A group of leading biologists on Thursday called for a worldwide moratorium on use of a new genome editing technique to change human DNA in a way that would permanently affect future generations.
The biologists fear that the new technique is so effective and easy to use that some physicians may push ahead with it before its safety can be properly assessed. They also want the public to understand the ethical issues surrounding the technique, which potentially could be used to cure genetic diseases, but also to enhance qualities like beauty or intelligence, a path that many ethicists believe should never be taken.
“You could exert control over human heredity with this technique, and that is why we are raising the issue,” said David Baltimore, a former president of the California Institute of Technology and a member of the group, whose paper on the topic was published in the journal Science.
Ethicists, for decades, have been concerned about the dangers of altering the human germ line — making changes to human sperm, eggs or embryos that will last through the life of the individual and be passed on to offspring. Until now, these worries have been theoretical. But a technique invented in 2012 makes it possible to edit the genome very precisely and with much greater ease than earlier methods. The technique has already been used to edit the genomes of mice, rats and monkeys, and few doubt that it would work the same way in people.
Any such use is tightly regulated in the United States and Europe. American scientists, for instance, would have to present a plan to treat genetic diseases in the human germ line to the Food and Drug Administration, which has not yet approved such a plan.
The biologists writing in Science, however, are concerned about those countries in which science is less well regulated. They urge that “scientists should avoid even attempting, in lax jurisdictions, germ line genome modification for clinical application in humans” until the full implications “are discussed among scientific and governmental organizations.”
Though such an appeal might seem unlikely to exert global sway, there is a precedent. In 1975 scientists worldwide were asked to refrain from using a method for manipulating genes, the recombinant DNA technique, until rules had been established.
“We asked at that time that nobody do certain experiments, and in fact nobody did, to my knowledge,” said Dr. Baltimore, who was a member of the 1975 group. “So there is a moral authority you can assert from the U.S., and that is what we hope to do.”
Recombinant DNA was the first in a series of ever-improving steps for manipulating genetic material. The chief problem has always been one of accuracy, of editing the DNA at precisely the intended site, since any off-target change could be lethal. Two recent methods, known as zinc fingers and TAL effectors, came close to the goal of accurate genome editing, but both are hard to use. The new genome-editing approach was invented by Jennifer A. Doudna of the University of California, Berkeley, and Emmanuelle Charpentier of Umea University in Sweden.
Their method, known by the acronym Crispr-Cas9, co-opts the natural defense system with which bacteria precisely target the DNA of the viruses that attack them. Researchers can simply prime the defense system with a guide sequence of their choice and it will then home in on the matching DNA sequence in any genome presented to it. Dr. Doudna is the lead author of the Science article calling for control of the technique and organized the meeting at which the statement was developed.
Though highly efficient, the technique occasionally cuts the genome at unintended sites. This does not matter in laboratory experiments but could be hazardous when applied to the human germ line. The issue of how much mistargeting could be tolerated in a clinical setting is unresolved and is one that Dr. Doudna’s group wants to see thoroughly explored before any human genome is edited.
Scientists also say that replacing a defective gene with a normal one may seem not be entirely harmless, given that there is insufficient research about how genes interact.
“We worry about people making changes without the knowledge of what those changes mean in terms of the overall genome,” Dr. Baltimore said. “I personally think we are just not smart enough — and won’t be for a very long time — to feel comfortable about the consequences of changing heredity, even in a single individual.”
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