where the blood brain barrier is not fully developed which is approximately two-thirds through pregnancy.  Early results show that the technology gets into the muscles very easily. This could have positive implications in the future for diseases such as Muscular Dystrophy. Musunuru explained that if these technologies can be further developed, this approach could further reduce the need for germline editing.

Ethical Concerns from Fyodor D. Urnov

Fyodor D. Urnov, who had reviewed and rejected the publication of the 2018 Chinese HHGE case in Nature, shared his concern about the ethical and scientific irresponsibility involved. He suspects more gene-edited children exist and stressed the need for full transparency about their health outcomes.

Urnov posed a hypothetical question to the audience: 
‘25 years from now we have addressed the regulatory and technological issues of HHGE.  If you had the opportunity to have a HHGE child what locus would you edit in you for your future children not to have’. 

He personally stated that he would edit the 9p21 locus, due to his family history, which is strongly linked with risk of cardiovascular related diseases and APOE4, that is linked to developing Alzheimer’s Disease. Urnov said that despite the appeal of using HHGE for preventative editing he cautioned that there is a risk of bad actors using HHGE for enhancement purposes, a view he deems as ethically unacceptable.

Urnov, who is the Director of the Innovative Genomics Institute, described an encounter with an individual of formidable wealth interested in using CRISPR to "improve their children" (something Urnov finds scientifically and ethically reprehensible).

Urnov emphasized that while he supports a future where we can equitably reduce genetic disease risk, he does not believe HHGE is a responsible or viable path. Instead, he advocated for greater focus on modifiable lifestyle factors. For example, he noted that smoking significantly increases the risk of abdominal aortic aneurysms in individuals with the high-risk 9p21 genotype. Urnov emphasized the importance of partnering with healthcare providers to educate and raise public awareness about disease risk modifiers.

He concluded by reminding the audience that humanity lacks a strong track record of always using transformative technologies for good use. From both an ethical and technological standpoint, Urnov explained that the risks of HHGE remain too great and for this reason he does not support using it.

Audience Engagement: Tough Questions and Real-World Concerns

During the open floor session, one audience member discussed clinical cytogenetics and raised the scenario of conceiving a child specifically to serve as a treatment source for an existing sibling. She asked the panel if HHGE could revive eugenic ideologies. In response, Kiran Musunuru cautioned that genetics is complex, and traits cannot be guaranteed simply by possessing specific genes. He warned against unscrupulous actors who may falsely market HHGE as a way to create a ‘better baby’ and highlighted the poor-quality work in China, where research-grade reagents were irresponsibly used in embryos. He concluded that while HHGE may appear promising in theory, it is not now scientifically feasible or safe, and may not be for a very long time. 

Another question asked from another audience member was whether HHGE could replace embryo selection in 50 years if the ethical and safety concerns were resolved. Musunuru said that it is hard for him to extrapolate 50 years from now, but he does not believe that HHGE will replace embryo selection as the risk incurred by doing HHGE is too high. Fyodor Urnov agreed, referencing BRCA1/BRCA2 in breast cancer. He explained if carriers of these genes decide to have children there is a 50% chance that the child will inherit this from a parent. Urnov acknowledged the potential desire of parents to use HHGE to edit out specific mutations, but the risk of off target effects is too high and for this reason he could not advocate for HHGE over embryo selection. 

Daniel J. Weiss (ISCT President Elect) asked ‘What exists as a safeguard against this? What can we do as a society or in partnership with other societies and alliances to weed out the bad actors in this space’? Bambi J. Grilley emphasized the critical role of public education, noting the complexity of HHGE makes it difficult even for scientifically literate individuals to fully understand. 

Miguel Forte echoed the need for ongoing debate and responsible discourse, stressing that HHGE is a “no go” today. Forte informed the audience that leaders from the scientific, biotechnology, patient, religious, bioethics, and policy communities met in Washington DC in March 2025 to discuss the risks and challenges associated with HHGE. 

[A communiqué related to topics discussed at this meeting has been since published as an editorial in Cytotherapy (https://www.isct-cytotherapy.org/article/S1465-3249(25)00718-2/fulltext) . This document has been endorsed by ISCT, The American Society for Cell and Gene Therapy and the Alliance for Regenerative Medicine.] 

When Bruce Levine questioned whether education alone was sufficient, Grilley and Urnov highlighted the need for global regulation and oversight. Grilley explained that although some countries have regulations addressing this issue, many do not. She emphasized the need to advocate for the implementation of regulations to prevent misuse. Urnov concurred, stressing the importance of establishing strategies and frameworks to ensure that in-vitro fertilization (IVF) clinics worldwide are held to strict regulatory standards.

An audience member asked whether alternative approaches, such as mitochondrial editing, are being explored as potentially safer options compared to HHGE. Urnov responded by mentioning that he knows a family affected by Leber Hereditary Optic Neuropathy (LHON) which is a mitochondrial disease. He acknowledged that mitochondrial editing could offer benefits to such families but emphasized that he would need to see how the technology performs in clinical trials before offering a definitive opinion.

Daniel J. Weiss asked ‘What can we do to prohibit or regulate HHGE? Do we need to try to convince the National Institutes of Health (NIH) to not review anything in future on this topic, or do we start putting people in jail?’ Levine responded by suggesting that there could be a consensus among scientific suppliers to refuse providing reagents for HHGE or related research, and that scientific journals could prohibit the submission of papers on this topic.

Quickfire Closing Messages from the Panel

As the roundtable discussion ended Levine asked each panellist to sum up their stance of HHGE in a quick elevator pitch style.

Fyodor D. Urnov: ‘No, no, no! We cannot do HHGE.’

Kiran Musunuru: ‘HHGE is not safe and should not be done.’

Miguel Forte: “We don’t have the tools to do HHGE in a risk-free way.”

Bambi J. Grilley: “Allowing HHGE to proceed violates the unborn child.”

The session ended and Bruce Levine thanked the panellists and the audience for their participation.

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