Prologue to: “Error and fraud. The dark side of biological and medical research.”

Note to readers. This is the prologue to an unpublished book about scientific error and research fraud. There are no URL links in the text but there is a bibliography at the end. Numerous other posts on this blog are edited extracts or case-studies from this book.

How did I become interested in research fraud?

I have for many years had an interest in major scientific mistakes and research blind alleys mainly in my specialist field of nutrition; four examples are listed below.

  • The mistaken belief in the thirty years following the end of WW2 that there was a major crisis in world protein supplies and that protein deficiency was the most important cause of malnutrition in the world. This apparent shortfall in world protein supplies was often referred to as the protein gap.
  • The promotion of front sleeping as the safest position for babies that led to large worldwide increases in cot death rates in the 1970s and 1980s. Eventually a back to sleep campaign started in the UK in 1991 and this led to immediate and sharply reduced rates of cot death.
  • The belief that some defect in the heat generating capacity of a tissue called brown fat was a major cause of human obesity. This stimulated hope that so-called thermogenic drugs which stimulated heat production and burning of calories by “switching on” brown fat might be an effective treatment/prevention strategy for obesity.
  • The belief that antioxidant supplements when taken by healthy well-nourished adults would reduce cancer and heart disease mortality and thus extend human life expectancy. The term rich in antioxidants is still widely viewed as an indication that a food or supplement might prevent cancer or heart disease and help to prolong life. Many clinical trials have failed to show any benefits of antioxidant supplements and some such supplements seem to actually increase mortality rates.

I have written about these four examples of apparently mistaken scientific beliefs in several books and articles where I have discussed and speculated on some of the causes and consequences of these “mistakes”. These are discussed as error case studies in chapter 2.

A common feature of these errors has been an uncritical and, in retrospect, clearly unjustified extrapolation from a relatively early stage in the evidence chain. For example:

  • Uncritically applying the results from small animal studies to people (the protein gap and the brown fat examples)
  • Applying suggested benefits for a small high risk group to the whole population (the sleeping position and cot death example)
  • Assuming that an epidemiological association is due to a cause and effect relationship (the benefits of antioxidant supplements example).
  • Assuming that a favourable change in some biochemical risk marker like a lowered blood cholesterol concentration will inevitably result in reduced disease incidence and increased life expectancy (antioxidant supplements example).

In some instances there has been widespread practical application of what was an inadequately tested hypothesis e.g. promotion of front sleeping for infants or a raft of measures designed to solve the illusory deficit in world protein supplies.

In recent years, evidence grading hierarchies have been developed. Normally changes in clinical practice or health policy should only be made if there is clear evidence at the pinnacle of this evidence hierarchy or pyramid. Rigorous application of this system would have prevented most of the practical consequences of these past errors. In chapter 1, I briefly review the observational and experimental methods availability to scientists in the biomedical sciences. I discuss the strengths and limitations of these various line of enquiry and explain how they should be integrated and graded to optimise the chances of making correct scientific, clinical and policy judgements.

A systemic problem with the soundness of published research?

The four case studies discussed above may be just extreme examples of a much wider problem with the credibility of published science. The public is bombarded with thousands of media reports of scientific claims and discoveries. Often these claims are refuted by other claims sometimes with oscillating claims and counter claims appearing regularly in the media. Some of the reported claims seem to be contrary to logic and many seem to have little obvious potential for improving scientific understanding or having any practical role in improving the treatment or prevention of ill-health. In chapter 3, I discuss persuasive claims that most published research is wrong and that perhaps 85% of research expenditure is wasted. Replication by other scientists is regarded as a key factor in sifting out erroneous or even fraudulent scientific claims but in many cases independent attempts at verification have failed to confirm published claims and for many others no attempt at replication has been made. This lack of replication applies to many very highly cited reports in top journals relating to treatment of major diseases like cancer. In chapter 3, I try to explain some of the reasoning and evidence used by those who suggest that most published research is wrong. I also discuss some of the structural factors driving the avalanche of false and low value research as well as some of the technical problems with the design, execution and analysis of scientific studies that often produce erroneous results or conclusions.

How are these apparent scientific mistakes relevant to a study of research fraud?

