As Technology Gets Better, Ethical Prohibitions on Genetically Modifying Human Embryos Are Getting Weaker

It's become too late to ask whether or not we should edit the human germline; we can now only ask how the experiments will proceed.
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Embryo.

Embryo.

In February of 1975, about 150 scientists gathered at the Asilomar conference center in Pacific Grove, California, to discuss what kinds of restrictions should be placed on genetic engineering. Thanks to new technologies that allowed them to directly splice together different pieces of DNA, molecular biologists were just beginning to make genetic combinations that had never before existed in nature. Some researchers were preparing to introduce completely foreign DNA into bacteria, something that critics worried might produce potentially harmful new types of microbes that could escape from the lab and into the environment.

Safety was one concern, but others thought that genetic engineering, dangerous or not, was a step that humans should never take. Erwin Chargaff, a biochemist whose work had helped lead to the discovery of DNA's central role in genetics, warned about "the awesome irreversibility of what is being contemplated. You can stop splitting the atom; you can stop visiting the moon; you can stop using aerosols; you may even decide not to kill entire populations by the use of a few bombs. But you cannot recall a new form of life. Once you have constructed a viable E. coli cell carrying a plasmid DNA into which a piece of eukaryotic DNA has been spliced, it will survive you and your children and your children's children."

In response to safety and other ethical concerns, scientists instituted a voluntary moratorium on genetic engineering in the year before the Asilomar conference. The idea was to hit pause so that the scientific community could carefully assess the risks before proceeding with experiments that might have unforeseen consequences. At Asilomar, the participants proposed a set of safety guidelines to govern genetic engineering experiments. Those guidelines soon became the basis of rules established by the National Institutes of Health, which are largely still in place today.

Biologists often cite the Asilomar conference as an example of scientists' self-restraint: Before unleashing a new technology on the world, researchers voluntarily halted their work to deliberate over its consequences. But the truth is that the recommended restrictions were minimal, focused mainly on how to contain potentially infectious material in the lab, rather than on what types of genetic experiments were acceptable. None of the recommendations addressed the concerns of those who thought that genetic engineering should not be done at all. The frustration of critics like Chargaff stemmed from their recognition that scientists were determined to proceed with genetic engineering no matter what. Once the technology became truly feasible, no larger ethical concerns—beyond basic issues of safety—would stand in the way.

A similar story is playing out today, now that scientists have developed an easy way to edit the DNA of human embryos. For a long time, such experiments were, as one recent overview put it, "a no-fly zone among molecular biologists," prohibited by scientific societies, university policies, and government regulations. Potentially, scientists could have made genetically engineered humans in the 1980s, when researchers began successfully modifying genes in mice. But using those inefficient techniques on humans would have produced dystopic levels of failed pregnancies and unhealthy, imperfectly edited babies. Proceeding was clearly unthinkable.

That is no longer true. The new CRISPR gene editing technology is so efficient and accurate that scientists can almost genetically edit human embryos in a way that is only slightly more cumbersome and risky than in vitro fertilization, a procedure carried out routinely every day in thousands of clinics around the world. A team of Chinese scientists was the first to genetically modify human embryos, testing the technique in 2015. They used non-viable embryos (produced from eggs that had been fertilized by more than one sperm at an in vitro fertilization clinic), but their work nonetheless raised an outcry.

As pre-publication rumors about the work of the Chinese scientists came out, one group of scientists called for a moratorium, writing that, "At this early stage, scientists should agree not to modify the DNA of human reproductive cells." One of their major concerns was that genetic edits made to human embryos are "germline edits," meaning that any babies born as a result would pass those genetic modifications on to their descendants. Echoing Erwin Chargaff, the scientists wrote that "genome editing in human embryos using current technologies could have unpredictable effects on future generations. This makes it dangerous and ethically unacceptable."

The National Institutes of Health also reiterated its longstanding prohibition on genetically modifying human embryos with NIH funding, adding that "the concept of altering the human germline in embryos for clinical purposes has been debated over many years from many different perspectives, and has been viewed almost universally as a line that should not be crossed."

But another group of prominent scientists, including some of the original organizers of the Asilomar conference, was willing to consider crossing that line. While they agreed that nobody should attempt to modify embryos with the intention of a live birth at this point, they did recommend that the scientific community "encourage and support transparent research to evaluate the efficacy and specificity of CRISPR-Cas9 genome engineering technology in human and nonhuman model systems," with the goal of determining whether making genetically modified babies could ultimately become useful in the clinic.

More than a dozen major scientific and medical societies have since issued statements that concur with this recommendation. In February, the National Academy of Sciences issued a report that concluded that clinical trials of human germline editing should be permitted for "compelling purposes of treating or preventing serious disease or disability," once researchers are sure that the technology is safe enough. Late this summer, the American Society of Human Genetics, together with 10 other medical and scientific societies from the United States, Europe, Asia, and Africa put out a new position statement on editing human embryos. While it is "inappropriate to perform germline gene editing that culminates in human pregnancy" at this point, the societies nevertheless actively encourage scientists to pursue scientifically worthwhile experiments with genetically modified human embryos, stating that "there is no reason to prohibit in vitro germline genome editing on human embryos and gametes."

As restrictions loosen, scientists are beginning to move ahead with experiments on human embryos. In a study published in August, Oregon Health & Science researcher Shoukhrat Mitalipov and his team reported that they were able to successfully correct a disease mutation in human embryos in 67 percent of their attempts, demonstrating a major improvement in the efficiency of the technique. And in October, Kathy Niakan and her team at the Francis Crick Institute in London published a study in which they deleted a critical gene from human embryos in order to study the earliest stages of human development. None of these researchers attempted to create pregnancies with the embryos, but by refining the technology, these studies are laying the groundwork for future clinical trials.

We can be certain that, within a few years, gene editing technology will become safe enough for doctors to correct a mutation for cystic fibrosis or Huntington's disease in a human embryo, and from that embryo produce a healthy child who won't have to worry about passing on a devastating disease to her children. But once we begin correcting genetic diseases with germline editing, there will be no technical barrier to using this technology for less medically urgent needs, as long as would-be parents of genetically enhanced children are willing to conceive by in vitro fertilization.

By that point, advances in the technology will have almost certainly outpaced any ethical debate over how to use it. Questions about what kinds of genetic edits should be allowed, whether it's even right to make a genetically modified child who had no say in the matter, and who gets access to this technology will give in to the relentless pressure of technological progress. Even if certain types of germline edits wind up banned in the U.S., they will certainly be available elsewhere in the world.

After Asilomar, the worst fears about genetic engineering did not come true. Biologists did not accidentally unleash a plague of genetically engineered pathogens. Just seven years after the conference, the Food and Drug Administration approved the first drug made with genetic engineering: bacterially produced human insulin, which revolutionized the treatment of diabetes. And most of the major biomedical advances since the 1970s would not have been possible without the tools of genetic engineering, which are now used routinely in thousands of research labs. The odds are that human germline editing will develop similarly, having some value as both a research tool and as therapy. And as with genetic engineering, it's become too late to ask whether or not we should edit the human germline; we can now only ask how the experiments will proceed.

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