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记忆可以移植吗?认识那些正通过复刻一项臭名昭著的研究来寻找答案的科学家Are Memories Transferable? Meet the Scientists Replicating an Infamous Study to Find Out

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本文原版发表于《宽特》杂志。那是波士顿严冬的正午。查尔斯河的水面已经冻得结结实实。但扎卡里·凯尔索冒着刺骨的严寒,终于去解开一个困扰了神经科学实验室半个多世纪的谜团。

The original version of this story appeared in Quanta Magazine. It was the dead of winter in Boston. The surface of the Charles River was frozen solid. But Zachary Kelso braved the biting cold to finally put to rest a mystery that has haunted neuroscience labs for over half a century.

为了做到这一点,神经科学家萨姆·格什曼哈佛实验室的研究助理凯尔索需要一些蠕虫。具体来说,就是涡虫:这种箭头状的扁形动物,是拥有与我们类似的大脑以及两侧对称神经系统的最简单生物之一。通常情况下,实验室会从生物供应公司订购这些广泛使用的模式生物。但邮购的蠕虫并不合标准。因此格什曼派凯尔索前往查尔斯河冰冷的河岸去捕捉一些野生的涡虫。

To do that, Kelso, a research assistant in the Harvard lab of the neuroscientist Sam Gershman, needed some worms. Specifically, planarians: arrow-headed flatworms, which are among the simplest creatures to possess a brain and a nervous system with bilateral symmetry like ours. Normally, labs order these widely used model organisms from biological supply companies. But the mail-order worms weren’t up to snuff. So Gershman had dispatched Kelso to the Charles’ icy banks to catch some wild ones.

“我想,‘我看起来一定像个疯子,因为我正用锤子砸开冰层,’”凯尔索回忆道,“‘所以我穿了一身比较商务休闲的衣服。’”这并不是凯尔索最后一次发现自己处于这种境地。事实证明,查尔斯河的涡虫也不行。他在2025年3月在俄勒冈州尤金市周边的小溪间穿梭时寻获的蠕虫不行。当年6月他在密歇根州的湖泊中垂钓时收集的蠕虫也不行——这一次他穿着及 thigh 的涉水裤,而野餐的家庭则在岸上惊奇地张望着。

“I thought, ‘I’m going to look crazy because I’m using a hammer to beat through the ice,’” Kelso recalled. “So I wore the more business end of business casual.”It wouldn’t be the last time Kelso found himself in this situation. The Charles River planarians, it turned out, didn’t cut it either. Neither did the worms he sourced while stream-hopping around Eugene, Oregon, in March 2025. Nor did the ones he fished from Michigan lakes that June—this time in thigh-high waders—while picnicking families gawked from shore.

凯尔索认真地翻开石头,用系在绳子上的肉块垂钓,甚至还按照一本名为《密歇根州淡水三肠虫》的老旧指南上的地图去寻找。但他的冒险毫无结果。当然,他抓到了大量的涡虫。但在格什曼的实验室里,它们没有一个能按预期做出反应。

Kelso diligently turned over rocks, angled with bits of meat tied to a string, and even followed maps from a vintage guidebook called The Fresh-Water Triclads of Michigan. But his adventure was fruitless. Sure, he caught plenty of planarians. But back in Gershman’s lab, none of them would do what they were supposed to do.

20世纪60年代,一位名叫詹姆斯·麦康奈尔的古怪行为心理学家让科学界相信,涡虫就像巴甫洛夫的狗一样,能够接受经典条件反射,而且这种训练产生的记忆可以通过同类相食在涡虫之间传递。这些奇异的发现得到了其他科学家的重复验证,涡虫训练也成了高中科学展上的一个常见项目。如今,60年后,这些涡虫却停止了学习,而且没有人知道原因。

In the 1960s, an eccentric behavioral psychologist named James McConnell convinced the scientific establishment that planarian worms, like Pavlov’s dogs, could be classically conditioned—and that memories of this training could be transferred from worm to worm through cannibalism. These bizarre findings were replicated by other scientists, and worm training became a staple of high school science fairs. Now, 60 years later, the worms have stopped learning, and nobody knows why.

