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发表于 2008-01-16 19:12 | Tags 标签:




One kind of life is all we know, but that’s about to change, right here on Earth, says Bob Holmes


WHEN the Nobel prizewinning physicist Richard Feynman died in 1988, his blackboard carried the inscription, “What I cannot create, I do not understand.” By that measure, biologists still have a lot to learn, because no one has yet succeeded in turning a chemical soup into a living, reproducing, evolving life form. We’re still stuck with Life 1.0, the stuff that first quickened at least 3.5 billion years ago. There’s been nothing new under the sun since then, as far as we know.

That looks likely to change. Around the world, several labs are drawing close to the threshold of a second genesis, an achievement that some would call one of the most profound scientific breakthroughs of all time. David Deamer, a biochemist at the University of California, Santa Cruz, has been saying that scientists would create synthetic life in “five or 10 years” for three decades, but finally he might actually be right. “The momentum is building,” he says. “We’re knocking at the door.”

Meanwhile, a no-less profound search is on for a “shadow biosphere” – life forms that are unrelated to the life we know because they are descendants of an independent origin of life. We know for sure that life got going on Earth once, so why couldn’t it have happened twice? Many scientists argue that there is no reason why a second genesis might not have taken place, and no reason why its descendants should not still be living among us.

So the appearance of an “alien” organism seems imminent – we may find one that arose naturally, or engineer one in the lab. Either way, it’s a momentous step. Until now, biologists have had to base their understanding of life on the plants, animals and microbes that surround us, which all share a common ancestor. That doesn’t give much perspective.

“When you have a single example, it’s very hard to know whether it’s representative,” says Carol Cleland, a philosopher of science and astrobiologist at the University of Colorado in Boulder. “If you were an alien biologist who’s interested in understanding what a mammal was, and all you had was zebras, it’s very unlikely that you would focus on their mammary glands, because only half the specimens have them. You’d probably focus on the stripes, which are ubiquitous.”

Discovering – or engineering – a second genesis wouldn’t just broaden our view of life. Alternative life forms could supply biotechnologists with fresh molecules and new functions that they could apply to practical problems. A synthetic, made-to-order living system might even serve as a self-maintaining, self-improving, adaptable assembly line for producing everything from pharmaceuticals to petrochemicals. Over the next four pages we first report on rapid progress in the lab, and then bring news from the field, as researchers race to make what could be one of science’s most far-reaching breakthroughs.

Part 1  Making new life

The name most frequently associated with the quest to breathe life into inanimate matter is the pioneer of genome-sequencing, Craig Venter. He, however, begs to differ. “I keep trying to make it clear – we’re not creating life from scratch,” he says.

Venter’s team at the J. Craig Venter Institute in Rockville, Maryland, plans to remove the genome from an existing bacterial cell and replace it with one of their own design. If successful, this will indeed result in a novel life form, but it is a far cry from the ultimate goal of a second genesis, as Venter would be the first to admit.

Other teams, however, are striving directly for that ultimate goal. The most ambitious of them do not even rely on the standard set of molecular parts, but seek to redesign a living system from first principles. If successful, they would provide an entirely new form of life unlike any that exists today, an achievement comparable to finding alien life on other planets – but one which would raise novel ethical and safety issues (see box, below).

Four years ago, New Scientist profiled one such effort, led by Steen Rasmussen of Los Alamos National Laboratory in New Mexico (12 February 2005, p 28). Instead of emulating the system used by existing cells – a watery soup of biomolecules enclosed in an oily membrane – Rasmussen’s “Los Alamos bug” consists of biomolecules studded into the surface of an oil droplet, like cloves stuck in an orange.

At the time, Rasmussen hoped success might be only a few years away. Today he’s more cautious. “No life yet,” he reports. “But we’re getting closer… we’re inching our way.” Rasmussen, now at the University of Southern Denmark in Odense, and his team, are steadily working through a checklist of intermediate goals. For example, they have persuaded their minimal DNA genome to direct the production of fatty acids, allowing the oil droplet to grow – a key step in their bug’s rudimentary biochemistry. They are now trying to prove that the genome can replicate while attached to the droplet, and that the droplet can be made to grow and divide in sync with the genome.

