There Still Aren’t Any Rules Preventing Rogue Scientists From Making Gene-Edited Babies

Around this time last November, Chinese scientist He Jiankui stunned the world when he revealed the birth of the first known gene-edited babies. Working in relative secrecy, he had used CRISPR to modify human embryos in the lab and then established pregnancies with those embryos. Twin girls with edited genomes were born as a result.

The scientific community’s condemnation of He was harsh and swift. He had edited the germline, making a heritable genetic change. There were safety questions about the effects on the twins, and he had not meant to fix a genetic defect to prevent a heritable disease. Instead, he tweaked a gene in an attempt to bestow an uncommon, protective genetic trait: resistance to HIV.

In the aftermath, leading scientists and ethicists published an open letter in the journal Nature calling for a temporary moratorium on human germline gene editing — that is, editing eggs, sperm, or embryos — to make genetically modified children. But it’s been a year, and there is still no unified set of rules to dictate whether or how scientists should conduct this research. Some scientists have rejected a blanket moratorium in favor of self-regulating, believing that they can chart a path toward responsible germline editing to prevent a number of inherited diseases.

But how to do so remains a point of contention.

Meanwhile, at least one scientist is already planning more gene-edited children. In June, Russian molecular biologist Denis Rebrikov said he wanted to use CRISPR to create more HIV-resistant babies, but in a more ethical way than He’s experiment. His plans have since shifted to editing embryos of couples with inherited deafness in an attempt to make hearing babies.

“The horse has already left the barn,” Jennifer Doudna, one of CRISPR’s inventors, tells OneZero.

The need for regulation in germline editing is urgent because the consequences may fundamentally change the human genome and be passed down through generations. And putting CRISPR directly into the human body, including into germline cells, hasn’t been proven safe yet. Doing so may cause so-called off-target effects, which are unintended edits to other parts of the genome that could result in genetic mutations that cause health problems in a baby. Another worry is the possibility of mosaicism, which happens when some cells in an embryo get edited but others do not, potentially causing many different kinds of genetic disorders.

Researchers that have reviewed He’s data suspect the twins are both mosaics and may also have off-target edits. “That’s a terrible combination,” says Dr. Kiran Musunuru, a physician and gene editing expert at the University of Pennsylvania who wrote a book about the Chinese CRISPR twins. “That means there may be harmful edits in some parts of the body where you can’t easily detect them, and you may have no idea that they’re there.”

Then there are the many ethical issues surrounding germline gene editing. Most scientists decried He’s experiment because they consider it a form of enhancement rather than an attempt to prevent disease by fixing a genetic flaw already present in the embryo. There’s also the widespread fear that tinkering with the human germline is a slippery slope to “designer babies” with custom-edited DNA. Many worry about a situation in which parents could visit a fertility clinic and choose what genetic traits to bequeath to their future children using in vitro fertilization and gene editing.

Right now, each country has its own sovereignty over germline editing and decides how to oversee it within its borders. A consensus on how and whether nations should collaboratively regulate the research has yet to be reached. “When technology moves forward quickly in laboratories or whatever setting it is being developed, it’s very difficult for governments and regulatory agencies to keep up with it,” says Doudna.

After He’s experiment, China reacted promptly to the news. In May, it proposed a new regulation that would make any scientist that manipulates the genes of an embryo or a person responsible for the outcome. Musunuru says this means that researchers could be held liable for anyone harmed in a gene-editing trial, even one that edits somatic cells — non-germline cells — in adults. China’s health ministry also drafted regulations requiring scientists to obtain approval before editing human embryos or risk penalties.

In Russia, Rebrikov will also need to get approval from the government before beginning his work, and if that happens, U.S. scientists say there’s nothing they can do to stop him. “We could see the birth of more gene-edited babies,” says Musunuru, who was one of 60 gene therapy and genome editing experts to sign the letter in support of a “global binding moratorium” in April. “Who knows how many silent individuals there are out there trying to do the same thing?”

Doudna is concerned that a moratorium will no longer be enough to deter researchers like Rebrikov, as she argued in a recent editorial in the journal Science. She and a group of prominent scientists strongly discouraged the use of human germline editing in 2015, a few years after the first published results of CRISPR’s powerful capabilities. That proclamation didn’t do anything to dissuade He, and she says reiterating it now won’t prevent future rogue gene editors either.