我最初是在为另一篇关于细胞如何记忆的报道进行采访时,了解到这个科学谜团的。随着我深入查阅记忆研究的历史文献,我不断遇到麦康奈尔那些奇怪的涡虫实验,这些实验曾迷住了一代科学家,随后却消失得无影无踪。涡虫的记忆本身已经被遗忘了。我本满足于将其当作历史上的一个偶然事件来忽略,直到格什曼在一次采访中顺便提到,除了对单细胞纤毛虫蓝色喇叭虫的研究外,他的实验室正试图重复20世纪60年代的一些古怪涡虫实验。我听说过这些实验吗?

I first learned about this scientific mystery while reporting another piece about what a cell can remember. As I dug into the historical literature on memory research, I kept coming across McConnell’s strange worm experiments, which captivated a generation of scientists before disappearing entirely. Planarian memory had itself been forgotten. I was content to dismiss it as a fluke of history until Gershman mentioned, in passing during an interview, that in addition to their work with the unicellular ciliate Stentor coeruleus, his lab was attempting to reproduce some wacky worm experiments from the 1960s. Had I heard of them?

我了解到,格什曼很想从麦康奈尔停下的地方继续研究。作为寻找记忆起源和基础线索、将目光投向大脑之外的不断壮大的认知科学家群体中的一员,他对任何似乎在没有神经和突触网络协助的情况下也能进行记忆的生物都着迷不已。例如,小小的蓝色喇叭虫就能根据以往的经验改变自己的行为——对于一个绝对不可能拥有神经元的单细胞生物来说,这可谓一项壮举。如果麦康奈尔的发现可信的话,涡虫可能会成为记忆研究的下一个伟大模式生物。

Gershman, I learned, was keen to pick up where McConnell had left off. As part of a growing cohort of cognitive scientists looking beyond the brain for clues to the origins and basis of memory, he’s fascinated by any creature that seems to remember without the benefit of neural, synaptic networks. Little Stentor coeruleus, for example, can modify its behavior based on previous experience—quite a feat for a single-celled creature that can’t possibly have a neuron. Planarian worms, if McConnell’s findings were to be believed, might be the next great model organism for memory research.

问题是,事情进展得并不顺利。事实上,无论格什曼如何努力训练它们,他的涡虫没有一条能学会任何东西。

The trouble was, it wasn’t going well. In fact, no matter how hard Gershman tried to train them, none of his planarians would learn a thing.

线虫能学会什么吗?当麦康奈尔在20世纪50年代初提出这个问题时,记忆与大脑中神经元之间突触联系有关这一观点才刚刚开始流行。当时是得克萨斯大学心理学研究生的麦康奈尔推断,涡虫作为拥有真正神经元的结构最简单的生物之一,因此应该能够学习。

Can a worm learn? When McConnell posed the question in the early 1950s, the notion that memory had something to do with synaptic associations between neurons in the brain was just beginning to gain currency. McConnell, then a graduate student in psychology at the University of Texas, reasoned that planarians—among the simplest creatures with true neurons—should therefore be able to learn.

他早期的涡虫实验并非特别新颖。他只是在当时标准的经典条件反射研究中用涡虫代替了老鼠:在让涡虫接触强光的同时对其进行反复电击。经过一段时间的这种训练后,涡虫开始把光线与电击联系起来,每当强光闪烁时,它们就会本能地蜷缩身体。瞧:涡虫学会了!

His early worm experiments were not particularly novel. He simply substituted worms for rats in what were, at the time, standard classical conditioning studies: repeatedly shocking the worms while exposing them to a bright light. After a period of this training, the worms came to associate the light with the shock and scrunched their bodies in anticipation whenever the light flashed. Voilà: worm learning!

涡虫还具有供实验用的更奇特的特征。如果将一条涡虫切成两半,这两半都会再生长成一条新的涡虫——尾部长出一个新头部,头部则长出一个新尾巴。小至原涡虫两百七十九分之一的碎片也能在几周内再生长成一条完全正常的成年涡虫,这种再生能力如此强大,正如一位早期自然学家所说,涡虫在刀刃下实际上是“不朽的”。对麦康奈尔来说,这种能力引出了一个问题:当你把一条涡虫切成两半时,两半都还记得吗?真正的涡虫折磨就是从这里开始的。

Planarians have stranger features to offer for experiments. If a planarian is chopped in half, both halves will regrow into a new worm—the tail will grow a new head, and the head will grow a new tail. A fragment as small as 1/279 of the original worm can regrow into a completely normal adult worm in a matter of weeks, a regenerative capacity so powerful that, as one early naturalist put it, planarians are effectively “immortal under the edge of the knife.”For McConnell, this ability begged the question: When you chop a worm in half, do both halves remember? This is where the real worm torture began.

