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The Alzheimer’s casino: Big money and bad science

The Alzheimer’s casino: Big money and bad science

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What happens when science and medical research meet Wall Street?

Why this story?

There is an unsavoury tension between pharmaceutical research and Wall Street, between science, money, and hope. It costs hundreds of millions – often billions – of dollars to develop a new drug. But, for the firms who do, the payout is vast. 

Big sums inevitably attract gamblers: stock-market investors who buy shares in the belief the drug will work; or who short the stock, hoping it will fail. With stakes so high, they all have an interest in backing their hunch, and sometimes stoop low to do so. The noise this creates can obscure those with a real life-and-death stake in the creation of working drugs: in this case, the 55 million people currently living with Alzheimer’s.

Science is at the root of all this. The only way to close down this unsavoury Pharma-casino is with scientific integrity, which starts in the labs and feeds into the scientific journals where research is published. Clean that up, stop the manipulated images and share the data, and the potential for mischief recedes. Jasper Corbett, Editor

Transcript

Elisabeth Bik: I feel that a person who cheats in science, should not be a scientist anymore. I think in general, scientists have always been a little naive and trusting in their peers and, and, and not being aware that some people will cheat. 

Samantha Weinberg, narrating: Elisabeth Bik is an unlikely detective. She’s tall, for a start, so she’d find it hard to melt into a crowd. And her special subject is … the microbiome. Bacteria, fungi, viruses…

Elisabeth Bik: I was born and raised and did my PhD in the Netherlands. And I moved about 20 years ago to the United States to work as a microbiologist at Stanford.

Samantha Weinberg, narrating: Which makes it more surprising that I’m coming to meet her in Gouda – where the cheese comes from – to talk to her about whether she still thinks scientists are naive and trusting. After all, she’s caught up in a vicious, multi-million-dollar battle over Alzheimer’s research. But we’ll get to that later.

On the journey over, I read that she collects tortoise figurines. I later find out that she has 1,837 of them described in a spreadsheet, plus a box still to be numbered.

She’s waiting in the drizzle of an October morning when the train pulls in, wearing grey slacks, a maroon jacket and sensible shoes…

[Sound of trains, beeping and footsteps]

Elisabeth Bik: Good morning!

Samantha Weinberg: Lovely to meet you. 

Elisabeth Bik: Nice to meet you, I’m Elisabeth.

Samantha Weinberg, narrating: Elisabeth Bik’s sleuthing career started in 2013, with an idle quest. 

Elisabeth Bik: Well somebody talked on a podcast about plagiarism. And I thought, let’s just take a sentence that I have written and put it between quotes in Google Scholar to see if somebody had stolen my sentence. And it was just… I expected it to be a 30-second thing and not to lead to anything. 

Samantha Weinberg, narrating: She was shocked to discover that the first sentence she Googled was copied verbatim in two other scientific papers. Papers which are meant to be a benchmark of scientific integrity: new research or surveys scrupulously checked over by scientific peers. 

Elisabeth Bik: And that sort of led me on a hunt to find more plagiarised papers, because a lot of these sentences, if I put them in Google Scholar again, I found other papers. And so it became this, this hairball of plagiarism cases where one case led to another and to more and more and more.

Samantha Weinberg, narrating: She began to realise that the problem wasn’t just with stolen words creeping into scientific journals. But images too… 

Elisabeth Bik: I flipped through the images and I just happened to notice that one of the images had been used twice, actually three times. I found a third one as well. And it made me even more angry because this looked like cheating. 

Samantha Weinberg, narrating: Sitting in the neat and spare – spare room of her mum’s apartment, she shows me how she does it. 

Samantha Weinberg: Do you mind just showing me what a problem looks like?

Elisabeth Bik: Oh, of course!

Samantha Weinberg: This is the… cause to me they just look like blobs

Elisabeth Bik: At some point you start to see this rectangle…

Samantha Weinberg, narrating: She picks out a series of images in a paper, magnifies them, rotates and flips them, and then peers closely at her screen to see if she can find any similarities. It’s like an inverse game of Spot the difference. 

Samantha Weinberg: Oh yeah!

Elisabeth Bik: So you have a rectangle around these lines… 

Samantha Weinberg, narrating: Then there are the photoshopped images. 

