Charles Piller is a multi-award-winning investigative science journalist at Science magazine, author of two investigative books about science, and founding board member of the Center for Public Integrity. His recent investigation into possible scientific misconduct and fabrication of images in Alzheimer’s disease research has sent shockwaves through the Alzheimer’s research community.

How did you get into science journalism?

My college degree is in psychology but I’ve always been interested in scientific and technical topics. I ended up doing a lot of freelance writing and writing books early in my career – one was on genetic engineering and biological warfare, and the other one was on public attitudes toward science and technology.

I covered technology for quite a while. I worked at computer magazines, then I worked as reporter at the Los Angeles Times covering first technology then science, infectious diseases, a wide range of subjects. I moved over to another newspaper in California, the Sacramento Bee, and I did a range of investigations. I did three years of reporting on bridge engineering, believe it or not, because there were some really serious problems with important bridges in California.

After the Bee, I went to a website called STAT, doing a variety of reporting, mostly enterprise and investigative reporting there. Now I’m in Science, and I’ve been here for the last four and a half years doing investigative reporting.

What are the principles that define investigative science journalism for you?

I identify primarily as an investigative reporter that writes on scientific subjects, so I think it pretty much is the same as any other kind of investigative reporting.

You have to be willing to commit the time to dig deep. Science subjects offer their own complexities, and it’s so easy to make what might seem like a small mistake to a lay person, a non-scientist. But if part of your audience is the scientific community, you can’t do that or your credibility is destroyed.

That adds on to the importance of having the investigative elements of the stories be bulletproof. With science, there’s that added layer of taking care to do the extra work and take the extra time to deeply understand the material.

How did this story start?

I get a lot of tips for stories, and many of them – most of them – I can’t do anything with them because they’re just not for me, or people have an inflated idea of the importance of their issue, or I look into it a little bit and it just doesn’t pan out, or it doesn’t seem like it would be good for my audience. There are all kinds of reasons why ideas don’t go anywhere.

This one came to me indirectly through a colleague, who was approached by a scientist who was in touch with a whistleblower associated with this drug, Simufilam, from Cassava Sciences. That was Matthew Schrag. At that time, he was not known publicly as being in any way associated with this controversy involving the Cassava drug.

I made contact with him, and it took literally weeks and many conversations to understand what he was up to, because it’s complex stuff. During the early period of my discussions with him, he was at the genesis of his exploration of this work beyond Cassava, involving Sylvain Lesné, and Karen Ashe and their work associated with Aβ*56 (amyloid beta star 56 proteins) and Alzheimer’s disease.

What was really amazing for me is that I was there at the ground floor, when he was just beginning to discover it, and realise the importance and potential significance to the field that his discoveries might have.

Schrag is quite a compelling character and almost ideal as a whistleblower: he’s very cautious. How important was his personality to his credibility?

I found his calm, deliberate and methodical approach and demeanour to be reassuring, in the sense of me being able to judge his credibility as a person.

But there’s a lot of different personalities out there. I’ve had stories where really credible sources have been ‘bomb-throwers’ – I use that term loosely, not literally – people who have been bombastic, excitable people, profane sometimes, but completely credible and reliable.

In either case, no matter what the scientist or the other source’s demeanour is, it’s really not a matter of that kind of credibility. It’s a matter of me being able to check out the story and validate it in all the ways I needed to to satisfy myself and my editors.

“He saw a skewing and pollution of the scientific record that could, in the Cassava case, potentially harm patients and in the Lesné/Ash case, could pollute the literature”

How did he feel about talking to you?

Understandably, he was reluctant to be named in the story. It took about four months into my work with him for him to agree to be named. The reasons were very understandable. One is that there are two aspects of the story: the Cassava Sciences aspect, and then the Lesné/Ashe aspect.

For the Cassava aspect, there’s the potential concern that this is a company with hundreds of millions of dollars, and other critics of the company had been savaged in social media. Schrag is a guy with a young family and like any of us values his personal privacy. And, of course, there’s always the concern or the possibility of being sued.

The other side of it was even a more compelling concern. He’s early in his career, and he depends on the relationships with eminent scientists in his field, and with the ability to publish his work in the leading journals that publish Alzheimer’s studies, and with institutional authorities at the National Institutes of Health that were also implicated in my story.

When you look at all that together, he was in a position of possibly putting his career at risk by alienating all these players who would be important in his own success, so he had to think long and hard about it.

But he’s a very principled guy. The bottom line was, he saw a skewing and pollution of the scientific record that could, in the Cassava case, potentially harm patients and in the Lesné/Ash case, could pollute the literature to misdirect the work in such a way where the scarce funding for biomedical research perhaps is going in directions that are not well supported and would delay ultimate success in curing the disease.

