671. 为什么阿尔茨海默病的进展如此缓慢？

你最近可能看到新闻了，美国FDA刚批准了两种新型血液检测，能在早期就发现阿尔茨海默病的迹象。

You may have seen the news recently about two new FDA approved blood tests that may detect Alzheimer's disease in the early stages.

任何疾病早发现都重要，但阿尔茨海默病尤其关键，因为它在出现症状前，可能已经在大脑里悄悄发展二十年了。

Early detection is important for any disease, but especially for Alzheimer's, which can take root for twenty years before symptoms develop.

这些症状，你应该也听说过，比如健忘，还有认知、生理和行为上的各种问题。

These symptoms, as you probably know, include memory loss and other cognitive, physiological, and behavioral issues.

我猜你了解这些，是因为美国现在有七百多万人患阿尔茨海默病，绝大多数都超过65岁了。

The reason I say that you probably know these symptoms is because Alzheimer's affects more than seven million people in The US, most of them 65.

年龄导致的记忆衰退自古就有，但直到1906年，德国医生阿洛伊斯·阿尔茨海默才首次正式记录下这种病。

Age related memory loss has been seen throughout human history, but the disease was not formally documented until nineteen o six by the German physician, Alois Alzheimer.

阿尔茨海默在解剖一位有健忘和幻觉的女性大脑时，发现她的脑组织明显萎缩，里面布满缠结和他称之为‘异常沉积物’的东西。

When Alzheimer autopsied the brain of a woman who had had memory loss and hallucinations, he found that her brain had shrunk and withered with numerous tangles and what he called peculiar deposits.

从那以后，科学家们就一直在琢磨这些沉积物和缠结到底是什么。

Scientists have been trying to figure out those deposits and tangles ever since.

美国国立卫生研究院每年在阿尔茨海默病和痴呆症研究上，投入大约40亿美元。

The National Institutes of Health spends around $4,000,000,000 a year on Alzheimer's and dementia research.

这比十年前的十亿美元高出不少，现在仅次于癌症研究的投入，这也合理，毕竟美国的老年人口庞大而且还在不断增加。

That's up from around $1,000,000,000 a decade ago, and that puts it second only to cancer spending, which makes sense because the elderly population in The US is big and getting bigger.

目前大部分阿尔茨海默病的研究都围绕着一个主流理论展开。

Much of this Alzheimer's research is centered around one dominant theory of the disease.

但如果这个理论根本就是错的呢？

But what if that theory is flawed?

这些药根本没让任何人好转。

No one's getting better with these drugs.

所有做这行的科学家、临床医生都会这么说。

Every scientist who works with them, every clinician will say the same.

要是他们不说，那就是在撒谎。

If they don't, they're lying.

所以‘错误’这个词还够准确吗？还是说，这根本就是欺诈？

So is flawed even the right word, or should it be fraud?

骗子嘛，总是会继续骗下去的。

Cheaters tend to cheat.

一旦我们发现某篇论文，或者一组论文里有明显的问题，这些问题往往会蔓延到这个人整个研究工作中。

When we find clear, overt problems in a paper, in a group of papers, often it propagates through somebody's entire work.

今天在《魔鬼经济学》播客中，我们追踪了一项调查，揭露了数十年来阿尔茨海默病研究中存在的诸多问题，同时带着一份经过验证的希望，探讨一下这种病的治疗未来该往哪儿走。

Today on Freakonomics Radio, we follow an investigation that found decades of problematic Alzheimer's research, and we ask with some sense of earned optimism, where does Alzheimer's treatment go from here?

欢迎收听《魔鬼经济学》播客，本节目由史蒂芬·都伯纳主持，带你探索一切事物背后不为人知的一面。

This is Freakonomics Radio, the podcast that explores the hidden side of everything with your host, Stephen Dubner.

这

The

我们今天讲的这个故事，既沉重又重要。

story we are telling today is a sobering one and an important one.

我们会采访两个人。

We'll hear from two people.

我们本来希望还能采访更多人，但最后其他人都不愿意开口。

We had hoped there would be more, but in the end, the others did not want to talk.

随着故事展开，你就明白为什么了。

You'll understand why as we go.

我们从这儿开始吧。

Let's start here.

我叫查尔斯·皮勒。

My name is Charles Piller.

我是《科学》杂志的调查记者，也是《被篡改》这本书的作者。

I am an investigative journalist with Science Magazine and author of the book Doctored.

皮勒这本书的全名叫《被篡改：阿尔茨海默病治愈之路上的欺诈、傲慢与悲剧》。

The full title of Piller's book is Doctored, Fraud, Arrogance, and Tragedy in the Quest to Cure Alzheimer's.

查尔斯·皮勒几乎整个成年生涯都在做记者。

Charles Piller has been a journalist pretty much his entire adult life.

我是在芝加哥地区长大的。

I grew up in the Chicago area.

我走上新闻这条路，跟我们这一代的很多‘婴儿潮’一代人一样，是受水门事件报道的启发。

I became interested in reporting kinda the way that so many people, boomers like me, did, being inspired by the Watergate investigations.

那时候我还太小，当不了记者，但已经足够懂事，会去思考这些问题，尤其是在越战时期，还有当时社会上那些种种动荡。

I was too young to be a journalist then, but not too young to be inspired and thinking about things, particularly during the Vietnam War period and all of the societal challenges there.

皮勒今年71岁。

Piller is 71 years old.

在加入《科学》杂志之前，他给《洛杉矶时报》《萨克拉门托蜜蜂报》还有生命科学新闻网站STAT写过稿。

Before coming to Science Magazine, he wrote for the LA Times, the Sacramento Bee, and the life sciences news outlet STAT.

过去几年里，他的报道一直聚焦在阿尔茨海默病的研究上。

For the past several years, his reporting has been focused on Alzheimer's research.

我问他为什么选这个方向。

I asked him why.

说白了，答案再清楚不过：跟癌症、糖尿病、心脏病这些常见病不一样，阿尔茨海默病这几十年来，全球砸了上千亿美元进去，可到现在，连一个能阻止或逆转认知衰退的疗法都没有。

Well, the answer is to me pretty clear, and that is that unlike cancer, diabetes, heart disease, and myriad other ailments that afflict us, Alzheimer's disease is something that the nation and the world has spent tens of billions of dollars on in recent decades, and yet we have no remedy that arrests or reverses the terrible cognitive decline of the disease.

虽然癌症或心脏病研究里也可能有腐败，但这些领域已经取得了巨大突破，甚至有些病已经真能治好了，给社会带来了实实在在的改变。

And so even though there may be corruption in cancer research or in heart disease research, we've seen enormous advances in those diseases and sometimes even real cures for specific ailments that have benefited society dramatically.