20世纪60年代,当时还是密歇根大学年轻教授的麦康奈尔开始斩首他训练过的涡虫。从断头处重新长出的虫子表现得和原来的一样,将光线与电击联系起来——鉴于它们原始大脑的保存,这是他预料到的结果。让麦康奈尔感到惊讶的是,从无头尾部再生出来的涡虫也拥有记忆。这意味着,无论涡虫的记忆采取何种形式,它们都不是大脑的专属领域。“记忆似乎遍布于动物的全身,”麦康奈尔后来回忆道。

In the ’60s, McConnell, by then a young professor at the University of Michigan, started beheading his trained planarians. The worms that grew back from the severed heads behaved as the originals had, associating the light with the shock—a result he expected, given the preservation of their primitive brains. What surprised McConnell was that the worms that regenerated from headless tails remembered, too. This meant that whatever form the worms’ memories took, they weren’t the exclusive purview of the brain. “It appeared that the memories were laid down throughout the animal’s body,” McConnell later reflected.

麦康奈尔兴奋不已,进一步推进了他的实验。他把涡虫切成越来越小的碎块;每一次,再生出的部分都保留了记忆。他把受过训练的涡虫的头部缝合到未受训练的尾部上,但它们总是掉落。他将受过训练的涡虫打成匀浆,并将其注射到未接受过实验的受体体内,这是一个精细的过程,历史学家拉里·斯特恩曾将其比作“用标枪刺穿一颗西梅干”。

Thrilled, McConnell pushed his experiments further. He cut the worms into smaller and smaller pieces; each time, the regenerated segments retained the memory. He stitched the heads of trained worms onto untrained tails, but they kept falling off. He pureed trained worms and injected them into naïve recipients, a delicate process that the historian Larry Stern has compared to “impal[ing] a prune with a javelin.”

最后,记起一些涡虫是食同类动物,他将受过训练的涡虫匀浆喂给了同类。在随后的试验中,这些“同类相食”的涡虫立即学会了对光线的反应,就好像它们是在回忆而不是在学习该怎么做。

Finally, remembering that some planarians are cannibals, he fed trained-worm puree to their brethren. In subsequent trials, the “cannibal” worms picked up the light response right away, as though they were remembering, rather than learning, what to do.

如果说麦康奈尔的实验看起来有些毛骨悚然,那么他的探究方向也是符合那个时代特征的。20世纪50年代DNA双螺旋结构的发现,揭示了蛋白质和核酸中蕴含着多么丰富的信息。对于许多科学家来说,记忆的物理痕迹即“印迹”可能具有某种化学基础的观点显得相当合理。麦康奈尔的食同类涡虫会是吃掉了一个记忆印迹吗?麦康奈尔当然是这么认为的。他坚信它们的记忆编码在RNA的结构中——并且可以在涡虫之间转移。

If McConnell’s experiments appear gruesome, his line of inquiry was of his time. The discovery of the DNA helix in the 1950s had revealed just how much information is packed into proteins and nucleic acids. The notion that the physical traces of memories, or “engrams,” might have some chemical basis seemed plausible enough to many scientists. Could McConnell’s cannibal worms have eaten an engram? McConnell certainly thought so. He was convinced that their memories were encoded in the structure of their RNA—and could be transferred from worm to worm.

“在计算机工程的行话中,信息总是被‘喂’进计算机,”记者阿瑟·库斯勒后来在一篇赞赏麦康奈尔工作的述评中写道。“在这里,这个比喻变成了现实。”

“In the jargon of computer engineering, information is always ‘fed’ into a computer,” the journalist Arthur Koestler later wrote in an appreciative survey of McConnell’s work. “Here the metaphor became flesh.”

