他们制造出了几乎具备生命特征的细胞。如今该如何处置它呢?这些“土豆细胞”未来或许能用于研发新药物及新材料。不过在此之前,科学家们必须先对其进行改良,并确保它不会被滥用。
They Created a Cell That’s Almost Alive. What to Do With It Now? SpudCells may one day produce new medicines and materials. But first scientists have to improve them — and make sure they aren’t misused.
凯特·亚当拉在费城的科学历史研究所舞台上踱步,她头顶的屏幕上正显示着一个发着红光的细胞影像。她身着黑色套装,翻领上贴着一张贴纸——上面画着一个微笑着的卡通细胞,正把旗帜插在月球上。
Kate Adamala paced the stage at the Science History Institute in Philadelphia, a glowing red blob looming on the auditorium screen above her. She wore a black suit with a sticker on a lapel. On it was a cartoon blob smiling as it planted a flag on the moon.
贴纸上写着:“为细胞界献上一颗小小的土豆。”这其实是对“土豆细胞”这一名称的戏仿。作为明尼苏达大学的合成生物学家,亚当拉博士正是用这个名字来称呼屏幕上那个红色细胞团。
“One Small Spud for Cellkind,” the sticker read — a riff on SpudCell, the name that Dr. Adamala, a synthetic biologist at the University of Minnesota, had given to the red orb floating above her.
“土豆细胞”能够生长、复制DNA、分裂成两个细胞,并重新开启整个细胞周期。不过这种细胞完全由人类制造,其原料原本并无生命。今年7月,“土豆细胞”一经问世便受到不少专家赞誉,称其为科学界迄今为止最接近“从零创造生命”的成果。
A SpudCell can grow, copy its DNA, divide in two, and start its cell cycle all over again. But this cell is made by people, created from lifeless ingredients. Unveiled in July, SpudCell was hailed by some experts as the closest that science has come to making life from scratch.
此次亚当拉博士来到费城,是为了与众多研究人员、伦理学家以及生物科技行业和政府代表共同商讨对策。现在正是决定如何让“土豆细胞”更接近生命形态,以及如何安全利用它来改善人类生活的关键时刻。
Now, Dr. Adamala had arrived in Philadelphia to meet with researchers and ethicists, along with representatives from the biotech sector and the government. The time had come to decide how to bring SpudCell closer to life, and to decide how to safely use it to make life better.
“随着合成细胞的诞生,我们终于拥有了能够完全理解并掌控的生物系统,”亚当拉博士对在场听众说道,“真正的精彩才刚刚开始。”今年7月,亚当拉博士与另外三位科学家共同创立了名为“Biotic”的非营利组织,旨在推动“土豆细胞”相关研究。他们的目标是制造出能够自我维持的细胞,供研究人员加以研究与改造,从而生产出常规生物学手段无法实现的药品、食品、燃料及其他产品。
“With the creation of synthetic cells, we have a biological system that we can fully understand and fully control,” Dr. Adamala told the audience. “And that’s where the fun can really start.”In July, Dr. Adamala and three other scientists founded a nonprofit called Biotic to support research on SpudCell. The idea was to make a self-sustaining cell that researchers could study and engineer to make medicines, foods, fuels and other items that could not be produced with ordinary biology.
上个月的会议便是“Biotic”组织的首次亮相。科学家们将其命名为“萌芽日”,以此作为“末日”的积极对应。共有十几位科学家在会上介绍了他们为推进“土豆细胞”研究而即将开展的各项具体工作。
The meeting last month was Biotic’s debut. The scientists called it Bloomsday, a hopeful counterpoint to Doomsday. A dozen of them described the nuts-and-bolts work they were starting in order to advance SpudCell.
当 SpudCell 在七月份首次亮相时,它引起了众多科学家的兴趣——不仅仅是因为它看起来非常“像活细胞”。实际上,天然细胞的结构极其复杂且充满神秘性;即便是最小的微生物,也拥有数十个科学家尚未完全理解的基因。
SpudCell intrigued many scientists when it made its July debut, and not just because it was so close to being truly alive. Natural cells are complex and deeply mysterious. Even the smallest microbes have dozens of genes that scientists don’t yet understand.
亚当阿拉博士(Dr. Adamala)和她的同事们是从零开始制造 SpudCell 的,因此他们对所使用的每一个组成部分都了如指掌。他们希望这种深入的了解能够使 SpudCell 的改造工作比改造普通细胞更加容易。
Having built SpudCell from scratch, Dr. Adamala and her colleagues have a clear understanding of every part they used. They hope that thorough knowledge will make SpudCells easier to engineer than ordinary cells.
