Trust "The Science"?
Fraud, Conflicts, and the Danger of Deifying Scientific Claims
“It is simply no longer possible to believe much of the clinical research that is published, or to rely on the judgment of trusted physicians or authoritative medical guidelines,” said Marcia Angell, a conclusion which she “reached slowly and reluctantly” over her two decades as editor of The New England Journal of Medicine.[i]
In 2015, The Academy of Medical Sciences – considered to be an independent, expert voice of biomedical research in the U.K. – held a symposium to address increasing concerns over reliability of scientific research, sparked in part by an uptick in retracted papers and a failure by the industry to replicate findings in “landmark” papers.[ii]
Following the symposium, Richard Horton, the Editor-in-Chief of The Lancet – one of the world’s most respected medical journals – ominously noted that “science has taken a turn towards darkness.” “Much of the scientific literature, perhaps half, may simply be untrue,” said Horton, whether due to poor study design, flagrant conflicts of interest, or otherwise.[iii]
In what had become the most widely cited paper ever published by the PLoS Medicine journal, entitled “Why Most Published Research Findings Are False,” the legendary epidemiologist from Stanford University, John Ioannidis, found that “There is increasing concern that in modern research, false findings may be the majority or even the vast majority of published research claims.”[iv] Ioannidis flatly stated, “It can be proven that most claimed research findings are false.”
At no time has more information been so readily available to the public, for better or worse. Perhaps never before has the public been more aware of scientific claims than over the last few years, when an unprecedented pandemic has put a stranglehold on the world, upending routine, everyday life. Never-before-seen levels of government control, involving Federal and State mandates – and, ultimately those implemented voluntarily by private businesses – often had the support of a considerable percentage of the population.
That support came in the name of “The Science” – whatever study or opinion, from someone in a position of authority, in which trust could be placed. Laypeople became self-proclaimed experts in an instant. Science – or “The Science” – was, more than ever, our common language, scientists and non-scientists alike.
‘Trust the science’ became the mantra – whether about the dangers of the virus itself, the usefulness of masks, or the efficacy of testing, vaccines or treatments. But what is “The Science”? When medical experts, or scientific papers, come to different - if not contradictory - conclusions on any issue, how do we know the truth? Considering the pervasiveness of fraud – or, at the very least, ubiquitous falsity in scientific research - it becomes difficult not to question those insisting on blind trust in “The Science.”
SCIENTIFIC FRAUD
“We wish to report the results of an unusual investigation…,” sheepishly begun a 1987 article in Nature entitled “The Integrity of the scientific literature.” It was reported that a highly regarded physician, Dr. John Darsee of Harvard Medical School, confessed to a single act of data fabrication in 1981. A subsequent investigation ultimately revealed that Dr. Darsee fabricated much of the data relied upon in the preparation of his more than 100 publications over a period of three years.[v]
Diederik Stapel, a psychologist once considered an “academic star” in the Netherlands and abroad, fabricated data in over 50 peer-reviewed articles, of which he provided a detailed account in his autobiography Ontsporing.[vi] Similarly, Joachim Boldt, a prominent German anesthesiologist, was found to have fabricated data in 88 out of 104 studies between 1999 and 2010.[vii] Yoshitaka Fujii, a Japanese anesthesiologist, however, was the “biggest scientific fraud in recorded history.”[viii] Fujii published more than 200 papers over two decades. In 2012, an investigation by the Japanese Society of Anesthesiologists found that Fujii falsified 172 papers over a period of 19 years. Out of the 172 papers, 126 of Fujii’s studies of randomized, double-blind, controlled trials “were totally fabricated.”[ix] “It’s as if someone sat at a desk and wrote a novel about a research idea,” wrote the investigating committee.[x]
While the jaw-dropping outright fabrication by Darsee, Stapel, Boldt, and Fujii may be rare in scientific research, other forms of fraud may be more common that most realize. A 2009 study published in the Public Library of Science found that 2% of scientists admitted to fabrication, falsification or plagiarism in their work, while up to one-third admitted to “questionable research practices.”[xi] When it comes to what scientists suspect their peers are doing, according to a 2012 Journal of Research of Medical Sciences study, 14% think their fellow scientists are committing serious misconduct, while up to 72% believe others engage in questionable practices.[xii]
The scientific process is supposed to be self-correcting. Peer review – a process involving other experts in a given field reviewing papers for originality, validity and significance – is considered the gold standard for publication. That "gold standard of reliability,” however, has “become tarnished by greed – the desire of the research community to tap into research funds, the pressure on scientists to publish or perish, and publishers of scientific journals seeking to maximize profits,” said Dr. Glen Miller, founding director of the U.S. FDA’s Office of Biotechnology.[xiii]
Peer review, of course, is imperfect. Many articles that pass through this “gold standard” process, according to Dr. Miller, are “methodologically flawed, contain fraudulently manipulated data or obviously implausible claims, and should not have been accepted.” The problem, warned Dr. Miller, is that “sometimes the editors and reviewers are part of the deception.”[xiv]
This vulnerability came to light in the Fall of 2022, when Hindawi – a subsidiary of multinational publisher John Wiley & Sons – announced a major cheating scandal involving editors and reviewers (“peer review rings”), resulting in the withdrawal of over 500 published papers across 16 journals.[xv] Nearly matching that number was the Institute of Physics’ IOP Publishing, which announced the retraction of 494 articles when an investigation revealed the papers “may have been created, manipulated, and or sold by a commercial entity,” also known as a “paper mill.”[xvi]
Paper mills have become big business, as recently reported by Nature, with fake research produced for scientists seeking to bolster their resumes. More recently discovered, in association with paper mills, have been advertisements of sale of authorship on papers to be published in reputable journals. Recent investigations of this growing concern have resulted in retractions of dozens of papers across several journals.[xvii]
Whether a scientific paper is retracted due to fraud or due to more innocent considerations, in either instance the paper can make its way across the globe, cited to by other scientists – or, perhaps even worse, relied upon by both scientists and the general public - long before the paper’s findings are ever discovered to be false or inaccurate.