She believes it’s time for government regulators to act. “Instead, we really need to have very clear restrictions around the use of genome editing in the human germline and clear consequences for defying that,” she says. At minimum, she says those should include losing funding and the ability to publish in scientific journals, which would represent major career blows.

In the absence of formal regulations, a World Health Organization committee convened in response to the Chinese CRISPR babies has proposed a stopgap measure to help dissuade bad actors. The committee said in August that it is launching a registry to track all clinical trials that involve human genome editing, both in people and in embryos, and is calling on researchers doing such work to register their trials in the database. The idea is to provide a clearinghouse for such studies. Presumably, if a study isn’t in the registry, then it won’t be considered appropriate research.

Doudna says the global transparency of an open-access registry would mean that anyone could see the intended purpose and process of such studies. “Does this prevent all bad actors? It doesn’t, but I don’t know if we can ever be 100% confident about that,” she says.

But Francis Collins, director of the National Institutes of Health, recently criticized the idea at an event in Washington, D.C., saying that registries like ClinicalTrials.gov already include that information. “I think that is a distraction from what the original concern was, which was to focus on human germline editing,” he said at a meeting of the American Society for Cell and Gene Therapy conference in November. Collins also supports a moratorium and believes the WHO committee should focus on germline, not somatic, editing.

The proposed registry will not be mandatory, a WHO spokesperson said in an email, so it will be up to researchers to list their own studies.

Janet Lambert, CEO of the Alliance for Regenerative Medicine, an industry organization in Washington, D.C., that represents biotech companies developing gene-editing treatments, also doesn’t see the registry as a pragmatic solution. Her organization proposes what she refers to as a “germline 911” — a central institution where scientists could report ethically dubious research happening outside their organization. In the months after the CRISPR babies news, it was revealed that many scientists, including some in the United States, knew about He’s plans to make gene-edited babies but didn’t tell anyone or try to stop him.

“For those who had concerns, there wasn’t a clear standard about when you should call someone, who you should call, and what someone on the other line would do,” Lambert says. She thinks the WHO, as a respected international agency, would be well-suited to operate such a hotline.

The WHO’s committee, for its part, is expected to propose global standards for germline editing research, and the U.S. National Academy of Medicine, U.S. National Academy of Sciences, and the Royal Society of the United Kingdom have together launched a commission for a similar purpose. But both groups are not expected to release their recommendations until 2020 at the earliest.

It’s unclear whether countries will wait for recommendations from the WHO and National Academies committees to act. These groups don’t have any enforcement power, so any recommendations they make to governments will be just that.

Until those reports come, Lambert thinks that the fear of being in the position that China was in last year might be enough to prompt countries into stopping research plans for gene-edited babies. “It seems like part of this international effort is to try to convince governments that this isn’t something they want to be encouraging or promoting,” she says.

In the United States, the debate over germline gene editing to create babies is virtually moot. That’s because a provision first passed by Congress in December 2015 stipulates that the Food and Drug Administration, which has to approve any human experiment involving the use of gene editing, cannot even consider research applications that involve modifying an embryo and implanting it. That provision needs to be re-upped every year, and thus far, Congress has decided to keep it. There’s also the Dickey-Wicker Amendment, passed in 1995, which also bans the National Institutes of Health from funding research involving the creation or destruction of human embryos. Musunuru says he doesn’t think these restrictions will change anytime soon.

Outside the United States, however, there is a patchwork of international regulations that exist for genome editing, but it leaves plenty of opportunities for scientists who want to do ethically dubious gene editing. About 30 countries currently have legislation that directly or indirectly bans the use of germline editing to create pregnancies. The legality of germline editing is murkier in many other places, like Russia and a handful of countries in South America, which could open the door to countries becoming a safe haven for more cavalier researchers.

As an inventor of the technology she’s now trying to control, what Doudna worries most about is a public backlash against CRISPR if something goes else wrong. “To me, one of the worst-case scenarios is having a public backlash against this powerful tool that has so much positive potential and having it become a pariah.”