Was there a particular thing that tipped him over into deciding to go on the record? What was that moment like?

It took a long time for him to make his peace with two things. One is that he could trust me. This was over dozens of conversations and a long visit to Nashville, where he’s located, and for him to be able to trust me as someone who would tell the story with care and in enough depth so that readers could understand the context. The second thing was that he had to make his peace with his wife and her valid concerns about how this might affect his family.

I had a few conversations with him where it was laid out like this: he and I had a confluence of interest, we both have the interests of writing the best, strongest, most evocative story that would reach the greatest audience and be compelling to people so that they would understand the significance of it. We both agreed that by using him as a character through whose eyes I could tell the story, we would be able to create a narrative that would be possible to have that kind of compelling story.

Where our interests diverged is that I’m a journalist; my highest and most important loyalty is to my readers. On the other hand, of course I care about him. I am not interested in manipulating anyone. He’s a sophisticated guy, so he wasn’t going to be manipulated anyway. I made it clear on many occasions that his interests are different from mine – we have a confluence of interests, but our risks and our needs are different.

I told him repeatedly, ‘I want you to be in the story, I think it’s critical to making this story work well, but there’s going to be a story if you decide not to anyway’. I also told him that I wouldn’t fault him or think less of him if he decided he didn’t want to do that.

But ultimately, he decided he did. He decided that he wanted to make it the strongest story that he could.

“I made it clear on many occasions, his interests are different from mine, we have a confluence of interests, but our risks and our needs are different.”

Did the scientific complexity of this mean it needed a scientifically-literate audience?

Schrag certainly had ample opportunity to do it with a major newspaper. But the reason why it came to me and it ended up in Science Magazine, is that both Schrag and the person who connected me with him viewed doing it with me as an opportunity that would be different from trying to do it with the Wall Street Journal or the New York Times.

His hope was that Science could give it the real estate and the depth and the nuance that could tell the different sides of the story more fully and more clearly. He cares a lot about how this was received by the scientific community, more than the general interest community.

How difficult was it for you to capture that scientific complexity and nuance?

I don’t think it was it was any harder than a lot of other stories I’ve done. You have to put in the time – I can’t be faking it until I make it. I can’t educate myself so much to become a true expert in Alzheimer’s disease in six months, but I can learn enough to be clear in the context, clear in the history, and to understand the science and technical details that are essential to get right and to put it into context in an accurate way.

Not everyone’s going agree with the story and there are people who are criticising it. But no one’s suggesting that I got any facts wrong. That’s the key.

How did you feel the night before it went to print?

I don’t do that many stories; all my stories are deep dives. But I do lose a lot of sleep in the last couple of weeks before they run. That’s the period in which I am obsessively checking and rechecking, every fact, every word, every sentence or its meaning.

Lots of eyes are poring over the story at the magazine, and then I’m taking a fresh look at it. I’m working on it so hard that I do achieve a degree of confidence that I’ve got it.

That said, I’m a human being. I have made mistakes. But my goal is if any mistakes are made, they’re extremely minor. I certainly try for perfection, but it’s hard to achieve, especially in an article that’s 5500 words long, and involves a lot of moving parts.

But yes, it can be nerve wracking. In a way, it’s overcome by the excitement of being able to do something that might be worthwhile.

“Not everyone’s going agree with the story and there are people who are criticising it. But no one’s suggesting that I got any facts wrong. That’s the key.”

Science conducted some of its own investigations for this story, getting researchers such as Elisabeth Bik involved. Is that unusual?

No, it’s not unusual. We do a lot of investigations. Science has a dedicated investigative fund that underwrites a lot of the investigative work the magazine does. We see it as an integral part of telling the story of science, in a way that serves the research enterprise.

Both Lesné and Ashe declined to comment. Did you expect that or was it a blow?

I expected it, only because I’ve had a lot of experience approaching people whose work has been challenged in a serious way, and if people don’t have a good story to tell, they are often reluctant to speak to journalists.

I make multiple efforts to talk to people in that circumstance, including those two. I begin by telling them in general what I’m writing about and asking them if they’ll talk. If those efforts are unsuccessful, I never ever want there to be any surprises. What I ended up doing was sending each of them the complete dossier by Matthew Schrag that details the concerns about their images, plus a list of detailed questions from me, so that they could judge by the questions what my article was going to be about in detail.

In my article there was a there was a short quote from Ashe basically defending her work without answering any questions. Of course, she has whatever obligation she might feel to follow whatever her university’s guidance might be on whether to talk to the media about something like this. But I told her that, in my experience – and this is completely true – it’s almost always better for the person who is the subject of this sort of an article to talk with the reporter.

