二十年前,《经济学人》曾刊登一篇关于能够制造龙的工厂的报道。那是一个愚人节玩笑,基于这样一个想法:活细胞可以在计算机内被精确建模。当时,这个想法只是幻想。但随后几十年中人工智能的蓬勃发展似乎让这一想法更接近现实。进步的迹象出现在10月7日,当时虚拟生物学倡议(Virtual Biology Initiative,VBI)——一个旨在收集创建细胞行为和变化预测模型所需数据的项目——宣布,自今年4月启动以来,已获得价值8亿美元的承诺。
Twenty years ago, The Economist ran a story about a factory that could make dragons. It was an April Fool, based on the idea that living cells could be modelled accurately inside computers. At the time, that idea was a fantasy. But the flourishing of artificial intelligence in the intervening decades appears to have brought it closer to reality. A sign of progress came on October 7th, when the Virtual Biology Initiative (VBI), a project to collect the data needed to create predictive models of how cells behave and change, announced that it had received commitments worth $800m since its launch in April.
VBI的目标是医学方面的。预测模型将使研究人员能够设计出更有效、更有可能在临床试验中成功通过的药物。但如果这一目标得以实现,未来一代的模型或许可用于设计现有生物体的改良版本,例如农作物植物——甚至最终可能用于设计全新的生命形式。
The VBI’s goals are medical. Predictive models will let researchers design more effective drugs that are more likely to pass successfully through clinical trials. But, if that works, future generations of models might be used to design modified versions of existing organisms, such as crop plants—and perhaps, eventually, entirely new living things.
使这些进展成为可能的技术是深度学习,即通过训练大型神经网络来解决复杂问题。正是这一技术奠定了支撑Anthropic、谷歌和OpenAI等公司所推出聊天机器人的基础模型。对这些基础模型而言,生物学核心的长链分子(核酸和蛋白质)与人类写作中的词语链没有区别。因此,将基础模型应用于这些分子是一个显而易见的想法。而事实证明,这一做法异常富有成效。
The technology that has made such advances conceivable is deep learning, wherein large neural networks are trained to tackle complex problems. It is this technique that underpins the foundation models that power the chatbots marketed by firms such as Anthropic, Google and OpenAI. To such models, the long-chain molecules at the heart of biology (nucleic acids and proteins) are no different from the chains of words in human writing. Letting foundation models loose on them was thus an obvious idea. And it is proving extraordinarily productive.
在圣地亚哥生物初创公司Genyro的商业负责人Adrian Woolfson看来,“生物学现在已经可计算、可预测,因此也可设计。”它同样也可以实例化。例如,由帕洛阿尔托Arc研究所的Brian Hie部分发明的基础模型Evo 2,能够分析长度达100万个碱基对的DNA片段(相当于小型细菌基因组的大小)。通过研究该分子双螺旋中化学碱基配对的顺序,它可以预测这种顺序的变化可能如何影响其母体生物。
In the words of Adrian Woolfson, the business brain behind Genyro, a bio-startup in San Diego, “Biology is now computable, predictable and therefore designable.”It is also instantiable. Evo 2, for example, a foundation model partly invented by Brian Hie, of the Arc Institute in Palo Alto, can analyse DNA segments up to 1m base-pairs long (the size of a small bacterial genome). By studying the order of chemical bases paired together in that molecule’s double helix, it can predict how changes to that order might affect its parent organism.
之所以能够做到这一点,是因为它的训练数据来自超过10万个物种的DNA序列,训练方式类似于聊天机器人对文本的训练。
It is able to do this because it was trained on DNA sequences collected from over 100,000 species, in the way that chatbots are trained on text.