In cases of major scientific mistakes or blind alleys, I believe that scientists have often been guilty of mass self-deception and have failed to give proper consideration to flaws in the logic and gaps or inconsistencies in the evidence chain for these theories. With the benefit of hindsight, some of these gaps and flaws now look fairly obvious. How could the protein requirements of rapidly growing laboratory animals whose mothers produce very protein-rich milk be used as evidence for the high protein needs of slow-growing human babies who naturally consume low protein human milk? How could very limited observations of possible reductionist benefits on high risk babies be deemed sufficient to justify and promote a change in sleeping position for all babies? My focus on such “mistakes” made me very aware of the fallibility not only of individual scientists but of the scientific establishment generally and particularly the way in which research findings have been translated into practical health advice or treatment. I was thus receptive to the idea not only that individual scientists might cheat but also that they might be able to escape detection in their misconduct by the scientific community. If a scientist produces papers based upon fabricated or manipulated data then this may go largely unchallenged for some considerable time despite glaring flaws or anomalies in their papers that now seem obvious. The focus of the second half of this book is on scientists trying to deceive others by the use of totally fabricated data or by trying to select or massage their real data so that it more firmly supports their interpretation and thus makes it more convincing to other scientists. Faked or manipulated data is used by the perpetrators for a number of purposes like those listed below.

  • As supporting evidence for a pet theory or belief of the author. The eminent botanist and Fellow of the Royal Society Professor John William Heslop Harrison faked the discovery of plants unique to Scotland on the Hebridean island of Rum. He used these discoveries to support his theory that they had survived from before the last ice age because he believed that the Hebrides had remained largely ice-free during this period when Scotland and Northern England were covered by a thick blanket of ice. The Austrian biologist Paul Kammerer faked data on amphibians and sea squirts to support his belief that characteristics acquired during an organism’s lifetime could be passed on to its offspring (Lamarckism).
  • To enhance their career and accompanying financial rewards. Ranjit Kumar Chandra the erstwhile “father of nutritional immunology” amassed considerable wealth and gained much prestige by generating what is now generally accepted to be fraudulent data. He was awarded the Order of Canada and supposedly was twice nominated for the Nobel Prize in medicine or physiology. Sir Cyril Burt was knighted for his services to educational psychology despite apparently fabricating much of his data, writing under assumed names and using fake collaborators in his publications.
  • To gain commercial advantage for a product which the author or their research sponsor has an interest in. Ranjit Chandra’s clinical trials suggesting that substantial health benefits resulted from using his patented blend of vitamins and minerals was used in the marketing of these supplements produced by a company founded by his daughter. His false claim that this supplement effectively cured dementia would have dramatically increased the commercial potential of this supplement. Scott Reuben’s fake data on the benefits of COX-2 inhibitors probably generated billions of dollars’ worth of worldwide sales for these analgesics although there is no suggestion that his commercial sponsors were aware of his deception.

Error and fraud may seem like two quite distinct issues:

Largely honest misinterpretation of data to generate or support a hypothesis that turns out to be false.

As opposed to:

Wilful fabrication of data or improving/selecting real data in order to convince others of the correctness of your hypothesis.

However, both error and fraud seem to be characterised by a collective suspension or suppression of critical evaluation by the rest of the scientific community. As already argued, some of the evidence used to support mistaken but very influential theories may in retrospect seem weak or seriously flawed. It is sometimes difficult in retrospect to see how these theories became so firmly established and in some instances persisted as the accepted textbook belief for decades. Even if one accepts that a theory seemed like a plausible interpretation of the available evidence, it is alarming that major policy decisions were made and implemented on the basis of these inadequately substantiated theories.

Was there ever enough evidence to justify programmes costing the equivalent of billions of pounds to develop new or improved protein sources to close the protein gap?

Was there ever any substantial evidence to support recommendations for parents to adopt the front sleeping position for their babies? In Holland in the early 1970s there seems to have been something amounting to a front to sleep campaign! Of course, few would have expected such a simple and seemingly innocuous behaviour change to have such a significant effect upon infant mortality risk. However, if a change in sleeping position was thought to have enough potential benefit to justify changing traditional practice then one must accept that such a change could do harm as well as good. It is clearly illogical and potentially dangerous to assume that change is a one way bet i.e.

If behaviour/dietary change can’t do any harm but may help then why not make it?

The history of medicine and surgery is littered with well-intentioned practices that turned out to do more harm than good. The phrase evidence-based practice has become the mantra of health professionals and health policy makers but has there always been proper and critical evaluation of the evidence that underpins practice and particularly evidence that leads to a change in the current practice?

