A committee of the world’s leading scientists has called the clinical use of gene editing technology on human reproductive cells — sperm or eggs — as “irresponsible” until confirmed to be safe. The committee, however, stopped short of calling for a full ban on research into gene editing technology, which has been billed as a possible cure for heritable diseases like Tay Sachs, sickle cell, Huntington’s or cystic fibrosis.
“If in the process of research, early human germline cells undergo gene editing, [these] modified cells should not be used to establish pregnancy,” said David Baltimore, California Institute of Technology biologist and committee chair of this week’s International Summit on Human Gene Editing. Baltimore’s remarks closed the three-day conference, which was convened by the National Academy of Sciences in Washington, D.C. with the joint support of the Chinese Academy of Sciences and U.K.’s Royal Society.
The summit is the latest landmark in an eventful year for human gene editing. In April, Chinese scientists at Sun Yat-sen University in Guangzhou reported that they had tweaked human embryos with an emerging genetic tool called CRISPR-Cas9. CRISPR-Cas9 is like gene editing with a missile guidance system. The technique uses an enzyme from bacteria — Cas9 — to target and edit a sequence of DNA with very high precision.
CRISPR-Cas9 isn’t new — it’s existed for a decade — but the Sun Yat-sen University team was the first to use the technique with human embryos, wherein they cleaved a gene involved in the blood disorder beta-thalassemia. CRISPR-Cas9 is also pretty darn cheap and easy to use, relative to older gene-editing methods, making it an attractive target for commercialization. The possibilities extend to animals too. Some scientists want to use CRISPR-CAS9 to grow human organs in pigs, while others have reprogrammed mosquitoes to be malaria-resistant.
The result was a media storm and public debate about the ethics of so-called “designer babies.” One issue is CRISPR-Cas9, like other methods of gene editing, can exhibit off-target effects, where an unintended sequence of DNA is altered. Even though CRISPR-Cas9 is one of the best marksmen to-date in terms editing, an off-target mutation in a reproductive cell opens the door to a heritable mutation being introduced into society. Soon after the Sun Yat-sen results, the U.S. National Institutes of Health banned funding for research that edits human embryos.
China has a federal law that bans gene-editing in human embryos for the purpose of reproduction, Peking University professor Zhihong Xu said on Wednesday at the summit. The embryos used by the Sun Yat-sen team in April were non-viable — ones that could not result in a live birth.
Xu spoke during a panel about who governs gene-editing on an institutional and national level. Another member of this panel — Barbara J. Evans of the University of Houston Law Center — explained how the U.S. doesn’t host a federal ban on the human use of gene editing in reproduction, and under current guidelines, the Food and Drug Administration could permit some versions of reproductive genome editing.
“The FDA’s definitions plausibly would let the agency categorize gene editing as either a drug or a device,” Evans said. “And the FDA doesn’t require sponsors to do $1.2 billion clinical trials to prove the effectiveness of a device that’s only going to serve 50 people.”
That means a genome editing drug could be approved tomorrow and used in an experimental trial for a limited number people if the drug doesn’t pose a significant risk for the research subjects. That isn’t to say they would, given the regulatory agency is currently deliberating the implications of embryo editing.
This gene editing is already being used in clinical trials with somatic cells, ones that aren’t involved in reproduction, such as in a case reported last month of a 1-year-old girl who was cured of leukemia. These genetic tweaks in somatic cells can’t be passed onto future generations.
Edited genomes tend to raise visions of children designed by parents to be “perfect,” eugenics, X-men or the introduction of mutations that could negatively alter the fate of humanity. This uncertainty has led some scientists to call for a moratorium for genetically modified humans.
“There’s been a lot of thought of how to analyze these very serious, generational risks. We need to draw on that. We need to get out of our medical bioethics silo and look at what the similar problems are finding,” Evans said. Yet she also warned against a complete moratorium or basing research decisions on only worse-case scenarios.
“You look at the potential for positive public health benefits, but also recognize that banning a technology might consign a lot of people to very harsh circumstances,” Evans said.
Neuroscientist and Huntington’s disease patient Jeff Carroll agrees, as he expressed to the MIT Technology Review this week: “I have no compunctions about it … I am saying, please, please do mess with our DNA.”
So what was once fodder for dystopian science fiction (Gattaca anyone?) has now become a very possible reality … not quite. Right now, geneticists know a lot about diseases caused by a single gene. However, they’ve barely begun to resolve complex traits, like personality or even ostensibly simple things like eye color. In fact, there might be thousands of genes responsible for your height.
“Many nations have legislative or regulatory bans on germline modification,” Baltimore said in his closing remarks. “However, as scientific knowledge advances and societal views evolve, the clinical use of a germline editing should be revisited on a regular basis.”