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我的基因我做主?科学家说不

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
我的基因我做主?科学家说不

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.

上周四(3月19日),一批世界顶尖的生物学家呼吁,在全球范围内暂时禁止在可遗传给下一代的人类DNA上使用一种新型的基因组编辑技术。

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.

生物学家们担心,新的技术非常有效且容易使用,一些医生有可能会在新技术的安全性尚未得到确认前推进其使用。他们希望公众意识到关于这项技术的伦理问题——新的技术可以用来治疗遗传性疾病,但同时可能用来改善诸如相貌或智力等方面的品质,后者被许多伦理学家认为是一条绝对不应该走的道路。

“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.

几十年来,伦理学家一直对改变人类生殖细胞(germline)心存忧虑,改变人类的精子、卵子或胚胎等遗传细胞可持续一生并能遗传给下一代。直到今天,这些担心还是理论上的假设。但是,2012年发明的这项技术使精确编辑基因组成为可能,而且更为方便。这种技术已经被用来编辑小鼠、大鼠和猴子的基因组,很少有人怀疑,它可能以同样的方式用于人类。

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.”

不过,文章的作者们担忧的是在科学领域缺少监管的国家。他们敦促,“在管辖不够严格的区域,科学家应该避免尝试在临床应用中对人类生殖细胞的基因组进行修改”,直至“科学和政府机构充分讨论”所有的可能的影响和后果。

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.

尽管这一禁令在法律上不会强制实施,看上去不太可能发挥全球性的影响力,但这样的先例还是存在的。1975年,全世界的科学家被要求停止使用重组DNA技术操纵基因,直到相应的规则建立起来。

“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.”

“那个时候我们要求任何人都不要做这方面的实验,据我所知,实际上也是如此,”巴尔的摩博士说,他是1975年呼吁停止使用重组DNA技术的科学家之一,“所以,在美国你可以相信依赖道德的威信,这也是我们所希望的。”

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.

这种基因编辑方法的首字母缩写为Crispr-Cas9,在类似于自然免疫系统的机制中,其细菌能够记住袭击自己的病毒的DNA,当相同的病毒再侵略时可以做好防御准备。研究人员通过对引导序列的选择,能够简单地装备好防御系统,对于任何出现在防御系统面前的基因组,这一系统都会破坏其DNA配对。杜德纳博士以通讯作者的身份在《科学》杂志发表文章,号召管制Crispr-Cas9技术的应用,并组织了形成这份声明的会议。

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.

Crispr-Cas9技术虽然高效,但偶尔会在人们意想不到的地方误切到基因组。临床中到底可以容忍多少错位编辑而不发生问题和危险,杜德纳小组希望对这一问题在人类基因被编辑前彻底探明。

Scientists also say that replacing a defective gene with a normal one may seem entirely harmless but perhaps would not be.

科学家也表示,用一个正常的基因去替换一个异常的基因看似完全无害,但可能并非如此。

“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.”

“我们担心人们在不了解改变基因后的效应之前,就盲然地把基因组做了改变。我个人以为,在很长一段时间内,我们都还没有聪明到对改变遗传特征的后果感到踏实,即使是在一个单一的个体中(做出基因改变)。”巴尔的摩博士说。

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.

许多伦理学家已经接受基因疗法的观念,这些基因改变在病人去世后也会随之消失,但他们完全不接受改变生殖基因的做法,因为这些基因变化会遗传给未来的几代人。今年2月,英国议会批准给自身线粒体缺陷的人类卵子转移线粒体,这是一种含有DNA的小细胞器。不过,这种技术影响并不大,因为没有基因被编辑。

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。

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