但阿尔茨海默病没有，这不仅更让人痛心，对那些可能正出现相关症状的人来说，也格外可怕。

We have not seen that in Alzheimer's disease, and that makes it not just more tragic, but also terrifying for people who are facing those possible symptoms.

那关于阿尔茨海默病的环境诱因，现在主流怎么看？

What is the thinking on potential environmental drivers of Alzheimer's disease?

是的。

Yeah.

这是个很好的问题，我觉得社会应该越来越重视护理和预防。

It's a great question, and I would say that care and prevention is one of the key things that I think our society should be increasingly concerned about.

众所周知，长期生活在高污染环境中的人，患阿尔茨海默病的比例更高，而且发病年龄也更早。

It's well known that people who are subject to highly polluted environments are experiencing Alzheimer's at a higher rate and also at a more severe age of onset earlier age of onset.

其次，就像我们社会里的很多疾病一样，阿尔茨海默病某种程度上也是一种不平等的疾病。

Secondly, I would say that like so many ailments in our society, Alzheimer's is in part a disease of inequality.

当然，任何阶层的人都可能得这病，但低收入人群的发病率确实更高。

Now, of course, anyone from any economic level can get the disease, but it's more prevalent among people who do not have the same level of economic opportunities.

这在多大程度上是因为医疗条件差或得不到及时治疗？

To what degree would that be caused by less or worse medical care itself?

换句话说，早期持续监测和治疗能带来多大优势？还是说，低收入人群的生活环境本身就会增加患病风险？

In other words, how much advantage is there to early or constant monitoring and then whatever kind of treatment there may be, or are you saying that low income people may have in their lives drivers that are responsible for Alzheimer's?

我觉得两方面都有。

I think it's both things.

很明显，肥胖这类问题对阿尔茨海默病也很重要。

Clearly, problems like obesity are important in Alzheimer's disease.

另外，研究一再发现，受教育程度越高的人，患阿尔茨海默病的严重程度会更低，发病年龄也会更晚。

The other thing is that they found over and over that the higher educational attainment that people have, it has a benefit that can reduce the severity or the age of onset for the disease.

明白了。

Okay.

刚才那是查尔斯·皮勒谈了几个阿尔茨海默病的潜在诱因。

So that was Charles Piller on a few potential drivers of Alzheimer's.

那这病本身到底是怎么运作的呢？

So how does the disease itself work?

这得请一位神经科学家来解释。

For that, we need a neuroscientist.

我叫马修·施拉格。

My name is Matthew Schrag.

我是范德堡大学医学中心的神经学副教授。

I'm an associate professor of neurology at Vanderbilt University Medical Center.

我负责治疗中风和记忆力问题的患者，同时经营一个实验室，研究血管疾病如何导致像阿尔茨海默病这样的记忆障碍。

I take care of patients who have strokes and memory problems, and I run a laboratory trying to understand how blood vessel diseases contribute to memory problems like Alzheimer's disease.

你能不能给我讲讲，你做的工作里，有多少是像我这样的外行会认为跟阿尔茨海默病直接相关的？

Describe for me how much of your work is what a layperson like me might consider Alzheimer's related.

大部分都是。

Most of it.

我们的观点是，血管疾病会加剧阿尔茨海默病的发展。

Our perspective is that blood vessel diseases contribute to Alzheimer's disease.

我们不把阿尔茨海默病看作一种血管病，但这些年我们一直在研究，这些过去被严重忽视的因素，到底在多大程度上影响着这种病的发病机制。

We don't think of Alzheimer's disease as a blood vessel disease, but that's one of the issues that we've been working on is trying to understand the degree to which these other factors that have been largely overlooked may play a key role in how this disease works.

那你简单说说，你都上过哪些学校，拿了哪些学位？

So just walk me through quickly all the schools you attended and all the degrees you got.

好的。

Yeah.

我本科是在北达科他大学读的。

I was at the University of North Dakota for my undergraduate work.

之后我去了罗玛琳达大学，拿了医学博士和哲学博士两个学位。

And then I went to Loma Linda University, and I got an MD and PhD there.

再后来我去耶鲁做住院医师培训。

And then I went to Yale for my residency work.

你从小就想当这样的科学家吗？

Were you wanting to be this kind of scientist since the time you were a kid?

是家人、学校或者成长环境鼓励你走这条路的吗？

Did your family or school or background encourage you?

倒也不是。

Not really.

其实吧，我后来走上这条路，是因为刚开始认真准备申请医学院的时候，找人聊了聊，问人家：我该做点啥才能提高录取几率？

You know, this happened partly because I sat down with somebody when I started getting serious about trying to get into medical school and said, what are the things I should do to improve my odds of getting in?

人家就建议我说：你最好去搞点科研。

And one of the things they said is, well, you should do some research.

我就直接去敲教授的门，问他：我能跟你做研究吗？

I went and knocked on my professor's office and said, can I do some research?

他跟我说：‘孩子，他们说的可不是植物学。’

And he said to me, son, they didn't mean botany.

他很体贴，没让我走弯路，直接把我引荐到了更合适的实验室。

And so he very graciously didn't take advantage of me and shuttled me to a more appropriate laboratory.

施拉格被安排去的实验室，是由一位研究阿尔茨海默病的神经药理学家负责的。

The lab that Schrag got shuttled to was run by a neuropharmacologist named who studied Alzheimer's.

我在实验室里特别喜欢那种氛围。

I really enjoyed the atmosphere in the laboratory.

我特别着迷于那种研究肉眼看不见的东西的方式，通过蛛丝马迹去推断复杂系统是怎么运作的。

I really loved the ways that you could try to study things that were too small to see and try to infer how complicated systems worked.

施拉格和格里维合作的研究，探讨了饮食对阿尔茨海默病发病和进展的潜在影响。

The research that Schrag worked on with Greevy looked at the potential impact that diet could have on the onset and progression of Alzheimer's.

2006年，他们和几位合作者在《神经化学杂志》上发表了一篇论文，题目是《长期高胆固醇饮食导致兔子大脑皮层细胞损伤，与铁和β-淀粉样蛋白斑块沉积有关》。

In 2006, they and a few other coauthors published a paper in the Journal of Neurochemistry called deposition of iron and beta amyloid plaques is associated with cortical cellular damage in rabbits fed with long term cholesterol enriched diets.

那篇论文的核心观点到底是什么？

So what was the idea of this paper?