Elisabeth Bik: This bit is darker

Samantha Weinberg: But look at that thin white line, it’s very pronounced 

Samantha Weinberg, narrating: She shows me a likely offender… a halo of white surrounding a black blob is clearly at odds with the background of the neighbouring blob. 

Elisabeth Bik: But it’s rectangular which nothing in nature is…

Samantha Weinberg, narrating: It’s as if an absent family member has been pasted into a wedding photo. 

It’s subtle, but you can feel her glee at finding it.

She has a rare gift for it and a dogged obsessiveness. To date, she has scanned around 100,000 papers.

They form the foundations of pyramids of science, on which companies… treatments… billions of dollars of research are built. 

Elisabeth Bik: For me, science is about finding the truth, about finding out how things work. And if you cheat or fake, that is just not what science should be. So it made me very angry and I feel I’m still powering on that, on that anger that I’m still feeling. To, to look at more papers and more papers and more papers. 

Samantha Weinberg, narrating: I’m fascinated. But what surprises me most is that her work, this scientific sleuthing, can be risky – borderline dangerous. She was one of the first people to call out publicly the French doctor who promoted hydroxychloroquine, Donald Trump’s favourite covid treatment. 

The doctor responded online, calling her a crazy woman, a witchhunter and a person of medium intelligence.

Elisabeth Bik: And at some point about a year ago, there was a statement by one of his, um, other professors who works also in that institution who said, we’re going to sue Elisabeth Bik – me – for harassment, for extortion and for blackmailing. And, uh, that was when they published my home address also. So they, uh, they showed a screenshot of the, the complaint they had filed against me with my home address. 

Samantha Weinberg, narrating: It’s an astonishing response – and a vicious one. 

But Elisabeth doesn’t spook easily. And her current battle may turn out to be the most brutal yet. And the sad thing, the mad thing, is that it centres on something that should be a cause for hope: an experimental drug that promises to help people suffering with Alzheimer’s Disease. 

Depending on which side you’re on – it’s either about stifling a treatment that could save lives…

Matt Nachrab: So me and my passion and my anger, is because I feel that there’s a wrong happening right now. 

Rob: Financial investors have been acting so aggressively to first prevent, and then when that failed, then halt the trial of a drug that has, you know, so much promise.

Samantha Weinberg, narrating: … or holding potentially suspect scientific practice to account. 

Matthew Schrag: And what I found in my evaluation of that work was that there were some pretty concerning red flags. 

Elisabeth Bik: So I thought, okay, let’s just take a look. And I agreed with most of these concerns.

Samantha Weinberg, narrating: I’m Samantha Weinberg and this is the Slow Newscast from Tortoise. In this episode – The Alzheimer’s casino – I’m going to open the doors into the world of medical research… where science, big money, and hope combine to create a toxic cocktail of greed and mistrust. 

What’s going wrong?

***

Samantha Weinberg, narrating: You might think that you know what Alzheimer’s Disease is like, but you don’t really – not until you’ve got a family member who has it, or you’ve watched a friend struggling to cope with it…

Hilary Metz: You know, he’s in his seventies. He’s been waking up and making his own coffee longer than I’ve been alive, and all of a sudden wasn’t able to make a simple pot of coffee. 

Samantha Weinberg, narrating: Hilary Metz is a lawyer based in Miami. We speak on Zoom, while her dog tries to distract her attention. I can see the sadness in her smile when she’s talking about her dad, who has early-stage Alzheimer’s. She started noticing the symptoms in 2021. 

Hilary Metz: It was very stressful for my mom. She was, she was very upset. I could just tell that it was not a good situation. 

Alzheimer’s doesn’t just affect the person with the disease: it threads through families and friendships, seeding disruption, and heartbreak. 

Hilary Metz: My dad was living in ignorant bliss, you know? But my mom was the one where we were getting to the point where we were thinking, I don’t know if he should be left in the house alone. 

Samantha Weinberg, narrating: Alzheimer’s Disease is the most-common cause of dementia. The brain atrophies. You forget your daughter’s dog’s name, then, that you have a daughter. You get confused and angry and ask the same question over and over. It’s like you shed the bits of you that made you who you were, the talents, tics, loves and hates, the experiences accrued over a lifetime – until you just exist in other people’s memories. 

