大脑的模样：大脑类器官正变得越来越像真正的大脑

What is a brain?

什么是大脑？

Synchronicity

同步性

Cerebral organoids are becoming more brainlike

大脑类器官正变得越来越像真正的大脑

At what point does a mass of nerve cells growing in a laboratory Petri dish become a brain? That question was first raised seriously in 2013 by the work of Madeline Lancaster, a developmental biologist at the Medical Research Council's Laboratory of Molecular Biology, in Cambridge, Britain. That year Dr Lancaster and her colleagues grew the first human-derived “cerebral organoid”. They did so using pluripotent human stem cells, which are cells that have the potential to develop into any type of tissue in the human body. The researchers coaxed these cells into becoming nervous tissue that organised itself, albeit crudely, as structures which had some of the cell types and anatomical features of embryonic human brains.

实验室培养皿中培育的神经细胞群到底在何种程度下才能变成大脑呢？2013年，英国剑桥医学研究委员会分子生物学实验室的发育生物学家马德琳·兰卡斯特，在她的研究中首次且严肃地提出了该问题。那一年兰卡斯特博士和她的同事们培育出了第一个由人类衍生出的“大脑类器官”。他们通过使用多功能人类干细胞做到了这一点，这类细胞有潜力发展成任何类型的人体组织。研究人员将这些细胞诱导成可自我有机化的神经组织，虽然很粗糙，但它们的结构中具有胚胎人脑的某些细胞类型和解剖学特征。

The twitch Since then, Dr Lancaster's work has advanced by leaps and bounds. In March, for example, she announced that her organoids, when they are connected to the spinal cord and back-muscle of a mouse, could make that muscle twitch. This means cerebral organoids are generating electrical impulses. And other scientists are joining the fray. One such, Alysson Muotri of the University of California, San Diego, has published this week, in Cell Stem Cell, a study that looks in more detail at cerebral-organoid electrical activity.

从那之后，拉卡斯特博士的研究进展一路高歌。例如，今年三月份她宣布她培育的类器官在连接老鼠的脊椎和背部肌肉时，可以使肌肉抽搐。这说明“大脑类器官”正在产生电脉冲。随后其他科学家也加入了这场科学潮流。来自加州大学圣地亚哥分校的（UCSD）艾利松▪莫特里便是其中一位，本周他在期刊《细胞--干细胞》发表了一项研究，更详细地研究了大脑类器官的脉冲活动。

To carry out their study, Dr Muotri and his colleagues grew and examined hundreds of organoids, each a mere half-millimetre in diameter, over the course of ten months. To probe individual neurons within these, they used tiny, fluid-filled pipettes that acted as electrodes small enough to maintain contact with the surface of an individual cell.

为了开展他们的研究，莫特里的博士团队在十个月的时间里，培育并研究了数百个直径仅为半毫米的类器官。为了将单个神经元注入这些类器官中，他们使用微型、载满液体的移液器作为电极，这些电极可以小到足以与单个细胞的表面保持接触。

Neurons probed in this way proved electrically active, so the researchers went on to employ arrays of electrodes inserted simultaneously into different parts of an organoid to study its overall activity. They looked in detail, once a week, at each of the organoids that were chosen for examination. This revealed that, by six months of age, the electrical activity in different parts of an individual organoid had become synchronised.

实验证明，植入的神经元是有电活性的，因此研究人员继续将电极阵列同时插入类器官中的不同部位，以研究类器官的整体电活性。他们每周都会仔细观察被选作研究对象的类器官。观察结果表明，六个月后，不同部位的电活动在单个类器官已经同步。

Such synchronicity is also a feature of real brains, including those of preterm human infants of about the same age as Dr Muotri's organoids. It is regarded as an important part of healthy brain function. So, to check how similar natural and organoid brain waves actually are, the research team ran those waves obtained from their organoids through a computer program that had previously been trained to recognise the electrical activity generated by the brains of premature babies. This algorithm proved able to predict to within a week the ages of laboratory-grown organoids 28 or more weeks old. That suggests those organoids are indeed growing in a manner similar to natural human brains.

这种同步性也是真正大脑的特征之一，包括那些早产儿的大脑，他们与莫特里培育的类器官发育时间相仿。同步性被认为是大脑功能健全的重要组成部分。因此，为了检验自然脑电波和大脑类器官电波的相似程度，该研究小组通过一个电脑程序去运行类器官中获得的电波，而该程序之前被用于识别早产儿大脑的脉冲活动。实验证明，该算法能够在一周内预测实验室培养的类器官的年龄，即28周或28周以上。这表明这些类器官确实在以类似于自然人脑的方式生长。

If further research confirms this opinion, then for medical science that conformity with natural development could be a boon. Neuroscientists have long been held back by the differences between human brains and those of other animals—particularly the brains of rodents, the analogue most commonly employed in medical research. The purpose of the work that Dr Lancaster, Dr Muotri and others involved in the field are engaged in has always been to produce better laboratory models of neurological and psychiatric diseases, so that treatments may be developed.

如果研究进一步证实这一观点，那么对于医学科学来说，这种与自然人脑发育的一致性可能是一种福音。神经科学家长久以来一直困扰于人类大脑与其他动物大脑之间的差异，尤其是啮齿类动物的大脑，因为它们是医学研究中最常用的类似物。兰卡斯特博士、莫特里博士和其他这一领域的工作者正在从事的这一研究，他们的目的始终是建立更好的神经和精神疾病的实验室模型，以便开发治疗方法。

And, although it may be some time in the future, there is also the possibility that organoids might one day be used as transplant material in people who have had part of their brains destroyed by strokes.

虽然可能还比较遥远，但未来某一天，类器官也许能被用于移植材料，治疗那些因中风而大脑部分受损的人。

For ethicists, however, work like this raises important issues. A sub-millimetre piece of tissue, even one that displays synchronised electrical pulsing, is unlikely to have anything which a full-grown human being would recognise as consciousness. But if organoids grown from human stem cells start to get bigger than that, then the question that was posed back in 2013 becomes pressing.

然而，对于伦理学家来说，这样的研究引出了一些重要的问题。一个亚毫米的组织，即使能显示同步电脉冲，也不可能产生任何一个成年人类能辨作意识的东西。但是，如果由人类干细胞培育出的类器官变得比一个亚微米要大，那么早在2013年提出的问题会变得愈发紧迫。