According to Retraction Watch – a database keeping track of all journal retractions or other expressions of concern – at least 289 Covid-19-related papers alone have been retracted since the beginning of the pandemic.[xviii] It’s through the work conducted by Retraction Watch and others, such as Science Integrity Digest - where Dr. Elisabeth Bik is considered an elite data-integrity sleuth – that discovery of scientific fraud has resulted in the retraction of hundreds of papers.[xix]
While these hundreds of retractions, and other exposures of fraudulent acts, involve lesser-known theories of science, two well-known, major scientific theories were upended in the Summer of 2022, each presenting a different form of fraud – one in Alzheimer’s research, and the other in psychiatric research – further highlighting the level of skepticism warranted in embracing or adopting scientific claims.
ALZHEIMER’S FRAUD & THE AMYLOID MAFIA
On July 21, 2022, Science published a report claiming a seminal Alzheimer’s study from 2006 was likely a fraud, contributing to an at least somewhat wasted (nearly) two decades of research in the Alzheimer’s field.[xx] As every single disease-modifying trial of Alzheimer’s treatment has failed, the introduction of fraud into its study – wasting time, money, and talented minds on advancing a lie – may have caused unnecessary suffering by patients and families alike.
The brains of those with Alzheimer’s Disease (AD) bear two cellular hallmarks: clumps of proteins called amyloid-β (amyloid-beta) - known as plaques - that form outside cells, and strings of protein called tau - known as neurofibrillary tangles - that form inside cells.[xxi] The accumulation of amyloid-β has been thought to trigger a cascade of processes that leads to the loss of memory and cognitive ability commonly observed in AD.[xxii]
“The amyloid (or Aβ) hypothesis has become the dominant model of AD pathogenesis and is guiding the development of potential treatments,”[xxiii] explained Dr. Dennis Selkoe, a neurologist at Harvard’s Brigham and Women’s Hospital. The answer seemed “obvious,” according to Rachel Neve, a neuroscientist best known for being one of the first to clone the Alzheimer’s precursor protein (APP). Just “clear the amyloid from the brain and cognitive function would be restored,” said Neve, summarizing the hopeful mindset of those in the field.[xxiv] The problem with this dominant hypothesis was (and is) that amyloid imaging has revealed many normal patients with amyloid deposits, and AD patients without (or very few) amyloid deposits.[xxv] In other words, experts in the field believed in this conceptually “obvious” answer, yet the clinical research findings continue to confound.