It currently affects an estimated 50 million people around the world; that’s projected to rise to 152 million by 2050. 

So an effective treatment is both longed for… and potentially very lucrative. 

Matt Nachtrab watched his grandfather fade from what he believes was Alzheimer’s…

Matt Nachtrab: I grew up with him. He played poker with me from the age of five. So, um, normally it was him and I interacting, um, at, at family gatherings, and we would sneak off and, and play poker by ourselves or some sort of card game. So I had a long history of, uh, spending time with him. And as he was going through the, the, um, deterioration from Alzheimer’s disease, he stopped being able to recognise me, um, which was tough for me. That was when I was around 18 or so. Like he recognised my brother, who never spent any time with him, but he thought he was a Toledo Mud Hens baseball player, which was totally, uh, incorrect…

Samantha Weinberg, narrating: Alzheimer’s is arguably the illness with the most stubborn resistance to human ingenuity. 

Between 2016 and 2021, the US Food and Drug Agency, the FDA, approved 207 new cancer drugs. There are close to 60 approved diabetes drugs. 

But for Alzheimer’s? No such luck.

Which is why, when a small biotech start-up… with around two dozen employees and no labs of its own… announced last year that clinical trials had shown marked improvements in memory and understanding… people paid attention. 

“At cassava sciences we have one mission and only one mission and that is to defeat Alzheimer’s disease.” CEO Remi Barbier speaking on the Being Patient podcast

Samantha Weinberg, narrating: Cassava Sciences became the hot new thing in Alzheimer’s research. 

“We’re a biotech company, we have a treatment, an investigational treatment I might add, for patients with Alzheimer’s disease, and we also have an investigational blood-based diagnostic to detect Alzheimer’s disease. That’s all we do.” CEO Remi Barbier speaking on the Being Patient podcast

Samantha Weinberg, narrating: And if they do it… it would be an enormous breakthrough. 

Up to now, most drugs have been targeted at dissolving build-ups of protein – plaques and tangles – that were first found in the brain of a woman who had died after exhibiting the symptoms we now associate with Alzheimer’s. That was in 1906.

But Cassava’s drug, Simufilam, takes a radically different line, working to restore the shape and function of yet another protein, Filamen A, that becomes distorted in the brains of people with Alzheimer’s. 

It’s an approach that has not even been thought of elsewhere. 

When we explained the treatment to one of the foremost Alzheimer’s experts in the world… he told us that the science seemed “difficult to justify” and that there is “really nothing solid connecting this protein to Alzheimer’s disease”. 

Simufilam is not on the market yet. 

But when Cassava Sciences announced the results of those small clinical trials… and that the National Institutes of Health, the US medical research agency, had approved funding for much larger Phase Three trials… its share price shot up. 

This was during the peak time of meme-stocks, when internet popularity on sites such as Reddit would create hype around specific stocks. 

Cassava Sciences became the darling of small, dedicated investors on the Nasdaq stock exchange. The stock is referred to as SAVA – and so the investors became known as “Savages”. (It works much better with an American accent – Cassava… savages).

“So Cassava Sciences, our best stock of the year, we said at the beginning of the year could be the best stock of the year and for a while it was and it’s still up there… “ Clip from Joe Springer’s Investors Club YouTube channel

“Would you believe me if I tell you that my Discord members gifted me $7,500 for my SAVA stock tip that jumped 700% in just two weeks? Clip from the Millionaires Investment Secrets YouTube channel

Samantha Weinberg, narrating: The investors we spoke to all say they had personal, as well as financial, reasons for investing in the stock. A family history of the disease… the fear that one day they, or their children, would be assaulted by it… and there wouldn’t be a cure. 

Many of these investors congregate online in subreddits or Discord servers to discuss Cassava’s work. To pore over reports and research, to pick apart criticism and competitors. 

Rob – that’s not his real name – is a lawyer based in California. His wife is genetically predisposed to Alzheimer’s disease, and he first bought Cassava stock in the summer of 2021, when the share price was surging upwards. He’s in regular touch with other investors from around the world. 

