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In Breakthrough, Scientists Edit A Dangerous Mutation From Genes In Human Embryo by mrkel(m): 10:51pm On Aug 02, 2017 |
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.” 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. “I expect these results will be encouraging to those who hope to use human embryo editing for either research or eventual clinical purposes,” said Dr. Doudna, who was not involved in the study. Much more research is needed before the method could be tested in clinical trials, currently impermissible under federal law. But if the technique is found to work safely with this and other mutations, it might help some couples who could not otherwise have healthy children. Potentially, it could apply to any of more than 10,000 conditions caused by specific inherited mutations. Researchers and experts said those might include breast and ovarian cancer linked to BRCA mutations, as well as diseases like Huntington’s, Tay-Sachs, beta thalassemia, and even sickle cell anemia, cystic fibrosis or some cases of early-onset Alzheimer’s. “You could certainly help families who have been blighted by a horrible genetic disease,” said Robin Lovell-Badge, a professor of genetics and embryology at the Francis Crick Institute in London, who was not involved in the study. “You could quite imagine that in the future the demand would increase. Maybe it will still be small, but for those individuals it will be very important.” The researchers also discovered something unexpected: a previously unknown way that embryos repair themselves. In other cells in the body, the editing process is carried out by genes that copy a DNA template introduced by scientists. In these embryos, the sperm cell’s mutant gene ignored that template and instead copied the healthy DNA sequence from the egg cell. “We were so surprised that we just couldn’t get this template that we made to be used,” said Shoukhrat Mitalipov, director of the Center for Embryonic Cell and Gene Therapy at Oregon Health and Science University and senior author of the study. “It was very new and unusual.” The research significantly improves upon previous efforts. In three sets of experiments in China since 2015, researchers seldom managed to get the intended change into embryonic genes. And some embryos had cells that did not get repaired — a phenomenon called mosaicism that could result in the mutation being passed on — as well as unplanned mutations that could cause other health problems. In February, a National Academy of Sciences, Engineering and Medicine committee endorsed modifying embryos, but only to correct mutations that cause “a serious disease or condition” and when no “reasonable alternatives” exist. Shoukhrat Mitalipov, director of the Center for Embryonic Cell and Gene Therapy at Oregon Health and Science University, is one of the authors of the new study. LEAH NASH FOR THE NEW YORK TIMES Sheldon Krimsky, a bioethicist at Tufts University, said the main uncertainty about the new technique was whether “reasonable alternatives” to gene editing already exist. As the authors themselves noted, many couples use pre-implantation genetic diagnosis to screen embryos at fertility clinics, allowing only healthy ones to be implanted. For these parents, gene editing could help by repairing mutant embryos so that more disease-free embryos would be available for implantation. Hank Greely, director of the Center for Law and the Biosciences at Stanford, said creating fewer defective embryos also would reduce the number discarded by fertility clinics, which some people oppose. The larger issue is so-called germline engineering, which refers to changes made to embryo that are inheritable. “If you’re in one camp, it’s a horror to be avoided, and if you’re in the other camp, it’s desirable,” Dr. Greely said. “That’s going to continue to be the fight, whether it’s a feature or a bug.” For now, the fight is theoretical. Congress has barred the Food and Drug Administration from considering clinical trials involving germline engineering. And the National Institutes of Health is prohibited from funding gene-editing research in human embryos. (The new study was funded by Oregon Health and Science University, the Institute for Basic Science in South Korea, and several foundations.) The authors say they hope that once the method is optimized and studied with other mutations, officials in the United States or another country will allow regulated clinical trials. “I think it could be widely used, if it’s proven safe,” said Dr. Paula Amato, a co-author of the study and reproductive endocrinologist at O.H.S.U. Besides creating more healthy embryos for in vitro fertilization, she said, it could be used when screening embryos is not an option or to reduce arduous IVF cycles for women. Dr. Mitalipov has pushed the scientific envelope before, generating ethical controversy with a so-called three-parent baby procedure that would place the nucleus of the egg of a woman with defective cellular mitochondria into the egg from a healthy woman. The F.D.A. has not approved trials of the method, but Britain may begin one soon. The new study involves hypertrophic cardiomyopathy, a disease affecting about one in 500 people, which can cause sudden heart failure, often in young athletes. It is caused by a mutation in a gene called MYBPC3. If one parent has a mutated copy, there is a 50 percent chance of passing the disease to children. 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.” https://mobile.nytimes.com/2017/08/02/science/gene-editing-human-embryos.html?referer=https://www.google.com.ng/ 1 Like |
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