Producing synthetic life would be an achievement comparable to finding alien life on other planets

Meanwhile, another group has leaped ahead by developing an information-carrying molecule that can help make copies of itself. This is one of the biggest obstacles to synthetic life. Most experts assume that a self- replicating molecule – most likely RNA – must have played a role in the origin of life on Earth, but no one has been able to build one.

Tracey Lincoln and Gerald Joyce of the Scripps Research Institute in La Jolla, California, tried a slightly different tack. Instead of a single RNA molecule, they made two, each able to construct a copy of the other by stitching together two half-molecules supplied by the researchers.

Some think the earliest life forms may have replicated in a similar chunk-by-chunk way, with evolution gradually reducing the size of the chunks until it arrived at the DNA letter- by-letter replication we see today. If so, Lincoln and Joyce’s cross-replicators would be the closest anyone has got to recreating the origin of life. Indeed, the molecules worked so well that their population began to grow exponentially (Science, DOI: 10.1126/ science.1167856). “That’s the first time that’s happened, except in biology,” says Joyce.

The RNAs even underwent a rudimentary form of evolution. When the researchers supplied them with varying precursor molecules, the replicators spontaneously selected a combination that worked most efficiently.

This, however, falls short of true Darwinian evolution. Selecting from a pre-ordained range of options is not the same as an open-ended capacity to create new variants by mutation. The cross-replicators cannot be considered alive until they meet this tougher test, says Joyce.

There are two other tests they would have to pass to cross the Rubicon from inanimate to animate: carry out some sort of metabolic processes and segregate themselves into some kind of package. Joyce’s team is trying to build new functions into the system in the hope of passing these tests – but that is probably a long way off. Other efforts to design living cells from scratch, notably those of Jack Szostak at Harvard University and Pier- Luigi Luisi at the Swiss Federal Institute of Technology in Zurich, are similarly unlikely to reach their goal soon.

There is, however, yet another approach that looks closer to paying off. Instead of going back to the drawing board and designing life from scratch, George Church of Harvard Medical School and Anthony Forster of Vanderbilt University in Tennessee are short-cutting the design process by using the familiar molecular tool kit of existing cells. Starting with a set of inanimate molecules, they intend to assemble a living, replicating system in much the same way as a hobbyist might assemble a kit car. “It’s complicated, but I think people are starting to realise that this may be the best chance we have to create a synthetic living cell,” says Forster.


Just as a first-time car builder might keep things as simple as possible by omitting cruise control and aircon, Forster and Church began by stripping their kit down to its barest bones. They ended up with a list of 151 essential biomolecules: the proteins and RNAs needed to replicate DNA, make RNA copies, and translate RNA into protein molecules (Molecular Systems Biology, DOI: 10.1038/msb4100090). The rest can be outsourced. For example, instead of having their cell extract energy from sunlight or turn food into the energy-carrying chemical ATP, the researchers supply them with ready-to-go ATP. They also plan to forgo a cell membrane for the time being, running the whole system as a loose soup in a test tube.


People are starting to realise that this is the best chance we have to create a synthetic living cell

Many of the components of this minimal cell already work well together. Biotechnology companies routinely sell commercial kits to synthesise DNA, RNA or proteins to order in a test tube. But these kits only work for a few hours or days before the components are used up and the reaction grinds to a halt. To create a system that runs indefinitely, Forster and Church will also need to add a DNA molecule that encodes all 151 components, so that the system can make new ones as needed. Once they have combined this DNA with a starting set of components, they should in theory end up with a replicating, evolving – in short, living – system.

Putting together so many complex parts remains a challenge but, suddenly, the finish line may be in sight. At a synthetic biology conference in Hong Kong in October 2008, Church and his Harvard collaborator Michael Jewett reported that they had solved one of the biggest assembly problems: putting together a ribosome.

The ribosome is the cell’s protein-making machine and is one of life’s most complex molecular contraptions, consisting of 57 proteins and RNA molecules that all need to come together in exactly the right way. Many have tried to achieve what Church calls “the biggest assembly in biology”. Now that Jewett and Church have succeeded, there is ground for hope that the production of any complex molecular machine is possible.

At the time, the pair had only assembled the ribosome from components extracted from cells. Now they have succeeded in repeating the assembly using a synthesised version of the largest RNA component. Church sees incorporating the rest of the synthetic RNAs as a relatively minor challenge. “There’s nothing you’d expect to go wrong, the way we expected things to go wrong with the assembly,” he says.