这些都是轰动一时的发现,麦康奈尔充分利用了由此带来的媒体关注。在成为科学家之前,他曾在电台有过短暂的职业生涯,知道如何将微妙的观点重新包装成简短有力的妙语。在《时代》和《时尚先生》等杂志上,他大谈特谈一个“食用记忆”的未来——“钢琴课药丸”和“教授汉堡”。他带着受过训练的涡虫登上《史蒂夫·艾伦秀》,尽管他发型利落、戴着角质架眼镜,却戏称自己为“麦食人魔”。

These were sensational findings, and McConnell took every advantage of the media attention they generated. Before becoming a scientist, he had had a brief career in radio, and he knew how to repackage nuanced ideas as pithy soundbites. In magazines such as Time and Esquire, he spoke grandly of a future of memory consumption—of “piano lesson pills” and “professor burgers.”He brought his trained worms onto The Steve Allen Show, and, belying his clean-cut hair and horn-rimmed glasses, dubbed himself “McCannibal.”

学生们开始写信给麦康奈尔在密歇根大学的实验室,请教如何在校园科学展上训练涡虫,麦康奈尔则分享建议。他相信科学应该属于人民;他把自己看作当代的大卫,向体制化的歌利亚投掷石子。这使他成为那个时代最著名的公众科学家之一,但并未为他赢得更严肃同行们的青睐。再加上他把全部研究都发表在《养虫人文摘》上——一份由他实验室发行的反文化期刊——这更是不利于他的形象。

Students began writing to McConnell’s lab at the University of Michigan to ask for worm-training tips for their school science fairs, and McConnell shared advice. Science, he believed, should be for the people; he saw himself as a latter-day David pitching stones at institutional Goliaths. This made him one of the most famous public scientists of his era, but it did not endear him to more serious peers. It also didn’t help that he published all his research in The Worm Runner’s Digest, a countercultural journal he distributed from his lab.

《养虫人文摘》“有点像《疯狂杂志》遇上了严肃科学期刊,”格什曼最近告诉我。在鼎盛时期,它在全球有大约2500名订户。 上的手绘盾徽绘有一只双头涡虫,还有一句拉丁文格言,大意是“以更未知者解释未知者”。1959年的创刊号只有14页油印内容,内容是涡虫的饲养与照料,但很快就发展壮大。除了发表数十篇记忆转移论文和相关学术著述,麦康奈尔还欢迎幽默内容,刊载了科幻小说、激昂的社论、学生绘制的涡虫漫画、恶搞文章和诗歌。

The Worm Runner’s Digest was “sort of Mad Magazine meets a serious scientific journal,” Gershman told me recently. At its peak, it had some 2,500 subscribers around the world. The hand-drawn shield on its cover featured a two-headed planarian and the Latin motto ignotum per ignotius, which roughly translates to “the unknown explained through the even more unknown.”Its 1959 inaugural issue consisted of only 14 mimeographed pages about the care and feeding of planarians, but it quickly grew. In addition to publishing dozens of memory transfer papers and related scholarship, McConnell welcomed humor and printed science fiction stories, rousing editorials, student-drawn planarian cartoons, spoof articles, and poems.

虽然《文摘》现在某种程度上已成为邪典经典,但这种混合内容让许多读者感到困惑。麦康奈尔最终将这份刊物一分为二,就像涡虫断尾再生一样,并将那本严肃的半本刊物更名为了《生物心理学杂志》(与1973年创立的现行同行评审期刊《生物心理学》无关)。但麦康奈尔作为异端和恶作剧者的名声已经根深蒂固。

While the Digest is now something of a cult classic, the mix proved confusing for many readers. McConnell eventually cut the publication in half, not unlike a planarian worm, and renamed the serious half The Journal of Biological Psychology (no relation to the current peer-reviewed journal Biological Psychology, founded in 1973). But McConnell’s reputation as a heretic and prankster was well established.

