Social Issues at the Annual Meeting: Perspectives on Germline Gene Editing Regulation

Posted by: Eve Granatosky, PhD, 2018-19 Genetics & Public Policy Fellow

Recent advances in human gene editing research have sparked widespread conversation in the international scientific community about the benefits, risks, limitations, and ethical considerations associated with editing technologies. ASHG collaborated with the National Academies of Science, Engineering, and Medicine to bring this dialogue to members, at the “Perspectives on Germline Gene Editing Regulation” forum at the 2019 Annual Meeting.

The National Academies, along with the Royal Society of the United Kingdom, leads the International Commission on the Clinical Use of Human Germline Genome Editing. The Commission is currently developing a framework for considering issues around germline genome editing, which would govern the use of the technique if and when society decides that such use is appropriate. A similar effort – the Expert Advisory Committee on Developing Global Standards for Governance and Oversight of Human Genome Editing – is currently underway at the World Health Organization (WHO). Both groups are writing reports articulating their recommendations for germline editing. Leaders from these projects convened in Houston to outline their progress so far and to engage in a discussion, moderated by Charles Rotimi, PhD, with ASHG attendees.

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Dr. Dzau addresses attendees at the Perspectives on Germline Gene Editing Regulation forum at ASHG 2019.

Victor J. Dzau, MD, President of the National Academy of Medicine, outlined previous international efforts that shape the Commission’s goals and scope. He noted that the November 2018 announcement of the first “CRISPR babies” was a wake-up call for experts to take stronger, more definitive action to confront the realities of a world where human germline editing was not only possible, but happening. In an interview with ASHG TV, Dr. Dzau said, “This forum is timely, because as both of these studies are ongoing, it’s a perfect place for the community to come together to talk about this, and to be aware of what we’re trying to do.”

Kay E. Davies, PhD, co-chair of the Commission, described her group’s mission and efforts thus far, which include the first of three planned commission meetings. She presented several prompting questions that the Commission hopes will guide the community in providing useful feedback to the group.

Kazuto Kato, PhD, a member of the WHO Expert Advisory Committee, shared that the group plans to leverage the global presence of the WHO to make appropriate international, national, and regional recommendations on governance mechanisms for human genome editing. He also noted that some nations, including his home country of Japan, were beginning their own conversations and projects on human genome editing.

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Forum attendees heard from international genetics leaders before being invited to voice their own perspectives.

The second half of the forum was dedicated to open conversation on germline gene editing regulation. Major themes included the need for any reports to be flexible and adaptable to future developments in the field, the need to represent a variety of geographic and demographic perspectives in international discussions, and the tensions between encouraging scientific and medical progress while exercising appropriate caution.

Dr. Rotimi and the panelists were enthusiastic about the level and quality of discussion and expressed interest in following up with the ASHG community next year as their groups’ work continues. As the forum concluded, Dr. Davies remarked,  “I look forward to the workshop next year when both reports will be out, and we’ll have another opportunity to address some of these issues because they’re so important for everyone in this room and everyone in the world…I’m an optimist too but there’s going to be a lot of hard work.”

Couldn’t make it to this session? Check out the recording!

Eve Granatosky, PhD, is the 2018-2019 Genetics and Public Policy Fellow, and is currently completing her third fellowship rotation in ASHG’s Policy and Advocacy Department.

Biology of Genomes 2018: The Past and Future of Genomics

Posted By: Emily C. Glassberg, PhD Candidate, ASHG Communications Committee

A few weeks ago, I attended the 31st annual Biology of Genomes (BoG) meeting at Cold Spring Harbor. In addition to highlighting the amazing research that comprises the current state of genomics, this meeting highlighted the storied past and bright future of the field. The enthusiastic participation of attendees, both at the meeting and on Twitter, shows incredible energy and momentum as we try to understand the genome’s role in biology, evolution, and disease.

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Attendees network at Biology of Genomes 2018 (Credit: Constance Brukin; copyright CSHL)

Genomics Present

The seven scientific sessions covered functional genomics, medical genomics, computational genomics, and evolutionary genomics, as well as genome engineering. Seeing this varied body of work at a single meeting clearly demonstrates that theory, experiment, high-throughput screening, and countless forms of new technology and data analysis all play central roles in shaping our current understanding of the human genome.

And, while the human genome was the primary subject of study, non-human genomes got coverage as well. Highlighted research included the genomes of near relatives, like Neanderthals; to those of best friends, like dogs; to those of model organisms, like yeast. Crowd favorites included Jaemin Kim’s and Elaine Ostrander’s talks using dogs as a system to learn about the genetic basis of complex traits (for the science as well as the adorable pictures).

The scientific programming also included two keynote speakers, Wendy Bickmore and David Page. Bickmore discussed her group’s work on how 3D chromatin structure relates to the mechanism by which enhancers – particularly long-range enhancers – interact with promoters to regulate gene expression.

Bickmore’s emphasis on the need to assay enhancer function in vivo was echoed elsewhere at the meeting. In particular, Emma Farley spoke about high-throughput measurements of enhancer function in the model chordate Ciona. In combination, these talks sparked a conversation about whether current computational models are looking in the wrong places when it comes to predicting enhancer activity and specificity.