这篇论文的核心观点是，胆固醇会在大脑里堆积。

The idea of this paper was that cholesterol accumulates in the brain.

我们养了一群兔子，给它们喂高胆固醇饮食，这种饮食在某种程度上被认为能模拟阿尔茨海默病。

We had raised a group of rabbits and fed them a high cholesterol diet, which was thought in some ways to mimic Alzheimer's disease.

论文的假设是，胆固醇会积聚在神经元内部，从而对神经元产生毒性作用。

And the thought with this paper was that cholesterol levels would accumulate within the neurons themselves and that that could have a toxic effect on the neurons.

你就当我是完全不懂神经科学的吧——其实我也确实不懂。

Pretend that I know nothing about the neuroscience here, which, you know, would be close to accurate.

你能给我简单说说，现在阿尔茨海默病的研究是个什么情况吗？

Can you just summarize the state of Alzheimer's research?

哪些是已知的？哪些还不清楚？哪些还有争议？

What's known, what's not known, what's disputed?

阿尔茨海默病挺复杂的，但目前主流的看法是，大脑里会堆积一些会抱团的蛋白质。

Alzheimer's disease is a complicated disease, but our current formulation of what happens in the brain is that there is an accumulation of these proteins that clump together.

其中有两个特别关键，一个是β-淀粉样蛋白，简称淀粉样蛋白，它会在脑细胞外面、细胞之间的空隙里聚集。

And two in particular, one is called beta amyloid or just amyloid, clumps together outside of the cells of the brain, sort of in between the cells.

另一种叫tau的蛋白会在神经细胞内部聚集，导致神经元逐渐失去正常功能，最终死亡。

And another protein called tau clumps inside of the cells of the brain, and that leads to the neurons eventually not functioning properly and eventually dying.

大脑会萎缩，人就开始记不住事了。

And the brain shrinks, and people begin to lose their memory.

在你刚才说的这个过程中，tau蛋白是怎么介入的？

Where did the tau cells come in in that scenario?

tau蛋白是在神经元里面的。

Tau is inside the neurons.

它是一种参与神经元结构的蛋白。

It's a protein that is involved in the structure of a neuron.

你要是回想一下高中生物课，就知道神经元是个特别复杂的细胞，长着一条超长的尾巴。

And if you think back to high school biology, you know, the neuron is this big complicated cell that has a very long tail on it.

它是人体里最大的细胞之一，而且得陪你活一辈子。

It's one of the biggest cells in the body, and they have to live for your entire life.

tau蛋白就是帮助细胞形成这种独特结构的关键，让神经元能像电线一样传导电信号。

And the tau protein is part of how the cell gets that unusual structure with the long tail that allows it to function like an electrical wire.

所以如果tau蛋白聚在一起，不再参与维持细胞骨架，细胞就没法正常工作了。

So if you have tau clumped together and no longer participate in maintaining the skeleton of the cell, the cell doesn't function properly.

这就是阿尔茨海默病的第二个关键问题——神经元的结构开始瓦解。

So that's the second key piece of what's going on in Alzheimer's disease, that the neurons are structurally destabilized.

大概从1990年左右开始，这个领域主流的观点一直认为，那些堆积在细胞外的β-淀粉样蛋白斑块，才是致病的主因。

So for at least since, I would say, about nineteen ninety in round numbers, the main thought in this field is that the plaques, this little beta amyloid protein that clumps outside of the cells, is the primary driver of the disease.

因此，大量药物研发的精力都花在阻止它堆积，或者把它打散、从大脑里清除掉上。

And a huge amount of the effort related to drug development has been dedicated to preventing it from accumulating or breaking it up and clearing it from the brain.

大家普遍觉得，斑块是第一块多米诺骨牌，后面才引发一连串复杂反应，最终导致神经元死亡。

The general idea is that plaque is the first domino, and then there's a complicated series of events leading up to the neurons dying.

但斑块仍然是阿尔茨海默病的罪魁祸首。

But the plaque is the primary driver of Alzheimer's disease.

这种多米诺效应叫作‘淀粉样蛋白级联假说’，几十年来，数十亿美金的研究经费都砸在这上面了。

This domino effect is known as the amyloid cascade hypothesis, and that is the hypothesis toward which many billions of research dollars have been directed.

那问题出在哪呢？

So what's the problem with that?

问题是，第一，这个想法可能根本不对，第二，背后的生物学机制很可能复杂得多。

The problem is, one, the idea may not be correct, and two, the biology of this is likely much more complicated.

我觉得核心问题不在于β-淀粉样蛋白跟阿尔茨海默病毫无关系，而在于人到晚年得的病，没几个是简单的。

And I think that this is the primary issue, is not that beta amyloid has nothing to do with what's going on, but most diseases at the end of your life are not simple.

我实在想不出还有哪种病，是靠一个单一的‘第一块多米诺骨牌’就引发整个连锁反应的。

I can't think of another disease where there is one single first domino that falls that causes the rest of the cascade.

我们只盯着这么一个特定因素下手，对疾病的干预效果实在有限。

By targeting just one very specific factor, I think we're not having a big enough impact on the disease.

施拉格自己的研究，关注阿尔茨海默病与血管疾病之间的关联，就是在挑战淀粉样蛋白级联假说，而且他还以举报人的身份发声。

Schrag's own research, which looks at the connections between Alzheimer's and blood vessel diseases, is a pushback against the amyloid cascade hypothesis, and Schrag has also been pushing back as a whistleblower.

我知道，除了你在范德堡大学的研究，以及你在学术圈的日常工作之外，你还兼职做独立的科研诚信顾问。

I understand that outside of your work at Vanderbilt and your work within the academic community generally, that you also work as an independent research integrity consultant.

这四个词——‘独立’、‘科研’、‘诚信’、‘顾问’——用得对吗？顺序没错吧？

Are all four of those words correct and in the right order?

这话说得挺准的，就是我平时干的活儿。

That's a good description of what I do.

你刚踏入学术研究这一行的时候，能想到现在会是这样吗？

When you first started pursuing a career in academic research, is this how you envisioned it was gonna work out?

完全没想到。

Not in the slightest.

对啊。

No.

那现在你对这一切感觉怎么样？

So how do you feel about it at this moment?

如果能重来一次，你还会选择走揭发这条路吗？

If you could start again, would you pursue the whistleblower detour or no?

我觉得我大概还是会，毕竟我这人就是这样的性格。

I think I probably would simply because of how I'm wired.

但说实话，当初走上这条路时，我就知道这很可能是个极其愚蠢的决定。

But I think that initially, when I started down this road, I did it knowing it might have been a pretty colossal lapse in judgment.