今年1月,Woolfson博士的科学合作伙伴——加州理工学院的Kaihang Wang和Noah Robinson——向世界推出了一种名为Sidewinder的高保真、高效率DNA组装系统。Sidewinder能够以高精度将长段DNA片段拼接在一起(目前最长可达12,500个碱基对),这本身就足以合成小型病毒的基因组。它还能简化更长DNA片段的构建,例如细菌基因组和小型人工染色体。
In January Dr Woolfson’s scientific partners, Kaihang Wang and Noah Robinson, of the California Institute of Technology, unleashed on the world a high-fidelity, high-efficiency DNA-assembly system called Sidewinder. Sidewinder can piece long stretches of DNA together (currently up to 12,500 base pairs) with high accuracy. That is enough, by itself, to synthesise the genomes of small viruses. It also simplifies the construction of yet-longer stretches, such as bacterial genomes and small artificial chromosomes.
结合Evo 2(Hie博士也是Genyro的创始人之一),该公司现在拥有了Woolfson博士付诸实践所需的工具。他希望通过合成携带耐热和抗旱基因的人工小麦染色体来实现这一目标。
Combined with Evo 2 (Dr Hie is another of Genyro’s founders) the firm now has the tools needed for Dr Woolfson to put his money where his mouth is. He hopes to do so by synthesising an artificial wheat chromosome carrying genes for heat- and drought-resistance.
Evo 2绝非唯一的基因组基础模型。谷歌旗下的人工智能实验室DeepMind已经开发出一个名为AlphaGenome的模型。它比Evo 2更具专业性。AlphaGenome几乎完全基于人类基因组进行训练,同样,来自中国深圳BGI研究院的产品Genos也是如此。
Evo 2 is by no means the only genomic foundation model out there. DeepMind, Google’s AI lab, has created one called AlphaGenome. It is more of a specialist than Evo 2. AlphaGenome was trained almost exclusively on human genomes, as was Genos, an offering from BGI Research, in Shenzhen, China.
深度学习模型同样适用于研究特定非人类物种群体的学者。植物、真菌、细菌、病毒和脊椎动物均可通过此方式获得服务。相反,总部位于伦敦的Basecamp Research公司正在扩大其研究范围。其模型的训练样本旨在捕捉某一特定地点水样中的全部DNA,以此研究其中微生物之间的化学战争——其目标是开发新型抗生素。
Deep-learning models are available, too, for those studying particular groups of non-human species. Plants, fungi, bacteria, viruses and vertebrate animals are all served in this way. Conversely, Basecamp Research, a company in London, is casting the net wider. Its model is trained on samples that attempt to capture all the DNA in, say, a water sample from a particular place, in order to study—with a view to creating new antibiotics—the chemical warfare going on between the microbes therein.
而这仅是基因组学的应用。各种类型的深度学习模型同样能够处理其他生物分子,尤其是蛋白质。这些模型能够计算由氨基酸链组成的天然蛋白质如何折叠,这对于理解其功能至关重要。它们还能预测特定氨基酸的改变会产生什么影响,甚至能够从零开始设计蛋白质,以实现特定目的——从更有效的蛇毒解毒剂到用于新型化学反应的定制酶。
And that is only genomics. Deep-learning models of various sorts can also handle other biological molecules, especially proteins. They are able to work out how natural proteins, which are long chains of chemical links called amino acids, fold up, which is crucial to understanding how they work. They can also predict what changing particular amino acids will do, and even design proteins from scratch, with particular purposes in mind—from better antidotes to snake venom to bespoke enzymes for novel chemical reactions.
DeepMind同样拥有此类模型,名为AlphaFold 3。其衍生公司Isomorphic Labs——使命宣言为“解决所有疾病”——计划将AlphaFold 3与AlphaGenome一起用于与三家规模更大、历史更悠久的制药公司:诺华、礼来和强生的药物发现合作。这些制药公司将提供靶点。Isomorphic将利用其AI提出药物候选者。随后,制药公司将对这些建议进行实验验证。
DeepMind also has one of these, called AlphaFold 3. And its spin-off, Isomorphic Labs—which has the modest mission statement “Solve all disease”—plans to use both that and AlphaGenome in drug-discovery partnerships with three larger, longer-established pharma firms: Novartis, Eli Lilly and Johnson & Johnson. The pharma firms will provide the targets. Isomorphic will use its AI to suggest drug candidates. The pharma firms will then test its suggestions experimentally.