然而,也有一些科学家对 SpudCell 持怀疑态度,他们希望看到这项技术是否真的能够实现其最初所宣称的功能。
But some scientists have reacted to SpudCell with skepticism and are waiting to see if the technology can live up to its promise.
“我认为这项研究并不具有说服力,”代尔夫特理工大学(Delft University of Technology)的物理学家西斯·德克尔(Cees Dekker)说道。德克尔指出,目前 SpudCell 的实际功能远不如其外表看起来那么强大。亚当阿拉博士的团队为 SpudCell 赋予了 36 个基因,但在实验中只有其中一个基因真正发挥了作用。
“I don’t find it a compelling study,” said Cees Dekker, a physicist at the Delft University of Technology. Dr. Dekker said that he felt that, for now, there was less to SpudCell than meets the eye. Dr. Adamala and her colleagues endowed it with 36 genes, he noted, but in their experiments, only one of those genes was active.
科学界的怀疑态度还体现在《细胞》(Cell)杂志拒绝发表一篇详细介绍 SpudCell 发明的论文上;目前这篇论文只能以预印本的形式在线阅读。在 Bloomsday 会议上,亚当阿拉博士表示该论文正在被其他期刊审稿中。
Another indication of scientific skepticism came when a journal, Cell, rejected a paper detailing the invention of SpudCell. For now, the paper is available online as a preprint. At the Bloomsday meeting, Dr. Adamala said the paper was being considered by another journal.
在会议上,亚当阿拉博士及其他 SpudCell 研究人员坦承:他们仍需完成大量工作,才能创造出一种能够由任何科学家使用现有材料自行制造的、具备自我维持能力的细胞。
At Bloomsday, Dr. Adamala and other SpudCell researchers readily acknowledged that they still had a lot of work to do to create a self-sustaining cell that any scientist could manufacture from prepared ingredients.
例如,生物细胞会在被称为“核糖体”(ribosomes)的分子工厂中合成蛋白质;但为了使用这些核糖体,细胞本身首先必须能够制造出核糖体。相比之下,SpudCell 无法自行制造核糖体,科学家们必须为它们提供从其他细胞中提取的核糖体。当 SpudCell 利用这些核糖体合成蛋白质时,这些核糖体会逐渐被消耗掉(即“磨损”)。
Biological cells make proteins in molecular factories called ribosomes, for example. But in order to use ribosomes, the cells have to make the ribosomes in the first place. SpudCells, by contrast, cannot make their own ribosomes. Scientists have to feed them ribosomes harvested from other cells. As a SpudCell makes proteins from the ribosomes, the factories wear out.
日本国立研究机构理研(RIKEN)的分子生物学家清水良(Yoshiru Shimizu)正在通过研究构成核糖体的数十种分子来尝试解决这个问题,希望能找到一种方法促使这些分子重新组装成新的“生物结构”(即新的生物单元)。
Yoshiru Shimizu, a molecular biologist at RIKEN, a national research institute in Japan, is tackling this problem by running experiments on the dozens of molecules that make up the ribosome, hoping to find a way to prompt them to assemble into new factories.
其他研究人员也在测试蛋白质,以确定是否能让 SpudCell 更精确地分裂;还有一些研究人员正在研究如何使 SpudCell 的 DNA 对光敏感,从而可以通过不同颜色的光来激活其基因。
Other researchers are testing proteins to see if they can make SpudCells divide more accurately. And still others are investigating how to make the SpudCell’s DNA light-sensitive, so that they can turn on its genes with flashes of different colors.
全球范围内所有与 SpudCell 相关的研究项目都面临着同样的挑战:可供选择的方案实在太多。对于核糖体或 SpudCell 的任何其他组成部分来说,可能的组合方式几乎是无穷无尽的。
All the SpudCell projects underway across the world face the same challenge: too many choices. There are a practically infinite number of possible recipes for a ribosome or any other feature of SpudCell.
密苏里大学的计算生物学家罗莎安娜·齐亚(Roseanna Zia)通过构建虚拟的 SpudCell 模型来缩小这些选择范围。她和她的同事们已经创建了天然微生物的详细计算机模型。
Roseanna Zia, a computational biologist at the University of Missouri, is narrowing down these options by building a virtual SpudCell. Dr. Zia and her colleagues have already created detailed computer models of natural microbes.
