Meet a mouse whose brain cortex is made up of human cells

认识一只大脑皮层由人类细胞组成的老鼠

EXECUTIVE SUMMARY Multiple cameras tracked a mouse as it wandered around a small arena. A computer charted its position and speed, leaving Pong-like traces on a monitor. The reason to watch this rodent so carefully? Nearly half its brain volume had been replaced with human cells.

执行摘要 多台摄像机追踪着一只在小型竞技场中徘徊的老鼠。计算机记录了它的位置和速度，并在显示器上留下了类似《乒乓》（Pong）游戏的轨迹。为什么要如此仔细地观察这只啮齿动物？因为它的脑容量中近一半已被人类细胞所取代。

The effort to mix the brain tissues of distant species is being reported today in the journal Nature by a team at Stanford University, led by neuroscientist Sergiu Pașca. Pașca’s group previously showed that human brain “organoids”—small blobs of neural tissue—could survive, and even function, after being injected into the heads of baby rodents.

这项混合不同物种脑组织的尝试由斯坦福大学神经科学家 Sergiu Pașca 领导的团队完成，并于今日发表在《自然》（Nature）杂志上。Pașca 的团队此前曾证明，人类大脑“类器官”（即一小团神经组织）在被注射到幼年啮齿动物头部后，能够存活甚至发挥功能。

Now, Pașca has taken things a step further by genetically modifying mice so their brains don’t fully develop in the first place. These modified mice are missing most cells of both the cortex and the hippocampus, two key brain areas. That creates much more room for the human cells to take hold, he says. “Human cells that are placed in these animals will divide, will grow, and within a few weeks to a few months they will take most of that space,” he says.

现在，Pașca 更进一步，通过基因改造使小鼠的大脑在发育初期就无法完全形成。这些经过改造的小鼠缺失了大脑两个关键区域——皮层和海马体——的大部分细胞。他说，这为人类细胞的植入创造了更多空间。“植入这些动物体内的人类细胞会分裂、生长，并在几周到几个月内占据大部分空间，”他说。

Pașca says one surprising discovery is that the mice lacking brain tissue seemed fairly normal—they walked around and squeaked. But they did have memory problems. In a maze test, they couldn’t remember what parts they’d explored. The mice with the added human cells, by contrast, performed better on the maze test. That means the human tissue is playing some role in the animals’ cognition.

Pașca 表示，一个令人惊讶的发现是，那些缺失脑组织的小鼠看起来相当正常——它们会四处走动并发出吱吱声。但它们确实存在记忆问题。在迷宫测试中，它们无法记住自己探索过的区域。相比之下，植入了人类细胞的小鼠在迷宫测试中表现更好。这意味着人类组织在动物的认知中发挥了一定作用。

Pașca believes what he is calling “xenocortical mice” could be useful in studying brain injuries. However, the report is also a dramatic demonstration of “the combined power of genetic engineering and stem-cell technology to reshape biology,” says Carsten Charlesworth, a scientist who works in a different Stanford lab and was not involved in the research.

Pașca 认为，他所称的“异种皮层小鼠”（xenocortical mice）可能有助于研究脑损伤。然而，未参与该研究的斯坦福大学另一实验室科学家 Carsten Charlesworth 表示，这份报告也戏剧性地展示了“基因工程与干细胞技术相结合以重塑生物学的力量”。

Already, brain organoids are being tested in labs to see if they can be connected to computers to play video games. Other scientists have proposed using them like replacement parts to treat stroke victims. “What’s most remarkable to me is the extent to which human neural tissue introduced after birth grew and connected with the mouse nervous system across a species barrier,” says Charlesworth. “As these technologies advance, they’ll increasingly force us to challenge our traditional assumptions.”

目前，实验室正在测试大脑类器官是否可以连接到计算机上玩电子游戏。其他科学家则提议将其作为“替换零件”来治疗中风患者。“令我最震惊的是，出生后植入的人类神经组织竟然能够跨越物种障碍，在小鼠神经系统中生长并建立连接，”Charlesworth 说，“随着这些技术的进步，它们将日益迫使我们挑战传统的假设。”

Last year, Pașca convened a group of ethics experts to study the implications of neural organoid technology, including the odds that an animal could develop human consciousness and the risk that “organoid therapy clinics” might offer scam treatments to desperate patients. For now, he says, he’s not concerned that the rodents have any type of human cognitive capacities. That is because their brains are relatively tiny and the evolutionary distance between man and mouse is so great.

去年，Pașca 召集了一组伦理专家来研究神经类器官技术的潜在影响，包括动物产生人类意识的可能性，以及“类器官治疗诊所”可能向绝望的患者提供欺诈性治疗的风险。他表示，目前他并不担心这些啮齿动物会具备任何类型的人类认知能力。这是因为它们的大脑相对微小，且人类与小鼠之间的进化距离非常遥远。

But that’s also why Pașca says this type of experiment should not be carried out on higher species: They could end up with large volumes of functioning human brain tissue, potentially blurring the cognitive boundaries between people and animals. Pașca specifically cautioned against adding human brain organoids to a monkey engineered to lack a cortex. “One of the things that I see as a very clear red line is doing this experiment in a primate,” he says. “I don’t think that is justified at this point in any way.”

但这也是 Pașca 认为此类实验不应在更高级物种身上进行的原因：它们最终可能会拥有大量功能性的人类脑组织，从而可能模糊人类与动物之间的认知界限。Pașca 特别警告不要将人类大脑类器官植入经过基因改造、缺失皮层的猴子体内。“我认为在灵长类动物身上进行这项实验是一条非常明确的红线，”他说，“我不认为目前有任何理由证明这样做是合理的。”