The UK’s Answer to Darpa Wants to Rewire the Human Brain

英国版“DARPA”计划重塑人类大脑

The UK’s Advanced Research and Innovation Agency (ARIA) was established in 2023 with the goal of pursuing “high-risk, high-reward” moonshots in sectors ranging from bolstering food security to new ways of ramping up human immunity. 英国高级研究与创新署（ARIA）成立于2023年，旨在追求从加强粮食安全到提升人类免疫力等各个领域的“高风险、高回报”登月计划。

With more than £1 billion (about $1.3 billion) worth of government funding earmarked between now and 2030, one of ARIA’s most ambitious programs is a £69 million initiative that aims to develop more tailored ways of modulating the human brain. The hope is to eventually address an entire range of disorders, from epilepsy to Alzheimer’s. 在2030年前，该机构已获得超过10亿英镑（约合13亿美元）的政府拨款。其中最雄心勃勃的项目之一是一项耗资6900万英镑的计划，旨在开发更具针对性的人类大脑调节方法，最终目标是解决从癫痫到阿尔茨海默病等一系列疾病。

Reports have previously estimated that this suite of neurological conditions costs the UK economy tens of billions of dollars each year. According to ARIA program director Jacques Carolan, the unifying link is that they are all disorders of brain circuitry. 此前有报告估计，这一系列神经系统疾病每年给英国经济造成数百亿美元的损失。ARIA项目总监雅克·卡罗兰（Jacques Carolan）表示，这些疾病的共同点在于它们都是大脑回路的紊乱。

“Sometimes there are circuits that are overconnected, that are underconnected, there’s different brain regions that are at play, there’s different cell types,” Carolan said, speaking at WIRED Health in London on April 16. “Our current set of interventions just don’t have the precision we need. The vision of the program is, ‘Can we build more precise neurotechnologies to interface at the circuit level?’” “有时是回路连接过度，有时是连接不足，涉及不同的大脑区域和不同的细胞类型，”卡罗兰在4月16日于伦敦举行的WIRED Health大会上说道。“我们目前的干预手段缺乏所需的精度。该项目的愿景是：‘我们能否构建更精确的神经技术，在回路层面进行交互？’”

So far, ARIA’s broad-brush approach to this particular moonshot has seen them fund 19 different teams. They’re working on ideas ranging from the use of ultrasound as a novel way to “biotype” a particular patient’s brain, to unique methods of deep brain stimulation that could both protect and regenerate different brain regions. 到目前为止，ARIA针对这一特定登月计划采取了广泛布局，资助了19个不同的团队。他们的研究方向涵盖了利用超声波作为“生物分型”特定患者大脑的新方法，以及能够保护和再生不同大脑区域的独特深部脑刺激技术。

At WIRED Health, Carolan highlighted the potential of ultrasound technologies not only to modulate the brain, but to allow scientists to obtain new information about the brain’s circuitry in a particular patient. One ARIA-funded team at Imperial College London is working on a project combining ultrasound and gene therapy to try to image gene expression in real-time in neurons, potentially enabling scientists to get a far more detailed picture of why certain brain networks are malfunctioning. 在WIRED Health大会上，卡罗兰强调了超声波技术的潜力，它不仅能调节大脑，还能让科学家获取特定患者大脑回路的新信息。伦敦帝国理工学院的一个ARIA资助团队正在进行一项结合超声波和基因疗法的项目，试图实时成像神经元中的基因表达，这可能使科学家能够更详细地了解某些大脑网络功能失调的原因。

Over the past 25 years, the idea of implanting electrodes deep within the brain and using them to stimulate a particular region, known as the basal ganglia, has emerged as a novel treatment for patients with advanced forms of Parkinson’s disease. It has provided a new avenue for managing motor symptoms when drug treatments no longer work. In future, Carolan claims, similar approaches could be used for a range of other debilitating neurological conditions, a concept which he views as the future of neurotherapeutics. 在过去25年里，将电极植入大脑深处并刺激特定区域（即基底神经节）的想法，已成为治疗晚期帕金森病患者的一种新疗法。当药物治疗失效时，它为控制运动症状提供了新途径。卡罗兰声称，未来类似的方法可用于治疗其他一系列严重的神经系统疾病，他认为这就是神经治疗学的未来。

“What people have discovered is that the same technology can actually be used to treat potentially things like depression, addiction, epilepsy, a whole series of intractable conditions,” he said. “It’s proof that we can have platform technologies that can address a broad range of conditions.” “人们发现，同样的技术实际上可以用来治疗抑郁症、成瘾、癫痫以及一系列顽固性疾病，”他说。“这证明我们可以拥有能够解决多种疾病的平台技术。”

Given the lofty nature of ARIA’s goals, many have questioned how to evaluate whether its programs ultimately succeed or fail. But as Kathleen Fisher, ARIA’s CEO, pointed out at WIRED Health, there may well be downstream benefits of these research investments which are completely unexpected. 鉴于ARIA目标的宏大，许多人质疑如何评估其项目最终是成功还是失败。但正如ARIA首席执行官凯瑟琳·费舍尔（Kathleen Fisher）在WIRED Health上指出的那样，这些研究投资可能会带来完全意想不到的后续效益。

Fisher, who previously worked at Darpa, the US Department of Defense agency on which ARIA has been modeled, noted the high-impact potential of early government investments. In 2013, Darpa awarded a grant for up to $25 million to facilitate the development of vaccine platforms that could be developed with unprecedented speed. 费舍尔曾在美国国防部高级研究计划局（DARPA）工作，ARIA正是以该机构为蓝本建立的。她指出了早期政府投资的高影响力潜力。2013年，DARPA授予了一笔高达2500万美元的拨款，用于促进疫苗平台的开发，使其能够以空前的速度进行研发。

“That company was Moderna,” Fisher recalled. “That technology was mRNA, technology that came online just in time for Covid.” The subsequent rollout of these vaccines went on to save countless deaths during the Covid-19 pandemic. “那家公司就是莫德纳（Moderna），”费舍尔回忆道。“那项技术就是mRNA，它恰好在新冠疫情期间投入使用。”随后这些疫苗的推广在新冠疫情期间挽救了无数生命。

Fisher’s goal is that by the early 2030s, ARIA will have already begun to show “seedlings of societal impact” either in its brain research or another area of focus that make it a no-brainer for the UK government to renew the agency’s funding. 费舍尔的目标是，到2030年代初，ARIA在脑科学研究或其他重点领域已经开始展现出“社会影响的萌芽”，这将使英国政府毫不犹豫地继续为该机构提供资金。

“It might be that we’re starting to see trials that show we can do [brain] circuit-level interventions in a way that doesn’t require surgery,” Fisher said. “Will we get all the way in seven years? Probably not, but we could have enough evidence that it’s going to be possible.” “我们可能开始看到一些试验，证明我们可以在不需要手术的情况下进行[大脑]回路层面的干预，”费舍尔说。“我们能在七年内完全实现吗？可能不会，但我们或许能获得足够的证据，证明这是可能的。”