“我们能够深入观察这些细胞的内部结构,精确地了解每个时刻所有分子在细胞内的具体位置,”她说。
“We have the ability to peer deeply inside these types of cells and see exactly at every moment in time where all the molecules are with position at every point in time,” she said.
目前,她的团队正在模拟单个 SpudCell 内部的数百万个分子。他们希望这些虚拟实验能够带来一种升级版的 SpudCell,任何实验室都可以使用 Biotic 公司提供的开放技术协议自行制造这种细胞。
Now her team is simulating the millions of molecules inside a single SpudCell. They hope these virtual experiments will yield an upgraded SpudCell that any lab can produce for itself, using an open protocol from Biotic.
科学家们的灵感来源于 Unix——这种开创性的计算机编程语言诞生于 20 世纪 70 年代。由于 Unix 具有开放性和简洁性,它吸引了全球的计算机科学家们,他们利用它进行创新。
The scientists draw their inspiration from Unix, a pioneering computer programming language created in the 1970s. Because it was open and simple, Unix attracted a global community of computer scientists who used it to innovate.
研究人员希望 SpudCell 能成为生物技术领域的“Unix”:一种可以被多种方式改造的简单细胞模型。
Researchers hope that SpudCell will be a Unix for biotechnology — a simple cell that can be engineered in scores of useful ways.
虽然费城会议的大部分时间都用于科学规划,但伦理学家和生物安全专家也讨论了 SpudCell 所引发的道德问题。
While much of the meeting in Philadelphia was consumed with scientific planning, ethicists and biosecurity experts also discussed the moral questions raised by SpudCell.
“这真的是‘生命的创造’吗?”芝加哥大学的生物伦理学家劳里·佐洛思(Laurie Zoloth)问道。
“Is this the creation of life?” asked Laurie Zoloth, a bioethicist at the University of Chicago.
亚当拉博士及其同事们一直强调:他们实际上并没有创造出生命;同时,也很难明确区分“生命”与“非生命”之间的界限。
Dr. Adamala and her colleagues have often stressed that they have not, in fact, created life — but also that it can be very hard to draw a line between life and non-life.
尽管如此,科学家们意识到“SpudCell”这种生物技术有可能被滥用,从而导致公众对这类生物技术的信任度大幅下降。佐洛斯博士指出,OpenAI与Biotic一样,最初都是以非营利组织的形式成立的,其宗旨是利用人工智能为人类带来福祉。
Still, scientists realize that SpudCell may be misused, and that public trust in this form of biology could crater. Dr. Zoloth noted that OpenAI, like Biotic, was first formed as a nonprofit, dedicated to safe artificial intelligence for the good of humanity.
“到底出了什么问题?”佐洛斯博士问道,“为什么人们对人工智能普遍缺乏信任,甚至愿意去抗议数据中心呢?”亚当拉博士及其同事们从一开始就非常重视安全问题。在将“SpudCell”广泛推广之前,他们对其DNA和蛋白质进行了特殊设计,使其只能依靠自然界中不存在的化学物质来生存。
“What went wrong there?”Dr. Zoloth asked. “Why are people so distrustful of A.I. in general that they’re ready to picket data centers?”Dr. Adamala and her colleagues are taking security seriously from the start. Before they make SpudCell widely available, they are engineering its DNA and proteins it so that it can only survive on an exotic diet of chemicals not found in nature.
研究人员希望这些措施能够确保“SpudCell”无法逃出实验室,也不会被用作生物武器。
The researchers hope these measures will ensure that SpudCell can’t escape from labs or be unleashed as a biological weapon.
“我们可以在最基本的层面上保护生物技术的安全性,”亚当拉博士说。
“We can safeguard biology on the most fundamental level,” Dr. Adamala said.
对于这种微观级别的生物技术来说,其潜在的应用前景(以及潜在的危险)是巨大的;目前,即使投入大量精力进行维护和喂养,它也几乎无法在自然界中存活。
The possibilities, and perhaps dangers, are immense for a microscopic bubble that for now can barely survive even with a lot of care and feeding.
“我们会尽可能争取到所有的好运与支持,”斯坦福大学的合成生物学家德鲁·恩迪(Drew Endy)说道,“我们确实需要这些。”德鲁·恩迪同时也是Biotic公司的创始人之一。卡尔·齐默(Carl Zimmer)为《纽约时报》撰写科学新闻,并负责“Origins”专栏的报道。
“We’ll take all the good karma and good luck we can get,” said Drew Endy, a synthetic biologist at Stanford University and a founder of Biotic. “We’re going to need it.”Carl Zimmer covers news about science for The Times and writes the Origins column.