Once a scientific theory has been widely accepted it starts to be treated as scientific fact and is presented as such to students in their textbooks and lectures. It quickly becomes unquestioned fact and very little further attempt is made to question or test the fundamental basis of the theory. Research is often focused upon narrow aspects of the theory or its application under the assumption that it is essentially correct. Sometimes a theory may become so much a part of the fabric of science and research in an area that careers, research grants and even whole research programmes and organisations may be dependent upon the continuation of the theory. In his watershed paper of 1974 in the Lancet entitled The great protein fiasco Professor Donald McLaren argued that so much money, scientific effort and political capital had been invested in measures to increase protein availability that it was very difficult to persuade people to look critically at the rationale that underpinned this effort and expenditure i.e. to question the belief that there really was a crisis in world protein supplies. In an interview in 2011 he states that

 “In my opinion, the belief in the “Protein Gap” is one of the greatest errors committed in the name of nutrition science in the past half-century”

The vested interests of many scientists and politicians with grants, reputations and careers that depended upon these protein related programmes made them reluctant to objectively respond to criticisms of what amounted in many cases to the foundation of their careers and reputations. McLaren went further in his 1974 paper and suggested that in 1966, when the protein gap idea was still at the top of the nutrition agenda, many scientists privately expressed sympathy with his opposition to this theory and to the practical measures to deal with it. He claimed that they were unwilling to support him for fear of damaging their careers and their protein-related research funding. He even suggested that there was some attempt to cynically suppress critical re-evaluation of the protein gap concept. An agency of the United Nations was set up 1955 to advise specifically on the safety and suitability of the new protein-rich preparations that were being developed to close the protein gap; the existence of a protein gap was its raison d’etre.

The antioxidant theory of disease and aging prevention has been seriously undermined in recent years but has by no means been abandoned by nutrition researchers. It is nonetheless very difficult to continue to believe that indiscriminate use of antioxidant supplements in basically well-nourished adults in industrialised countries will prolong life. This theory has generated tens of thousands of research papers, dozens of books and has been the justification for countless research grants and programmes. Many scientific reputations and careers have been built upon it. This theory has also had considerable wider commercial impact; it has been used to promote the sale and manufacture of many foods, drinks and supplements on the basis of their high antioxidant content. Drugs have been designed to have high antioxidant activity and food varieties developed with increased antioxidant content. If it is confirmed that extra antioxidants given to normally nourished people have no long term benefits then these products would lose the prestige they have gained from their high antioxidant activity.

A similar mass suspension of fundamental critical analysis also characterises many of the examples of deliberate fraud that are discussed in the second part of the book. There now seem to be obvious flaws and inconsistencies in the fraudulent data, some of the claims now seem outrageous and unbelievable and the sheer volume and scope of work said to have been done by some fraudulent researchers seems beyond belief.

How can fraudulent scientists have long successful careers based upon fabricated data?

With the benefit of hindsight, one might question:

  • Why some obvious and major statistical flaws in a person’s research output were not noted earlier; impossible standard errors/deviations, regression coefficients that remained constant to 3 decimal places despite large increases in sample size, exactly the same number of people with a particular side effect in multiple clinical trials, distributions of baseline subject characteristics that could not have occurred if subjects were randomly assigned as claimed.
  • How it could be accepted that a single individual could generate data and research papers at a phenomenal rate often when carrying a heavy burden of other work like clinical duties, conference attendance, teaching and administrative work. Sometimes these individuals published papers as sole authors when normally papers of this scope and complexity would have involved multiple co-authors with differing areas of expertise.
  • How it was possible for someone to get away with using totally fictitious collaborators on their papers, or even more surprisingly use real people as co-authors without their knowledge or consent over a period of several years.
  • Why data that is completely out of line with the results of other groups can remain largely unchallenged for decades.
  • How it is possible for someone to repeatedly report finding fossils and plants in places where no-one else has even seen them and perhaps thousands of miles from where anyone else has ever seen them without being openly challenged and their papers rejected.
  • How it can go unchallenged that a person claims to have used impossibly large samples of fictitious subjects with narrow or rare selection criteria in their clinical trials despite sometimes relying upon recruiting subjects from a relatively small local population.
  • How someone is able to report analytical data or clinical assessments that would require an army of laboratory assistants or clinicians and massive research expenditure to generate it without any commensurate level of observed activity and expenditure.
  • How someone can claim to have used drugs, databases or other materials that were not available when the work was said to have been carried out.
  • How someone who cannot be traced and almost certainly does not exist can publish papers.
  • How someone can publish papers using a fictitious institution as their professional address or using the address of an institution which has no record of their having any formal affiliation with it.
  • How someone can publish data purportedly acquired from using many laboratory animals, even large animals like dogs, when the institution’s animal house has not supplied them.
  • How someone can report experiments using radioactive chemicals when there is no record of their use in the legally required log of their use and safe disposal.

