Closely-watched international CRISPR ethics panel leaves door ajar for germline editing — one day
In 2017, some of the world’s top scientists and ethicists emerged from over a year of deliberations with a report meant to finally lay down guiding principles for how CRISPR, the awesome-power-awesome-responsibility genome editing tool, should be safely and morally used.
Then, just months later, a scientist named He Jiankui announced he had used the tool to edit embryos and create so-called “CRISPR babies.” That was baffling to the experts who universally preached caution, but so was his next claim: That he had done so while following the — in hindsight, vague — principles set out in the report.
So the scientists went back to the drawing board. Less than two years after the initial project, the National Academy of Sciences launched a second panel to produce a report less open to interpretation.
Yesterday, they released the results. Unlike the previous report, the new one starts with a list of declarative and unambigous declarations: Without closing the door on editing embryos, the panel concluded that the scientific tools were not yet available to do so safely, and even when they were available, they could only be ethically applied in a narrow set of circumstances. They also called for the creation of international bodies that could counsel scientists and governments and track reports of scientists, such as He Jiankui, carrying out potentially dubious projects.
One of the key points of contention around the 2017 report was the question of where germline editing may one day be allowable. These types of edits are particularly concerning because, unlike editing cells in an adult, the changes to the genome become heritable, altering human evolution. There are also concerns around consent — the person being edited can’t give it. Still, the 2017 panel ruled that such an edit might be used in cases of “serious, unmet medical need.” He interpreted that to cover a gene that affected HIV transmission. Many other scholars did not.
The new guidelines are far more tailored. Initial uses, they write, should be “limited to serious monogenic diseases,” ones that “cause severe morbidity or death.” That could include muscular dystrophy, beta-thalassemia, cystic fibrosis, and Tay-Sachs disease, among others, they write. Notably, they exclude diseases caused by multiple genes, even when a particular gene variant such as APOE4 in Alzheimer’s puts someone at a greater risk of developing that disease. APOE4, they note, only correlates with a 5% greater risk of Alzheimer’s between ages 60 and 69.
“Editing a gene variant associated with a complex disease is likely to have only a minor effect on the risk of developing that disease,” the report’s authors, chaired by Oxford’s Kay Davies and Rockefeller University’s Richard Lifton, write, “while also potentially introducing unknown effects because of other biological roles the gene may play and other genetic networks in which it may interact.”
Even in cases of severe monogenic diseases, though, CRISPR use would be severely curtailed. With IVF and neo-natal screen, doctors can already screen embryos for Tay-Sachs and other conditions and select the best ones. So such edits would only be permissible in cases where there are no alternatives, such as when every one of a prospective parent’s embryos carry the genetic variant. The edit would also have to correct a variant into the common form of the gene, eliminating the form of editing He used, where he tried to cripple the CCR5 gene HIV uses to enter cells.
And editing for those disorders would only be permissible once scientific techniques catch up to these scientific ideas, the authors wrote, which they haven’t. Science writers have compared using CRISPR to editing the human genome like a Word document, but it might be more apt to compare it to editing a Word document on coffee-stained keyboard. It works often, but invariably there are unwanted changes both at the site of the edit and other sites on the genome.
The report warns strongly against germline editing before researchers develop methods to not only systematically edit embryos without those unintended changes, but to adequately screen the embryos to assure they’ve been edited safely.
“No attempt to establish a pregnancy with a human embryo that has undergone genome editing should proceed unless and until it has been clearly established that it is possible to efficiently and reliably make precise genomic changes without undesired changes in human embryos,” they write in recommendation #1. “These criteria have not yet been met and further research and review would be necessary to meet them.”
While cautioning that decisions on germline editing are left to individual countries, the report calls for international bodies that could set recommendations and manage reports of unethical behavior. That would include an International Scientific Advisory Panel with “diverse, multidisciplinary membership” and “independent experts who can assess scientific evidence of safety and efficacy of both genome editing and associated assisted reproductive technologies.” That panel would give insight before any new form of germline editing was used in humans.
The unspecified body for reporting unethical behavior would pass those concerns to national authorities and publicly disclose them. Notably, multiple scientists knew of He’s work before the announcement but said they lacked authorities to report to.
Since He’s announcement – which ultimately landed him a 3-year prison sentence in China — there have been no other known cases of a researcher editing an embryo before pregnancy. A Russian scientist, though, has pursued a project to correct blindness in embryos, raising similar alarm among outside experts. He told Science’s Jon Cohen he opposed the new recommendations as “far too narrow.”