情况在20世纪60年代中期开始土崩瓦解。尽管麦康奈尔曾享有过一段时间的名望和资金支持——包括在密歇根大学获得终身教职的捷径——但试图复制其记忆转移的实验却得出了前后矛盾的结果。虽然许多人表面上取得了成功,但失败的案例却更加显眼。1965年,曾荣获诺贝尔奖的生物化学家梅尔文·卡尔文试图复制麦康奈尔的涡虫实验却以失败告终,当时他甚至得到了麦康奈尔几位前助手的协助,并使用了相同的装置。他高调发表的实验结果引发了一场激烈的争论,争论的焦点之一是如何正确处理涡虫。

The wheels started to come off in the mid-1960s. Although McConnell enjoyed a period of fame and funding—including an accelerated path to tenure at the University of Michigan—attempts to replicate his memory transfers yielded inconsistent results. While many apparently succeeded, the failures were more visible. In 1965, the Nobel Prize–winning biochemist Melvin Calvin tried to replicate McConnell’s worm experiments and failed, even with the help of some of McConnell’s former assistants and using the same device. His high-profile publication of the results sparked an acrimonious debate about, among other things, proper worm handling.

到20世纪70年代,涡虫记忆的热潮已经来来去去。科学家们已转向老鼠、猫、金鱼,甚至螳螂。研究人员通过将一只动物的大脑RNA注射到另一只动物体内,成功在老鼠身上实现了记忆转移,并将研究结果发表在《自然》和《科学》等权威期刊上,相比之下,涡虫模型显得不值一提。但当进一步的实验未能得出确凿结论时,人们对记忆转移这一问题的兴趣便逐渐消退。

By the 1970s, the planarian memory fad had come and gone. Scientists had moved on to rats, cats, goldfish, and even praying mantises. Researchers showing successful memory transfers in rats—by injecting brain RNA from one animal to another—had published their findings in prestigious journals such as Nature and Science, making the planarian model seem unimpressive in comparison. But when further experiments proved inconclusive, interest in the question of memory transfer petered out.

正如科学史学家哈里·柯林斯和特雷弗·平奇所说:“记忆转移从未被真正证伪;它只是不再占据科学界的想象。”麦康奈尔于1971年关闭了他的实验室,此后长期默默无闻,只在1985年一次被打破——那一年他成为“大学航空炸弹客”的受害者。(爆炸后他一度失去听力。)他于1990年去世。格什曼说,如果年轻一代的科学家听说过他的同类相食涡虫,那也是作为“神经科学家在睡前讲给学生、吓唬他们远离注定失败项目的警示故事”。

As the science historians Harry Collins and Trevor Pinch put it, “memory transfer was never quite disproved; it just ceased to occupy the scientific imagination.”McConnell closed his laboratory in 1971, and his long period of subsequent obscurity was broken only once, in 1985, when he became a victim of the Unabomber. (He lost his hearing temporarily after the blast.) He died in 1990. If a younger generation of scientists is familiar with his cannibal planarians, it’s as “a cautionary tale that neuroscientists tell to their students at bedtime to scare them away from ill-fated projects,” Gershman said.

尽管如此,麦康奈尔非传统的研究和反主流的态度仍在神经科学界流传,记忆转移的想法也仍然是人们私下着迷的话题。万一麦康奈尔真的成功地把一段记忆喂给了一条虫子呢?对于正在寻找方法在分子层面研究记忆并将其与可观察行为联系起来的格什曼来说,这个问题是一个必须挠一挠的痒处。他决定一劳永逸地解决这个问题。

Still, McConnell’s unconventional work and contrarian attitude has lingered in neuroscience lore, and the idea of memory transfer remains a subject of private fascination. What if McConnell really did manage to feed a memory to a worm? For Gershman, who is searching for a way to study memory at a molecular level and connect it to observable behavior, the question was an itch that had to be scratched. He decided to settle the matter once and for all.

这一切看起来很简单。2025年春天,格什曼与他的博士后之一马迪·斯奈德着手重复麦康奈尔的一名学生艾伦·雅各布森的涡虫训练方案。雅各布森的论文是扁形虫记忆转移时代最严谨的,格什曼和斯奈德严格遵照执行。“我们需要一个行为学基础来研究驱动这些极其不稳定的动物记忆的回路,”斯奈德说,“这些回路到底有没有被用于记忆巩固或存储?因为如果你失去了头部,所有这些回路都消失了,那么存储记忆的机制是什么?”

It all seemed straightforward enough. In the spring of 2025, Gershman and Maddie Snyder, one of his postdocs, set out to reproduce the worm-training protocol of one of McConnell’s students, Alan Jacobson. Jacobson’s papers were the most rigorous of the planarian memory transfer era, and Gershman and Snyder followed them to the letter. “We wanted a behavioral basis to be able to study the circuits that are driving memory in these extremely unstable animals,” Snyder said. “Are those circuits at all being used for memory consolidation or storage? Because if you lose your head and all those circuits are gone, then what is the mechanism of storing memory?”

