Scientists using the Crispr gene-editing technology in human embryos to try to repair a gene that causes hereditary blindness found it made unintended and unwanted changes, frequently eliminating an entire chromosome or large sections of it.
The study published Thursday in the journal Cell comes as the international scientific community continues to grapple with the potential use of Crispr for editing human embryos that would be intended for creating a pregnancy and birth.
In September, an international commission sponsored by the U.S. National Academy of Medicine, U.S. National Academy of Sciences and the U.K.’s Royal Society issued a report stating that the gene-editing technology isn’t ready for such a use because scientists don’t understand how to make precise fixes without also introducing potentially dangerous changes.
Dieter Egli, assistant professor of developmental cell biology at Columbia University and the study’s senior author, said, “This study is not going to stop the field. But we have to ask what to do with these powerful tools, and in which context they are safe and efficacious.”
Two separate papers published earlier this month indicate that the ethical debate continues over whether and under what circumstances creating genetically modified children could be permissible.
One paper, published in the Crispr Journal, solicited views of more than three dozen experts on issues raised in the international commission’s September report on Crispr germ-line editing. The technique—which involves making changes to eggs, sperm and embryos—is controversial because any changes can be passed to future generations. The paper revealed major differences of opinion among leading scholars, including Jennifer Doudna, the University of California, Berkeley, biochemist who with a colleague was awarded the Nobel Prize in chemistry this year for pioneering work on Crispr.
In her comments on the report, Dr. Doudna said the commission’s recommendations reflect consensus in the field that the technology shouldn’t be used for embryo editing in the clinic at this time. She added that she was struck by the inclusion of certain diseases that are already being managed, such as cystic fibrosis, with disorders where embryo editing might someday be permissible.
The other paper, also published in the Crispr Journal, surveyed policies across 106 countries regarding germ-line gene editing. The researchers found 96 of the countries already had applicable policy documents, such as legislation, regulations or international treaties. Of those 96 countries, 75 bar the use of genetically modified embryos for the purpose of starting a pregnancy—an indication that it might be possible to create an international consensus on the issue, the researchers said.
Crispr enables scientists to cut, edit and insert DNA and has been an object of excitement, fascination and controversy since its discovery in 2012. The technology opens up the possibility of treating severe illness for which there are no effective therapies. Trials are under way or expected to start soon in patients with cancer, sickle-cell anemia and other conditions in China, Europe and the U.S.
The potential to use Crispr to create genetically modified babies has been an area of major concern, especially after the 2018 announcement of the birth of twin girls from embryos whose DNA had been changed using the Crispr technology.
A second woman implanted with a genetically modified embryo is also believed to have given birth.
Very little is known about the health of the babies. He Jiankiu, the Chinese researcher who spearheaded the experiments, was sentenced to three years in prison after being found guilty last year in a court in China of conducting illegal medical practices.
Researchers in the new study published in Cell said they used sperm from a single human donor to create 40 embryos. The man has hereditary blindness caused by a mutation on the EYS gene, which is located on chromosome 6, one of the 23 pairs in humans.
The scientists used Crispr-Cas9 to cut the father’s DNA at the site of the gene mutation they wanted to correct. When a cut is made in the DNA, the cell tries to repair the DNA.
From the Archives
He Jiankui, the Chinese doctor who claims to have engineered the birth of the first two genetically tailored humans, said that another woman has been implanted with a genetically modified embryo. The doctor faced criticism from his peers at a gene-editing conference in Hong Kong. Photo: EPA (Originally Published November 28, 2018)[object Object]
Scientists injected a Crispr-Cas9 enzyme into 37 embryos, and three other embryos served as controls.
The scientists found that about half of the embryos lost large segments of the chromosome, or the entire chromosome, on which the EYS gene is located.
“This is a very adverse outcome,” Dr. Egli said.
More on Gene Editing
Scientists still don’t know a lot about the mechanisms of human embryo development. The U.S. government doesn’t permit the use of federal funding to conduct research on human embryos. The research for the Cell study was funded by private donations from the New York Stem Cell Foundation and the Russell Berrie Foundation Program in Cellular Therapies.
Dr. Egli said scientists know more about the cell and molecular biology of flies, worms and mice embryos than human embryos. He said the current study seems to indicate that “the human embryo seems unique in its poor ability to fix a DNA break.” The significance of the biological finding “goes beyond the debate” over the use of Crispr in embryos, he said.
Nonetheless, the ethical debate will likely continue alongside development of the technology. Françoise Baylis, university research professor at Dalhousie University in Canada, one of the authors on both Crispr Journal papers, said that much of the debate within the scientific community over editing human embryos focused on whether the technology is safe and effective enough to use. “That’s not the right question to start with,” Dr. Baylis said. “I am not asking if the science is ready. I am asking what problems do we want to solve, and what science will help us solve them.” Dr. Baylis is a member of a World Health Organization expert advisory panel set up last year to issue global standards and guidelines for editing of the human genome. The panel hasn’t yet issued its guidance.
Marcy Darnovsky of the Center for Genetics and Society in Berkeley, Calif., a public-interest advocacy group in human genetics and assisted reproductive technologies and one of the authors of the global policy study, said the Cell paper indicates the substantial technical challenges that remain surrounding Crispr gene editing of embryos. “It gives us time,” she said. “There is still a window to have a meaningful conversation about the social questions.”
From the Archives
He Jiankui, the Chinese doctor who claims to have engineered the birth of the first two genetically tailored humans, said that another woman has been implanted with a genetically modified embryo. The doctor faced criticism from his peers at a gene-editing conference in Hong Kong. Photo: EPA (Originally published Nov. 28, 2018)[object Object]
Write to Amy Dockser Marcus at email@example.com