Have doctors been wrong about how to treat Alzheimer’s disease?

医生们治疗阿尔兹海默症的方法是否一直存在谬误？

A new book argues that dogma and bad science led Alzheimer’s research astray

一本新书揭露：教条主义与伪科学如何将阿尔兹海默研究引入歧途

Alzheimer’s disease affects more than 30m people worldwide, mostly the elderly. After the age of 65, the chance of developing it doubles every five years. By 85, the odds are one in three. 

阿尔兹海默症影响着全球超3000万人，患者多为老年人。65岁后罹患此病的风险每五年翻一番，85岁人群患病率高达三分之一。

Its symptoms, which include memory loss, difficulty with basic tasks and depression, progressively worsen. As global life expectancy rises, so will cases of Alzheimer’s, making it one of the big public-health challenges of an ageing world.

其症状包括记忆衰退、基础行动困难与抑郁情绪，且会持续恶化。随着全球预期寿命延长，阿尔兹海默症病例将持续攀升，成为老龄化社会面临的重大公共卫生挑战。

There is no cure. Between 1995 and 2021, around $42bn was poured into more than 1,000 clinical trials. Yet only a handful of drugs has made it to market. Even those mostly treat the symptoms of the disease, rather than stop it.

目前该病尚无根治之法。1995至2021年间，超420亿美元资金投入到1000多项临床试验，但仅有寥寥数款药物成功上市。即便获批药物也仅能缓解症状，无法阻止病程发展。

The leading explanation of Alzheimer’s is the “amyloid hypothesis”, which suggests that deposits of beta-amyloid, a type of protein, accumulate between neurons and disrupt their function. 

主流理论"淀粉样蛋白假说"认为，β-淀粉样蛋白在神经元间沉积导致功能紊乱。

But the theory remains controversial: all brains with Alzheimer’s show beta-amyloid plaques, yet not everyone with these plaques experiences cognitive decline. Whether amyloid build-up causes Alzheimer’s, or is merely a symptom, remains unresolved.

但该理论始终存在争议：所有阿尔兹海默患者脑部均存在淀粉样斑块，但具有此类斑块者未必都会出现认知衰退。淀粉样蛋白堆积究竟致病还是仅为病症表现，至今未有定论。

In “Doctored” Charles Piller, a science journalist, details how groupthink and dishonesty steered Alzheimer’s research off course. In 2006 a Nature paper by researchers at the University of Minnesota appeared to provide a major breakthrough. The study claimed that a subtype of beta-amyloid caused memory impairment. It quickly became one of the most cited papers and inspired hundreds of millions of dollars in public-research grants. 

科学记者查尔斯·皮勒在《篡改的科学》一书中详述了群体思维与学术不端如何扭曲阿尔兹海默研究。2006年明尼苏达大学研究团队在《自然》发表的论文看似取得重大突破，声称某种β-淀粉样亚型会导致记忆损伤。这篇高被引论文催生了数亿美元公共研究经费。

Another influential paper published in 2012 by scientists associated with Cassava Sciences, a biotech firm, bolstered the amyloid theory by linking insulin resistance to amyloid plaque formation. The finding fuelled a wave of research into the idea of Alzheimer’s being a “diabetes of the brain” that could be managed with drugs. There was just one problem—both studies were based on falsified data.

2012年生物科技公司木薯科学关联科学家发表的另一重磅论文，通过论证胰岛素抵抗与淀粉样斑块形成的关联进一步巩固该假说，引发"脑部糖尿病"治疗理念的研究热潮。但问题在于——两项研究均基于伪造数据。

“Doctored” follows Mr Piller’s investigation into the deception. Central to the story is a group of image sleuths, with a sharp eye for manipulated pixels of Western blots (a lab technique used to study proteins, which were doctored in the studies). 

《篡改的科学》记录了皮勒对学术造假的调查历程。故事核心是一群图像侦探，他们以专业眼光识别蛋白质印迹实验（研究中遭篡改的蛋白质检测技术）的像素篡改痕迹。

Some chapters read like a scientific whodunnit. In one, Mr Piller has to work hard to earn the trust of a reluctant whistleblower. In another, he travels to Prague for a private meeting with a group of image detectives with cryptic pseudonyms.

部分章节犹如科学探案：皮勒需费尽周折赢得泄密者信任；又专程赴布拉格与化名神秘的图像分析专家秘密会面。

Despite clear evidence of manipulated research results, journals and regulators were slow to act. Mr Piller blames powerful backers of the amyloid hypothesis who ignored red flags. 

尽管篡改证据确凿，期刊与监管机构却反应迟缓。皮勒指责淀粉样假说的权势支持者刻意忽视危险信号。

It was only in June 2024—two years after allegations first surfaced—that the Nature paper was retracted by its authors. Cassava Sciences, while denying wrongdoing, stopped trials of its Alzheimer’s drug, Simufilam, in November after it failed to show clinical benefits.

首起学术不端指控浮现两年后，《自然》论文才于2024年6月被作者撤回。木薯科学虽否认过失，其药物Simufilam因缺乏临床疗效已于去年11月终止试验。

These papers’ consequences go beyond the lab. For patients and their families, experimental treatments often represent a final lifeline. Encouraging people to pin their hopes on medicines that are ineffective, or even unsafe, is a betrayal. Fixation on a theory offering limited success in human trials may also have diverted resources from other more promising therapies.

这些论文的影响远超实验室范畴。对患者家庭而言，实验性疗法常是最后希望。诱导人们寄望于无效甚至危险的药物实属背叛。执着于临床试验屡屡受挫的理论，可能已挤占其他更具前景疗法的研发资源。

Since 2023 the Food and Drug Administration, America’s drug regulator, has approved two new medicines that modestly slowed cognitive decline by attacking the amyloid plaques. 

2023年以来，美国食药监局批准了两款通过清除淀粉样斑块延缓认知衰退的新药。但部分患者出现脑肿胀、脑出血等严重副作用。

They also come with dangerous side-effects for some, which include brain swelling and bleeding. Mr Piller remains sceptical of these treatments. So will many of his readers, after his gripping story of medical groupthink and warped incentives.

皮勒对这些疗法持怀疑态度。随着这部揭露医学界群体思维与扭曲激励机制的作品问世，相信众多读者也将产生同样疑虑。

（红色标注词为重难点词汇）

重难点词汇：

bolster [ˈboʊlstər] n. 长枕；支持物 v. 支持；增强；巩固
sleuth [sluːθ] n. 侦探；私家侦探 v. 像侦探般调查；搜寻
whodunnit [ˈhuːdʌnɪt] n. 侦探小说；推理小说
reluctant [rɪˈlʌktənt] adj. 不情愿的；勉强的
whistleblower [ˈwɪslbloʊər] n. 告密者；检举者；揭发者
betrayal [bɪˈtreɪəl] n. 背叛；出卖；辜负
warp [wɔːrp] n. 弯曲；变形 v. 弯曲；变形；歪曲（事实等）