[2008.01.24] Nearly there

Artificial life 人造生命

Nearly there 即将到来

Jan 24th 2008
From The Economist print edition

The penultimate step towards the creation of artificial life has just been announced    通向人工生命的倒数第二步公诸于众

LIKE a striptease artist in front of an eager audience, Craig Venter has been dropping veils over the past few years without ever quite revealing what people are hoping to see: the world’s first artificial organism. He has been discussing making one since 1995, when he worked out the first complete genetic sequence of a natural living organism. And, after a lot of hard graft and blind alleys, he and his team have almost got there. As they report in this week’s Science, they have replicated the genome of Mycoplasma genitalium, the species that was the subject of that original sequencing effort. It is not actual life, but it is surely the tease before the last veil finally falls away.
就像热切观众面前的脱衣舞“表演艺术家”一样,克雷格·文特(Craig Venter)正在揭去——世界第一个人造组织——这一过去几年人们翘首以盼而又不为人知的神秘面纱。自1995年以来他就一直在讨论制造人造组织这一话 题,其间他破解出第一份自然活组织的完整基因序列。经过大量艰苦工作和碰壁,他和他的小组几乎达到了目标。根据他们在本周《科学》杂志上发表的报告,他们 复制了尿道支原体的基因组,最初基因测序工作就是利用这种支原体进行的。它们还不是真正的生命,但这就像最后一件衣服落下之前的挑逗一样。

Though Dr Venter (pictured above at the helm of his yacht, Sorcerer II) is the public face of the effort, and the 17-strong team that did the work are all employed by the J. Craig Venter Institute in Rockville, Maryland, the synthetic genome project is equally the brainchild of his collaborator, Hamilton Smith. Indeed, it is in Dr Smith’s name that the paper announcing the synthesis is published—along, of course, with the 16 others including Dr Venter himself.
虽然这项工作表面上是由文特博士领导(上图中在他的帆船女巫二号掌舵),实际上完成项目的17人小组都是马里兰州罗克韦尔“J·克雷格·文特研究所”的雇 员。文特博士的合作者汉密尔顿·史密斯也共同参与了人造基因组项目,事实上,该项目的论文是以史密斯博士为第一作者发表的,当然也署了包括文特博士在内的 其他16人的名字。

It is a formidable effort. But what is, perhaps, most noteworthy is that the starting point for the project was not the raw nucleotides (the chemical letters of which DNA is composed), but a set of pre-assembled “cassettes” of DNA that the team had ordered from commercial suppliers. The point where any Tom, Dick or Harriet with a reasonably well equipped genetics laboratory could do likewise is not, therefore, that far off.

All you create


M. genitalium’s genome is a single, circular chromosome that is 580,076 letters long, and contains 485 protein-coding genes. The team divided it on paper into 101 units (the cassettes), each containing four or five genes. They also took the precaution of editing one gene in particular, so that it would not work. The gene in question is crucial to M. genitalium’s ability to stick to mammalian cells, and thus become infective (it lives naturally in the urinary tract and is thought to cause urethritis). Disrupting it thus forestalled the risk of creating anything nasty.
尿道支原体的基因是一个单链圆形的染色体,有58万零76个字符长,包含了485个蛋白编码基因。研究小组在纸上把它分为101个单位(基因片断),每个 片段包含4到5个不等的基因。他们也采取了单独剪裁单个基因的预防措施,这样它就不会发挥作用。上述基因对尿道支原体黏附哺乳动物细胞的能力有重要作用, 因此使其具有感染性(它在尿道中自然存在,被认为是引发尿道炎的原因)。破坏它提前防止了引起麻烦问题的危险性。