Even if the questions are uncomfortable and awkward and difficult to answer, and even if as a scientist, you have gaps in your ability to respond in a way that maybe doesn’t reflect well on you, it’s almost always better to give some of your point of view, and to be able to let readers see you as a person, and someone who can own up to the difficulty of the circumstances, even if you can’t answer every question. I firmly believe that. Of the many stories I’ve done that have involved possible malfeasance or problems or other kinds of harm in science, I think people always benefit by talking to the reporter.

But it’s not typical, most people will refuse. That’s just the way it goes.

Was there a sense of the inevitable about this; that there had to be a weak link somewhere to explain why so many drugs targeted targeting amyloid protein in Alzheimer’s disease have failed to have an effect?

I would put it a little differently: skepticism in the amyloid hypothesis is warranted. When you have decades of research, drug after drug, trial after trial, failure after failure after failure, any reasonable person would ask the question, ‘is there something more fundamentally dubious about making this the dominant hypothesis associated with Alzheimer’s disease?’ To me, that’s an eminently reasonable question.

I think what my story seems to be doing, and perhaps has the opportunity to do, is to create a watershed moment where it becomes impossible to look away.

There’s been a lot of scepticism about the amyloid hypothesis for a long time. My story about this one body of research doesn’t invalidate all the work being done on amyloid. But it does create an opportunity for people to take a step back and say, what do we need to think differently about? How could this go so badly wrong? What is our obligation to families, patients and the research community to clean this up and to use it as an object lesson for how we can adjust our thinking going forward?

What has the response been to the story?

It’s been mixed. There are a lot of people who are grateful for this opportunity to take that hard look and to rethink and to question the dominance of the amyloid hypothesis and the amyloid toxic oligomer hypothesis.

There are others, including some prominent voices in the field, who disagree. I can’t really speak for them, but I can reflect on a little bit on what has been said.

Karen Ashe has responded in a way that I find troubling. She has minimised and misrepresented the degree of apparent manipulation in work that she was directly involved with, and that is fundamental to her ideas about Aβ*56. She has said ‘it’s lamentable that a colleague of mine might have manipulated images, but it means nothing, all of my ideas are fine, all the experiments are fine’.

This is illogical. It’s beyond illogical – it’s troubling, because for her to make that kind of declaration, even before a real investigation has been done by her own university, to me is certainly not very scientific.

There has been some pushback from leading advocates and proponents of the amyloid hypothesis. It goes something like this, ‘well, we were always sceptical of this Aβ*56 stuff and it really didn’t affect the field very much and the rest of this work in oligomers is very strong and vital, and people should just not worry about this, because it doesn’t have any impact.’

This is also so unscientific and so contrary to the known scientific record. This study has been cited more than all but four other basic research papers on Alzheimer’s disease since 2006. There’s been thousands of studies, so its influence is undeniable. Some of the people who are discounting this now have been citing this study as the underpinning of their own ideas for years.

I think it’s natural for people to be a little defensive when, to some degree, their own life’s work – namely the amyloid hypothesis – and proving it out has come under some question as a result of academic colleagues having perhaps engaged in improper activities in the field. So I can understand the defensiveness. I think it would be beneficial for those folks to show a bit more humility.

“Oh, they’re shooting the messenger, believe me. But you have to have a thick skin if you’re going to be doing this kind of work.”

How has been the response for you personally?

Oh, they’re shooting the messenger, believe me. But you have to have a thick skin if you’re going to be doing this kind of work. I’m not concerned about that. What I’m happy about is that there’s just been an enormous amount of public interest in the story. And once there’s been so much media interest, you just have to let it play itself out and let the field adjust and people come to their own understanding of it. I obviously can’t control that.

Some of the some of the coverage has been terrible, and some of it’s been used for purposes that I abhor. For example, Tucker Carlson [conservative political commentator and TV host in the US] has done two segments on my story. He basically is using it as a way of saying that if this one set of research was invalid because it was manipulated improperly, then all Alzheimer’s research for the last 16 years is fake, and if all Alzheimer’s research is fake, all science is fake and can’t be trusted. Of course, this is beyond abhorrent, and it’s being used and manipulated for political purposes.

Even though that’s painful for me, I’ve actually been asked, ‘do you have any misgivings about doing such a story when it can be used in that way?’ And, my view is, what alternative do we have? It’s our responsibility as science journalists to try to help move public understanding, and the only way the field is going to advance is by cleaning up this kind of stuff and by science self-policing. I think the example of Matthew Schrag shows that the field is capable of policing itself.

Charles Piller spoke to Bianca Nogrady