In 2006, Nature published the alleged fraudulent study, authored by Sylvain Lesne, a neuroscientist at the University of Minnesota. The study seemed to prove that a certain Aβ subtype caused dementia in rats, thereby supporting the dominant – yet still unproven – theory in the field, that Aβ plaques in brain tissue are a primary cause of AD.[xxvi]
Lesne’s paper revealed what “was a really big finding that kind of turned the field on its head,” said Donna Wilcock, a Professor at the University of Kentucky and Editor-in-Chief Alzheimer’s & Dementia: The Journal of the Alzheimer’s Association.[xxvii] This sentiment was echoed by Stanford University’s Dr. Thomas Sudhof, who described the findings as providing an “important boost” to the amyloid hypothesis, which, at the time, faced rising doubts.[xxviii]
It was Dr. Matthew Schrag, a neuroscientist and physician at Vanderbilt University, who discovered doctored images in Lesne’s 2006 Alzheimer’s study. Schrag’s findings were corroborated by independent experts, including Donna Wilcock, who found what she described as “shockingly blatant” examples of image tampering in Lesne’s study.[xxix]
This misdirection of Alzheimer’s research only further solidified the influence on the prevailing theory on AD. The theory was so dominant in the research field that “Scientists who advance other potential Alzheimer’s causes, such as immune dysfunction or inflammation, complain they have been sidelined by the ‘amyloid mafia,’” said Charles Piller, author of the Science report.[xxx]
According to the late Sharon Begley, a science journalist, the disturbing reason for the lack of progress in AD treatment is that “the most influential researchers have long believed so dogmatically in one theory of Alzheimer’s that they systematically thwarted alternative approaches.” According to Begley, “Several scientists described those who controlled the Alzheimer’s agenda as ‘a cabal.’”[xxxi]
Whether a “mafia” or “cabal,” for the pro-amyloid crowd, “Things shifted from a scientific inquiry into an almost religious belief system, where people stopped being skeptical or even questioning,” said Begley.[xxxii] According to Rachel Neve, “The amyloid fiasco has been one of the greatest tragedies of modern biomedical research.”[xxxiii]
Lesne’s Nature paper has been cited in about 2300 scholarly articles—more than all but four other Alzheimer’s basic research papers published since 2006, according to the Web of Science database.[xxxiv]
According to Dr. Sudhof, an Alzheimer’s expert and Nobel laureate, in considering the fallout of Dr. Lesne’s fraud, “The immediate, obvious damage is wasted NIH [National Institutes of Health] funding and wasted thinking in the field because people are using these results as a starting point for their own experiments.” In other words, Lesne’s alleged fraud “misdirected Alzheimer’s research for 16 years.”[xxxv]
CHEMICALLY IMBALANCED?
85-90% or more of the public believes that science has established that depression is caused by a “chemical imbalance,”[xxxvi] generally understood as referring to low levels of serotonin, a neurotransmitter that carries signals between nerve cells throughout the body.
In June of 2022, Nature published The serotonin theory of depression: a systemic umbrella review of the science, wherein the authors concluded, “Our comprehensive review of the major strands of research on serotonin shows there is no convincing evidence that depression is associated with, or caused by, lower serotonin concentrations or activity.” The authors suggested that “it is time to acknowledge that the serotonin theory of depression is not empirically substantiated.”[xxxvii]
Selective serotonin reuptake inhibitor (SSRI) “antidepressants,” such as Zoloft, Prozac, and Paxil, are the primary treatment for depression. These medications prevent neurons from removing serotonin by blocking a transporter protein, allowing more of the neurotransmitter (serotonin) to interact with neurons for a longer period of time.
According to Professor Joseph Glenmullen, clinical instructor of psychiatry at Harvard Medical School, in his book Prozac Backlash (2000), “A serotonin deficiency for depression has not been found.”[xxxviii] That sentiment was echoed by psychiatrist David Healy, former secretary of the British Association for Psychopharmacology, stating in his book Let Them Eat Prozac (2004), “Indeed, no abnormality of serotonin in depression has ever been demonstrated.”[xxxix] Florida State Professor Jeffrey Lacasse, in a 2005 PLOS Medicine article confirmed that “In fact, there is no scientifically established ‘chemical balance’ of serotonin, let alone an identifiable pathological imbalance.”[xl]
Direct-to-consumer advertising campaigns, largely based upon the claim that SSRIs correct a “chemical imbalance” caused by lack of serotonin, have been extraordinarily successful in expanding the antidepressant market.[xli] According to Dr. Ronald Pies, professor of psychiatry at SUNY Upstate Medical Center (Syracuse, NY) and Editor-In-Chief of Psychiatric Times, “Throughout the 1990s and beyond, the pharmaceutical industry promoted the idea that depression was the result of an ‘imbalance’ or deficiency of brain serotonin, and that SSRIs were ‘magic bullets’ that reversed this underlying abnormality.”[xlii]
“Research provides evidence that the psychiatric profession acted as a willing and often enthusiastic conduit of the serotonin theory of depression, despite the protestations of” some in the field, said Dr. Pies.[xliv] Considering this massive pharmaceutical campaign, “…It is not surprising that the ‘theory that never was’ has taken hold in the minds of so many.”[xlv]
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“Trust the science” is an appeal to authority – a plea for blind allegiance - for those looking to weaponize science, often with a political or financial motive. “You always have to be allowed to question science,” said Dr. Martin Kulldorff, former professor at Harvard Medical School. “We should never silence that debate, pretend that there’s some person who is ‘The Science,’ who has all the truths. “I think that happened during this pandemic and that’s an embarrassment for the scientific community.”[xlvi]
As noted by Dr. Jay Bhattacharya, a professor at Stanford University’s world-renowned medical school, “The public should understand that many of those urging them to ‘trust the science’ on complicated matters of public concern are also those working to ensure that ‘the science’ never turns up answers that they don’t like.”[xlvii]
Despite plenty of historical fraud, deceit, and scandal, science still commands enormous respect. The reputation of those in scientific fields, however, remains reliant upon loyalty to the objective pursuit of truth. The respect commanded by science is warranted, but trust in science - or those looking to weaponize “The Science” - must be earned.