Rob: Many of them are very, either from their own background, you know, scientifically literate in this area, or willing and able to really dig into the papers, dig into the release numbers, and tease out as much as possible from the, you know, information that’s released.

Samantha Weinberg, narrating: Speaking to Cassava investors… I recognise the same level of obsession that I see in Elisabeth Bik. 

They are almost evangelical about Simufilam. 

Samantha Weinberg: If either of you had a family member with, uh, showing symptoms of Alzheimer’s, would you encourage them to go on a trial?

Matt Nachtrab: Absolutely. 

Rob: That’s a decision 100% based on the like, uh, underlying data and the papers – not based on any kind of financial incentive. 

Samantha Weinberg, narrating: Last summer, the future was looking really bright for Cassava. By July 2021 it had a market capitalisation of 5 billion dollars. That’s about twice the current market cap of Marks & Spencers. For a firm with no lab, no customers, no approved product. Just hope.

That was… until August. 

When a citizen’s petition was filed to the FDA. 

It was filed by Jordan Thomas, a Wall Street lawyer who specialises in representing whistleblowers, on behalf of two unnamed clients. In the opening salvo of his covering letter he wrote: “Cassava Sciences apparently didn’t get the Theranos memo.” 

“We have some breaking news we want to get to out of California, concerns the Elisabeth Holmes trial. The verdict is in: the disgraced Theranos founder and CEO found guilty on four of 11 counts in her landmark Silicon Valley fraud case. The jury reaching a verdict just moments ago after 7 days of deliberations…” NBC News clip

Samantha Weinberg, narrating: The petition, which was accompanied by a 42-page scientific report, claimed that some of the research behind Cassava’s drug raised “red flags,” and that the data associated with the trials “strongly suggest scientific misconduct” and “systematic data manipulation”. 

It urged the FDA to pause upcoming clinical trials. 

And it implied that Cassava Sciences is built on a house of cards. Or, perhaps more accurately… a house of shaky science. 

Within days the Cassava stock collapsed. The company lost billions of dollars in value. 

With this great new hope shattering around them, not to forget the dwindling value of their shareholdings… the Savages were furious.

Rob: We have 6 million people in the US dying of this disease and effectively zero real treatment. You know, it, it blows my mind and it’s, uh, it’s, it’s hard not to get, you know, physically angry, talking about it, you know, this could affect my family again.

Samantha Weinberg, narrating: But they weren’t angry at Cassava Sciences. They were angry at the men who filed the petition. 

Because here’s the rub: Jordan Thomas’s clients turned out to be two scientists who had never worked at Cassava. 

And they’d shorted the stock – sold an undisclosed number of shares that they didn’t yet own, at a high price, in the expectation that it would fall. In essence, the whistleblowers had bet on Cassava failing, and, from their point of view, the quicker the better. 

For them, Cassava’s crash would have been set to the music of clattering coins. 

***

You can see the dramas hitting Cassava Sciences by tracing the alpine profile of its share price. 

Matt Nachtrab, who you heard earlier telling his grandfather’s story, is a full-time investor. 

He decided to buy shares after the citizen’s petition. And he was so outraged by what he considered to be unfair criticism, that he became a significant investor. (He bought a total of 500,000 shares which, even after the price slumped, must have still put him back… well, do the math): 

Matt Nachtrab: They’re using the term whistleblowers. And the standard definition that you think of with whistleblower is somebody from the inside. They’re not from the inside. They’ve never been from the inside. They didn’t process data for Cassava. They were not a contractor for Cassava. They had nothing to do with any of it. 

Samantha Weinberg, narrating: Anyone can submit a citizens’ petition to the FDA. 

And Jordan Thomas’s clients also filed a whistleblower tip with the Securities and Exchange Commission, the SEC. That’s the US financial watchdog. 

It’s a quirk of the whistleblower’s programme that you don’t need to work within a company to submit a complaint. 

Whistleblowers do stand to earn a bounty, if their complaint is upheld. And, let’s not forget, in this case, they’d already earned an undisclosed amount from shorting the stock. (It’s worth pointing out that shorting stock is not illegal.)