Even after that hurdle has been cleared, unforeseen problems are likely to pop up when the researchers try to assemble all 151 genes and their products into a functioning whole. “Until you actually try this, you won’t know,” says Forster. “Having said that, we know cells can do it, so we should be able to do it – sooner or later.”

Already, some other subsystems are beginning to come together. A team led by Tetsuya Yomo at Osaka University in Japan has created a system similar to Church’s, but consisting of 144 parts instead of 151 – partly because he leaves out the DNA step. In Yomo’s system, a tiny RNA genome contains the directions for making a single protein which, in turn, helps the RNA molecule replicate. Gene makes protein makes gene, closing the loop for the first time in a synthetic system – a feat Church’s team has yet to accomplish (ChemBioChem, vol 9, p 2403). “We’ve spent 10 years to reach this level,” says Yomo.

Synthetic life is not yet a newspaper headline waiting to happen. But every research team that has embarked on the quest reports good progress, and the goal of creating a living being from nonliving chemicals is now less a vague possibility than a definite target with clear roadmap leading to it. “I’m getting more confident in my five to 10 year prediction,” says Deamer.

Part 2  The search for shadow life

While some researchers are attempting to create brand new life in the lab, others are searching for alien life on Mars and, eventually, elsewhere in the solar system. This burgeoning field of astrobiology has a less well-known offshoot right here on Earth: the search for a “shadow biosphere”– a second, independent form of life unrelated to sort we know (Astrobiology, vol 5, p 154).

After all, many astrobiologists now think that given the right conditions any sufficiently complex molecular soup has a good chance of generating life if it simmers long enough. If that’s so, it seems plausible that life may have arisen on Earth not once, but several times. New origins of life are unlikely today, because existing life would gobble up any aggregations of prebiotic molecules before they could edge over the threshold. However, opportunities for the origin of life may well have existed for long periods on the early Earth. Some of these origins may have been dead ends, out- competed by other life forms – but others could still be living among us, unnoticed.

As big as Darwin

“I think if we found a second sample of life on Earth, it would be as big as Darwin’s theory of evolution,” says cosmologist and astrobiologist Paul Davies at Arizona State University in Tempe. “It would answer the most fundamental question we can imagine, which is: are we alone in the universe?”

Sceptics might scoff that shadow life could pass unrecognised for so long, but Davies and his collaborators have a simple rejoinder: we’ve never looked properly. Such life would probably take the form of single-celled microbes, so we would not expect naturalists to spot it casually like some rare parrot. And the techniques microbiologists use to detect life – staining for DNA, sequencing DNA, and culturing microbes in the lab – assume that the target microbes have the normal biochemistry.

“They couldn’t detect an alternative form of microbial life,” says Carol Cleland, a philosopher of science and astrobiologist at the University of Colorado in Boulder. Given that fewer than 1 per cent of microbes have been cultured and described, there is plenty of room for shadow life to be living right under our noses.

However, the task of searching for shadow life on Earth is much tougher than looking for life on other planets. “This planet is heavily contaminated with life as we know it,” says Shelley Copley, a biochemist at the University of Colorado. That means researchers can’t just look for evidence of metabolism or the presence of large biopolymers, because ordinary life would swamp any signal from shadow life. Instead, shadow-stalkers have to get more creative.

One promising avenue is to explore extreme environments that are beyond the reach of conventional life, such as ultra-dry deserts, ice sheets, the upper atmosphere or the hottest hydrothermal vents.

Another is to devise ways of detecting alternative biochemistries. In the first and so-far only experiment of this kind, Richard Hoover, a microbiologist at NASA’s National Space Science and Technology Center in Huntsville, Alabama, went looking for “mirror life”. Normal organisms use right-handed sugars and left-handed amino acids almost exclusively, and eschew their mirror-image equivalents. But what if shadow life developed the opposite preference? Hoover and his colleague Elena Pikuta created nutrient broths containing only left-handed sugars and right-handed amino acids, inoculated them with unusual extremophile microbes and waited to see if anything grew.


Is “desert varnish” a manifestation of shadow life, or something more mundane?

“Much to our great astonishment, we found that we did have some microorganisms that were capable of growing,” Hoover recalls. But on closer examination, the shadow microbes turned out to be ordinary bacteria with unusual metabolisms.

