'Doctored' by Charles Piller exposes scientific misconduct in neuroscience

A deep dive into research fraud, its impact on clinical trials, and the need for reform.

Illustration by Kateryna Kon

By Raisa Hani

Doctored: Fraud, Arrogance, and Tragedy in the Quest to Cure Alzheimer's, by Charles Piller

In Doctored: Fraud, Arrogance, and Tragedy in the Quest to Cure Alzheimer's, Charles Piller delivers a compelling work of investigative journalism, concentrating on malfeasance in neuroscience research. While it occasionally explores broader scientific theories, such as the potential causes of Alzheimer’s, the book truly shines in its riveting exposé of scientific misconduct.

Much of Piller’s investigation stems from the meticulous work of Matthew Schrag, a neurologist at Vanderbilt University. In 2021, Dr. Schrag was approached by a pseudonymous source who claimed to have critical information about the drug company Cassava Sciences. The company was under investigation for allegedly manipulating research data to promote its experimental Alzheimer’s drug, Simufilam.

Dr. Schrag’s analysis uncovered major issues in research conducted by Hoau-Yan Wang, a Cassava contractor, and Lindsay Burns, the company’s chief neuroscientist. Using advanced image analysis, Schrag identified evidence of manipulated images in their papers, which raised “egregious red flags.” Piller’s reporting confirms that these findings led to federal investigations, with Wang and Cassava facing charges of fraud and misleading investors. Cassava eventually settled with the SEC for $40 million, though no wrongdoing was admitted.

Schrag’s efforts also revealed manipulated images in unrelated Alzheimer’s research, including a 2006 Nature paper led by Sylvain Lesné. This paper, which identified a protein linked to Alzheimer’s, has been widely cited and funded by millions of dollars in NIH grants. Lesné and his colleagues faced scrutiny, leading senior author Karen Ashe to retract the paper, acknowledging that some images had been manipulated.

Piller’s Doctored underscores the vulnerabilities within the scientific research process. Peer review, often regarded as the gold standard, lacks the thorough safeguards needed to detect fraud. Reviewers rarely have access to raw data, relying instead on the accuracy of the submitted manuscript. Additionally, identifying manipulated images requires expertise and resources that many reviewers do not possess.

These shortcomings are exacerbated by the pressures of grant funding and professional advancement. Researchers are incentivized to produce groundbreaking results, sometimes at the expense of ethical integrity. As Piller notes, this creates an environment where misconduct can thrive, with devastating consequences for scientific progress and public trust.

The dramatic climax of Doctored occurs when Schrag himself faces allegations of misconduct. Critics on PubPeer, a platform for discussing scientific publications, pointed out manipulated images in papers he co-authored as an undergraduate. Although Schrag denied any wrongdoing, his mentor, Othman Ghribi, admitted to issues in multiple papers. This revelation left Schrag devastated, highlighting how pervasive scientific fraud can be, even among those dedicated to uncovering it.

Piller uses Schrag’s story to illustrate the personal and professional challenges faced by whistleblowers. Their work often involves significant sacrifices, from strained relationships to lost opportunities. Yet their efforts are crucial for holding the scientific community accountable and preventing further harm.

The misconduct documented in Doctored extends beyond individual researchers. It raises fundamental questions about the integrity of scientific institutions and the mechanisms designed to uphold it. Piller criticizes the NIH, pharmaceutical companies, and regulatory agencies for their complacency and, in some cases, complicity in perpetuating fraud.

The book also highlights the ripple effects of scientific misconduct. False data can mislead subsequent research, waste valuable resources, and jeopardize patient safety. In the case of Cassava Sciences, the manipulation of data not only misled investors but also delayed the development of legitimate treatments for Alzheimer’s.

Piller proposes several measures to address the systemic issues that enable fraud. These include:

Increased transparency: Requiring researchers to share raw data with peer reviewers and the public.
Enhanced oversight: Strengthening the review process to include experts capable of detecting image manipulation.
Reducing conflicts of interest: Limiting the influence of funding agencies and pharmaceutical companies on research outcomes.
Cultural change: Promoting ethical conduct and discouraging the pressure to produce sensational results.

While these reforms would require significant investment, they are essential for restoring trust in the scientific process.

Until systemic changes are implemented, investigative journalism remains a vital tool for exposing misconduct. Piller’s work exemplifies the power of journalism to hold powerful institutions accountable and protect public interests. His commitment to uncovering the truth serves as a reminder that science, at its core, relies on honesty and integrity.

Charles Piller’s Doctored is a sobering exploration of scientific fraud and its far-reaching consequences. Through meticulous reporting and compelling narratives, Piller sheds light on the ethical breaches that undermine the foundations of medicine and research.

For anyone invested in the future of science, Doctored is an essential read. It not only exposes the flaws in the current system but also offers a roadmap for creating a more accountable and transparent research environment. By championing the work of whistleblowers like Matthew Schrag, Piller reminds us of the importance of vigilance and the enduring pursuit of truth in science.