By Leo Barolo
The rapid advancement of CRISPR technology promises to revolutionize medicine, and its application will have broad societal impacts. Multiple social, political, and religious factors play into public perception and opinions about human gene editing research and its application. Given that human genome editing is on the cusp of broader application, leading scientists at the first International Summit on Human Gene Editing declared that broad societal consensus should be achieved before advancing the field.
Surveying what society as a whole considers valuable, virtuous, and inviolable is a daunting task, given the diversity of perspectives and populations. Associate Professor Krishanu Saha and colleagues decided to create an institution to gather those perspectives.
The Global Observatory for Genome Editing is a group dedicated to promoting and analyzing the ethical discussions surrounding gene editing.
The Observatory is directed by social scientist Sheila Jasanoff at Harvard and co-directed by Saha and Ben Hurlbut at Arizona State. A primary goal of the endeavor is to help set the stage for both policymakers and scientists, to guide scientific developments that foster the eventual ethical and equitable accessibility of human genome editing.
Saha points out that one goal of the initiative is to align the science for future application. “We should be anticipatory and also inclusive in terms of hearing about risks and perhaps not be too maverick in pushing the frontiers,” he says.
Human genome editing, which modifies a patient’s genes to cure genetic diseases, has come a long way in recent years. Several therapies are on the brink of approval, following high-profile results from clinical trials. One landmark example is Victoria Gray, a 37-year-old woman with sickle cell disease who attended the latest summit. Gray spoke about how her disease was cured by genome editing and how she no longer lives with excruciating pain as a result of that treatment.
Saha expects that this is only one of several genome-engineered therapies that could be approved in the next few years. His lab is exploring technologies to address diseases of the retinas and other visual disorders through in vivo somatic cell genome editing, and cell therapies that at least initially would be used in cancer applications.
With new applications of human genome editing on the horizon, the dialogue around the ethics and guidelines for treatments and techniques is more important than ever. How the technology and its application will be affected by market forces, insurance restrictions, interests of disease communities, and public opinion at large is difficult to predict. Thus, the Global Observatory brings people together to collect opinions and information about laws being imposed around the world, to centralize resources for reports and investigations, and to bring this knowledge back to scientists and policymakers.
“I think scientists certainly hear about these concerns, and [engaging with them] can guide how they design their various experiments.” Krishanu Saha
The group organizes several events around the world to hear from factions beyond academia, such as patient nonprofits, advocacy groups for reproductive medicine or disability rights, faith communities, and the general public.
The conversation addresses several ethical concerns surrounding genome editing, from development to application:
- Equitable access that overcomes cost and accessibility. Many of these therapeutics will be very costly and hard to manufacture with high standards for quality and distribution. What those standards are and when they can be relaxed must be discussed with regulatory authorities, but these decisions could impact patient safety and accessibility. Conversations also touch on modes of distribution that focus on social justice and equitability.
- Genome diversity and editing efficacy. Saha points out that many tools and reagents in development have been established on a narrow set of individuals and ethnicities, predominantly Caucasian. Yet genomes from other ancestries may carry genetic variants that are subject to off-target effects. This could have terrible ramifications for patients due to unintended genetic changes. Ensuring that therapeutics are vetted on diverse genotypes is an important step in equitable application.
- Experimental practices. Questions around how technologies are developed can also arise. One question is the welfare of animals used during development. Different communities have different values regarding the use of non-human primates in technology development, particularly regarding the extent to which animals should be used and when alternatives are sufficient.
- Use of human embryos/fetal tissue. Communities have diverging perspectives regarding if, how, and to what extent research using human embryos or fetal tissue should be permitted. These perspectives are influenced by moral and sometimes religious concerns.
- Ethics of “enhancement”. While current applications focus on disease treatment, genome editing could feasibly be applied toward enhancing other traits, for example cosmetic or performance traits such as hair color or vision. Once again different communities may vary on where they draw the line on what is ethical.
As genome editing technologies evolve, so will the discussion on their applications. The field of reproductive medicine is next, since in-utero editing is becoming a reality in some states, with fetal-stage intervention based on early pregnancy diagnosis. The Global Observatory is already engaging in debate on the risks of such treatments as well as how they intersect with laws, especially in cases of fetal demise.
Saha anticipates that conversations on the use of artificial intelligence and other ways of designing therapeutics that may have blind spots should also be discussed. “Those are conversations that I think we can and probably should be having in academia and at UW-Madison,” he says.
While it is unclear if there will be more International Summits on Human Gene Editing, the scientific community is considering other mechanisms to meet and discuss these ethical issues. The debate is moving into a new phase with institutions like the Global Observatory gathering and analyzing broad perspectives around the world. This work is elevating ideas and voices that were previously at the periphery of the discussion.
“We’re seriously thinking that the Observatory could be part of that next set of conversations, if not even lead it,” predicts Saha.