然而,尽管他们尽了最大努力,他们还是没能做到雅各布森、麦康奈尔以及20世纪60年代许多其他人所做的事情:训练涡虫对光线作出身体收缩的反应。(他们在2026年4月将结果发表在biorxiv.org网站上。)“我对此真的百思不得其解,”格什曼说。他曾以为记忆转移会是实验中最棘手的部分——而不是一开始就让涡虫形成记忆。

Despite their best efforts, however, they couldn’t do what Jacobson, McConnell, and so many others had done back in the 1960s: condition the worms to scrunch their bodies in response to light. (They reported the results on biorxiv.org in April 2026.) “I was really scratching my head about this,” Gershman said. He’d assumed that the memory transfer would be the dodgy part of the experiment—not getting the worms to form a memory in the first place.

他们与其他扁形虫实验室进行了交流。他们尝试了不同的刺激。他们通过机器学习流程运行了扁形虫的录像。在绝望中,凯尔索和斯奈德甚至参观了哈佛科学博物馆,检查了一台老式的“感应器”,这是20世纪中期涡虫科学中使用的一种电击装置。但它没有提供任何线索。

They talked to other planarian labs. They tried different stimuli. They ran the planarian footage through a machine-learning pipeline. In desperation, Kelso and Snyder even visited the Harvard Science Museum to examine a vintage “inductorium,” an electric-shock contraption used in midcentury worm science. But it offered no clues.

凯尔索寻找了任何可能仍然在世的麦康奈尔的前合作者,通过一次运气,他找到了丹尼尔·金布尔和他妻子里瓦的联系方式,两人都曾在麦康奈尔的实验室工作过。如今他们已经九十多岁,住在俄勒冈州尤金市。当凯尔索打电话给他们时,他发现他们在20世纪60年代不仅做过许多麦康奈尔的实验,而且还将《涡虫跑者文摘》的整套印刷档案保存在地下室的一个箱子里。

Kelso searched for any of McConnell’s former collaborators who might still be alive, and through a stroke of luck he found contact information for Daniel Kimble and his wife, Reeva, who had both worked in McConnell’s lab. Now in their nineties, they live in Eugene, Oregon. When Kelso called them, he discovered that not only did they run many of McConnell’s experiments in the 1960s, but they’d also kept the entire print archive of The Worm Runner’s Digest in a box in their basement.

凯尔索和斯奈德购买了前往尤金的车票。两天之内,一边吃着自制饼干和无数杯茶,他们一边尽可能多地从金布尔夫妇那里汲取知识。在手动翻阅《消化》杂志旧期的间隙,他们附近溪流间穿梭,用砂锅装满含沙的淡水。回到金布尔夫妇的厨房桌前,两代科学家看着淤泥沉淀,看看会有什么蠕虫浮现出来。

Kelso and Snyder bought tickets to Eugene. Over the course of two days, while consuming plates of homemade cookies and countless cups of tea, they absorbed everything they could from the Kimbles. On breaks from hand-scanning back issues of the Digest, they went stream-hopping nearby and filled casserole dishes with silty fresh water. Back at the Kimbles’ kitchen table, the two generations of scientists watched the silt settle to see what worms might emerge.

毕竟,这就是麦康奈尔所做的。他没有使用实验室培养的扁虫,而是从密歇根大学附近的一个湖泊中获取。因此,为了不留任何死角,凯尔索最后一次前往密歇根州麦康奈尔的旧钓鱼场。他带回了装满蠕虫的塑料试管,但没有一条是“学习者”。“到某个时候,我们大约有12种不同的扁虫品系,没有一种显示出任何学习能力,”格肖曼说。

This, after all, is what McConnell did. Rather than using laboratory strains of planarians, he sourced his from a lake near the University of Michigan. And so, not wanting to leave any stone unturned, Kelso made one final trip to McConnell’s former fishing grounds in Michigan. He returned with plastic tubes full of worms, but not a single one was a learner. “At some point, we had like 12 different strains of planaria, none of which showed any learning,” Gershman said.