When we approached Jordan Thomas, he declined to comment, on behalf of himself and his clients, but added: “Cassava is a very interesting case…”

We know from other interviews, though, that his clients, who both have backgrounds in neuroscience research, decided that the data behind the company just didn’t stack up. 

They’re not alone. 

Matthew Schrag: I’m Matthew Schrag, and I live in Nashville, Tennessee, and work at Vanderbilt University. And I run a little research laboratory studying the relationship between Alzheimer’s disease and blood vessel diseases of the brain.

Samantha Weinberg, narrating: Matthew Schrag is a neuroscientist, and a practising doctor, who’d been vocal with safety concerns about clinical trials for another potential Alzheimer’s drug. 

Which was probably why Jordan Thomas approached him last summer to compile the scientific report which underpinned the citizens’ petition.

Matthew Schrag: And what I found in my evaluation of that work, um, was that there were some pretty concerning red flags. And that the pattern of red flags was pretty pervasive. It was, um, you know, it’s distributed through a fairly large body of the work that underlined the development of this drug. 

Samantha Weinberg, narrating: Matthew found some images that he believed had been duplicated, rotated, or spliced together.

And it wasn’t just images that he claimed smelled a bit fishy… 

Matthew Schrag: So as we got deeper into the analysis one of the things that struck me was that some of the methodologies that they were using simply didn’t seem viable. And one of the most striking elements was that they were testing the drug on dead human brain, um, that had been archived for prolonged periods of time, and they were showing, um, pretty remarkably complex biological effects of the drug in dead minced-up brain that had been frozen for a long time, which just to me didn’t make a great deal of sense. And some of the things that they were suggesting that they could show required the tissue to synthesise, uh, new proteins very rapidly. And of course, dead brain simply doesn’t do that. 

[Pause]

Samantha Weinberg: Um, sorry, you kind of got me at the minced up dead brains…

Samantha Weinberg, narrating: This is where Elisabeth Bik stormed in. If anyone can spot a manipulated image, it’s Elisabeth. It is her domain. 

She started looking into the Cassava research herself….

Elisabeth Bik: And so all of these concerns, most of them, at least, I agreed with. I found some additional ones. And I posted all of these on a website called PubPeer, where you can comment on papers. But I like to post there because I like to warn other readers that there might be a potential problem with a paper. 

Samantha Weinberg, narrating: And she did what Elisabeth Bik does: she wrote about it in her blog, and she tweeted about it, to her 130,000 followers. And, it provoked attention, and pushback, from supporters of Cassava. But once Elisabeth gets something between her teeth, she doesn’t let go. 

She’s at pains to tell us that her concerns about the images don’t necessarily mean that the drug doesn’t work. She doesn’t have an opinion on that. 

But, it seems to me that she can’t stop herself from diving into controversies.

Most of the research and development related to Cassava Science’s drug Simufilam was done by Hoau-Yan Wang, an associate professor at the City University of New York. 

In fact, he’s the author of every paper written about the drug, and the leading researcher working on the mechanism it uses. His lab receives funding from Cassava. 

Several of Dr Wang’s papers were co-authored by Cassava’s senior scientist, Dr Linsday Burns. Dr Burns, who won a silver medal for rowing at the Atlanta Olympics, is married to Remi Barbier, the company’s CEO.

Following the citizen’s petition, Remi Barbier issued a statement…

Voiced by an actor: Let me be very clear: I think these allegations are false… We intend to vigorously defend ourselves and our stakeholders against false and misleading allegations.

You can see how they line up. On one side, the ranks of people who benefit financially from the stock going up. They include the Cassava bosses – and Dr Wang, who is eligible to receive bonuses linked to the company’s share price. 

On the other side, the people who short the stock and profit from it falling. 

And in the middle, in no-man’s land, are the Alzheimer’s patients on the Simufulam clinical trial.

These include Hilary Metz’s dad, who you heard about earlier. She believes Simufilam has made a difference. He’s making his own coffee again, and driving. Her mum feels able to leave him alone at home.

Samantha Weinberg: And so when the criticism and controversy surrounding Simufilam started sort of whirling around, how did that make you feel?

Hilary Metz: Uh, pretty angry, especially because I’m probably 99.9% sure that the people criticising it and wanting to shut it down don’t know anyone in the study I’d, I’d love to hear from a critic or someone trying to, you know, make a financial gain off the company that has a family member on the drug.

