Our world is changing at an astonishingly rapid pace and, as described a few weeks ago, CRISPR is poised to become a major source of change in many fields, from medicine to animals to crops. With any new technology, but especially one that has the power to transform the world to the extent that CRISPR and other gene editing technologies could, it is imperative that we are proactive in developing a deep understanding of the technology and the changes it can bring about, as well as determining where the ethical limits lie and creating a universal set of rules and governing bodies to implement and enforce the rules.
Recognizing this, a series of Summits have been held with participants from many countries contributing to the discussion. The First International Summit on Human Genome Editing was held in 2015, with the goal of looking at the scientific, medical, ethical, and governance issues associated with advances in human gene-editing research. It was co-hosted by The Chinese Academy of Sciences, the U.S. National Academy of Sciences, the U.S. National Academy of Medicine, and the Royal Society.
The science of genome editing advanced so rapidly that, by 2018, many new lines of research employed CRISPR, and clinical trials were already planned using genome editing to treat diseases. Yet, many of the questions involving ethics, governance, science, and application of human genome editing still remained unanswered. The Second International Summit on Human Genome Editing took place in Hong Kong, in 2018. It was co-hosted by the Academy of Sciences of Hong Kong, the Royal Society of London, the US National Academy of Sciences, and the US National Academy of Medicine.
At this summit, an incredible announcement was made that shocked the world. This is the stage in which He Jiankui declared that twin girls had been born whose embryos had been edited with CRISPR to disable the CCR5 gene, in the hopes of preventing them from contracting HIV, as their father is HIV positive. This announcement brought even greater urgency to the discussion of issues surrounding both somatic and germline human genome editing.
Numerous human trials are underway, and many different gene-editing technologies have been developed. Yet, no single set of rules or international governing body has been established to ensure that ethical lines are not crossed. Thus, the need for further discussion is imperative and measures need to be implemented.
The Third International Summit on Human Genome Editing was held on March 6-8, 2023, to discuss “progress, promise, and challenges in research, regulation, and equitable development of human genome editing technologies and therapies.” Contributors from countries around the world, including China, Canada, Italy, the Netherlands, France, Tanzania, Brazil, the UK, the USA, South Africa, India, Argentina, and more, built on the global discussion of the previous two events.
Sessions covered a range of topics, such as Hopes and Fears for Human Genome Editing, which included talks about international equity for access to gene therapies, and Sickle Cell Disease: a case study affecting millions. One important session, the Role of Civil Society in Setting Research Agenda, discussed the role of patient organizations, activists and DIY community, and the role of cultural beliefs. Speakers provided updates on science, techniques, and clinical research involving somatic editing, and discussions of accessibility, price, regulation, and policy approaches to increase accessibility for somatic editing. Finally, a vital question was asked and discussed: Are there compelling reasons for heritable human genome editing? All sessions are available to view here.
A session on the first day of the summit did cover regulation changes that have been made in China since 2018. Changes included an update to China’s criminal code in which implantation of gene-edited embryos into humans is now punishable by prison time. Furthermore, new guidelines were released regarding ethical reviews that are required to edit human organs, cells, fertilized eggs, and embryos. The new guidelines also impose new sanctions on those who do not comply.
Yet, Dr. Joy Zhang, a Chinese-born British sociologist, explained that “Governance in practice is still confined to traditional medical, scientific, as well as educational establishments. The new measures fail to directly address how privately funded research and other social ventures will be monitored.”
The Organising Committee released a statement after the Summit that included the following conclusions:
“Remarkable progress has been made in somatic human genome editing, demonstrating it can cure once incurable diseases. To realise its full therapeutic potential, research is needed to expand the range of diseases it can treat, and to better understand risks and unintended effects. The extremely high costs of current somatic gene therapies are unsustainable. A global commitment to affordable, equitable access to these treatments is urgently needed.”
“Heritable human genome editing remains unacceptable at this time. 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.”
“Governance mechanisms for human genome editing need to protect ongoing, legitimate research, while preventing clinics or individuals from offering unproven interventions in the guise of therapies or ways to avoid disease.”