Scientists may be trained to criticise the methodology of other scientists and the way they analyse and interpret their data but they generally do not question the honesty of what has been written or said and this trust protects the dishonest researcher. When I was involved in refereeing papers in the past, I would have looked for flaws in the design of a study, questioned whether the correct statistical analyses had been performed and whether the interpretation of the results was sound. Like many other reviewers, I would have made these judgements under the assumption that the methods were honestly described and the data submitted had actually been generated and analysed in the way described by the authors. I would not have actively considered that the authors were deliberately trying to deceive me and would almost certainly have looked for some scientific rationale for anomalous data. This trust acts as a powerful shield for the deliberate fraudster.

In some cases, the revelation that a prominent scientist has been faking data for years comes as an apparent surprise to the scientific community. In other cases, however, there appear to have been deep and widespread suspicions for some years about a scientist’s work prior to the general acceptance or admission of misconduct. Several of these cases are discussed at length as case-studies but the brief summaries of the examples below illustrate how suspicions can be largely ignored or suppressed for years and perhaps even decades.

In 1948, a Cambridge academic John Raven visited the island of Rum and compiled a report for the authorities of Trinity College Cambridge that made a persuasive and meticulously argued case for Professor John Heslop Harrison having committed multiple acts of scientific fraud. This report was buried in an academic library and went unpublished and largely unread by other botanists for over half a century. His public reputation as an eminent and respected botanist remained largely intact until well after his death in 1967 and was not openly and widely challenged until in 1999 Karl Sabbagh wrote a book entitled “A Rum Affair” and sub-titled “The Exposure of Botany’s Piltdown Man”.

The Canadian physician, nutritionist and immunologist Ranjit Chandra was first accused of fabricating data in the early 1990s and in 1994 a university panel decided that he was almost certainly guilty of misconduct:

With respect to the allegations, the committee is, therefore led to conclude that scientific misconduct has been committed by Dr Chandra.

This report was not released and Chandra continued to work at the university until around 2002 when further public accusations of fraud were made. He published prolifically during these intervening years including many influential scientific reviews and keynote lectures at scientific conferences. He became an acknowledged expert about how diet and dietary supplements affect the immune system and he was regarded by some as the father of nutritional immunology. In the citation to his 1995 inclusion on the honour roll of Canadians who had made a difference published annually by Maclean’s magazine it is said that he was twice nominated for the Nobel Prize. Most of his published work is now widely seen as suspect and disregarded by most other scientists.

The Japanese anaesthesiologist Yoshitaka Fujii was found guilty in 2012 of faking at least 172 scientific papers including many clinical trials. Suspicions about the veracity of his work had been first raised in a letter published in April 2000 in the journal Anesthesia and Analgesia. The authors of this letter (Kranke et al, 2000) pointed out that the incidence of headaches as a side effect appeared to be almost exactly the same in all the groups his 21 clinical trials published up to that time. They concluded from a statistical analysis that it was essentially impossible that these reported identical incidences could have occurred by chance and that:

“There must be an underlying influence causing such incredibly nice data reported by Fujii et al”.

Despite this warning signal he continued to publish prolifically for a further decade and more.

Why were these and other serial fraudsters allowed to pollute the scientific record with fabricated data for so long? In some cases fraudsters may have been sophisticated in their data fabrication or manipulation and avoided suspicion but in cases like these, strong suspicion preceded outright public accusation by many years and in some cases by decades.  If flaws in a scientist’s work that suggest misconduct are highlighted then how can they carry on obtaining research grants, holding on to senior academic positions and continuing to publish further flawed data? Did colleagues and particularly senior colleagues at the host institution not question how these individuals were able to publish so prolifically without creating a whirlwind of research activity in their laboratories and clinics? Were senior academics and managerial staff reluctant to question the integrity of the data of their star performer who was generating research income and publications to enhance the standing and prestige of their institution? Did they fear that any attempt to investigate the suspected offender would risk scandal and damage their institution’s reputation? Were research sponsors happy to accept favourable data even though there might be some suspicion that there had been irregularities in its generation? Were junior colleagues too in awe of the eminent professor to question their integrity or were they concerned that their own career might be blighted by any attempt at whistle blowing? Did the tradition of trust amongst scientists and a failure to consider the possibility of data fabrication help them to remain unexposed for so long?

