The climate change confab in Paris is getting the headlines, but a far more historic meeting took place this week in Washington, D.C. For three days, the International Summit on Human Gene Editing brought together more than 400 scientists, ethicists, policy makers, and activists to consider the revolutionary implications of the cheap, fast, and flexible new gene editing technique known as CRISPR.
Derived from what amounts to a bacterial immune system for fighting off attacking viruses, the CRISPR gene-editing technique was first developed barely three years ago. CRISPR can edit genes much like a word processing program can edit text. Researchers hope it will allow them to cure cancer, correct genetic diseases, generate more productive and nutritious crops and farm animals, spread desired genetic modifications through wild ecosystems, engineer pigs as organ donors for people, and prevent heritable diseases by altering the genomes of human embryos—all in the not-so-distant future.
"Everything is possible with CRISPR," the Baylor geneticist Hugo Bellen told Science News this week. "I'm not kidding."
Others view the technology more darkly. The Brazilian bioethicist José Roberto Goldim argues that CRISPR has endowed humanity with "dangerous knowledge"—that is, knowledge that supposedly "accumulates more rapidly than the wisdom required to use it."
The summit was convened on Tuesday at the headquarters of the National Academy of Sciences, which co-hosted the meeting with the National Academy of Medicine, the British Royal Society, and the Chinese Academy of Sciences. In his opening remarks, the Caltech biologist David Baltimore declared: "The overriding question is when, if ever, we will want to use gene editing to change human inheritance." Few researchers or ethicists object to eventually using CRISPR to fix broken genes in adults, but many are haunted by the specter of the much-dreaded "designer babies."
These fears were ratcheted up earlier this year, when researchers at Sun Yat-Sen University published a study that described using CRISPR to modify genes for the inheritable disease beta thalassemia in nonviable human embryos. While some of the targeted genes were successfully changed, there were many off-target changes in the genomes too. The high rate of off-target edits could have been the result of using very early versions of the technology and the fact that the embryos had been double fertilized, which means that they carried three sets of chromosomes rather than the standard two.
In any case, improvements in the specificity of CRISPR editing have come very rapidly. Just a day before the conference, Science published a study by the MIT-Broad Institute geneticist Feng Zhang in which he described a simpler versions of CRISPR that reduces off-target errors by a factor of ten, and some versions produced no detectable off-target effects. One safety benchmark is to get the level the off-target editing down to around the natural rate of mutations in the human genome.
After the outcry against the Chinese study, a team of British researchers applied in September for permission from the United Kingdom's Human Fertilisation and Embryology Authority to attempt genetic modification of human embryos. The goal is not reproduction, but rather to better understand embryonic development. The edited embryos would be destroyed before reaching 14 days of development.
"Will our grandchildren—or perhaps even children—be born all equally subject to the vicissitudes—and the joys—of the genetic lottery?" asks the Monash University bioethicist Robert Sparrow. Sparrow thinks joyfully leaving future generations to Mother Nature's not-so-tender mercies is the moral thing to do. The left-leaning Center for Genetics and Society and the Friends of the Earth agree. In a joint declaration issued the day before the summit, they argue for permanent "national and international prohibitions on the use of gene editing…to alter the human germline for reproductive purposes."
The two groups fully expect that we will one day be able to make safe inheritable changes to the genomes of human embryos. Their fear is that the "advent of human germline intervention could lead to the development of new forms of social inequality, discrimination and conflict"—basically, that rich people will use the technology to endow their children with better life prospects than are available to the poor. Of course, the rich already have access to lots of non-genetic enhancements for their children, such as, tutors and coaches. In addition, genetic engineering may well ameliorate rather than exacerbate human inequality by providing access to more people the benefits that were once apportioned only to the genetically fortunate.
The two groups' declaration also asserts that the precautionary principle should be applied to human germline interventions, on the grounds that they are irreversible and could have unintended consequences. As far as irreversibility goes, it's worth noting that if a person whose genome was modified using CRISPR decides he wants his children to inherit the old genome, he can use the technology to make it so. And if unintended consequences are a reason to ban CRISPR, it's a reason to ban any new technology, since it is impossible to foresee the all of the consequences of nearly any activity.
Let's turn now to some of the other dazzling and disturbing prospects offered by the new gene editing technology. By enabling the development of gene drives, CRISPR allows researchers to violate Mendelian inheritance, in which offspring get half their corresponding genes from each parent. When a gene drive is inherited from one parent, it edits the corresponding gene from the other parent to match itself. So every time a creature carrying a CRISPR-enabled gene drive mates, essentially all of its offspring will bear its version of a specific gene on both sets of their chromosomes. In late November, a paper in the Proceedings of the National Academy of Sciences revealed that researchers had created a gene drive that can spread genes for producing antimalarial antibodies throughout mosquito populations. Similar gene drives could eliminate all kinds of insect-borne maladies, from Lyme disease to dengue fever. Gene drives could be also used to eliminate unwanted invasive species, such as Australia's cane toads, by ensuring that all subsequent progeny are born male. Or to make weeds that have become resistant to herbicides once more susceptible to them.
In 2014, Harvard Medical School researcher Kevin Esvelt and his colleagues suggested some sensible guidelines for scientists developing gene drives. One recommendation is that researchers should always create a reversal drive before releasing any gene drive into the world outside of the laboratory. If something goes wrong, they could then restore the original genome of the targeted plant or animal population.
In November, the Harvard biologist George Church and his colleagues reported that they had used CRISPR to make some 60 simultaneous edits in the genomes of pig embryos, with the aim of eventually making their organs safe to use as transplants for people. Other scientists have used CRISPR to disable the gene in that limits the amount of muscle a pig may develop. The result is much meatier farm animals.
Plant geneticists are using CRISPR to make crops more pest- and disease-resistant. Often, all a breeder would have to do is edit a gene in one crop variety to match another naturally occurring gene for disease or pest resistance in another variety of the same species. Since the same results could be obtained through years of tedious crossbreeding, it will be interesting to see if the opponents of current biotech crops will also object to these genetically engineered varieties.
The good news is that at the close of the summit, the organizers issued a statement that, while noting current safety issues with regard to using CRISPR for germline interventions, nevertheless declined to recommend a permanent ban on making inheritable changes in the human genome. The statement also rejected calls for a temporary moratorium on basic and preclinical research using gene-edited gametes and embryos. However, such gene edited cells should not be used to establish a pregnancy.
The Paris summit of 140 world leaders garnered more press attention this week, but history may recall the Human Gene Editing Summit as far more consequential for humanity's future.