Page presented his group’s work on the evolution of sex chromosomes with an eye to understanding sex differences in health and disease. Page’s question of whether and how males and females “read their genomes differently” connected to broader questions that recurred throughout this year’s meeting –  how do we understand the genome dynamically? When and how does the same genome lead to different outcomes?

The ways in which the genome and its downstream effects change over time and space is a big open question, and this year’s BoG showcased many approaches to tackling it:

  • Ben Strober and Jonathan Griffiths both used time-course gene expression data to track how gene regulation changes throughout cellular differentiation and development.
  • Jake Yeung shared an example of dynamic chromatin interactions and rhythmic promoter-enhancer contacts that are connected to circadian rhythm.
  • Christina Leslie presented work on how the chromatin state of tumor specific T-cells changes during cancer progression and how that influences disease treatability.

And that’s just a sample of the exciting work in this space! While we don’t yet have clear answers to these questions, the research discussed at BoG reveals a landscape that is complex, nuanced, and fascinating. What a great time to be in genomics!

Genomics Past

In addition to discussions spanning the range of the current field of genomics, BoG included a brief talk in memoriam of molecular and developmental geneticist John Sulston, who passed away on March 6, 2018. Dr. Sulston was well known for his seminal work in the now-model organism C. elegans, as well as his role in the Human Genome Project. Eric Lander also toasted Jim Watson for his role in the Human Genome Project, and to celebrate his 90th birthday. Lander and other BoG organizers later apologized for the toast, as it was seen by many in the community as minimizing Watson’s history of racist and sexist commentary.

Genomics Future

And, finally, no meeting would be complete without a vision for the future of the field.

A panel on the Ethical, Legal, and Social Implications of genomics research included four perspectives on the promises and pitfalls of germline genome editing. While there is considerable excitement around using CRISPR to cure genetic disease, many issues remain regarding proof of safety as well as ensuring equal access to the technology. Following a lively discussion during the question-and-answer, the consensus seemed to be that germline genome editing is a distant future. In the meantime, we can focus on the application of currently available options, like genetic screening and assisted reproductive technologies.

The National Human Genome Research Institute (NHGRI) also engaged researchers in its current strategic planning initiative, which began in February 2018 and will be completed in 2020. NHGRI is collecting input on priority areas to help the institute live up to its mantra, The Forefront of Genomics.

Of course, the scientific discourse at Biology of Genomes isn’t limited to the talks. The three lively poster sessions were great opportunities to exchange ideas. And many spirited discussions took place during the coffee breaks, over the traditional Cold Spring Harbor banquet, and down at Blackford bar. All told, there’s a lot to look forward in genomics!

Emily C. Glassberg is a PhD Candidate in the Department of Biology at Stanford University. She serves on ASHG’s Communications Committee and has been an ASHG member since 2014.

ASHG’s New Policy Statement on Human Germline Genome Editing

Posted by: Derek Scholes, PhD, ASHG Director of Science Policy

I am delighted to announce that ASHG’s statement on germline genome editing was published today in The American Journal of Human Genetics. This statement, written by a workgroup co-led by Kelly Ormond and Doug Mortlock and approved by ASHG’s Board of Directors, gives the Society’s perspective on the use of CRISPR/Cas9 or other similar tools to alter the genome of an embryo or germ cell. Importantly, it incorporates feedback that members provided when the workgroup solicited their perspectives early in the writing of the statement.

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The Germline Genome Editing Workgroup asked for member input at the 2015 Business Meeting, before developing draft recommendations and writing the statement. L-R: Douglas Mortlock, Kelly Ormond, William (Andy) Faucett, Rosario Isari, Kiran Musunuru, and Lawrence Brody.

The statement makes three main points:

  1. Concurring with many in the scientific community who have considered this question, it declares that it would be inappropriate at the present to carry out germline genome editing culminating in pregnancy, given the many questions about its safety and the associated ethical issues.
  2. However, it says we should allow in vitro germline genome editing as part of research to explore possible future clinical applications, and there should be no prohibition on the use of public funds for this research.
  3. That said, it makes clear that the Society believes germline genome editing should only ever be performed in humans if several important criteria are met. There needs to be not only a compelling medical reason, backed up by a strong evidence base, but also the ethical and policy questions need to have been addressed through a public process.

ASHG did not reach these conclusions alone. Rather, the workgroup that wrote the statement included representatives from the Association of Genetic Nurses and Counsellors, the Canadian Association of Genetic Counsellors, the International Genetic Epidemiology Society, and the National Society of Genetic Counselors. These organizations endorsed the final statement, as did the American Society for Reproductive Medicine, the Asia Pacific Society of Human Genetics, the British Society for Genetic Medicine, the Human Genetics Society of Australasia, the Professional Society of Genetic Counselors in Asia, and the Southern African Society for Human Genetics. The statement is all the more powerful for enjoying support from such major organizations from across five continents, that represent a variety of scientific and clinical perspectives.

This position statement is the latest in a series that the Society issues periodically on a range of genetics policy issues and different uses of genetic information. If there is a topic that you would like the Society to consider addressing, please let us know by emailing policy@ashg.org.

Derek Scholes, PhD, is ASHG’s Director of Science Policy. To learn more about ASHG’s policy priorities and positions, visit the Policy page.