对你自己的事业来说。

For yourself, for your own career.

没错。

That's right.

但我觉得，这个领域该换个方向了。

But my viewpoint is that it's time for a direction change in this field.

有时候，你得做个决定，然后就放手去做。

And I just think that sometimes you need to make a decision and just go with it.

马修·施拉格第一次验证科研成果，其实是个非正式的尝试。

Matthew Schrag's first exercise in validating scientific research was unofficial.

那是在他读博士期间，他试着复现一篇论文的结果，那篇论文和他本科时参与过的兔子研究有相似之处。

It came during his PhD training when he tried to reproduce the findings of a paper that had parallels to the rabbit paper that he had worked on as an undergrad with.

他发现，这项研究根本无法复现。

He found that the work was not reproducible.

到了2021年，这件事的规模一下子扩大了。

In 2021, this work took on a new scale.

一位律师找到我，希望我帮忙协助一群举报人，调查一种叫simulphurum的药物的数据真实性问题——这种药是由一家得克萨斯的小型生物技术公司Cassava Sciences开发的。

I was approached by an attorney and asked to help a group of whistleblowers investigate their concerns about the integrity of the data underlying this drug simulphurum, which was being developed by a little biotech company out of Texas called Cassava Sciences.

卡萨瓦科学公司以前叫止痛疗法公司。

Cassava Sciences had been known earlier as pain therapeutics.

他们花了好几年想打进阿片类药物市场，后来转而专注一种治疗阿尔茨海默病的实验性药物——simulphurum。

They spent years trying to break into the opioid market, and then they switched their focus to simulphilim, an experimental drug for Alzheimer's.

这家公司的研究合作者是纽约市立大学医学院的一位教授，叫王浩岩。

The company's research collaborator was a medical school professor at City University of New York named Hao Yan Wang.

他的研究发现，simulfolam能逆转淀粉样蛋白纤维的错误折叠，而这种错误折叠被认为是阿尔茨海默病的诱因。

His research had found that simulfolam could reverse the misfolding of the protein filament a, which was hypothesized as a cause of Alzheimer's.

符合淀粉样蛋白假说，simufulin还能通过靶向大脑中tau蛋白和β淀粉样蛋白的堆积，来减轻炎症。

Consistent with the amyloid hypothesis, simufulin also promised to reduce inflammation by targeting the buildup of tau and beta amyloid in the brain.

他们公布的二期临床数据让这些举报人感到非常不安。

They had produced some data from their phase two trials that raised alarm bells for these whistleblowers.

这些举报人是谁？

Who were the whistleblowers?

他们是两位科学家，一位心脏病专家和一位神经科学家，对这个领域有经验，直接说这药的药理机制说不通，基础研究里有些问题根本没法合理解释。

They were a pair of scientists, a cardiologist and a neuroscientist, who had some experience in this space and basically said they didn't think the pharmacology of this drug made sense, that there were some problems in the basic science that were just hard to interpret.

后来他们看了图像数据，发现很多照片明显被修过。

And then when they looked at the image data, a lot of those photographs looked like they had been retouched.

所以我被雇来帮他们做研究，整理一份记录他们疑虑的报告，同时也为负责此案的律师提供尽职调查支持。

So I was paid a fee to help them research this and produce a document cataloging their concerns, but also to provide due diligence to the attorneys that were pursuing this.

这个案子是因为这些科学家举报，认为这种药无效，而且数据是造假的，所以想阻止它上市吗？

Was the case about these scientists whistleblowers trying to prevent this drug from going forward because they thought it would be ineffective and was based on misrepresented data?

那你卷入这件事，最初就是因为这个吗？

Was that the genesis of your involvement in this?

这确实是促使我冒着风险公开谈论这个问题的主要原因。

It was certainly the driver for me to take the risk of speaking publicly on an issue like this.

你敢跟一家几十亿美元的大公司对着干，风险可不小。

You take a substantial risk to engage on a topic like this against a multibillion dollar company.

那时候你职业生涯到什么阶段了？

And where were you in your career at this point?

哦，我当时还是个新人。

Oh, I was very junior.

我当时是个助理教授，还没拿到终身教职，刚起步不久。

I was an assistant professor, pretenure, just getting started.

那你是怎么被代表这些举报科学家的律师选中的呢？

How did you then get on the list of people to be called by an attorney representing these whistleblower scientists?

我之前接受过一些全国性媒体的采访，我想他们可能是想找一个敢说话、同时又有一定公信力的人。

I had given some interviews in the national media, and I think they were looking for somebody who was a bit outspoken perhaps, but also who had some credibility.

到那时候，你的公信力是从哪儿来的？

Where did your credibility come from to that point?

那时候我已经当了挺长时间的阿尔茨海默病研究员了。

I had worked as an Alzheimer's researcher for quite a period of time at this point.

当时有个叫阿杜卡努单抗的药，特别火。

And at the time, one particular drug, aducanumab, was getting a lot of oxygen.

我之前就公开讨论过这种治疗阿尔茨海默病的方法存在不少问题。

And I had been talking publicly about some of the weaknesses of this approach to treating Alzheimer's disease.

明白了。

Okay.

我们再回过头说说卡萨瓦科学公司的事，那些代表举报人的律师联系了你，你说那些图片看起来像是被修过图的。

Getting back to the Cassava Sciences case, the attorneys for the whistleblowers reached out, and you said the images looked like they had been retouched.

你具体说说看，是怎么回事？

Give me some detail there.

那些图完全不符合科学实验该有的样子。

The images just didn't fit what a scientific expectation would be.

看起来像是被人为处理过的吗？

Did they look visually manipulated?

确实是被处理过的。

It looked visually manipulated.

有些结果明显是复制粘贴的痕迹，比如东西被挪来挪去、重复使用，或者图像某部分的亮度被调过。

Some of these results had copy and paste type changes where it looked like things had been moved around or duplicated or where the intensity of one part of the image had been adjusted.

说到底，我们分析数据时，靠的就是照片上那些深色斑块的深浅程度。

And, ultimately, a lot of these results, how dark a splotch on the photograph is is what we ultimately measure to turn it into data.

所以一旦改了亮度，底层的数据也就被篡改了。

So changing the intensity of those values changes the underlying data.

对普通人来说，这听起来就像个儿戏般的造假。

To a layperson, that sounds like a sort of Mickey Mouse misrepresentation.

我不是说 Mickey Mouse 有什么不好，但科学论文里的图片，肉眼就能看出被改过，这确实太业余了。

And I don't mean to insult Mickey Mouse, but it seems kind of amateurish that to the naked eye, the images in a scientific paper could be seen to be manipulated.

