CHAPTER 2 The Value and Limits of Statements from the Scientific Community: Human Genome Editing as a Case Study

David Baltimore and Robin Lovell-Badge

In late November 2018, when we arrived in Hong Kong for the Second International Summit on Human Genome Editing, we were met with the news that a researcher, He Jiankui of the Southern University of Science and Technology in Shenzhen, China, had edited embryos that developed into twin girls who were born just a month earlier. We had invited Dr. He to speak at the summit as part of an ongoing global discussion, started in 2015, about the appropriate use of breakthrough gene editing tools, including CRISPR-Cas9. At the time we sent our invitation to Dr. He we were not aware of his experiment. When we did become aware of this in Hong Kong, all of us on the summit organizing committee, a group convened by the US National Academy of Sciences and National Academy of Medicine, UK Royal Society, and the Academy of Sciences of Hong Kong, were deeply concerned. Fortunately, the statement issued by the organizing committee (of which we were also members) at the end of the first summit on human genome editing, held in Washington, DC, in late 2015, provided a guidepost to help us respond effectively to the news of Dr. He’s experiment.

The first summit convened in 2015 by the US National Academy of Sciences and National Academy of Medicine, the UK Royal Society, and the Chinese Academy of Sciences, drew worldwide attention. After three days of lively discussions, the organizing committee issued a statement, in which the key conclusion declared:

It would be irresponsible to proceed with any clinical use of germline editing unless and until (i) the relevant safety and efficacy issues have been resolved, based on appropriate understanding and balancing of risks, potential benefits, and alternatives, and (ii) there is broad societal consensus about the appropriateness of the proposed application. Moreover, any clinical use should proceed only under appropriate regulatory oversight. At present, these criteria have not been met for any proposed clinical use: the safety issues have not yet been adequately explored; the cases of most compelling benefit are limited; and many nations have legislative or regulatory bans on germline modification.¹

When we learned on the eve of our 2018 summit in Hong Kong that Dr. He had used CRISPR/Cas-9 to edit the embryos of newly born twin girls, specifically targeting a gene, CCR5, that codes for a protein that HIV-1 uses to enter cells, a few members of our organizing committee met with him to ask exactly what he had done. What we learned from him indicated that he had acted irresponsibly, given that the conditions set forth in the 2015 statement had not yet been met (nor have they currently been met). We agreed, however, that in the interest of scientific openness, Dr. He should be allowed to remain on the agenda and given an opportunity to report on his work. When he spoke on the second day of the summit, there were nearly 100 reporters and photographers in the auditorium, along with approximately 400 attendees, and a worldwide audience of over one million watching a live webcast. Immediately after Dr. He’s presentation, I (David Baltimore, as chair of the 2018 summit organizing committee) took the lectern to condemn He’s experiment as “irresponsible,” and to criticize him for his lack of transparency; then I added: “There has been a failure of self-regulation by the scientific community.” Although our 2015 statement provided important principles that we expected the scientific community to follow, it had failed to stop a rogue scientist from pursuing heritable genome editing.

At the end of the Hong Kong summit, the organizing committee, comprising representatives from eight countries, issued a new statement updating the 2015 statement. While expressing deep concern with Dr. He’s reported experiment, we also took note of the progress that had been made in further developing genome editing tools, the attention that various countries were giving to genome editing, and the need for ongoing public engagement. We noted the “rapid advance of somatic gene editing into clinical trials,” but at the same time, emphasized that we “continue to believe that proceeding with any clinical use of germline editing remains irresponsible at this time.”² (Somatic gene editing is the editing of genes in adult cells, whereas heritable genome editing via germline cells involves edits that may be passed onto future generations.)

The word “irresponsible” in both statements was not used lightly. Responsibility is a hallmark of scientific excellence and integrity. As science advances and our understanding increases, it is essential that the scientific community maintains high expectations for its members.

Statements such as these are not meant to be set in stone but rather should be updated as the science moves forward and societal concerns change. Our first statement, therefore, acknowledged that “as scientific knowledge advances and societal views evolve, the clinical use of germline editing should be revisited on a regular basis.”³ Thus, the 2018 statement called for a more defined approach to determine whether germline editing in clinical settings could someday be permitted in accordance with scientific and medical norms and values. We stated that

the scientific understanding and technical requirements for clinical practice remain too uncertain and the risks too great to permit clinical trials of germline editing at this time. Progress over the last three years and the discussions at the current summit, however, suggest that it is time to define a rigorous, responsible translational pathway toward such trials.⁴

In addition, the statement emphasized that the pathway must adhere to

widely accepted standards for clinical research, including criteria articulated in genome editing guidance documents published in the last three years. Such a pathway will require establishing standards for preclinical evidence and accuracy of gene modification, assessment of competency for practitioners of clinical trials, enforceable standards of professional behavior, and strong partnerships with patients and patient advocacy groups.⁵

Following the 2018 summit numerous organizations issued reports detailing such a pathway.⁶ When we convened in London in 2023 for the Third International Summit on Human Genome editing, chaired by Robin Lovell-Badge, coauthor of this essay, the world had just begun emerging from a global pandemic. The organizing committee, which included representatives from eleven countries, sought to continue the discussion about the science and ethics of genome editing, given the tremendous advances that had been made in somatic cell editing. We also drew even greater attention to issues of access, cost, and equity, especially given the price of emerging gene editing treatments.

Just as we did at the first two summits, the organizing committee issued a statement at the conclusion of the third. That statement noted “remarkable” progress in somatic genome editing, based on demonstrations, including a first-person account by a patient, that it could be used to cure once incurable diseases. Further, the statement indicated that to realize the full therapeutic benefits of somatic editing, “research is needed to expand the range of diseases it can treat, and to better understand risks and unintended effects.”⁷ It noted that “the extremely high costs of current somatic gene therapies are unsustainable” and identified an urgent need for “a global commitment to affordable, equitable access to these treatments.”⁸

With respect to heritable genome editing, the committee reiterated that it “remains unacceptable at this time.”⁹ Moreover, we added that: “Public discussions and policy debates continue and are important for resolving whether this technology should be used. Governance frameworks and ethical principles for the responsible use of heritable human genome editing are not in place. Necessary safety and efficacy standards have not been met.”¹⁰

Having set the foundation at our 2015 summit for the pursuit of somatic gene editing technologies while expressing extreme caution about the use of heritable editing, over the next eight years the statements were able to reaffirm, clarify, and take note of advances in science and societal responses. Each statement built on the knowledge that the scientific community had gained and the ever-evolving expectations and demands of society to participate in decisions about the clinical applications of the science. Even though it is difficult to obtain universal consensus on contentious issues such as this, the statements were authored by diverse organizing committees and with the input of diverse audiences. They served as a reference point for the scientific community and the public and spurred ongoing engagement with diverse stakeholders. Although we do not have the capacity for global monitoring, and despite Dr. He’s demonstration of the relative ease at which heritable genome editing could be done, albeit very badly, we are unaware at this time of any additional attempts at human heritable germline editing. We are reluctant to credit the summit statements for this restraint, but we do believe that such statements provide guidance and grounding for the scientific community in its consideration of emerging technologies. Artificial intelligence, especially generative AI, is a case in point. This technology will likely have huge impacts on all aspects of science and society. More stringent governance may be necessary, but in the meantime, proposing guiding principles for AI’s development and deployment in research is an appropriate step for leaders in the scientific community to take to convey that it should be utilized responsibly in ways that uphold the integrity and norms of science and bolster public trust.