Global summit opens door to controversial gene-editing of human embryos

WASHINGTON — The organizers of the International Summit on Human Gene Editing left the door open to one of the most controversial uses of that technology, altering human eggs, sperm, or early embryos in a way that allows those changes to be inherited by future generations.

In a statement issued on Thursday as the summit ended, the organizers said the promise of such “germline editing” was so great that “intensive basic and preclinical research” on non-human animals “is clearly needed and should proceed.”

It added: “If, in the process of research, early human embryos or germline cells undergo gene editing, the modified cells should not be used to establish a pregnancy.”

The summit saved the drama and controversy for the last of its three days. Even before the final statement was issued, both featured speakers and audience members criticized the organizing committee for failing to invite important constituencies to the table, and one scientist raised an unexpected concern: that genome editing might not be as safe as often assumed.

The three-day meeting drew scientists, ethicists, patient advocates, regulators, and others from around the world to wrestle with profound questions: Is it ethical to rewrite the genetic code of the human race in sperm, eggs, or early embryos — the human “germline” — so that the repairs are passed down to any future children? And should scientists voluntarily limit this unprecedented — some would say frightening — power, even though it might be used to wipe out inherited diseases such as thalassemia or Tay-Sachs once and for all?

This debate has been propelled by a genome-editing technology developed in the last few years, called CRISPR-Cas9, which has given scientists the ability to easily and quickly eliminate or replace sections of DNA in everything from bacteria to people.

Organizing committee chairman David Baltimore of Caltech, a Nobel laureate, pointed out that the statement does not use the words “moratorium” or “ban” when discussing research on human germline genome editing.

But the committee, composed of 10 scientists and 2 bioethicists, agreed that “it would be irresponsible to proceed with any clinical use of germline editing unless and until (i) the relevant safety and efficacy issues have been resolved, based on appropriate understanding and balancing of risks, potential benefits, and alternatives, and (ii) there is broad societal consensus about the appropriateness of the proposed application. Moreover, any clinical use should proceed only under appropriate regulatory oversight.”

In another indication that the summit organizers were not proposing to shut the door to editing the human germline genome, their statement said “the clinical use of germline editing should be revisited on a regular basis.”

The group endorsed research on so-called somatic genome editing, in which only affected cells (such as blood cells in the case of sickle-cell disease) have their genome altered. Such work, as well as its use in patients, “can be appropriately and rigorously evaluated within existing and evolving regulatory frameworks for gene therapy,” according to the prepared statement.

The backing of basic research on germline genome editing is at odds with the position of the National Institutes of Health, which earlier this year said it would not fund such studies in human cells.

The statement has no legal or regulatory force, but should offer guidance as countries decide whether or how to regulate germline and other genome editing. The committee therefore called on the US National Academies of sciences and medicine, Britain’s Royal Society, and the Chinese Academy of Sciences — which jointly hosted the meeting — “to take the lead in creating an ongoing international forum to discuss potential clinical uses of gene editing.”

Earlier in the day, speakers questioned why certain constituencies weren’t invited to the meeting. Although summit speakers included bioethicists, activists who question the use of genetic technologies, and legal scholars, as well as scientists and clinicians, there were no representatives of other important groups, said sociologist Ruha Benjamin of Princeton University. Among those missing: people from the disabled community who oppose being “fixed” by genome editing.

Patient advocates are “at the table,” she said, but not those who oppose “able-ism,” a form of discrimination akin to racism or sexism that argues that people with disabilities are inferior.

One concern raised by genome editing — either of germline cells or of other tissue — is that people with medical conditions who choose not to undergo genome editing or therapies based on it will be even further marginalized, Benjamin said. She criticized what she called “the illusion of opening up the science” through an event like the summit, adding that “we can create something that appears public but really is meant to insulate the science” from full public scrutiny.

Also missing were representatives of the Latino, African-American, indigenous, and LGBT communities, said Charis Thompson, chair of the department of gender and women’s studies at the University of California, Berkeley. Absent, too, she said, were biohackers, the do-it-yourself “garage biologists” whose easy access to genome-editing technologies such as CRISPR-Cas9 raises the specter of problematic research being conducted regardless of what the summit recommends.

An audience member pointed out the most glaring omission: religious leaders. Representatives of faith communities have participated in many other National Academy of Sciences and other meetings about reproductive technologies, embryonic stem cell research, and other scientific advances that raise ethical issues similar to those of genome editing.

In the walk-up to the summit, scientists said that the comparison to a 1975 meeting on recombinant DNA, the original genetic engineering, was not really apt, partly because the greatest concern at that Asilomar meeting was that something dangerous would escape the lab and wreak havoc on human health or the environment. Any risk from germline genome editing was thought to be to the individual who received it, or possibly to society’s values as scientists monkeyed with “human dignity” or “the sanctity of the human genome.”

But Dr. David Relman of Stanford University suggested that complacency might be misplaced.

CRISPR-Cas9 has been used to make animal models of human diseases, he pointed out. In one 2014 paper, for instance, scientists used an adenovirus (which causes the common cold) to deliver a segment of DNA edited with CRISPR-Cas9. The edited genome caused lung cancer in the mice. A nightmare scenario would be if the virus escaped or was released from the lab, spreading lung cancer in an unwitting population.

“Why would you turn to this technology to do harm?” Relman asked rhetorically. Because release of such a bioweapon “could be covert,” impervious to early detection (because lung cancer takes years to develop), and “insidious, causing fear and anxiety” once society realized that a genetically-engineered virus was causing not sniffles but lung cancer.

Changing the DNA in reproductive cells changes not only the resulting individual but all of that individual’s descendants, essentially allowing humans to direct their own evolution. Scientists at the summit voiced deep concern that we’re not smart enough, let alone wise enough, to do that. If time-traveling scientists had edited out the gene for sickle-cell disease a few thousand years ago, for instance, humankind might have been wiped out by malaria; the sickle-cell gene protects against that disease. Germline engineering, critics contend, also brings us closer to designer babies whose traits parents pick and choose, exacerbating inequality and violating basic principles of self-determination.

The meeting exposed a divide between patients with a genetic disease (themselves or in their family) and the doctors who treat them on one side, and basic scientists on the other. Dr. George Daley of Boston Children’s Hospital, a member of the organizing committee, told the summit that he sees his patients and thinks, “If I can help them via germline genome editing, I have a moral duty to do so.” Columbia University neuropsychologist Nancy Wexler, who lost many family members to Huntington’s disease and who decided not to have children for that reason, said, “If you have it in your capacity to make a difference, you owe it to us to do it.” In contrast, many of the academic scientists at the meeting were focused more on the safety and ethical arguments against germline genome editing.

CRISPR-Cas9 is already being widely used to modify the genomes of mice and other laboratory animals to tease out the genetic causes of diseases. Scientists also are using the technique in hopes of developing cures for human ailments ranging from HIV to autism. And George Church of Harvard Medical School is using CRISPR to “humanize pigs,” editing 62 pig genes at once to make the animals’ organs suitable for transplanting into humans.

The summit was organized after Chinese researchers caused a stir in April when they announced that they had used CRISPR to edit the genomes of nonviable human embryos, which could not develop into babies. They were interested in better understanding early human development.