你有没有过这种经历：别人给你看个东西，问你看到了什么？

I don't know if you've had the experience of somebody showing you something and saying, what do you see?

你盯着看了半天，啥也没看出来，结果别人一指点，你才恍然大悟。

And you don't see anything, and then somebody explains to you what you're supposed to see.

可一旦你明白了，就再也回不去那种‘看不见’的状态了。

And now all of a sudden, you couldn't possibly turn the clock back and not see that.

我觉得这里头就有这种效应。

And I think there's some of that.

一旦你发现了那些模式，确实会觉得它们太明显了。

I think once you've seen the patterns, you're right that they seem quite obvious.

不过我也得说，觉得可疑是一回事，能拿出确凿证据又是另一回事。

But I'll also say there's a difference between seeing something suspicious and being able to prove it.

我们当时做的，就是想用一种非常系统、严谨的方式来处理这件事。

And that's part of what we were working on was trying to do this in a very systematic and thorough way.

同时也要证明，这些不是随机的错误，也不是疏忽大意，而是有明确模式的，这种模式彻底改变了数据的解读方式。

And then also show that these are not random things, that these are not accidents or slips, but that there is a coherent pattern to it that changes the interpretation of the data.

你跟我讲讲，你当时跟谁一起做的？看这些数据的时候是什么情况？最后得出了什么结论？

Tell me about who you worked with and what that work was like to look at these data and what your conclusions were.

我是独立完成的。

I worked independently.

一旦我确信这些投诉确实有道理，下一步就是对相关材料、支持这种药物研发的科学论文做更深入的调查和分析，看看还有没有其他问题。

And once I settled in my mind that there was some legitimacy to these complaints, the next step was then to do some additional research and forensics on the material, on the scientific publications that were supportive of developing this drug and see if there were additional problems.

于是我帮他们整理了一份材料，最终提交给了FDA，反对这个药物继续研发。

And so I helped them build a dossier that was eventually sent to the FDA to contest the continued development of this drug.

现在这事就交给FDA了。

And now it's in the FDA's hands.

你可能觉得，既然你这么有信心，FDA肯定照你说的办吧。

Maybe you're thinking that, of course, the FDA will follow your prescription because you had a lot of confidence in your data.

对。

Right.

但我也不确定。

But I don't know.

你有没有怀疑过，FDA会就此叫停？

Did you have any skepticism that the FDA would wind it down?

我真没想到FDA没采取更多行动。

I was shocked that the FDA didn't take more action than they did.

我本来以为几天内这事儿就该板上钉钉、必须叫停了，结果进展和最终决定都让我大吃一惊。

I expected within days for this to be a no brainer that this could not continue, and I was really surprised by the pace and the ultimate decisions.

但后来我们发现一个模式：作弊的人，总会一而再、再而三地作弊。

But one of the things that happened was we've noticed this pattern where cheaters cheat.

这听起来可能不稀奇，但当我开始调查这位科学家时，发现他的问题远不止在这家公司做的这项工作里。

That shouldn't maybe shock people, but when I started investigating this scientist, what we found is that the problems extended well beyond the work that he had done for this company.

所以我们得决定怎么处理这些事。

And so we had to decide what we were going to do with that.

律师们当然对这家公司很感兴趣，但我总觉得，我们还有个更广的科学目标——那就是纠正整个科学界的错误记录。

Obviously, the attorneys were very interested in this company, but I felt like there was an additional scientific objective here to correct the scientific record more broadly.

所以我们达成一致，允许我继续追查这个人的其他研究问题。

So we agreed that I would be permitted to continue to pursue the problems in the rest of this individual's work.

原来如此。

I see.

这是来自纽约城市大学的王浩岩。

This is Hao Yan Wang at City University of New York.

是这样吗？

Is that right?

没错。

That's right.

王浩岩是卡萨瓦科学公司主要的科研人员。

Hao Yan Wang was the primary scientist working for cassava sciences.

最后，我把一整套材料发给了美国国立卫生研究院，详细说明了他在和他合作者的研究中暴露出的那些系统性问题。

And so I ultimately sent a set of dossiers to the National Institute of Health describing more broadly the patterns that we saw in his work and in the work of his collaborators.

那 NIH 给你回了什么消息？

And what did you hear back from the NIH?

这个过程啊，特别不透明。

Well, that's a very opaque process.

他们只会谢谢你提供的意见，之后就没什么下文了。

So they thank you for your input, and then you hear very little.

在卡萨瓦科学公司案中，有一位举报人联系了《科学》杂志的一名记者，这位记者把马修·施拉格介绍给了他们的同事、调查记者查尔斯·皮勒。

One of the whistleblowers in the Cassata Sciences case reached out to a reporter at the prestigious journal Science who connected Matthew Schrag with a colleague of theirs, the investigative journalist, Charles Piller.

我后来发现，他想挖的深度，远超我之前接触过的那些记者。

And it became clear to me he was looking to go a lot deeper than most of the reporters that I had talked to.

到那时为止，我接受媒体采访基本都是匿名的，身份也只是那位律师和他所支持的举报人的顾问。

Up to that point, my comments in the media had been mostly on background, and my role had been as a consultant for this attorney and the whistleblowers he was working for.

但很明显，那时候这个故事的规模已经大不一样了。

But, obviously, the story was bigger at that point.

这已经不只是卡萨瓦科学公司的事了。

It was more than just cassava sciences.

这牵扯到很多科学家。

It involved a lot of scientists.

你知道，问题越扩越大了。

You know, the problem was expanding.

广告后，我们会听到这个问题是怎么越闹越大的。

Coming up after the break, we will hear how the problem expands.

我是斯蒂芬·杜布纳，欢迎收听《魔鬼经济学》广播。

I'm Stephen Dubner, and this is Freakonomics Radio.

在广告前，范德堡大学的神经科学家马修·施拉格讲述了他发现的生物科技公司卡萨瓦科学的造假研究。

Before the break, the Vanderbilt neuroscientist Matthew Schrag described what he considered doctored research coming out of the biotech firm, Cassava Sciences.

调查记者查尔斯·皮勒听说了施拉格的工作，提议他们合作。

The investigative journalist Charles Piller heard about Schrag's work and suggested that they collaborate.

这是马修·施拉格的讲述。

Here's Matthew Schrag.

我同意给查尔斯看我准备并提交给NIH的那些材料。

I agreed to show Charles the dossiers that I had prepared and had sent to the NIH.