Cleland thinks there are other places to look. “What I think we should do is go out looking for anomalies,” she says. For example, some researchers have reported nanobacteria which show some of the characteristics of life but are too small to be ordinary cells.

An even more promising anomaly, Cleland says, is “desert varnish” – a thin, manganese- rich layer that forms on the surface of rocks, especially in hot, dry places. “Everyone thinks they know what desert varnish is, but everyone disagrees,” says Cleland. “There is no agreement on whether it is produced by living or nonliving processes.” The layered varnish looks a lot like the primitive microbial mats called stromatolites, but for the most part, microbes are absent. Bacteria-like objects are occasionally present, but have never been fully characterised. “What they really are, I have no idea,” says Ronald Dorn, a who studies rock varnish at Arizona State University.

In September 2008, Cleland and her colleagues took samples of desert varnish. They hope to find unusual ratios of elements that might point to some sort of metabolic process, but with a signature that differs from that of familiar life. They hope to have some results later this year.

Not likely, says Norman Pace, a microbiologist at the University of Colorado who is one of the researchers Cleland has recruited to examine the desert varnish. “The only reason to invoke [shadow life] is that we don’t know what causes desert varnish,” he says. Still, he’s willing to have a look.

Davies hopes that more researchers will start looking for shadow life. Even if they don’t find it, the search could turn up previously unknown branches on the familiar tree of life. “So it’s worth doing anyway,” he concludes, “even if you’ve convinced yourself that we’re alone in the universe.” ■

Bob Holmes is a writer based in Edmonton, Canada


13 Responses to “Second genesis”

  1. SNOW LEE说道:


  2. Can说道:


  3. fly2free说道:


  4. margaredi说道:


  5. margaredi说道:

    1988年,诺贝尔物理学奖得主理查德.费里曼去世。他的墓碑(黑板?)上刻上了这样的一句话:我不能创造的就是我不理解的。由此观之,生物学家还有许多要学,因为还没有哪位生物学家能把一锅元素汤变成有生命力,繁殖力和进化力的生命形式。我们仍纠缠在生命1.0 版本中,这个版本的最近一次加速更新是在35亿年前。在那以后,生活在太阳下的地球生命就没有变过,至少目前看来是。



    因此,“异生物”的出现意义重大。 我们可能发现他们是自然生长着的,我们也有可能在实验室里把他们培育出来。不管是哪种方法,这都将是意义非凡的一步。到如今,生物学家的知识只能建立在对现有的动植物和微生物的观察上,而他们都源自同一祖先。因而,这样的观察并不能完全客观。

    “只有一项例证时,你很难说它是否具有代表性。” 科罗拉多大学的科学哲学家、宇宙生物学家卡洛.克里兰德说。“如果你是一名想弄清楚哺乳动物的外星宇宙生物学家,而手头的研究对象只有斑马,你很有可能注意不到他们的乳腺,因为只有一半的斑马有。相反,你很可能会关注它们的条纹,因为所有的斑马都有。”

    无论是发现还是培育生命的第二次进化,其意义都不止在扩展我们对生命的认识。 另一种生命形式会展示给生物科技工作者不一样的分子和机能,他们或许能用其解决实际问题。人工合成的定制型生命系统有可能像一条自行维护、改进、修整的生产线一样,生产出小到药片,大到石化的产品。在下面四页中,我们将首先报道实验室里的迅猛发展,之后会有实际作业的新闻,在这个领域里,研究者们你追我赶,争当这项可能是科学史上意义最为深远的突破的第一人。


  6. Sonia说道:

    第一部分 制造新生命
    Craig Venter是基因组序列领域的先锋人物,他的名字常常令人联想起“把呼吸着的生命变为无生命物质”的追求。然而他?“我再一次重申——我们不是?创造生命,”他说道。
    Venter的团队位于马里兰州Rockville的Craig Venter研究中心。他们计划将活体细菌细胞中的基因移除,并用他们自己研制的对应物取代。如果成功的话,这将导致一个新的生命形式的诞生,但这离第二种生命起源的终极目标还很遥远,Venter是首个这样承认的人。
    四年前,《新科学家》介绍了这样的一次努力,由新墨西哥州Los Alamos国家实验中心的Steen Rasmussen带领下进行。与其与活体细胞使用的系统—— 一层油状薄膜包裹在含水的生物分子周围去竞争,Rasmussen的“Los Alamos细菌”的生物分子被钉在油滴表面,就好象橘子上钉上了丁子香的蓓蕾一样。

