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更新时间:2015-3-25 9:35:28 来源:纽约时报中文网 作者:佚名

Scientists Seek Ban on Method of Editing the Human Genome

A group of leading biologists on Thursday called for a worldwide moratorium on use of a new genome-editing technique that would alter human DNA in a way that can be inherited.


The biologists fear that the new technique is so effective and easy to use that some physicians may push ahead before its safety can be assessed. They also want the public to understand the ethical issues surrounding the technique, which could be used to cure genetic diseases, but also to enhance qualities like beauty or intelligence. The latter is 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.

“利用这项技术可以调控人类遗传,这就是我们要提出这个问题的原因,”在《科学》杂志撰文讨论这一话题的作者之一、曾担任加州理工学院院长的戴维·巴尔的摩(David Baltimore)说。

Ethicists, for decades, have been concerned about the dangers of altering the human germline — meaning to make changes to human sperm, eggs or embryos that will last through the life of the individual and be passed on to future generations. Until now, these worries have been theoretical. But a technique invented in 2012 makes it possible to edit the genome precisely and with much greater ease. 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.


The technique holds the power to repair or enhance any human gene. “It raises the most fundamental of issues about how we are going to view our humanity in the future and whether we are going to take the dramatic step of modifying our own germline and in a sense take control of our genetic destiny, which raises enormous peril for humanity,” said George Q. Daley, a stem cell expert at Boston Children’s Hospital and a member of the group.

这种技术有能力修复或增强人类的任何基因。“它提出了一个最根本的问题:我们将如何看待我们人类的未来,我们是否会采取戏剧性的举措,修饰我们自己的生殖细胞,甚至在一定程度上控制我们的遗传命运。这使人类面临巨大的风险,”乔治·戴利(George Q. Daley)说。他是波士顿儿童医院(Boston Children’s Hospital)的干细胞专家,也是在《科学》杂志发表这篇文章的作者之一。

The biologists writing in Science support continuing laboratory research with the technique, and few if any scientists believe it is ready for clinical use. 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 germline to the Food and Drug Administration.

此次在《科学》撰文的生物学家支持这项技术继续在实验室进行研究,几乎没有科学家认为这项技术可用于临床使用。任何此类的使用在美国和欧洲都受到严格的监管。例如,美国科学家在用这项技术改变人类生殖细胞以治疗遗传性疾病前,必须向美国食品与药物管理局(Food  and Drug Administration)提交治疗方案。

The paper’s authors, however, are concerned about countries that have less regulation in science. They urge that “scientists should avoid even attempting, in lax jurisdictions, germline genome modification for clinical application in humans” until the full implications “are discussed among scientific and governmental organizations.”


Though such a moratorium would not be legally enforceable and might seem unlikely to exert global influence, 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.

DNA重组技术是第一个用来改进遗传性物质的技术。但该技术的主要问题是它无法在标靶位置编辑DNA,而任何基因上的非精确改变都可能是致命的。最近的两种方法,锌指(zinc fingers)和TAL效应子(TAL effector),接近了精确编辑基因的目标,但是这两种方法技术上难度较大。新的基因组编辑方法为加州大学伯克利分校的詹妮弗·A. 杜德纳与瑞典于默奥大学(Umea University)的埃马纽埃尔·卡彭蒂耶(Emmanuelle Charpentier)所发明。

Their method, known by the acronym Crispr-Cas9, co-opts the natural immune system with which bacteria remember the DNA of the viruses that attack them so they are ready the next time those same invaders appear. Researchers can simply prime the defense system with a guide sequence of their choice and it will then destroy 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. The issue of how much mistargeting could be tolerated in a clinical setting 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 entirely harmless but perhaps would not be.


“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.”


Many ethicists have accepted the idea of gene therapy, changes that die with the patient, but draw a clear line at altering the germline, since these will extend to future generations. The British Parliament in February approved the transfer of mitochondria, small DNA-containing organelles, to human eggs whose own mitochondria are defective. But that technique is less far-reaching because no genes are edited.


There are two broad schools of thought on modifying the human germline, said R. Alta Charo, a bioethicist at the University of Wisconsin and a member of the Doudna group. One is pragmatic and seeks to balance benefit and risk. The other “sets up inherent limits on how much humankind should alter nature,” she said. Some Christian doctrines oppose the idea of playing God, whereas in Judaism and Islam there is the notion “that humankind is supposed to improve the world.” She described herself as more of a pragmatist, saying, “I would try to regulate such things rather than shut a new technology down at its beginning.”

威斯康星大学的生物伦理学家R. ·阿尔塔·沙罗(R. Alta Charo)说,对修改人类生殖细胞的态度大致存在两大派别:一个是务实派,寻求利益与风险之间的平衡;另外一派则呼吁要“针对人类应该多大程度上改变自然,建立起内在边界”。基督教的一些教义反对人类扮演上帝的做法,而在犹太教和伊斯兰教的观念里,“人类应该改善这个世界”。沙罗认为自己更像是实用主义者,“我会试图管控这些事情,而不是在一个新技术刚开始时就否定它。” 沙罗也是杜德纳小组的成员之一。

Other scientists agree with the Doudna group’s message. “It is very clear that people will try to do gene editing in humans,” said Rudolf Jaenisch, a stem cell biologist at the Whitehead Institute in Cambridge, Mass., who was not a member of the Doudna group. “This paper calls for a moratorium on any clinical application, which I believe is the right thing to do.”

爱德华·兰菲尔(Edward Lanphier)和其他科学家上周在《自然》杂志撰文,呼吁暂停修改人体生殖细胞,此前他们参与开发另一项基因组编辑技术——锌指技术。兰菲尔等人认为,对当前技术的使用可能“存在危险,伦理上不可接受”。

Writing in Nature last week, Edward Lanphier and other scientists involved in developing the rival zinc finger technique for genome editing also called for a moratorium on human germline modification, saying that use of current technologies would be “dangerous and ethically unacceptable.”

国际干细胞研究学会(the International Society for Stem Cell Research)周四说,它支持该禁令。