其他成熟的制药公司也在内部开展类似的AI工作。罗氏、诺和诺德、GSK和阿斯利康均拥有或持有用于此目的的超级计算机的股份。事实上,礼来公司也通过自行建造一个名为LillyPod的超级计算机来分散风险,该计算机独立于Isomorphic。该系统将把深度学习方法应用于公司150年历史档案中的数据,该档案既包含未发表的失败案例,也包含已发表的成功案例。这应能得出仅依赖已发表科学文献而无法获得的见解,而这些文献存在对有效方法的偏见。
Other established pharma companies are doing similar AI work in-house. Roche, Novo, GSK and AstraZeneca all either own or have stakes in supercomputers for that purpose. Indeed, Lilly itself has hedged its bets by building one, called LillyPod, independently of Isomorphic. This will apply the deep-learning approach to data from the company’s 150-year-old archive, which is replete with unpublished failures as well as published successes. That should yield insights unavailable to those relying solely on the published scientific literature, with its bias towards what worked.
与此同时,在农业领域,AI正被用于解决若干此前难以解决的问题。其中之一是多倍体,这是一种在植物中常见的现象,即生物体具有多套相似的染色体。包括小麦、棉花和马铃薯在内的几种重要作物都是多倍体。这使得难以确定哪些基因负责何种影响,从而难以知道在何处进行有利的基因编辑。
In the field of agriculture, meanwhile, AI is being brought to bear on several hitherto-intractable problems. One such is polyploidy, a phenomenon common in plants in which an organism has multiple sets of similar chromosomes. Several important crops, including wheat, cotton and potatoes, are polyploid. This makes it hard to determine which genes are responsible for what effects, and thus know where to make advantageous genetic edits.
合适的AI可以理清这些关系。它还能帮助理解植物免疫系统,该系统在动物免疫系统独立演化的同时同样复杂。这应能使其被调整以利于农民。甚至还有尝试利用AI来调整光合作用的基本机制,以尝试提高其效率——尽管进化已有数十亿年时间来优化它,这几乎是不可能的,但如果成功,其价值将是不可估量的,因为它能提高产量。
Appropriate AI can sort out what’s what. It can also help make sense of plant immune systems, which have evolved independently of those in animals but are similarly complex. That should allow them to be tweaked to farmers’ advantage. And there are even attempts to use AI to tinker with the fundamentals of photosynthesis, to try to make it more efficient—a long shot, given that evolution has had several billion years to optimise it, but one that would be of incalculable value if it could be pulled off to increase yields.
不过,最大的收益将是将AI赋能的生物学方法相结合,以制定计算机模型来阐明细胞如何工作。VBI正是朝着这一目标迈出的一步。
The big prize, though, will be to combine the approaches to biology enabled by AI to devise computer models of how cells work. The VBI is a step towards this.
这项倡议是由一个由公共研究机构、学术机构和私营研究组织组成的联盟发起的,该联盟由 BioHub 领导。BioHub 是一家位于旧金山的组织,由 Meta 公司的首席执行官马克·扎克伯格(Mark Zuckerberg)和他的妻子普里西拉·陈(Priscilla Chan)共同创立。DeepMind、Isomorphic Labs 和 Arc Institute 都是该联盟的成员。
The initiative itself is a coalition of public, academic and private research organisations led by BioHub, an organisation in San Francisco set up by Mark Zuckerberg, boss of Meta, and his wife Priscilla Chan. DeepMind, Isomorphic Labs and the Arc Institute are among its members.
其目标是收集大量新的生物数据,并将这些数据以适合人工智能处理的格式进行整理,以便用于构建预测模型。虽然这些模型无法完全模拟细胞的所有行为,但它们仍能在模拟的疾病环境中像真实细胞一样作出反应。
The aim is to gather, in AI-friendly format, the vast amounts of new biological data needed to create predictive models. Though these will not replicate all aspects of cellular behaviour they will respond like real cells to simulated disease and treatment.
