A cascade of mistrust

Charles Piller is an investigative journalist for Science. In Doctored, he describes in considerable detail two examples of fraud concerning well-publicised findings. His key helper in this endeavour is Matthew Schrag, a neuroscientist at Vanderbilt University, Nebraska, who is an expert in digital manipulation of images. 

In the first case, suspicions had been aroused concerning a drug being trialled that the makers claimed arrested brain tissue decay. The other major investigation, probably better known, is the 'discovery' by Karen Ashe and Sylvain Lesné of Amyloid-Beta star 56, claimed by Ashe to be 'the first substance ever identified in brain tissue in Alzheimer's research that has been shown to cause memory impairment'. 

This 'finding' was important because it gave credence to the 'amyloid cascade hypothesis' – the idea that amyloid beta protein set off a chain reaction of cell damage, proposed by the British neurogeneticist John Hardy and Gerald Higgins in a 1992 paper. This offered a paradigm for understanding Alzheimer's and pointed the way to drug development – destroy the accumulation of beta protein in the brain. But as Schrag pointed out, 'Even if amyloid does cause Alzheimer's disease it does not necessarily mean you can cure the disease by removing it…. If someone came to the emergency room with a stab wound, removing the knife wouldn't cure them either' (p.73).

The amyloid cascade hypothesis was heavily backed by drug companies, who needed that single mechanism to counter. It became a near-requirement of gaining research funding to link it to supporting the amyloid cascade. Yet as the gerontologist Mario Garrett wrote in Current Neurobiology some two decades after the hypothesis had proved unproductive, 'it was dead on arrival, existing evidence at the time already refuted this hypothesis, and researchers working in the field knew this'.

Piller documents the various ways in which the cascade came to dominate the research community. The proponents, and thereby the receivers of large research funding from drug companies and government, are often referred to as 'the Amyloid church' or 'Amyloid mafia'. Arguably, they came to control all the channels of communication – the journals, the research submissions – and of career advancement. 

This was helped by 'regulatory capture' by the drug companies of the Federal Drug Agency, responsible for the licensing of new drugs. A revolving door of its advisers joined or rejoined drug companies; the companies funded Alzheimer charities, who would then advocate for the licensing of the new drugs. 

Finally, when tasked with assessing whether fraud had been undertaken by one of their staff, universities worked very slowly and, on occasion, using equipment inadequate to show detection. Clearly, they were unwilling to incur reputational damage.

Thankfully, Schrag was joined in his detective work by a group of other concerned scientists, the best known probably being Elizabeth Bik. Widening their area of concern picked up dubious work by leading practitioners in the field. Scientific fraud is not new, and not restricted to the amyloid cascade hypothesis or to research into Alzheimer's. One has to ask whether it is now much more widespread, and not just in America.  

The book ends by returning to the two characters who were introduced at the beginning. Knowing that, because of his claims, every paper he ever (co-) authored would be scrutinised, Schrag looked at the work he did as an undergraduate with Othman Ghribi, for whom he had the greatest respect. Sadly, he and his investigative colleagues found that there was 'a litany of questionable research spanning most of Ghribi's career' (p.189). He called the episode 'the most agonising of my professional career' (p.193).

Meanwhile, Matt Price, an epidemiologist looking to help his father's dementia, read of the indictment for fraud of the scientist whose work underpinned the drug trial that he had encouraged his father to be part of. He said 'There's a kind of poisoning of the well… There's a dire need for medical research and the trust upon which that always depends' (p.274). 

How regain that trust, and whether that's even possible, not just in America but throughout the western world, are questions that the reader will be asking themselves after reading this deeply disturbing book.

• Dr Michael Bender, Honorary Research Fellow, Centre for Medical History, University of Exeter