The team placed orders for the cassettes with three firms that turn such things out routinely. They then used a variety of techniques, some old and some specially invented, to link the cassettes together into larger and larger units until they had two half chromosomes which, with the aid of some yeast cells, they turned into a whole one. All that remains to create what most researchers in the field would be willing to recognise as an artificial organism is to insert such a chromosome into a bacterial cell that has had its own chromosome removed. At the moment, no one is clever enough to make all of the cellular machinery that translates genes into the stuff of life. Hence the need for this shortcut. But if the newly reconstituted cell were able to grow and reproduce, the nature of its progeny would be dictated by the implanted chromosome. That, not the nature of the host “shell”, would define the species of the progeny.
该小组通常从三家公司订购基因片断以完成这种日常操作。然后他们运用一系列方法,有旧方法也有特别开发的新方法。运用这些方法他们把基因片断不断合成更大 的单位,直到他们得到两个一半的染色体。借助酵母菌细胞的帮助,他们合成出完整的染色体。要合成出生化领域大多数研究者认可的人造组织,还需要将这样的染 色体植入已被去除染色体的细菌细胞。现在还没有人能够完成从基因到生命的细胞机制。因此需要走这种捷径。但如果新改造过的细胞能够生长繁殖,细胞后代的性 状将由植入的染色体而不是由母细胞的染色体决定。

Dr Venter’s purpose in synthesising artificial genomes is twofold. Scientifically, he wants to understand how life works. One way to do this is to discover what he refers to as the minimal genome. This is a Platonic ideal of life, which would contain only the genes absolutely necessary for survival and reproduction, and might shed light on the nature of Luca, the last universal common ancestor of life on Earth. In practice, that ideal is difficult to realise, since many genes cover for each other. He knows that 100 of M. genitalium’s genes can be eliminated individually without killing it, but eliminate all of these and it dies. Assembling mix-and-match genomes with lots of different combinations of cassettes that each contain but a handful of genes should shed light on the question.
文特博士合成人造基因组的目的有两方面:科学上,他希望能了解生命工作的原理。达到这一目的的途径之一就是发现他所说的最小基因组。这是一种柏拉图式的生 命,只包含使细胞存活繁殖的最必需的基因。这项研究也能为研究Luca这一地球生命的共同祖先提供一些帮助。在操作层面,这个理想却很难实现。因为很多基 因相互交叠。文特博士知道,单独去掉尿道支原体的100个基因并不会杀死衣原体,但把100个基因一起去掉衣原体就死亡了。用含有一些基因的不同基因片断 组装混合配对基因可以为这一问题的解决提供帮助。

But Dr Venter is also a practical man, who wants to turn genomics into technology. Indeed, one of his other enterprises is a firm called Synthetic Genomics and he is one of the leading lights of the emerging field of synthetic biology. This seeks, among other things, to create a parts list of biological components such as DNA cassettes that could be ordered from catalogues in the way that electronic components can be.
但文特博士也是个实际的人,想把染色体转化为科技。事实上他的其他产业之一就是一个叫做合成染色体的公司。他也是正在兴起的合成生物学的领军人物之一。该 领域寻求的目的之一,就是提供一个生物组分(比如DNA片段)的“零件”库,这样就可以像订购电子元件一样从目录中订购生物“零件”。

Synthetic Genomics itself is a bit cagey about exactly which molecular products it is working on, but one of Dr Venter’s interests is in using modified bacteria to make fuels. Natural bugs can turn out both hydrogen and methane. There is talk of modifying them to produce high-value liquid fuels, for jets, say.

He is not alone in this idea. Several Californian firms are also seeking to make advanced biofuels using modified bacteria. But if Dr Venter can take the final step of kicking the new, wholly synthetic genome into reproductive life, he will not only have made a great technological leap forward, he will also have erased one of the last mythic distinctions in science—that between living and non-living matter. Watching that veil drop will have been worth the wait.
在这一领域,文特博士并不孤单。几个加州的公司也在寻求运用改良过的细菌制造高级生物燃料。但如果文特博士能迈出最后一步,将崭新的完全人造的基因组转化 为有生殖能力的生命,他将不仅把科技推进一大步,而且也将消弭科学中最后一个神秘的——生物和非生物间的——区别。看着面纱落下将值得我们期待。

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