Do the libel laws in particular so frighten employers, authors, editors and journal owners that they become very reluctant to do anything that could be construed as questioning the integrity of an author? English libel laws have been criticised in this respect and there has been a partially successful campaign initiated by the journalist Simon Singh to reform these laws. One of my case study subjects, Jatinder Ahluwalia has been found guilty of fabricating data at both University College, London and at Cambridge University and was a colleague of mine for a while. When his co-authors retracted a seemingly very important paper in Nature for which he was lead author, they wanted to include a link to the published UCL report on the investigation into his misconduct. This was refused despite the detailed and closely argued evidence of deliberate fraud in this now publicly available UCL report.

My interest was stimulated by personal involvement with research fraud

Whilst preparing new editions of two books, I was faced with the decision about how to deal with several papers discussed in earlier editions that I now suspected were based upon fabricated/falsified data or were from authors accused of scientific fraud (Ranjit Chandra and Jatinder Ahluwalia). Should I simply omit all reference to the offending articles or should I acknowledge that these papers had been expunged from the texts and the reasons for their removal? This issue was made even more difficult because one of the accused authors (Ahluwalia) was at the time a colleague of mine and he continued to be a full colleague for eight months after the detailed accusations against him were made public. By increasing awareness of this particular case I might be perceived to be embarrassing or damaging the reputation of my employer even though the public allegations related to work carried out in other institutions.

Where it was possible, I chose the second option. I took this decision because I thought that it was important that readers were made aware that this previously discussed material was no longer considered trustworthy. I felt a personal responsibility to those who might have used earlier editions of my books, particularly as I had helped to promote the now suspect or discredited papers. At several places in this book, I criticise journals, editors, publishers and employers for not doing more to highlight and make the scientific community aware of papers that have been retracted for suspected fraud or that unretracted papers are from an author who has been accused of fraud. I am also critical of employers who have allowed fraudulent scientists to continue to generate fraudulent data for many years after suspicions of research fraud were first raised. It would therefore have been hypocritical of me then not to acknowledge that my previous writing had made use of fraudulent data.

I first cited one of Chandra’s reviews in a book published in 1995 and continued to cite his reviews and clinical trial reports in material published as late as 2008. I cited his review articles as support for summaries of the effects of malnutrition upon immune function and most of this material is still accepted by nutritionists because although reviewed by Chandra it is based on the work of other researchers not just that of Chandra himself. However, I did also cite his clinical trial data which purported to show that a mixture of vitamins and minerals combined in his patented supplement formula improved immune function and reduced infection time in elderly people. His data in regard to supplements, which is now largely disregarded and considered by many to have been fabricated, certainly did influence my conclusions about the possible benefits of vitamin and mineral supplements in the elderly. Even though all of his reviews and most of his papers remain within the scientific literature (as at mid2015), I would now not regard any of Chandra’s writings as a citable source even if some of the material, particularly in his reviews, is still considered to be accepted fact.

I also used the Nature paper (now retracted) summarising the fabricated data of Jatinder Ahluwalia (Ahluwalia et al, 2004) in my writings about the likely benefits of large amounts of antioxidants in the form of supplements and so-called superfoods. This paper was generally seen at the time of its publication as tending to undermine the theory that large intakes of antioxidants from supplements and even drugs might reduce the risk of chronic diseases like cancer and heart disease. I used this paper in my writing because it tended to add support to my own scepticism; I felt confident about the conclusions because it was published in a very prestigious journal with a very distinguished list of co-authors from one of Britain’s foremost centres of research excellence. I actually quoted this paper before Ahluwalia became a colleague at the University of East London.