我还另外给NIH提交了一份关于明尼苏达大学问题的材料，那些问题其实跟我研究卡萨瓦科学公司的事儿没啥直接关系。

And I had sent an additional dossier to the NIH about the issues at the University of Minnesota, which were incidental to the work that I was doing on cassava sciences.

但我早就注意到了这个问题，自己试着用了一些图像分析技术，干脆就把在明尼苏达大学发现的这些有问题的论文当成了测试案例，看看这招管不管用。

But I had become aware of this problem and had been dabbling with some image analysis techniques and basically used this set of problem papers that I had found at the University of Minnesota as a test case to see how this technique would perform.

其中有一篇论文特别有影响力，2006年发表在《自然》期刊上。

One of these papers was a hugely influential study that had been published in the journal Nature in 2006.

论文标题叫《大脑中一种特定的β淀粉样蛋白聚集体损害记忆》。

It was called a specific beta amyloid protein assembly in the brain impairs memory.

这篇论文的合作者里有两个明尼苏达大学的研究人员，叫西尔万·莱斯奈和凯伦·阿什。

Among the coauthors were two University of Minnesota researchers, Sylvain Lesnay and Karen Ash.

这项研究用的是基因改造的小鼠，它们的大脑会产生过量的淀粉样蛋白。

The research used genetically engineered mice whose brains produced excess amounts of amyloid protein.

研究人员从这些小鼠身上提取蛋白，注射到大鼠脑里，结果大鼠很快就出现了认知能力下降的迹象。

The researchers extracted that protein from the mice and injected it into the brains of rats, who soon after showed signs of cognitive decline.

这篇论文出现的时候，正好是淀粉样蛋白假说遭遇重大挫折的时刻。

This paper came along at a moment where the amyloid hypothesis had a big stumble.

当时有个临床试验，想用疫苗把大脑里的β淀粉样蛋白清除掉，这想法其实挺巧妙的，但试验失败了。

Clinical trial looking to remove beta amyloid from the brain with a vaccine, which frankly is a really clever approach, but the trial failed.

有时候，再好再聪明的想法也不管用，这个就是个例子。

And sometimes really good, really clever ideas don't work, and this was one of them.

于是大家开始怀疑，这个假说是不是根本就错了。

And people started questioning whether this was the right hypothesis.

后来有人提出新的说法，也许真正致病的不是那些大块的淀粉样蛋白斑块。

So this reformulation came along that perhaps it wasn't the big clumps, the plaques of beta amyloid that was the primary driver of the disease.

而是在单个分子和成千上万分子聚成的大团块之间，某种中间状态的东西。

Perhaps somewhere in between a single molecule of beta amyloid floating around and where it was millions of these molecules in a giant clump.

可能是一些能溶于水的小型淀粉样蛋白聚集体才是有毒的，他们管这叫‘寡聚体’，其实就是希腊语里‘小团块’的意思。

Perhaps there's some soluble small clump of beta amyloid that was the toxic component, And they call those oligomers, which is just Greek for small clump, I guess.

Sylvain Lesney声称他找到了那个‘银弹’——某种特定数量的β淀粉样蛋白链组成的聚集体，才是真正的元凶。

Sylvain Lesney proposed that he had found that silver bullet, that a clump of a certain number of strands of beta amyloid was the primary cause.

他的论文被大量引用，一直被引用到我们开始质疑它为止。

And his paper was cited and continued to be cited right up until we challenged it.

这项实验让整个领域的人重新燃起了信心，到2022年为止，它成了该疾病研究史上被引用最多的实验之一。

This experiment gave new confidence to people in the field and became one of the most cited experiments in the history of the disease through 2022.

这又是记者查尔斯·皮勒说的。

That again is the journalist Charles Piller.

那后来发生了什么？

So what happened next?

施拉格和我开始仔细研究这件事，最后我在《科学》杂志上发表了一篇相关报道。

Schrag and I started to look carefully at this, and, ultimately, I wrote a story about it in Science Magazine.

他们发现莱斯尼和阿什那篇论文的主要问题，出在作为证据的图片上。

The major issue they found with the paper by Lesney and Asch had to do with the images that were used as evidence.

这次主要涉及一种叫西方印迹的图像技术。

Primarily in this case, it involves something called Western blot images.

这种技术在科学界非常非常普遍，尤其在阿尔茨海默病研究和其他领域里用得特别多。

Now these are a very, very common technique used in science, particularly often in Alzheimer's research and in other fields as well.

简单说，它就是蛋白质的一种照片式呈现。

And what they are are a photographic representation of proteins.

所以你可以通过这个方法检测出样本里有哪些蛋白质，以及它们的含量。

So you can test a protein sample for the type and amount of different proteins within it.

这在阿尔茨海默病研究里特别关键，因为你得搞清楚动物大脑里到底有哪些蛋白，可能跟疾病有关。

This is very important in Alzheimer's research because you're trying to determine what proteins are in an animal brain, for example, that might be behind the disease in some way.

施拉格在他的研究中发现了一些问题，后来其他图像 forensic 专家、我去找他们核实，还有阿尔茨海默领域的权威专家，也都确认了这一点。

And so what Schrag found from his work, and this was validated by other forensic image experts, by me going to them, and also by leaders in the field of Alzheimer's research.

结果发现，这些图片被严重篡改了，明明实际数据不支持实验假设，图片却硬是往支持的方向改。

What was found was that these images apparently were manipulated in severe ways that tended to support the hypothesis of the experiment when the actual data did not support it.

所以我猜你后来联系了莱斯尼？

So I assume that you contact Lesney.

你们是怎么谈的？

What's that conversation like?

可惜的是，我们根本没谈成，他压根儿不回我。

That conversation is one that regrettably never occurred because he wouldn't speak to me.

明白了。

Okay.

那你的合作者马修·施拉格呢？

And what about Matthew Schrag, your coinvestigator?

莱斯尼或者他实验室的人，包括那个凯伦·阿什，有没有跟施拉格沟通过？回应过他的质疑吗？

Did Lesney or anyone else from his lab, including, I guess, Karen Ash, did they speak with Schrag or respond to any comments?

他有没有把关于数据造假的指控发给他们？

Is he sending them information about his charges of manipulation?

施拉格毕竟是个科学家。

I mean, Schrag's a scientist.

作为写这篇文章的记者，我可是使出了浑身解数，想让莱斯尼和他的合作者——当时还是他老板的凯伦·阿什——跟我聊聊。

I was the one who, as a journalist writing the article, of course, I did everything I could possibly do to get Lesney and his co investigator, who at the time of the experiment was his boss, Karen Ash, to speak to me.