这应该会大大加快医学研究和药物测试的进程。例如,通过使用具有不同基因组的虚拟细胞,我们可以在临床试验开始之前就判断出哪些细胞可能对某种药物有良好的反应。这样一来,临床试验将不再像目前那样漫长且充满不确定性,而更像是一种形式上的程序。
That should greatly speed up medical research and drug testing. Virtual cells with different genomes, for example, might indicate which are likely to respond well to a drug even before clinical trials start. That would make such trials more of a formality, rather than the nail-biting, years-long exercise they currently are.
要构建这样的虚拟细胞,我们需要深入了解生物学知识,并建立相应的模型来处理远不止单个 DNA 分子和蛋白质分子的组成信息。这些新模型还需要能够准确描述这些分子在细胞内的位置、它们之间的相互作用,以及它们与脂质、糖类等其他生物化学分子之间的相互作用;同时,这些模型还需要能够理解整个细胞系统如何对激素等信号分子作出反应。
To understand enough biology to make such a virtual cell will require looking at, and building models to handle a lot more than just the composition of individual DNA and protein molecules. These new models will need to know where those molecules are, how they interact with each other and with the other molecules of biochemistry (such as lipids and sugars) and how this whole network responds to signalling molecules such as hormones.
VBI 将资助相关工具的研发,例如冷冻电子断层扫描技术(cryo-electron tomography),该技术能够以接近原子级别的精度观察细胞内部的结构。此外,美国能源部(DoE)和国立卫生研究院(NIH)也在 10 月 7 日宣布将与 BioHub 合作提供支持:NIH 将提供价值 5 亿美元的现有生物数据供 BioHub 使用并尝试对这些数据进行标准化处理;而 DoE 则会投入类似的资金用于支持计算资源及其他相关研究工作。
The VBI will sponsor the development of tools to do this, such as cryo-electron tomography, which can resolve the insides of a cell at close to atomic detail. Meanwhile, in a collaboration with BioHub also announced on October 7th, America’s Department of Energy (DoE) and National Institutes of Health (NIH) will chip in too. The NIH will contribute $500m-worth of already-collected data that BioHub will attempt to standardise, and the DoE will spend a similar sum on computing and other resources needed for the endeavour.
虚拟细胞仍然只是计算机模型罢了。而合成生物学的真正“杰作”——按照这个词的原始含义(即那些旨在展示人类对生命过程掌握程度的研究成果)——应该是从零开始创造出全新的生物体。
Virtual cells will still be just computer models. Synthetic biology’s masterpiece—in the word’s original sense of a work created to prove mastery—will be to create completely novel organisms from scratch.
当然,这是否已经实现,取决于我们如何定义“生物体”和“全新的生物体”。2025年9月,Hie博士及其在Arc研究所的同事们宣布,他们利用Evo 2及其前身Evo 1技术,基于一种名为Phi-X174的噬菌体设计了16种全新的病毒。这种噬菌体在病毒学研究中具有重要地位,但新设计的病毒与Phi-X174在基因组成上存在显著差异。
Depending on how you define the words “organisms” and “novel”, this may already have happened. In September 2025 Dr Hie and some of his colleagues at the Arc Institute announced that they had used Evo 2 and its predecessor, Evo 1, to design and synthesise 16 viable viruses based on, but significantly different from, a bacteriophage called Phi-X174 that is one of virology’s workhorses.
顾名思义,噬菌体以细菌为宿主。有趣的是,Hie博士研发的一些新型噬菌体的生存能力(即“适应性”)甚至超过了野生噬菌体;这些新型噬菌体组合能够突破三种大肠杆菌(另一种在医学研究中具有重要作用的肠道细菌)对病毒的天然抵抗力。这一点尤其值得关注,因为这种定制化的噬菌体可能具有潜在的医疗应用价值。所谓的“噬菌体疗法”(即利用噬菌体而非化学抗生素来控制有害细菌)曾一度被视为异想天开的技术,但现在正受到广泛关注。
Bacteriophages, as their name suggests, prey on bacteria. Intriguingly, some of Dr Hie’s novelties had higher fitness than their wild equivalents. Cocktails of them proved able to overcome the normal resistance to viruses shown by three different strains of E. coli, a gut bacterium that also has workhorse status. This is of particular interest because custom-built phages might have medical applications. So-called phage therapies, in which hostile bacteria are kept under control by viruses rather than chemical antibiotics, were once widely regarded as eccentric, but are now under active consideration.
