Utah researcher says premature use of embryonic gene editing ‘shocking’

SALT LAKE CITY — A prominent University of Utah researcher was among those rocked by the revelation at a Hong Kong conference this week that a Chinese researcher crossed ethical boundaries in performing gene editing experiments on human embryos.

And according to the man who conducted the research, Dr. He Jiankui from the Southern University of Science and Technology in Shenzhen, China, at least three of those embryos were successfully implanted and two have already been carried to term.

Dana Carroll, longtime U. biochemistry department chairman and National Academy of Sciences member, was in attendance at the Second International Summit on Human Genome Editing and told the Deseret News from Hong Kong he was disturbed to learn, on his way to the summit, of He’s claimed research.

“I only became aware of Dr. He’s experiments a day before the meetings began, on my way to Hong Kong,” Carroll said. “It was really kind of a shock.”

Carroll is concerned the news could fundamentally alter the worldwide progress of gene editing research which, in most instances, is making ethical advancements in the fight against numerous diseases and disorders.

Carroll, who headed the U.’s biochemisty department for 24 years, has spent his career conducting cutting-edge research on genome editing and is among pioneers whose work led to the novel, and relatively new CRISPR-Cas9 technique that He says he used in his controversial research.

The method can be used to edit virtually any plant or animal gene and functions in two steps — first locating a particular gene, then “snipping” it out. CRISPR, short for Clustered Regularly Interspaced Short Palindromic Repeats, was adapted from specialized, virus-fighting DNA discovered in bacteria. Cas9 is an enzyme that can cut apart DNA.

Scientists have developed the method, which is relatively simple to execute and very precise, to the point where it can be used to locate a target gene, snip it out and replace it with a different gene.

While He’s research has yet to be validated, and reportedly was carried out covertly, he claims to have used the CRISPR-Cas9 to edit a gene in 31 in vitro embryos to create a natural resistance to the HIV virus. Seven different couples, according to He, participated in the research and three gene-edited embryos were implanted in mothers, and one set of twins has already been carried to term by one mother.

The couples who participated each had fathers who are HIV-positive and mothers who are HIV-negative. Many critics of He’s research have pointed out that numerous, nongenomic methods are currently available to parents with one or both partners carrying the virus to conceive a noninfected child.

Carroll said the ability to do this kind of genetic editing has been around for some years, and clinical trials for therapies on somatic (nonreproductive) cells are already taking place. But, he noted the scientific community at large has, until this point, been successful at self-regulating appropriate paths of research, particularly in work that alters so-called germline genes — those in sperm, eggs or embryos — that can be passed down to subsequent generations.

Concerns about germline gene editing are myriad, and include a lack of sufficient knowledge about how altering one gene impacts the function of other genes and whether or not the modification of a gene to be more resistant to one virus may induce higher susceptibility to other viruses and/or infections.

Carroll was one of a number of scientists who reviewed a report issued in 2017 by the National Academy of Sciences that noted germline editing was crossing an “ethically inviolable” line. The report reflected an unequivocal stance on whether the scientific knowledge base was sufficient to experiment with altering embryonic genes.

“Heritable germline editing is not ready to be tried in humans,” a summary of the report reads. “Much more research is needed before it could meet the appropriate risk and benefit standards for clinical trials.”

Carroll noted with dismay, however, that a breach in the widely accepted protocols may have been unavoidable.

“I’ve said for some time that it was inevitable that someone would try to initiate pregnancy with the genome editing technology,” Carroll said. “We called for everyone working in this area to not go this far. The shock regarding what Dr. He has done is that he didn’t pay attention to those admonitions.

“He went ahead with his procedures in the face of knowing that we didn’t have the technology under control.”

On Thursday, the final day of the summit, China’s government ordered a halt to work by He’s team, as a group of leading scientists, echoing Carroll’s concerns, declared that it’s still too soon to try to make permanent changes to DNA that can be inherited by future generations.

Chinese Vice Minister of Science and Technology Xu Nanping told state broadcaster CCTV that his ministry is strongly opposed to the efforts that reportedly produced twin girls born earlier this month. Xu called the team’s actions illegal and unacceptable and said an investigation had been ordered, but made no mention of specific actions taken.

Researchers are rapidly learning how to edit DNA to fight such conditions as Huntington’s, Tay-Sachs and hereditary heart disease, conducting legally permissible experiments in lab animals and petri dishes without taking the ultimate step of actually creating babies.

Now they worry about a backlash against their work, too.

“The alarmists who claimed that scientists won’t behave responsibly in the development of the next generation of gene editing now have ammunition,” said Kyle Orwig, a reproductive specialist at the University of Pittsburgh.

“This is what we’re afraid of: Not legitimate scientists — it’s crazy people that would just try it without even worrying about consequences,” said Shoukhrat Mitalipov of the Oregon Health & Science University, who is conducting laboratory-only experiments on how to repair gene defects in human embryos.

If the outcry results in more restrictions being added to the current patchwork of rules on what can be studied and how, the field “will be, probably, thrown back for decades,” he added.

While He did take the stage at the Hong Kong summit and fielded questions from colleagues, Carroll noted the researcher was evasive when asked to explain the reasoning behind his decision to pursue this questionable line of research.

“I think the motivation there is very hard to fathom … and he was not forthcoming at all,” the U. researcher said.

As the fallout from He’s research continues, Carroll said his worries are two-fold.

“First, I am concerned that people will be so stunned by this that they will place more stringent bans on research, even legitimate uses of the technique,” Carroll said.

“The other is that there will be people around the world who may think the door has been opened (by He’s research) and we can step through it.”

At the conclusion of the genome editing summit, organizers issued a statement roundly condemning He’s work and calling for an investigation, but also outlined some suggested next steps in working to build consensus on appropriate current research practices and defining a transitional, and ethical, pathway toward future advances.

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“At this summit we heard an unexpected and deeply disturbing claim that human embryos had been edited and implanted, resulting in a pregnancy and the birth of twins,” organizers wrote. “We recommend an independent assessment to verify this claim and to ascertain whether the claimed DNA modifications have occurred. Even if the modifications are verified, the procedure was irresponsible and failed to conform with international norms.

“Its flaws include an inadequate medical indication, a poorly designed study protocol, a failure to meet ethical standards for protecting the welfare of research subjects, and a lack of transparency in the development, review, and conduct of the clinical procedures.”

Contributing: Associated Press