据斯奈德讲述,金布尔夫妇深信他们在1960年代的条件反射实验取得了成功。蠕虫学会了——他们确信无疑。那个时代的文献似乎支持他们的确信;至少有36个实验室报告了类似结果。那么,为什么当今天用完全相同的实验、相同的实验室规程,甚至使用相同的蠕虫——从密歇根州同一片水域捕获——来做这些实验时,扁虫却完全无法被教育?

As Snyder tells it, the Kimbles were absolutely convinced that their conditioning experiments in the 1960s had worked. The worms learned—they were sure of it. The literature of the era seems to support their certainty; at least 36 labs reported similar results. So why is it that when the exact same experiments are done today, using the same laboratory protocol and even the same worms, fished from the same Michigan waters, planarian worms are utterly uneducable?

斯奈德表示,一种解释是,麦康奈尔、金布尔夫妇以及所有其他“涡虫研究者”在记录涡虫行为时的评分标准并不一致,可能把一些无害的涡虫“转身”误认为是光反应中明确的“收缩”。毕竟,每位科学家都是其时代的产物,会受到社会条件、资金压力,以及在本案中一位极具个人魅力的领导者以无数通常隐蔽的方式所影响。

One explanation, Snyder said, is that McConnell, the Kimbles, and all the other “worm runners” were inconsistent in how they scored the planarians’ behavior and may have misinterpreted more anodyne worm “turns” for the definitive “scrunch” of the light reaction. Every scientist is a product of their time, after all, influenced in myriad, often invisible ways by sociological conditions, funding pressures, and, in this case, a highly charismatic leader.

这种解读让斯奈德对自身潜在的偏见保持了高度警惕。“在整个项目期间,”她对我说,“我都在想:‘在我们当前对神经科学的模型中,在我们对已知和未知的各种假设中,有哪些是我现在视为理所当然、而我真正应该去注意的?’”一种可能性较小的推测是,涡虫本身在过去六十年里发生了某种改变——沦为了污染或遗传漂变的受害者。

This interpretation made Snyder hyperaware of her own potential biases. “Throughout this entire project,” she told me, “I was like, ‘What are the things that I am taking for granted now in our models of neuroscience, and our assumptions of what is known and unknown, that I should really notice?’”A more remote possibility is that planarian worms themselves have somehow changed over the last six decades—falling victim to pollution or genetic drift.

格什曼认为这种情况不太可能发生。“一帮研究人员恰好在这个现象发生的特定时间段开展这些研究,这种几率有多大?”他带着怀疑的语气问道,“在涡虫长达数百万年的进化历程中,他们就偏偏运气好到了极点?然后我们的好运气就用光了?”无论原因如何,到2026年,尽管拥有神经系统和简单的脑部,涡虫依然不会学习。

Gershman finds this scenario unlikely. “What are the chances that a bunch of researchers just happened to do these studies at the particular time when this phenomenon happened?” he asked, incredulous. “They just got extremely lucky, in the millions of years of planarian evolution? And then our luck ran out?”No matter the reason, in 2026, despite their nervous system and simple brains, planarians don’t learn.

从演化的角度来看,这其实可能合乎情理。“我们在某种程度上学习建立关联,是为了能够预测危险并避开它,”斯奈德说道。但涡虫与危险的关系则有所不同。它们强大的再生生理机能——这对麦康奈尔的实验至关重要——能保护它们免受钝性创伤。被咬成两半后,它们能直接重新长出来。对于这样一种生物,记忆有什么用呢?“那是另一个哲学难题,”她说。

From an evolutionary perspective, this might actually make sense. “The reason that we learn associations, to some degree, is so that we can predict danger and avoid it,” Snyder said. But planarians have a different relationship to danger. Their regenerative physiology, so key to McConnell’s experiments, protects them from blunt trauma. Bitten in half, they simply grow back. What use is memory to such a creature? “That’s a whole other philosophical conundrum,” she said.