Somatic human genome editing was emphasized at the summit, which is fitting as it currently has the greatest potential for improving human health. Somatic editing refers to editing non-reproductive cells, in which changes to DNA only affect the person who receives the genome editing. Incredible progress has been made in this area, with many human trials underway.
Victoria Gray, a 37-year-old who suffers from sickle-cell disease, gave a moving speech in which she described the incredible ways that her life has improved since receiving treatment for the disease, in which her stem cells from her bone marrow were edited and returned to her body. She previously had lived a life marked by severe pain and being hospitalized for months at a time.
Victoria explained that “at one point in my life, I stopped planning for the future because I felt I didn’t have one. Now, I can dream again without limitation.” 75 patients with either sickle-cell disease or Beta-thalassemia have received the treatment in clinical trials, and it may be approved by the end of the year in multiple countries (1).
Another interesting case was highlighted by David Liu, PhD, of the Broad Institute of MIT and Harvard. He described using CRISPR to modify healthy T cells from a donor, altering the T cells so they would not be rejected by the patient, Alyssa’s, immune system, but could still find and attack her cancerous T cells. It was successful, and her cancer remains undetectable ten months later.
Although the overall progress in somatic human genome editing has been positive, there have been tragedies, as a few volunteers in clinical trials have died. Furthermore, while results of many trials show that treatments are safe and effective in many cases, gene editing techniques are still very young, and we do not have decades worth of data to prove there are no long-term adverse effects. The members of the organizing committee did stress that “extended long-term follow-up is essential to fully understand the consequences of an edit and to identify any unanticipated effects, should they occur.”
Heritable human genome editing refers to the editing of human embryos or gametes that are meant to be used for human reproduction. The organizing committee stated that “preclinical evidence for the safety and efficacy of heritable human genome editing has not been established, nor has societal discussion and policy debate been concluded.” Conditions have not been met that would make it safe or effective, nor has it “been developed and tested under a system of rigorous oversight that is subject to responsible governance.”
Although the World Health Organization (WHO) did issue recommendations on human genome editing in 2021, there is no international law on the matter.
Governance would provide countries with a uniform set of standards to which they should adhere, especially on the topic of heritable human genome editing. With the global economy and ease of travel, human germline editing would not just affect the country that allows it, but the entire human race. International ethical standards may be difficult to establish, though, as there are widely varying cultural beliefs that influence the topic. Yet, it seems as if an idea that would have been widely thought of as taboo just a century ago is now viewed as a logical, acceptable progression of scientific knowledge, and the consideration is where to draw the line and how much knowledge must first be obtained, rather than whether or not it is acceptable.
Governance of human genome editing, both somatic and heritable, would offer the additional benefits of minimizing the risks of rogue scientists or companies offering procedures that have not been approved or may even be dangerous, to people desperate for hope. As mentioned when discussing the new regulations in China, it should also address any privately funded research and track scientific practices that occur outside of conventional scientific institutions.
Equitable access was another consideration that received much discussion at the 2023 summit. Not only do more genetically diverse populations need to be included in the studies, but it would also be optimal if the range of those who conceive and conduct the research is greatly expanded, as it is believed that this would play a vital role in achieving equitable outcomes.
It was pointed out that many gene-therapy clinical trials are run in wealthy countries, while many low and middle-income countries have a higher percentage of those needing the therapy. Additionally, as these therapies are likely to cost millions of dollars, it will be necessary to intentionally develop systems in which the therapies can be made affordable or be provided for those who are not wealthy. Not only do the therapies need to be made affordable, but infrastructure, such as bone-marrow transplant centers, would need to be put into place to allow patients to receive the lifesaving treatments.
Although human genome editing provides a phenomenal opportunity to improve human health, it is still very young. In addition to long-term safety and efficacy considerations that face any new medication, human gene editing therapies face the additional necessity of ethical considerations, including equitable access, and developing an entire international governance system. Hopefully, these considerations will be addressed quickly enough that gene-editing technologies such as CRISPR can reach their full potential and vastly improve the lives of billions of humans in the future.