在文章发表之前，他们俩都死活不肯跟我谈。

Prior to the article appearing, they both refused to speak with me.

这些细节我都写在书里了，也写进了那篇报道里。

This is detailed in my book and also in the article that I wrote about it.

其实吧，这事儿说起来也没那么意外。

And it was, I think, not that surprising in a way.

我做了这么多年这类报道，发现很多人其实没啥好说的，或者因为机构限制，根本不敢或不能跟记者开口。

I found over many years of experience doing these sorts of articles that people don't have a great story to tell often are unwilling or unable by their institutions restricting them from saying anything to a reporter.

我和Ash确实有过交流，她挺有意思地说，她其实想跟我谈，但学校劝她别谈，最后她听从了学校的建议。

Ash, I did have a dialogue with, and she very interestingly replied that she wanted to talk with me, but her university advised her not to, and she decided that she would go along with their advice.

我当时就跟她说，我觉得这建议太糟糕了——这可是她向公众表达自己观点的绝佳机会，这是最广为阅读、最深入的一次调查。

I explained to her at the time that I thought it was terrible advice because this was her opportunity to get her perspective into the most read, deepest look at the subject.

让我恼火的是，大学也是公众信任的一部分，它们拿的科研经费可都是纳税人的钱。

The thing that frustrates me about that is universities are also part of the public trust, and they get a lot of research funding from taxes.

所以我觉得，至少该回应一下，至少该认真对待这些指控。

And so I feel like it should be incumbent upon them to at least respond, at least take the charges seriously.

当你发现她根本没认真回应时，你接下来是怎么做的？

When you found that you weren't getting a serious response from her, what was your next step then?

在这种情况下，通常会由资助这项研究的美国国立卫生研究院介入调查。

In this case, what happens is the National Institutes of Health, which is the funder of this work, take a look at it.

他们也认为，这里确实可能存在一些问题。

They agreed that there was a possible problem there.

他们把这事转交给了卫生与公共服务部下属一个名不见经传的机构，叫科研诚信办公室。

They referred it to a obscure government agency called the Office of Research Integrity at the Health and Human Services Department.

就一小撮人而已。

This is a tiny little group.

他们根本没足够的人手去查遍科学界每一起可能的造假或不当行为。

They don't have the manpower to examine every possible example of fraud or misconduct in the scientific world.

所以他们就把案子扔回给事发的大学——这次是明尼苏达大学。

And so what they do is they give it back to the university where the alleged misconduct took place, in this case, the University of Minnesota.

在我看来，这做法完全搞反了：你居然让最怕曝光、最没动力去彻底查清问题的机构，去自己查自己。

To me, this is exactly the wrong approach because you're entrusting the organization that has the most to lose and the least to gain from a robust, complete, and publicly accessible examination of possuminous conduct to do that examination.

结果他们花了好几年才做完对莱斯尼的调查。

So they took years to assess Lesney.

可在这期间，他还在继续拿数以十万计的联邦经费，干着早就被质疑的研究。

In the meantime, he was still collecting many hundreds of thousands of dollars in federal funds to continue the same lines of research that had already been proved questionable.

我还得说一句，我那篇报道出来后，他又发了一篇论文，我们发现里面明显篡改了科学图像。

And I might add, published a paper after my initial story came out that we found had apparently manipulated scientific images in it.

这事一拖再拖，大学那边照样该干嘛干嘛。

This goes on and on, and the university is going about their business.

直到2025年，莱斯尼才退休。

Finally, in 2025, Lesney retires from his job.

他辞去了终身正教授的职位。

He resigns from his post as a tenured full professor.

这人其实还挺年轻的。

This is a pretty young guy.

所以说，他等于直接断送了自己的科研生涯。

So what you're talking about is a guy who ended his scientific career, in effect.

那所大学的调查到底查到什么地步了？

What was the extent of that university investigation?

谁知道呢，他们啥细节都没公布，就说了句‘建议期刊撤回莱斯尼的其他论文’。

Well, we'll never know because they never released any of the particulars except to say that they had asked for journals to consider retracting other Lesney articles.

当初那篇发表在《自然》上的开创性论文，对阿尔茨海默病领域影响巨大，我觉得，很多人也同意，它在推动整个领域前进上起了关键作用。

Now the initial story, this seminal paper in Nature that was influential in the field of Alzheimer's disease, and I would argue, and I think many people agree, had a very, very high degree of importance in moving the field forward.

这篇论文最终被撤稿了。

This paper was retracted, ultimately.

正式向《自然》期刊申请撤稿的是合著者凯伦·阿什。

It was coauthor Karen Ash who formally requested that the paper be retracted from the journal Nature.

她在其他地方发表的声明中承认数据存在问题，但表示自己之前完全不知情，直到有人提出来才了解到。

In a note she published elsewhere, Ash acknowledged problems with the data, but said she had had no knowledge of it until it was brought to her attention.

我们联系了凯伦·阿什和西尔万·莱斯尼。

We reached out to both Karen Ash and Sylvain Lesnay.

莱斯尼拒绝了我们的采访，阿什那边也没回音。

Lesnay declined to speak with us, and we didn't hear back from Ash.

那卡萨瓦制药公司和他们的实验性阿尔茨海默病药物simphilim呢？

And what about Cassava Sciences and their experimental Alzheimer's drug simulphilim?

查尔斯·皮勒和马修·施拉格也一直在深挖这件事。

Charles Piller and Matthew Schrag kept digging into that as well.

皮勒在《科学》杂志上发表了一篇文章，披露了纽约城市大学的一份内部报告，指出黄远华的研究中存在大量图像篡改和数据管理混乱的问题。

Piller published an article in Science about an internal report from the City University of New York, which found numerous signs of image manipulation in Hauyuan Wang's work and bad data management.

2024年，美国司法部指控王浩元在与simulphilim相关的NIH资助申请中伪造和篡改数据。

In 2024, the Department of Justice indicted Wang for allegedly fabricating and falsifying data in NIH grant applications related to simulphilim.

王被控多项罪名，包括对美国政府的重大欺诈、电汇欺诈和作虚假陈述。

Wong faced multiple charges, including major fraud against The United States, wire fraud, and false statements.

几个月后，卡萨瓦科学公司同意向证券交易委员会支付四千万美元，以和解其在simulfolam疗效上误导投资者的指控。

A few months later, Cassava Sciences agreed to pay $40,000,000 to the Securities and Exchange Commission to settle charges that it misled investors on the effectiveness of simulfolam.