Samantha Weinberg, narrating: But wanting something to work, and even believing it does, doesn’t mean that it will. 

That first shot fired by the whistleblowers has set off an avalanche of trouble for Cassava. 

The NIH, which provided nearly $20m in grants for Simufilam, has withdrawn funding and is reportedly investigating the company. 

Nine clinical research sites have reversed out of running patient trials… and the Alzheimer’s Association, the largest US dementia charity, no longer wants Cassava to sponsor several fundraising events. 

That’s not all. 

Although the original FDA petition was rejected, there are purported to be two active on-going investigations by the SEC, which polices fraud and market manipulation. An SEC spokesperson declined to confirm or deny these investigations. 

And according to Reuters… 

“The US justice department has reportedly opened a criminal investigation into the austin texas based biotech company cassava sciences…” News clip

Samantha Weinberg, narrating: (The Department of Justice did not respond to our request for confirmation.)

Cassava Sciences declined to confirm whether any of these investigations were taking place. 

In a statement last year it said it had been cooperating with requests for company information from government agencies, but had not been informed that the company, or anyone associated with it, had engaged in wrongdoing. 

Meanwhile, the City University of New York is investigating Dr Wang. Some of the journals have retracted the papers containing suspect images; others are sticking by the research and say they’ve found no evidence of manipulated data. 

Neither Dr Wang nor Dr Burns responded to our request for comment. 

Cassava stock has failed to bounce back to the highs – though it’s still very much alive; at time of writing, the company was valued at $1.41 billion. The original whistleblowers have kept their counsel since the publicity over the original petition. 

Online, the battle rages on. 

More short sellers – separate from the whistleblowers – have swooped in, clearly thinking that the only way is down. 

And these new, opportunistic shorters have embarked on an aggressive publicity campaign of their own, setting up dedicated websites, which repeat many of the claims in the original petition, and worse. This is one of the things that really incenses the Savages.

But it’s Elisabeth Bik who seems to draw most of their ire. 

“Hello investing friends, welcome into Investors Club. Got a great show for you, got a great takedown of the not-great, ha, not-great Elisabeth Bik.“ Clip from Joe Springer’s Investors Club YouTube channel

Elisabeth Bik: I mean, it’s all, it’s, you, you could call it sort of innocent, but it’s, it does eat on me because you… if you get a constant stream of negativity and, and people calling you all kinds of names, like you’re a failed scientist, that actual, that one hurts even more than calling me a bitch because I, I do like, you know, to be considered a scientist.

Um, yeah. And, and, and threats of lawsuits, threats of, um, you know, we’ll take, uh, we’ll avenge you or wording like that. There was a photo of… my photo was photoshopped on the grave with, you know, the people of, um, the Cassava Science, um, CEO standing next to it, smiling, you know, photoshopped, heads on on another photo. But I find those things pretty threatening. 

Samantha Weinberg: Yeah. I mean, do you feel…

Elisabeth Bik: If it’s a grave, yeah. 

Samantha Weinberg: Do you feel physically threatened? Has it made you look behind you? 

Elisabeth Bik: Not physically, no. But some of these people, you can figure out who they are. They live close to me and, and that is sometimes scary. I, I think in general I’ve become a little bit more careful about not saying where, where I am at a specific moment. Um, or not in general disclosing my home address. 

Samantha Weinberg, narrating: In early November there was an attempt to vandalise her Wikipedia page. The page editor called her “a failure of a woman,”, “an evil person” and accused her of taking bribes. 

Elisabeth Bik is often accused of profiting from her criticisms, but she assures us that’s not the case. She says she earns money through speaking events, consulting and donations on Patreon – and has never been paid to look at Cassava Sciences. To the best of her knowledge none of her donors have short positions in the company. She’s critical of anyone using this to make money. 

Elisabeth Bik: Trying to bring down the, the, the stock price. And so you, you, you actually win a lot of money, I don’t know if that’s illegal or not but that’s far outside my expertise, but that’s not good. But I do not own any stock, uh, in Cassava or in any of its, uh, competitors.

