The third – and perhaps final – act of the Human Genome Editing Initiative ended last week. The first summit (Washington 2015) was held amid enthusiasm for the invention of CRISPR, with the aim of fostering a constructive dialogue between science and society. The second edition (Hong Kong 2018) was dominated by the birth in China of the first edited human beings. The main points in the agenda of geneticists and bioethicists meeting a few days ago (London 2023) was to overcome the shock and focus on the next challenges: broadening the range of treatable diseases, reducing the costs of therapies, simplifying them so they can be administered anywhere in the world, and reach as many sick people as possible.
The key words of this third summit, held March 6-8 at the Francis Crick Institute, were equity and access (see the closing statement from the organizing committee). The image that has gone down in the annals of CRISPR is undoubtedly that of Victoria Gray. The first patient treated with CRISPR has took part in a scientific conference for the first time to tell how the treatment developed by CRISPR Therapeutics and Vertex Pharmaceuticals changed her life.
The 37 yo woman from Mississippi recounted the suffering and hardships imposed by sickle cell disease when she was younger, the hopes placed in the new experimental therapy, the struggle to recover from the chemotherapy required to make room for the super-cells gene-edited to produce functioning hemoglobin, the newly won normality, with a full-time job and the joy of watching her children grow up.
On the podium before and after Victoria were many scientists, bioethicists, and representatives of the instances from middle- and low-income countries (generally more women than men, with a clear prevalence of public over private research). The mix of geographic origins pictures a CRISPR community concentrated in the United States, interested in understanding how the other biotech superpower (China) moves, concerned not to leave out Africa. Despite the scarcity of European voices, Italy was well represented by Luigi Naldini and Angelo Lombardo, who discussed epigenetic editing.
The concluding statement from the organizing committee points out that “the extremely high costs of current somatic gene therapies are unsustainable. A global commitment to affordable, equitable access to these treatments is urgently needed”. Achieving the goal will require a paradigm shift, with new approaches to research organization and regulation, as well as technical advances that avoid invasive steps such as chemotherapy.
According to an estimate presented by Emily Turner of the Gates Foundation, in vivo editing (by injecting CRISPR components directly into the patient’s body, rather than harvesting and then reinfusing the edited cells) might bring down the cost of a single shot in developing countries from $100,000-$500,000 to $1,000-$2,000 over ten years. The testimony of the Indian patient representative, Gautam Dongre, also left a mark: if not even hydroxyurea is guaranteed to everyone – despite its low cost and decades of use for anemia sickle cell in advanced countries – what about gene therapy?
The summit program gave space to the many promising advances, for example for muscle diseases, and in the Car-T technology for cancer. Clinical trials based on genomic editing now number in the dozens, but most efforts continue to focus on few big targets, such as the most common of rare diseases, sickle cell anemia, which has become the training ground of choice for new advanced therapies.
The concern of Fyodor Urnov and other researchers is that too many rare and ultrarare diseases are in danger of being left untreated without standardization of genetic strategies, simplification of rules, and a leading role for the nonprofit sector.
Topics and talks of particular interest include the European consortium Agora that wants to ensure access to gene therapy for rare diseases, the Gates Foundation project for sickle cell anemia and HIV-AIDS, the evolution of the regulatory framework initiated in China in response to the CRISPR babies scandal.
Regarding embryos and germ cells, the summit confirms the positions already outlined in reports by the U.S. academies and World Health Organization: yes to editing human embryos for basic research (i.e. to better understand embryonic development), and no to embryo editing for reproductive purposes that would have effects heritable from generation to generation. “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,” they say (although a few days earlier a jury of British patients had expressed hope that Britain might reconsider the ban).
The only breaking news announced at the summit was the birth in Japan of the first mice with two dads, but sci-fi applications for the human species are really far off. Outside
of the Crick Institute, protesters concerned about children design could be counted on the fingers of one hand. The audience of specialists, by and large, displayed
unity of purpose, despite the diversity of strategies and nuances.
It is not yet known whether the Human Genome Editing Initiative will have a follow-up beyond the triplet of summits already organized by the U.S. and British academies, most recently involving the World Academy of Sciences. But certainly the CRISPR community will meet again: the debate is not concluded and, as one participant noted, it is neither foreseeable nor desirable that it might end.