卡萨瓦公司在公开宣称该药物在人体临床试验中未能显示出优于安慰剂的认知效果后，停止了该药的研发。

Cassava stopped development of the drug after publicly stating that it had failed in human clinical trials showing no cognitive advantage over a placebo.

卡萨瓦的总裁兼首席执行官雷米·巴比耶，以及高级副总裁兼神经科学家林赛·伯恩斯都已辞职。

Cassava president and CEO Remy Barbier and senior vice president and neuroscientist Lindsay Burns both resigned.

上个月，卡萨瓦科学公司宣布再次更名，这次改名为Falana Therapeutics。

And last month, Cassava Sciences announced that it was once again changing its name, this time to Falana Therapeutics.

郝燕王也同意就SEC的指控缴纳罚款，而到了2025年，司法部对王的所有欺诈指控都被撤销了。

Hao Yan Wang also agreed to pay a fine related to the SEC charges, and in 2025, all charges of fraud made by the DOJ were dropped.

我们试图联系王，但没得到直接回应；不过他的律师表示，鉴于新证据的出现，他们对指控被撤销感到满意，并坚持认为王是无辜的。

We tried to reach Wang and got no response directly, but his lawyers said they are pleased that the case against Wong was dropped in light of new evidence and maintain that Wong is innocent of the accusations made against him.

我们也联系了Falana，想听听他们的说法。

We also reached out to Folana for comment.

公司发言人说，他们现在主要专注于研发一种罕见癫痫的治疗方法。

A spokesperson for the company said they are currently focused on researching and developing a treatment for a rare form of epilepsy.

与此同时，查尔斯·皮勒在为写书做调研时，一直在梳理众多阿尔茨海默病研究者的背景。

Meanwhile, Charles Piller, as part of his book research, had been looking into the track record of many Alzheimer's researchers.

我挑了大约五十个人，他们要么影响力大，要么行为值得深挖。

I focused in on about 50 who were both influential and who seemed to be people who needed a closer look.

最引人注目的一个，是这个叫埃利亚·莫斯利的人，他以前是国家老龄化研究所神经科学部的负责人。

Probably the most interesting one is this guy, Elijah Mosleya, who was previously the head of the division of neuroscience for the National Institute on Aging.

他每年掌管着将近27亿美元的预算，可以说是全球最有权势的人之一，直接左右着神经科学研究的方向——毕竟他是这领域最大的金主。

This guy was overseeing a budget of about $2,700,000,000 per year, and this made him one of the most influential people in the world by far to steer the agenda of neuroscience research because this is the biggest funder worldwide for this work.

几十年来，他一直在加州大学圣地亚哥分校做研究。

He, for decades, had been a researcher at the University of California in San Diego.

他在帕金森和阿尔茨海默病研究领域都成了权威人物。

He became an eminent scientist in both Parkinson's and Alzheimer's research.

所以他被聘为NIA神经科学部门负责人时，简直是天选之人——德高望重、人脉广、声誉好，自己也做过不少有影响力的研究，还同时在NIA内部运营着自己的实验室，负责整个部门的项目。

So when he was hired to be the head of the neuroscience division at NIA, it made him a logical choice, someone who had respect, had contacts, had prestige, had himself demonstrated a propensity for influential research, and he operated his own lab within NIA as well as directing their programs.

那时候，有没有人怀疑他科研不端或者PS图片呢？

And at that time, were there any suspicions of research misbehavior or image doctoring?

没有。

No.

据NIH的说法，当时没人对他有任何疑虑。

There were no suspicions of him according to the NIH.

于是，我们请了四位顶尖的法医图像专家帮忙，其中包括马特·施拉格，还有来自哥伦比亚大学的杨慕女士，她现在可是越来越有名的法医图像分析专家。

So with the cooperation and assistance of four leading forensic image experts, and that included Matt Schrag, a woman by the name of Mu Yang, who is at Columbia University, who's becoming a pretty well known forensic image expert.

还有凯文·帕特里克，他不是科学家，但是个经验老到的独立研究者，特别擅长分析这类图像；另外还有伊丽莎白·贝克，她是全球顶尖的科学图像分析专家。

Also, Kevin Patrick, who is not a scientist, but is a independent researcher who is excellent and very seasoned at looking at these images, and Elizabeth Beck, who is a world renowned expert in scientific image analysis.

这四位专家一起审查了莫斯利发表的论文。

And the four of them took a look at Mosley's papers.

我们最终挑出了132篇有问题的论文，总共看了800篇。

We found a 132 papers out of the 800.

我们没看全部800篇，那活儿太庞大了。

We didn't look at all 800 because it was too massive a task.

我们挑了132篇，发现都有图像异常，比如明显被篡改的图、重复使用或不当复用的图，还有些图被拆开用在不同论文里，硬凑出不同的科学结论。

At a 132 where image irregularities, including apparently doctored images, apparently misused or reused images, apparently images that were published separately in different papers in an improper way to make different scientific points.

最后整理出了一份300页的报告，把所有疑点都列得清清楚楚。

What came out of it was a 300 page dossier detailing all of the concerns.

这些问题是追溯到Mosley三十年前的工作，包括他在加州大学圣地亚哥分校的成果，还有他在国家老龄化研究所实验室的成果。

And this traces back to Mosley's work going back thirty years, including at UC San Diego and also the work coming out of his lab at the National Institute on Aging.

是他亲自在带的项目吗？

Work that he's directing personally?

是他亲自在自己实验室里带的项目。

Or That he's directing personally in his own lab.

那你们整理出这份报告，指出这132篇论文有图像造假的迹象，然后怎么跟他说的？他啥反应？

So you compile this dossier that identifies a 132 papers with signs of apparent image doctoring.

你们是怎么把这情况告诉他，他又是怎么回应的？

How do you present this information to him, and what's his response?

嗯，我就用了最直接的方式。

Well, in the most straightforward way possible.

我给他写了信。

I wrote to him.

我把这份报告直接交给了他。

I presented the dossier to him.

他手上有全部的信息。

He had a 100% of the information.

我问他了一大堆问题，关于我们发现的那些问题，当然，我们也给了他机会，让他提供证据来证明我们哪里弄错了。

I asked him a wide range of questions about the problems that we found, and, of course, we offered him the opportunity to present evidence that would suggest that we had it wrong in some way.

结果呢，他压根没回。

And so the response was that he didn't respond.

机构那边的反应倒是挺有意思。

The response from the agency was fascinating.

一开始他们死活不搭理，但等到出版日期越来越近，就在文章发表前三天，他们突然说：等等。

At first, they would refuse to respond, and then as the date of publication became closer and closer, literally three days before the story was published, they said, wait.