Samantha Weinberg, narrating: Matthew Schrag is upfront about being paid $18,000 by Jordan Thomas, the lawyer, to look at the research. He tells us he’s never held a short position or any other investment in the stock or a competitor. 

When asked if he stood to gain financially from any of the investigations into Cassava Sciences, or was promised any money beyond his original fee, he said he had “no ongoing commitments from Jordan Thomas”. 

What strikes me most about the Cassava Sciences story is how murky this whole world is. Abuse bombs are being lobbed every which way… Perhaps naively, I thought that the science, at least, would be clear.

***

Samantha Weinberg, narrating: At some point last week, I had to check myself. I was getting hooked on the big-money bets around Cassava Sciences. 

Whatever the Savages may think, I’ll wager that Elisabeth Bik doesn’t have it in for them, not personally.

She isn’t trying to tell us whether Simufilam works or not, only that the images in the papers about it appear to have been manipulated. 

She scans around 300 papers a day, in all manner of scientific journals. And she is only really looking at the images – whether they are being used to validate a vaccine, or to detect pancreatic necrosis virus in chum salmon. 

Elisabeth is seeking out chinks in their integrity. 

Elisabeth Bik: There are papers in science where people have cheated, and this is the complete opposite of what science should be, in my opinion. And we should, as a society, be mad about that. We should believe in science, but we should be mad about people cheating in science because science in general is funded by government money. In the end, all of us taxpayers pay for science. So science should be public, but it should also be done correctly. It shouldn’t be corrupt. It shouldn’t be, uh, resulting in fraud. And if people fraud in science, there should be consequences for them. And there seems to be very, very little. 

Samantha Weinberg, narrating: She wants there to be consequences, so she publishes all her findings online.

Of the 100,000 papers she’s looked at she’s found problems in 6,578. 

935 of those have been retracted, 956 of them corrected. Expressions of concern have been slapped on 121.

She used to write to each of the journal editors, but she found that ultimately frustrating, as they often didn’t respond. 

Safe to say, she’s not their favourite correspondent. 

Holden Thorp is the editor-in-chief of the peer-reviewed academic journal Science

Holden Thorp: But the thing about Elisabeth to keep in mind is that every journal editor hates hearing from her because it means there’s something that we have to deal with. But she’s usually right. 

Samantha Weinberg, narrating: Science publishing isn’t the same as normal journalism or book publishing. It’s woven into academia.

For a scientist working in a university lab to progress – to get their own lab, promotion, funding – they need to publish. 

Elisabeth Bik: If you try to rush that by demanding so many papers to be published, then you, it becomes very tempting to cheat. And also it’s much easier to publish positive results, good, shiny, beautiful findings than what most of science is, which are negative results. Like, it doesn’t work. And, and so a lot of cases the results are negative and a lot of journals do not want to publish that.

Samantha Weinberg, narrating: Shiny new ideas are also good for the publishing companies’ bottom line, it appears.

At a time when mainstream newspapers and glossy magazines are dying, the business of scientific publishing is booming. Elsevier, which owns nearly 3000 journals, regularly posts ten-figure profits – that’s over a billion dollars.

It does this largely by a clever form of double dipping. Publicly funded scientists submit papers, for which they are not paid, which are peer reviewed by other academics, who are also not paid. Institutions and individuals then pay hefty yearly subscriptions to access these papers… or in some cases pay thousands to get them published with “open access”. 

It’s a nice business model, if you’re in it.

So with all that money… what are they doing about fraud

Here’s Holden Thorp again from Science – which, he took care to emphasise, gives its profits to the American Association for the Advancement of Science. 

Samantha Weinberg: I mean, it does seem that there’s just so much temptation, um, for the scientists and so many push and pull factors to submit these, these papers with fraudulent images.

Holden Thorp: Yeah, and you have these commercial, you have these commercial juggernaut publishers that are making money on every paper that comes in, so that’s, that’s the pull factor.

Samantha Weinberg: So it’s a real, it’s it’s like a systemic failure with… ? 

Holden Thorp: Yeah. But it’s probably, it’s probably too big to change dramatically because the universities don’t have the capacity to evaluate scientists for promotion or hiring without using the journals as a proxy. And so unless somebody figures out how to solve that, um, which some people are trying to do, then we’re gonna have to keep trying to fix this plane while it’s flying . 

