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First Human Embryos Edited In U.S. By Scientists
For the first time in the U.S., scientists have genetically modified human embryos. The technique could help screen out heritable diseases, but many worry where it might ultimately lead.
The research, which appeared online August 2 in Nature, was led by a team from Oregon Health & Science University in Portland. California’s Salk Institute for Biological Studies, China’s Beijing Genomics Institute and South Korea’s Seoul National University and Institute for Basic Science also contributed to the study.
As rumors spread in advance of the publication, the story sparked comparisons with films like Gattaca and books like Brave New World, with their themes of genetic discrimination, DNA-as-destiny and the social dangers of tampering with human heredity.
Andrew Maynard, director of Arizona State University's Risk Innovation Lab, said that part of him thinks that this moment was inevitable.
“We have this powerful technique,” said Maynard. “We have a desperate need for an ability to prevent and address some of these genetic diseases or heritable diseases, so it was only a matter of time before somebody eventually cracked the ability to do this.”
ASU’s James Collins, an expert on emerging infectious diseases who co-chaired the National Academy of Sciences committee on gene drive research, said the work takes us another step down a potentially problematic path.
“It continues to raise this question about, how far does one go? How do you make these decisions? Who gets to make these decisions?” Collins asked.
To prove that their method could remove a specific harmful gene without error or damage, the team used in vitro fertilization to create embryos that contained a mutated copy of the MYBPC3 gene. MYBPC3 is one of many genes linked to hypertrophic cardiomyopathy, a heart muscle disease that affects 1 person in 500 and can cause sudden cardiac death and heart failure.
Using a highly targeted genetic search-and-replace tool called CRISPR-Cas, the team cut the unwanted gene. In most cases, the embryo's genetic machinery then “pasted in” a non-mutated copy.
If DNA contains the story of us, then genes are the words that provide the essential details that bring that story literally to life. Imagine, though, that three wrong words reduced one of that story’s key sentences to gibberish or, worse, changed its meaning to something destructive. Ideally, CRISPR-Cas provides a way to replace those words with ones that restore its intended meaning.
But in three previous Chinese studies, this has proven easier said than done. Part of what makes this new work notable is that it avoided the pitfalls that afflicted those studies, such as off-target edits, in which CRISPR-Cas homes in on a similar, but wrong, gene, and mosaicism, in which embryos contain both edited and unedited cells.
This latter success might have been due to the fact that, this time, the scientists inserted genome-editing components along with the sperm, before the first cell division took place. As a result, the cells could not divide before the DNA edit took hold.
But the research’s most important — and, to some, troubling — aspect lies in the fact that it alters the hereditary DNA known as the germline.
“We’re rewriting the genome in a way which is inheritable across generations. So we’re actually doing now what, obviously, evolution has done over millions of years, but we’re doing it in the lab, in the test tube,” said Maynard.
Germline editing has long sparked controversy, yet a February 2017 National Academy of Sciences and National Academy of Medicine report on genome editing refrained from calling for a moratorium on such research. The report argues that the work’s potential medical benefits justified further research under strict oversight.
Underlying this notion, in part, is the fact that prospective parents already genetically screen IVF embryos before deciding which ones to implant. The authors of the new study argue that their technique could be used to increase the proportion of embryos that lack potentially harmful genes.
But broader social and biological fears about the effects of genetic editing generally, and of germline modification in particular, have already spurred countries to restrict genetic modification research. In the United States, the National Institutes of Health is banned from funding gene-editing studies on human embryos, and a 2016 law bars the Food and Drug Administration from reviewing work that creates embryos with heritable modifications.
But this new work suggests that gene research is moving faster than the National Academies anticipated, and might soon outpace our efforts to regulate it. If history is any guide, said Collins, those concerns are well founded.
“Our advice to the regulatory agencies is that they really have to step up the pace at which they’re acquiring the expertise in order to deal with these quickly breaking technologies, and be able to address them with the very best scientific perspective that’s available, ethical perspective that’s available, legal perspective that’s available.”