  7. Sonia说道:

    加里弗尼亚州位于La Jolla的Scripps研究中心的Tracey Lincoln和Gerald Joyce尝试了一种略有不同的路径。 他们制取两个,而不是一个RNA分子,其中任一个RNA分子都可以通过“缝补”由研究者提供的两个半分子,来合成出另一个RNA分子。
    他们还要进行两项其他的测试?从无生命的变成有生命的:进行某种新陈代谢过程并将自身分离成几部分。Joyce小组正尝试对系统创建新的功能来通过上述测试,但那可能还有很长的一段路要走。其他试图从?中创造出活体细胞的努力,其中较为瞩目的有哈佛大学的Jack Szostak和Zurich瑞士联邦技术研究中心的Pier-Luisi,也相类似地很难较快实现他们的目标。
    然而,有另一条捷径值得关注。与其回到画板上从?中创造生命,哈佛医学院的George Church和田纳西州Vanderbilt大学的Anthony Forster通过使用我们所熟悉的活体细胞分子工具来缩短了创造过程。以某系列无生命的分子开始,他们力图汇集成一个生命,复制系统运行的方式尤如一位兴趣爱好者在装配一辆汽车的零件。“这很复杂,但我想人们开始意识到这是我们创造出一个合成细胞的最好的机会了,”Forster说。

  8. Sonia说道:

    要把那么多复杂的部分组合起来仍然是一大挑战,可忽然间?又指日可待了。2008年10月在香港召开的合成生物学会议上,Church和他的哈佛合作者Michael Jewett报告了他们已经解决了合成中最大的问题之一:?核糖体。
    一些其他的子系统已经开始聚集在一起了。一个由日本Osaka大学Tetsuya Yomo带领的团队已经创设了一个类似于Church的系统,但包括144个而不是151个部分。这部分是因为他去除了DNA这一步。在Yomo的系统中,一个微小的RNA基因组包含了制取单一蛋白质分子的路径,该蛋白质分子反过来帮助RNA分子进行复制。?首次在合成系统中?,这是Church小组目前完成的业绩。“我们花了十年的时间达到了这个水平,”Yomo说到。
    第二部分 寻找?生命
    当一些研究者正试图在实验室中创造全新的生命时,另一些研究者则正在寻找土星上,甚至太阳系其他地方上的外星球生命。这一迅速成长起来的天体生物学领域在地球上鲜有分支:寻求“?生物圈”——一种与我们所知的类型不相关的,第二种独立形式的生命体(Astrobiology,vol 5,P154)。
    “我认为如果我们能发现地球上第二种形式的生命,那将象达尔文发现进化论一样伟大,”亚里桑那州立大学宇宙哲学家和天体生物学家Paul Davies这样说。“它将回答我们所能想象到的大多根本性的问题,例如:我们是宇宙中唯一的生命吗?”
    “他们不能探测到微生物的其他生命形式,”Boulder Colorado大学的科学哲学家和天体生物学家Carol Cleland这样说到。考虑到目前只有少于百分之一的微生物被?和?,?生命有大量的空间可以生存,而且就在我们的鼻子下面。
    然而,在地球上寻找?生命的任务要比到外星球上寻找生命要艰难得多。“正如我们所知,这个星球已被生命体严重污染,”Colorado大学的生化专家Shelley Copley说到。那意味着研究者不能仅寻求新陈代谢的证据或大量生物聚合物的存在,因为普通生命会掩埋?生命发出的任何信号。相反,向?生命大步前进的人应该更有创造性。
    另一条道路是设计出探测其他生物化学的方法。到目前为止,只有这种类型的实验条件在寻求“镜象体生命”,Huntsville Alabama的NASA国家空间科学和技术中心的微生物学家Richard Hoover这样说。正常器官几乎无一例外地使用右旋糖和左旋氨基酸,并避开它们的镜象对应体。

  9. Sonia说道:


  10. [...] 原文,译者:SNOW LEE(简介见后),另一译文在此。 [...]

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