Family involvement

My involvement with the Chandra and Ahluwalia affairs came at a time when my daughter Kate was about to start on a Master’s course in Publishing at UCL (also the site of Ahluwalia’s major alleged fraud). She was frequently exposed to my heated discussion of these cases. This meant that when she came to think about a suitable topic for her Master’s project in the spring of 2012, the area of research fraud was uppermost in her mind. She proposed a project that focused on the burden of responsibility of the various parts of the publication chain to detect and prevent publication of fraudulent research. She also discussed options for dealing with fraudulent authors and their tainted publications once they had been identified as fraudsters. It was her research and her discussions with me about what she had found out from her readings and contacts with other interested people that broadened my interests in research fraud. She helped to convert what had been a general interest with sporadic bouts of reading about individual cases to a more systematic research project capable of filling a book. She made me aware of more of the infamous historical cases and showed me that there is a substantial body of academic literature dealing with various aspects of research fraud. She made me more aware of the organisations that had been set up to try and deal with research fraud like the Office of Research Integrity (ORI) in the USA, the UK Research Integrity Office (UKRIO) and the Committee on Publication Ethics (COPE).

Structure of part II of the book

Part II starts with a series of case studies of people accused of major research fraud drawn from many different areas of the biological, medical and behavioural sciences. The nature, extent and impact of the perpetrators’ fraudulent activities are discussed in the context of prevailing scientific understanding. There is also explanation of how each fraudster was unmasked and any subsequent attempts at investigating the extent of their fraudulent activities. These case studies serve as a reservoir of examples to illustrate the general points discussed in the final four chapters of the book.

Chapter 4 starts with a definition of research fraud and some of the attempts that have been made to estimate its prevalence. The bulk of the chapter deals with the consequences of research fraud in hindering scientific progress, wasting of research resources, distorting medical treatment choices and damaging the lives and careers of those professionally associated with fraudsters. In extreme cases research fraud kills people.

Chapter 5 is focused on the safeguards that aim to prevent the publication of false or incorrect data. Peer review is seen as the primary safeguard against the publication of studies that are poorly designed, poorly executed or inappropriately analysed and interpreted. This peer review process relies upon the reviewer’s trust that the author is giving a true account of what was done and what was found and so it is not effective where authors deliberately distort or fabricate their findings i.e. deliberately deceive the peer reviewer. Some journal editors have also been guilty of effectively by-passing the peer review process in order to fill their journal and have accepted deliberately and obviously flawed spoof papers. Some notorious fraudsters have published much of their fraudulent work in journals that they edit.

Chapter 6 is primarily concerned with the detection of fabricated or falsified data after publication. Just as peer review is seen as the primary defence against publication of fraudulent data so independent replication is seen as a key way in which fraudulent or incorrect data will be identified. However, these safeguards have rarely been responsible for unmasking well known fraudulent researchers. Most fraudsters have been identified when vigilant colleagues have acted as whistle blowers and reported suspicions about a colleague’s activities. Others well known fraudsters have been unmasked by eagle-eyed readers who have spotted signs of data fabrication or falsification in published work. In several well known cases, whistle blowers have suffered as a consequence of performing what is an important service to scientific progress. Some of the characteristics that have led to suspicion or even proof of fraudulent data in published work are also discussed.

The final chapter deals with the ways in which the total output of a fraudulent researcher should be investigated once a well-founded accusation has been made so that the literature can be disinfected of all of the tainted or suspect work published by the guilty author. Finally there is discussion of some measures that might reduce the amount of fraudulent material that reaches and remains in the scientific literature.

This book aims to increase awareness of the extent of research fraud, some of its tell-tale signs and characteristics and of the great damage that it can do. This increased awareness should make life harder for the dishonest researcher, increase the chances of exposure and maybe increase the chances of their being quickly identified and severely penalised for their dishonesty.

What do I hope to achieve by writing this book?

One of the things that surprised me in the past was the relative paucity of discussion about the “mistakes” that I had written about previously. One of my main motivations for writing about them was to encourage open discussion of why they had occurred, and how we could learn from them and thus be less likely to make similar mistakes in the future. These errors have had major practical repercussions such as those listed below.

  • The mistaken belief in a protein gap cost the equivalent of billions of pounds in wasted research and development projects and had wider negative effects such as exaggerating protein requirements and the value of high protein intake to a healthy human diet.
  • The belief that front sleeping was best for all babies and the promotion of front sleeping in the 1970s and early 1980s probably resulted in hundreds of thousands of extra cot deaths worldwide.

