Breakthrough: Scientists Edit A Dangerous Mutation From Genes In Human Embryos
Scientists for the first time have successfully edited genes in human embryos to repair a common and serious disease-causing mutation, producing apparently healthy embryos, according to a study published on Wednesday.
The research marks a major milestone and, while a long way from clinical use, it raises the prospect that gene editing may one day protect babies from a variety of hereditary conditions.
But the achievement is also an example of human genetic engineering, once feared and unthinkable, and is sure to renew ethical concerns that some might try to design babies with certain traits, like greater intelligence or athleticism.
Scientists have long feared the unforeseen medical consequences of making inherited changes to human DNA. The cultural implications may be just as disturbing: Some experts have warned that unregulated genetic engineering may lead to a new form of eugenics, in which people with means pay to have children with enhanced traits even as those with disabilities are devalued.
The study, published in the journal Nature, comes just months after a national scientific committee recommended new guidelines for modifying embryos, easing blanket proscriptions but urging the technique be used only for dire medical problems.
“We’ve always said in the past gene editing shouldn’t be done, mostly because it couldn’t be done safely,” said Richard Hynes, a cancer researcher at the Massachusetts Institute of Technology who co-led the committee. “That’s still true, but now it looks like it’s going to be done safely soon,” he said, adding that the research is “a big breakthrough.”
“What our report said was, once the technical hurdles are cleared, then there will be societal issues that have to be considered and discussions that are going to have to happen. Now’s the time.”
Gene Editing in Embryos
Scientists tried two techniques to remove a dangerous mutation. In the first, genetic “scissors” were inserted into fertilized eggs. The mutation was repaired in some of the resulting embryos but not always in every cell. The second method worked better: By injecting the “scissors” along with the sperm into the egg, more embryos emerged with repaired genes in every cell.
When gene-editing components were introduced into a fertilized egg, some embryos contained a patchwork of repaired and unrepaired cells.
When gene-editing components were introduced with sperm to the egg before fertilization, more embryos had repaired mutations in every cell.
Scientists at Oregon Health and Science University, with colleagues in California, China and South Korea, reported that they repaired dozens of embryos, fixing a mutation that causes a common heart condition that can lead to sudden death later in life.
If embryos with the repaired mutation were allowed to develop into babies, they would not only be disease-free but also would not transmit the disease to descendants.
The researchers averted two important safety problems: They produced embryos in which all cells — not just some — were mutation-free, and they avoided creating unwanted extra mutations.
“It feels a bit like a ‘one small step for (hu)mans, one giant leap for (hu)mankind’ moment,” Jennifer Doudna, a biochemist who helped discover the gene-editing method used, called CRISPR-Cas9, said in an email.
Using sperm from a man with hypertrophic cardiomyopathy and eggs from 12 healthy women, the researchers created fertilized eggs. Injecting CRISPR-Cas9, which works as a genetic scissors, they snipped out the mutated DNA sequence on the male MYBPC3 gene.
They injected a synthetic healthy DNA sequence into the fertilized egg, expecting that the male genome would copy that sequence into the cut portion. That is how this gene-editing process works in other cells in the body, and in mouse embryos, Dr. Mitalipov said.
Instead, the male gene copied the healthy sequence from the female gene. The authors don’t know why it happened.
Maybe human sex cells or gametes evolved to repair themselves because they are the only cells that transmit genes to offspring and “need special protection,” said Juan Carlos Izpisua Belmonte, a co-author and geneticist at the Salk Institute.
Out of 54 embryos, 36 emerged mutation-free, a significant improvement over natural circumstances in which about half would not have the mutation. Another 13 embryos also emerged without the mutation, but not in every cell.
The researchers tried to eliminate the problem by acting at an earlier stage, injecting the egg with the sperm and CRISPR-Cas9 simultaneously, instead of waiting to inject CRISPR-Cas9 into the already fertilized egg.
That resulted in 42 of 58 embryos, 72 percent, with two mutation-free copies of the gene in every cell. They also found no unwanted mutations in the embryos, which were destroyed after about three days.
The method was not perfect. The remaining 16 embryos had unwanted additions or deletions of DNA. Dr. Mitalipov said he believed fine-tuning the process would make at least 90 percent of embryos mutation-free.
And for disease-causing mutations on maternal genes, the same process should occur, with the father’s healthy genetic sequence being copied, he said.
But the technique will not work if both parents have two defective copies. Then, scientists would have to determine how to coax one gene to copy a synthetic DNA sequence, Dr. Mitalipov said.
Otherwise, he said, it should work with many diseases, “a variety of different heritable mutations.”
R. Alta Charo, a bioethicist at University of Wisconsin at Madison, who led the committee with Dr. Hynes, said the new discovery could also yield more information about causes of infertility and miscarriages.
She doubts a flood of couples will have “edited children.”
“Nobody’s going to do this for trivial reasons,” Dr. Charo said. “Sex is cheaper and it’s more fun than IVF, so unless you’ve got a real need, you’re not going to use it.”