To rid families of the curse of inherited diseases, medical geneticists have dreamed about changing human DNA before birth. The dream is also a nightmare, however, because it raises the specter of designer babies or creating harmful mutations. Now a precision genome-editing technique known as CRISPR-Cas9 has brought both dream and nightmare to the edge of reality.
The technique makes snipping out troublesome DNA from a cell's nucleus incredibly easy and cheap, compared with other methods. Scientists have been testing whether it can be used to treat genetic diseases, such as cystic fibrosis, and other scourges, such as HIV, in mature human cells. But no one had attempted to edit cells that can pass DNA down through generations: those of sperm, eggs or very early stage embryos. Such cells belong to what is known as the germ line. In April a team at Sun Yat-sen University in China revealed that it had crossed that line.
Rumors of such work had already elicited alarm. In March authors of a widely publicized editorial in Nature called for a moratorium on all human germ line modification, whether for research or clinical use, as did the Center for Genetics and Society in Berkeley, Calif. But total prohibition would be a mistake.
The Chinese team used CRISPR on early-stage embryos that carried genetic material from two sperm instead of the usual one. Such embryos do not develop normally and are therefore discarded by fertility clinics. The investigators tried to repair a mutation in a gene that causes a potentially fatal blood disorder known as beta thalassemia. The results of their study, published in the journal Protein & Cell, showed that CRISPR failed to repair the targeted mutation in most of the embryos and caused unintended changes elsewhere in the genome. (Scientific American, Nature and Protein & Cell are part of Springer Nature.) The research demonstrated that the technology involves far too many unknowns at present to justify any risks to human life.
Clearly, we need a moratorium on genome modification of germ line cells intended for establishing pregnancy. Scientists have much to learn about how CRISPR works. More fundamentally, they still know very little about how genes interact with one another and with the environment to cause disease. Funding agencies should not support studies with embryos suitable for implantation in the uterus, nor should journals publish such work.
But scientists should be permitted to conduct basic research on human germ line modification, as the International Society for Stem Cell Research and other groups have argued. This work could involve early-stage, nonviable embryos. Such engineering could conceivably stop devastating genetic disorders such as Huntington's disease and muscular dystrophy before they start in offspring—and keep the DNA from being transmitted to further descendants. The risk, though, is that inadvertent, harmful changes would also get passed on. Researchers need to conduct extensive studies before clinical use can be contemplated. Currently prospective parents using in vitro fertilization can have early embryos screened for certain genetic disorders. Some couples, however, may be unable to produce disease-free embryos or may have ethical concerns about making more embryos than they will use. Germ line editing could eventually help them.
In the U.S., we wish basic work on the germ line could be carried out with federal funding because it would provide more resources and greater transparency, but such research will have to get money from private and state-funded initiatives. In the wake of the Protein & Cell study, the National Institutes of Health reiterated that it will not fund research involving modification of human embryos, citing legal prohibitions as well as safety concerns.
Those issues show that scientific and government groups must engage the public in discussions about germ line changes and use that dialogue to form new policies. CRISPR is the most powerful genome-editing tool that scientists have. We need to explore its potential to avert the horrors of genetic diseases but do so without jeopardizing our values or harming generations of human lives.