在Genyro公司,没有人会指责Woolfson博士目光短浅。他相信,通过结合生物学基础模型与低成本、大规模的DNA合成技术,人们将能够探索自然选择尚未发现的无数可能性——他将其称为“整个DNA世界的所有可能性”。
Back at Genyro, no one could accuse Dr Woolfson of thinking small. He hopes the combination of biological foundation models and cheap, large-scale DNA synthesis will enable the exploration of the myriad possibilities offers that natural selection has not yet discovered—what he calls “the whole of DNA space.
这些创新设想很可能会从一些“新型生物”开始;虽然这些生物在形态上很新颖,但它们仍与自然界中的某些生物存在相似之处(就像 Hie 博士研究的噬菌体一样)。正如自然选择通过微生物、鱼类、两栖动物、类哺乳动物以及猴子等逐步进化出人类一样,人工智能驱动的渐进式变革也可能带来一些听起来像科幻小说中的应用:比如能够“生长”而非被建造的建筑;拥有翅膀而非螺旋桨的送货无人机;以及拥有腿而非轮子的越野汽车。
This would, presumably, start with creatures that, though novel, still had, like Dr Hie’s phages, a recognisable resemblance to something natural. But, just as natural selection, proceeding one step at a time, went from microbes to humans via fish, amphibians, mammal-like reptiles and monkeys, so AI-driven incremental change might result in applications that sound, today, like fantasy. Growing buildings rather than constructing them, perhaps? Delivery drones with wings instead of propellers? Off-road cars with legs instead of wheels?
此外,DNA 的潜力可能比乍看之下要大得多。人工智能设计的人工细胞可以通过重新编写遗传代码来推动生物化学乃至合成生物学的发展。天然蛋白质仅使用 20 种氨基酸,但 DNA 本可以编码更多种类的氨基酸(如果蛋白质合成机制能够被优化、消除重复的氨基酸的话)。这或许会催生出自然界中目前还不存在的各种有用化学物质。
And DNA space itself may prove bigger than it looks at first sight. AI-designed artificial cells might assist the extension of biochemistry, and therefore synthetic biology, by rewriting the genetic code itself. Natural proteins employ only 20 types of amino acid, but DNA would have the ability to encode three times as many if the machinery of protein synthesis could be re-wired to eliminate duplicates. That might permit all sorts of useful chemistry that is currently not seen in nature.
不过,这种技术也可能带来意想不到的“危险后果”。Hie 博士和他的同事们选择噬菌体作为研究对象,部分原因就是它们不会变成病原体;Evo 2 的开发者们在训练该模型时也确保数据库中的所有病毒都不具有致病性,以防模型意外学会制造有害物质。然而,随着这项技术的普及,相关风险也会随之增加。
It could also, though, unleash accidental monsters. Dr Hie and his colleagues chose phages for their work on synthetic viruses in part because they pose no conceivable threat of turning into pathogens. And the creators of Evo 2 made sure when they were training it that none of the viruses in the databases were pathogenic, lest the model accidentally learn to do something dangerous. As the technology spreads, though, risks will proliferate.
正如人工智能本身一样,人工智能所推动的生物学发展既可能带来美好的未来,也可能带来可怕的后果。下次当你读到《经济学人》杂志上关于“龙工厂”的故事时,可别以为我们只是在开玩笑。
Like AI itself, then, the biology that ai will enable offers possible worlds that are both wonderful and terrifying. The next time you read a story about a dragon factory in an issue of The Economist, don’t be so sure that we’re joking. ■