Despite these costs there has been a relative lack of published analysis and discussion of these past mistakes; it seems as if there is a reluctance of the scientific community to acknowledge just how important and damaging these mistakes were and some of the fundamental errors in the ways in which research was conducted and interpreted which caused them. This code of relative silence and an apparent reluctance to openly address serious problems in scientific research seems also to characterise the way in which research fraud is sometimes handled although some journals like the BMJ (formerly the British Medical Journal) have made major efforts to publicise and discuss some of the cases highlighted in this book. Perhaps all science courses in universities should include direct coverage of research fraud as a curriculum topic? Students could be given analysis of individual cases of proven fraud and made more aware of the possibility of fraud and shown some of the characteristics of fraudulent papers:

Today’s undergraduates and postgraduate students are tomorrow’s journal referees and editors. 

This more open discussion and awareness may make it more likely that other cases will be detected more quickly and dealt with effectively once allegations have been made or suspicion aroused. One recurring comment made after a fraudster has been exposed is that referees, editors, co-authors and employers had not even considered the possibility that they were being deceived and so they unquestioningly accepted the authenticity of data provided by the fraudster; they looked for error and misjudgement but did not consider the possibility of deliberate deception. In a lead article in The Times Higher Education Supplement commenting upon the case of Jatinder Ahluwalia, John Gill appeals for more openness in the way allegations of research fraud are dealt with by institutions, colleagues and journals:

“Sunlight is the best disinfectant, and the UK’s institutions and researchers must be fearless in shining a light on misconduct”.

Referees and editors need to be overtly conscious of the possibility that some of the data they review may be fabricated or dishonestly manipulated; they should take this possibility into account and be aware of some characteristics of fraudulent papers/authors. They should ask themselves questions like:

  • Are the results consistent with previous findings? If not, then do the authors give any credible rationale for differences with other published work?
  • Are the results credible? For example, how probable is it that a simple dietary supplement is more effective in its actions than the most powerful drug available? This question must be applied with caution to avoid rejecting truly innovative work or breakthrough discoveries.
  • Are the statistics believable? At the very simplest level do the standard deviations/errors translate into likely or even possible ranges and are they consistent with other data in the paper?
  • Are the baseline characteristics of subjects consistent with other established data?
  • Do the authors give a clear and believable account of key parts of their methodology such as how subjects were recruited and allocated to study groups?
  • Are the numbers of subjects with specific and uncommon characteristics feasible? British obstetrician Malcolm Pearce claimed to have recruited almost 200 women with uncommon characteristics for a fertility clinical trial that would have taken even a major referral centre a decade to find.
  • Do authors give adequate details of what ethical approval was obtained for the study and is any evidence of this approval supplied? Sometimes fraudulent authors have been found to have by-passed normal ethical approval before they have been found guilty of fraud e.g. as in the cases of both Yoshitaka Fujii and Joachim Boldt.
  • Is the workload and expertise involved in generating the data consistent with the contributor list and the acknowledged assistance? The workload involved in conducting some of Ranjit Chandra’s single author papers would have required an army of research assistants and investigators and a huge input of physical resources and analytical work.
  • Are the co-authors all aware of their involvement and have they signified their willingness to accept responsibility for the quality and veracity of the methods and results submitted. One of the ploys used by Yoshitaka Fujii to add credibility to his work and the very high number of patients enrolled on his studies was by making them appear as if they were multi-site studies. He did this by adding the names of co-authors without their consent and on occasion even forging “co-authors” signatures on the form required by journal attesting to authorship. Some of Fujii’s collaborators were it seems completely unaware of the use of their names.

These questions would, in most cases, be a formality unless a referee’s or editor’s suspicion is aroused. Once misconduct is suspected then other more time-consuming investigations into the publication record of the suspect could be initiated. Often such wider investigations do generate evidence of research fraud; the evidence is often very clear once detailed analysis of the accused’s work begins. The unmasking of Yoshitaka Fujii by an intensive analysis of the baseline data in his clinical trials and the demonstration by Carlisle (2012) that it could not possibly have arisen by random allocation of subjects provided compelling evidence of data fabrication that was taken as essentially proof of research fraud. The finding that Sir Cyril Burt used exactly the same correlation coefficients to three decimal places in several papers despite different sample sizes convinced many psychologists that he had manufactured his results. The size of Burt’s sample of identical twins who he claimed were all separated soon after birth and each brought up in households that were in totally different socioeconomic classes seems highly improbable. A detailed analysis of raw data requested by the BMJ to support one of the papers submitted to the journal by Ram Bahadur Singh showed that there was overwhelming evidence of data fabrication or falsification (Al-Marzouki et al, 2005).

Several fraudsters seem to have used other authors’ names without permission to give credibility to their work and some have used fictitious co-authors or have written papers in the name of fictitious authors to support and add credibility to their own published findings.