I think if we get better and better at picking these things up, we’ll get more efficient at correcting these things. And, uh, it’s, it’s totally fair to criticise science for some that, that this happens. But it’s also not fair to say that science is just groupthink that, uh, proceeds based on ambition, uh, and corruption – because in the long run we all are bought into a system that will correct these things eventually, and that’s why people Elisabeth Bik are very important to the way science goes, goes forward. 

Samantha Weinberg: I like the idea that when Elisabeth Bik finds a fraudulent image, that’s both a success and a failure. You know, it’s a failure of the scientist in the first place, but she’s, she’s highlighted something, which then can be corrected. 

Holden Thorp: Yeah. Correct. And congratulations to her for capturing people’s imagination. She’s an activist and she’s really skilled, and in the long run, science is better off because she’s doing all this. 

Samantha Weinberg, narrating: I don’t know if I’m as buoyed by Elisabeth Bik’s solo campaign against systemic failure as Holden Thorp. 

These things don’t happen in a vacuum. The doctored images the journals fail to sift out can be used to prop up shaky science that could be sending researchers – who, let’s not forget, are largely funded by our taxes – down the wrong path for decades. They could provide false hope, sheltering in billion-dollar companies. 

Which is how we arrive back at Cassava Sciences. 

A year on from the citizen’s petition, Cassava Sciences is caught in a thicket of investigations. 

The drama is still unfolding. 

In early November, there was an editorial published in the Journal of Clinical Investigation, one of the journals that has not rowed back on papers by Dr Wang. 

It decried so-called “short and distort” campaigns, an illegal practice whereby short investors spread rumours in an attempt to drive down their stock’s price. The editorial also called for whistleblowers to declare conflicts of interest.

The very next day, Cassava Sciences issued a muscular writ against a rag-bag of short sellers – as well as the two original whistleblowers. It accused them of spreading lies and disinformation so as to manipulate the share price and line their pockets.

In a statement, CEO Remi Barbier told us:

Voiced by an actor: We believe certain individuals, including some located in Europe, have waged a ‘short & distort’ campaign against Cassava Sciences and its research. Cassava Sciences recently filed a lawsuit against such individuals.

He went on to ask the media not to enable this campaign by republishing false allegations against the company and its research. 

To borrow a term used by Elisabeth, it’s a hairball of conflicting accusations, largely flung by people with lots of money on the line, being played out in journals, which themselves are raking in profits. 

What upsets me is the people caught in the crossfire – like Hilary’s dad.

Hilary Metz: You can say someone’s family member has Alzheimer’s but until you get a look inside that home and see how it affects everyone, and potentially everyone’s lives and how that’ll change, and feeling like you’re losing a family member, one memory at a time. It’s, um, you know, it’s not a good feeling at all. 

Samantha Weinberg, narrating: In the giant pharma casino, the stakes are hope and despair. 

Matt and Rob, the Cassava evangelicals, are sitting at the green baize table. Alongside the Cassava bosses, and the whistleblowers and the short-sellers. 

The Savages would say Elisabeth Bik is there too, but I like to think of her as the casino detective, trying to figure out who is counting the cards. 

Just not very undercover.

Thanks for listening to this episode of the Slow Newcast from Tortoise. It was reported by me, Samantha Weinberg, and produced by Claudia Williams. The editors were Jasper Corbett and Ceri Thomas. With sound design by Mau Loseto. 

How we got here

A few months ago, a story halfway down the news agenda caught our attention: an important paper about Alzheimer’s research, published in an august science journal in 2006, was said to have been based on manipulated images. We went to meet Elisabeth Bik, a full-time “science sleuth”, to see how widespread an issue it was. 

Wide, it turns out. 

But by the time we left we had been sucked into another story, about a revolutionary new drug for Alzheimer’s Disease, that – depending on who you listen to – is either going to provide hope for millions of people living with the disease, or is based on a load of scientific hooey.

Before long, we were wading through a morass of allegations and insults, lawsuits and investigations that threaten to engulf Cassava Sciences, the firm that developed the drug. Jasper Corbett, Editor


Past reporting

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