[i] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4572812/
[ii] https://acmedsci.ac.uk/policy/policy-projects/reproducibility-and-reliability-of-biomedical-research
[iii] https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(15)60696-1/fulltext
[iv] https://journals.plos.org/plosmedicine/article?id=10.1371/journal.pmed.0020124
[v] chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://tauruspet.med.yale.edu/staff/edm42/IUPUI-website/emorris.tar/emorris/emorris/Ethics%20Course%2009/Journal%20articles/325207a0-Feder%20and%20Steward%20comment%20re%20Darsee%20co-authors%20and%20fraud%20Nature%201987.pdf
[vi] https://www.psychologicalscience.org/observer/derailed-the-rise-and-fall-of-diederik-stapel
[vii] chrome-extension://efaidnbmnnnibpcajpcglclefindmkaj/https://www.bmj.com/bmj/section-pdf/187846?path=/bmj/346/7900/Feature.full.pdf
[viii] https://www.theguardian.com/science/audio/2017/sep/14/statistical-vigilantes-the-war-on-scientific-science-weekly-podcast
[ix] https://www.science.org/content/article/new-record-retractions-part-2;
[x] Ibid.
[xi] https://leaps.org/researchers-behaving-badly-why-scientific-misconduct-may-be-on-the-rise/
[xii] Ibid (Leaps)
[xiii] https://www.acsh.org/news/2023/01/31/how-scientific-%E2%80%98peer-reviewed%E2%80%99-science-16803
[xiv] https://www.acsh.org/news/2023/01/31/how-scientific-%E2%80%98peer-reviewed%E2%80%99-science-16803
[xv] https://retractionwatch.com/2022/09/28/exclusive-hindawi-and-wiley-to-retract-over-500-papers-linked-to-peer-review-rings/
[xvi] https://retractionwatch.com/2022/09/09/physics-publisher-retracting-nearly-500-likely-paper-mill-papers/
[xvii] https://www.nature.com/articles/d41586-023-00062-9
[xviii] https://retractionwatch.com/retracted-coronavirus-covid-19-papers/
[xix] https://www.nature.com/articles/d41586-020-01363-z
[xx] https://www.science.org/content/article/potential-fabrication-research-images-threatens-key-theory-alzheimers-disease
[xxi] https://www.nature.com/articles/d41586-018-05719-4
[xxii] https://www.nature.com/articles/d41586-018-05719-4
[xxiii] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4888851/
[xxiv] https://goodscienceproject.org/articles/essay-rachael-neve/
[xxv] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797629/
[xxvi] https://www.science.org/content/article/potential-fabrication-research-images-threatens-key-theory-alzheimers-disease
[xxvii] https://www.science.org/content/article/potential-fabrication-research-images-threatens-key-theory-alzheimers-disease
[xxviii] https://www.science.org/content/article/potential-fabrication-research-images-threatens-key-theory-alzheimers-disease
[xxix] https://www.science.org/content/article/potential-fabrication-research-images-threatens-key-theory-alzheimers-disease
[xxx] https://www.science.org/content/article/potential-fabrication-research-images-threatens-key-theory-alzheimers-disease
[xxxi] https://www.statnews.com/2019/06/25/alzheimers-cabal-thwarted-progress-toward-cure/
[xxxii] https://www.statnews.com/2019/06/25/alzheimers-cabal-thwarted-progress-toward-cure/
[xxxiii] https://goodscienceproject.org/articles/essay-rachael-neve/
[xxxiv] https://www.science.org/content/article/potential-fabrication-research-images-threatens-key-theory-alzheimers-disease
[xxxv] https://www.science.org/content/article/potential-fabrication-research-images-threatens-key-theory-alzheimers-disease
[xxxvi] https://www.nature.com/articles/s41380-022-01661-0
[xxxvii] https://www.nature.com/articles/s41380-022-01661-0
[xxxviii] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1277931; Glenmullen, Joseph. Prozac Backlash.
[xxxix] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1277931; Healy, David. Let Them Eat Prozac.
[xl] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1277931/
[xli] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1277931/
[xlii] https://doi.org/10.1016/j.ssmmh.2022.100098
[xliii] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1277931/
[xliv]https://doi.org/10.1016/j.ssmmh.2022.100098
[xlv] https://www.psychiatrictimes.com/view/debunking-two-chemical-imbalance-myths-again
[xlvi] https://invesbrain.com/former-harvard-prof-martin-kulldorff-science-and-public-health-are-broken/
[xlvii] https://www.tabletmag.com/sections/arts-letters/articles/stanford-failed-academic-freedom-test