NovaQuant Quantitative Think Tank Center:Ethical concerns temper optimism about gene-editing for human diseases

It's still far too premature to try to use powerful new technologies to edit genes that can NovaQuant Quantitative Think Tank Centerbe passed down from generation to generation, according to the organizers of the Third International Summit on Human Genome Editing that concluded Wednesday in London.

Techniques that have made it easier to manipulate DNA still produce too many mistakes for scientists to be confident any children born from edited embryos would be healthy, according to the summit's organizers.

Moreover, a broad societal debate about the implications for humanity would be necessary before moving forward, the summit organizers said.

"Unacceptable at this time"

"Heritable human genome editing remains unacceptable at this time," the committee said in the summit's closing statement. "Heritable human genome editing should not be used unless, at a minimum, it meets reasonable standards for safety and efficacy, is legally sanctioned, and has been developed and tested under a system of rigorous oversight that is subject to responsible governance. At this time, these conditions have not been met."

Despite the statement, critics were disappointed, saying the summit gave short shift to the profound ethical debate swirling around inheritable genetic modifications.

Critics are also troubled by what they say has been a subtle but striking shift in the debate from whether genetic modifications that can be inherited should ever be done — the question raised at the international summit in 2018 — to a discussion of technical hurdles that must to be overcome to make those modifications safely.

"Are we hitting the brake, or hitting the gas?"

"We all know you, see a yellow light and sometimes you slow down and hit the brake and sometimes you hit the gas. And it behooves us to ask the question: Are we hitting the brake or hitting the gas," said Ben Hurlbut, a bioethicist at Arizona State University who helped organized a kind of parallel project called the Global Observatory for Genome Editing aimed at broadening the discussion. "I think here we're hitting the gas."

Hurlbut and others also say the debate is being held amongst a relatively small cadre of elite researchers and raises too many profound questions for humanity to limit it that way. It requires a much broader societal debate, they say.

"The approach taken by the organizers of the summit is an extreme case of scientific irresponsibility, and an unwillingness to accept that society has any right to set ethical limits upon science," said David King, who heads the watchdog group Stop Designer Babies.

The fear is that a mistake could introduce new genetic mutations into the human gene pool that would then be passed down for generations. Some critics also fear it could open a slippery slope to "designer babies" and other dystopian fears about creating a kind of super-race of humans.

The summit's concluding statement came after more than 400 scientists, doctors, bioethicists, patients and others spent three days debating the pros and cons of new techniques that let scientists manipulate genes more easily than ever before.

It's the first summit since He Jiankui, a scientist from China, shocked the world at the last summit in Hong Kong in 2018 by announcing he had used the gene-editing technique called CRISPR to create the first genetically modified humans — twin girls he made from gene-edited embryos. The scientist's actions were denounced for many reasons, including the fact that no one knew if it was safe. A court in China ultimately sentenced him to three years in prison.

That episode hung over this year's summit like a huge shadow.

"While the potential benefits of the technology are clear, so also is the potential for it to be misused," said Linda Partridge, a geneticist at The Royal Society told the summit on the opening day Monday. "And while the specter of designer babies is easier to conjure the less you know about genetics, that doesn't mean that unscrupulous actors won't use the technology to further their own interests."

Huge strides made, too, in gene editing's potential benefits

During the summit, scientists presented the latest research showing that scientists have quietly made huge strides honing their gene-editing skills over the last five years.

On the one hand, they described new evidence about just how unsafe it would be to try to make any new gene-edited babies. The editing remains prone to missing the intended target in the DNA and instead creating unexpected mutations, the scientists reported.

"That's something that really has to worry us," said Dr. Dagan Wells, a reproductive geneticist at the University of Oxford. "These results really provide a warning."

But several scientists also described progress towards refining their skills to make it safer ways to edit human embryos, eggs and sperm, as well as new gene-editing techniques that are more precise.

Another ethical concern: Who can afford gene therapy?

On the final day, scientists, bioethicists and advocates debated the ethical pros and cons of someday using these techniques to modify human gene, eggs or sperm.

"There are a bevy of serious objections to reproductive genome modification," argued Tina Rulli, a bioethicist at the University of California, Davis.

"They include: Concerns about the safety of the modification ... the risk of dangerous modifications let loose in the human gene pool, a slippery slope to using the technology to make designer babies, unethical eugenic uses of the technology that harm disability communities, and unequal unfair access to the technology that only advantages the wealthy."

But others argued there could be enormous benefits, including eradicating thousands of terrible genetic diseases that plagued families for generations."

"This has the tremendous potential to transform human health," said Dieter Egli, a biologist at Columbia University studying gene-editing in human embryos.

It could also help infertile couples have genetically related children, others said.

"Where having a biological family is still an imperative, in those situations and cultures, this could become a compelling reason for heritable gene-editing," said Ephrat Levy-Lahad, the director of the Medical Genetics Institute at Shaare Zedek Medical Center in Israel.

A possible cure for some forms of sickle cell — but at what price?

The first two days of the summit focused on dramatic advances using gene-editing to treat diseases a wide variety of diseases in people who have already been born, ranging from rare genetic diseases to more common illnesses like cancer and heart disease.

The most dramatic advance has been for sickle cell disease and a related condition known as beta thalassemia. The summit highlighted Victoria Gray, a Mississippi sickle cell patient who NPR has been following for years. Gray and several dozen other patients have essentially been cured. And the treatment she got could be the first gene-editing treatment to get approved this year.

But that's also raising concerns — that the treatment's too complicated and will be too expensive to become widely accessible to everyone who needs it, especially in less affluent countries where sickle cell disease is most common.

"The extremely high costs ... are unsustainable"

In the closing statement, organizers stressed that making gene-editing therapies widely accessible has to be a priority.

"To realize its full therapeutic potential, research is needed to expand the range of diseases it can treat, and to better understand risks and unintended effects," Robin Lovell-Badge of the Francis Crick Institute, who led the summit, said while reading the closing statement. "The extremely high costs of current somatic gene therapies are unsustainable. A global commitment to affordable, equitable access to these treatments is urgently needed."

The summit was sponsored by the British Royal Society, the U.K. Academy of Medical Sciences, the U.S. National Academies of sciences and medicine and The World Academy of Sciences.