现在正是与这类难题较量的好时机。涡虫学习可能是一条死胡同,但针对其他生物的记忆转移实验正重新成为科学界的热门——而且这些实验似乎正在奏效。2018年,加州大学洛杉矶分校的神经科学家戴维·格兰茨曼对海兔(Aplysia californica)进行了一次记忆移植。海兔因神经系统相对简单、神经元巨大而成为记忆研究中备受青睐的模式生物。

It’s a great time to be wrestling with such conundrums. Planarian learning may be a dead end, but memory transfer experiments with other organisms are back in scientific vogue—and those experiments appear to be working. In 2018, the neuroscientist David Glanzman of the University of California, Los Angeles, performed a memory transplant on the sea slug Aplysia californica, a darling model organism for memory research owing to its relatively simple nervous system and gigantic neurons.

在训练这些海兔对尾部电击作出反应后,格兰茨曼通过直接注射遗传物质,将敏化从一只海兔转移到了另一只身上。这表明记忆的某些方面储存在RNA中,这正是麦康奈尔的主张。

After training the slugs to respond to a shock to their tails, Glanzman was able to transfer the sensitization from one slug to another via a direct injection of genetic material. This suggested that some aspect of the memory was stored in RNA, which was McConnell’s contention.

随后,在2021年,普林斯顿大学遗传学家科琳·墨菲发现,秀丽隐杆线虫(Caenorhabditis elegans)——一种拥有302个神经元的微小线虫——可以通过食用那些以惨痛代价学到经验的同类打成浆的线虫,甚至只是在其中游动,来学会避开一种致病细菌。墨菲团队发现了一种名为Cer1的逆转录转座子,即一段跳跃的遗传物质,她说它似乎在个体之间“携带记忆”。

Then, in 2021, the Princeton University geneticist Coleen Murphy found that Caenorhabditis elegans worms—microscopic roundworms with 302 neurons to their name—could learn to avoid a pathogenic bacterium by eating, or even just swimming around in, pureed worms who had learned the hard way. Murphy’s group identified a retrotransposon, a jumping segment of genetic material, called Cer1, that appears to “carry a memory” between individuals, she said.

几年后,印度科学研究所的一个团队发表论文称,经过训练的秀丽隐杆线虫会释放细胞外囊泡——含有遗传信息的小脂质颗粒——从而将它们的训练传递给未受过训练的同类。

A few years later, a group at the Indian Institute of Science published a paper suggesting that trained C. elegans worms release extracellular vesicles—small lipid particles containing genetic information—that can impart their training to their naïve counterparts.

这些研究人员中没有一位有麦康奈尔一半的张扬,但他们的工作表明,他关于蠕虫记忆的看法也许终究是对的。他只是押错了蠕虫的种类,并在证据不一致的情况下仍加倍下注。最终,他失去了名声,但他那十足的热情激发了另一位非常规科学家的好奇心。幸运的是,这位科学家遵循着证据。

None of these researchers are half as flashy as McConnell was, but their work indicates that he may have been right about worm memory after all. He just bet on the wrong kind of worm—and doubled down on it, despite inconsistent evidence. In the end, he lost his reputation, but his sheer gusto sparked the curiosity of another unconventional scientist. Fortunately, this one’s following the evidence.

在哈佛大学,格什曼正将他的研究重点从难以捉摸的涡虫转移到更易读懂的秀丽隐杆线虫身上。它可能在被切成两半时无法再生,但秀丽隐杆线虫是神经科学中长期使用的模式生物——并且已被持续证明具备学习能力。随着新实验的展开,格什曼保持着谨慎的乐观。“我只希望我们没有陷入另一个死胡同,”他对我说道。另一方面,一个虫洞(wormhole)——那是确定无疑的。

At Harvard, Gershman is shifting his focus from the inscrutable planarian to the more legible C. elegans. It may not regenerate when it’s cut in half, but C. elegans is a long-standing model organism in neuroscience—and it’s been consistently shown to learn. With new experiments underway, Gershman is cautiously optimistic. “I just hope we’re not going down another rabbit hole,” he told me. A wormhole, on the other hand—that’s for certain.

原文经《量子杂志》(Quanta Magazine)许可转载。《量子杂志》是西蒙斯基金会(Simons Foundation)下属的一个编辑独立的出版物,其宗旨是通过报道数学、物理以及生命科学的研究进展与趋势,来增进公众对科学的理解。

Original story reprinted with permission from Quanta Magazine, an editorially independent publication of the Simons Foundation whose mission is to enhance public understanding of science by covering research developments and trends in mathematics and the physical and life sciences.

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