  • Yoshitaka Fujii used the names of other anaesthesiologists on his papers without their knowledge.
  • A paper in the name of Amrit Jain was published in a journal edited by RK Chandra in 2001 that supported Chandra’s findings about the effects of vitamin supplements on immune function in elderly people. This paper was accepted the day after submission and it is widely believed that the paper was written by Chandra and that Jain does not exist or at least played no part in the paper.
  • Sir Cyril Burt is accused of writing papers, reviews and articles for the psychology journal he edited (British Journal of Statistical Psychology) using various pseudonyms. It was suggested by his commissioned biographer (Professor Leslie Earnshaw) that half of those who contributed notes, reviews and letters to this journal during Burt’s period as editor were not identifiable and that the material was probably written by Burt himself. Two of his long time assistants have never been traced despite co-authoring articles with him and even publishing independent articles in the journal that Burt edited. It is thought that he used their names as co-authors to make the accumulation of so much data after his retirement seem more credible.

Awareness of such ploys and acceptance that they are a possibility makes their earlier detection more likely. Journals should take reasonable steps to ensure that all of the authors listed on a submission really exist and that they are aware that the paper is being submitted in their name. Journal editors obviously play a pivotal role in journals’ efforts to prevent publication of fraudulent research and also in dealing with previously published suspect material. Journal editors also hold a position of trust and as can be seen from the Burt and Chandra cases this trust can be abused and the journal manipulated to suit the editor’s own agenda. Many of the fraudsters dealt with in the case-studies had held one or more editorial positions with journals. Journal editors must be scientists of the highest integrity and any reasonable doubts about their past behaviour should rule them out of holding such a position of trust. Journal owners and publishers must ensure that their journals do not become the personal fiefdom of a dominant or long serving editor. Checks should be embedded in the editorial process to prevent editors publishing anything they choose and they should not be involved in handling papers that they have co-authored or papers that support or contradict their own work.

In addition to phantom collaborators and people listed as collaborators without their knowledge, some eminent and respected co-authors seem to have been inadvertently duped into adding credibility to fraudulent findings. Some of the discredited papers published by the Indian palaeontologist Vishwa Jit Gupta were co-authored by other highly respected academic palaeontologists from around the world. He claimed to have found numerous fossils in the Himalayas that had never otherwise been found within thousands of kilometres. These were genuine fossils that he had probably acquired from shops and museums around the world and then falsely claimed that he had discovered them in the Himalayas. One of Gupta’s ploys was to send his fossil to an authority on that type of fossil who would authenticate it as a genuine example and help in the description of the fossil and because of this role they would be listed as a co-author. The presence of these other experts on the author list would have added to the authority and credibility of Gupta’s claims that he had found it in the Himalaya’s and his interpretation of the significance of its presence there.

Limiting the influence of fraudulent authors

Another aim of writing this book is to encourage editors and owners of journals to do more to restore the integrity of the scientific record. They should be more proactive in trying to retract suspect papers and warn readers about data in unretracted papers of known fraudsters. Unless journals take strong action against papers written by these fraudsters then they will continue to influence those searching and/or reviewing the scientific literature and continue to be used by commercial organisations to give false credibility to their products and even affect clinical decisions. Data reported by RK Chandra in the 1990s about the hypoallergenic properties of some commercial infant formulae were used by the manufacturers to support the claims for their products despite an unpublished internal inquiry at Memorial University having concluded that he had been guilty of research misconduct in the generation of this data. Yoshitaka Fujii’s prolific clinical trials clearly distorted conclusions about the best way of treating post-operative nausea and vomiting.  A 2012 meta-analysis by John Carlisle showed that the apparent efficacy of different treatments for post-operative nausea and vomiting were quite different when analysed with and without the inclusion of Fujii’s fabricated data. In practice, Fujii’s mass of data relating to drugs for preventing postoperative nausea and vomiting was already largely ignored by anaesthesiology policy makers because they seem to have privately accepted that his data was unreliable.

Fraudsters exert influence not only by publishing their fraudulent output but also by being given opportunities to influence scientific opinion by invitations to write and speak and to sit on policy making bodies. They will also supervise, teach and perhaps write the books used by students who will become the next generation of scientists. Review articles written by serial fraudsters should also be considered for retraction. These reviews were only published because of the author’s reputation gained by use of fraudulent data. Most fraudsters freely cite their own tarnished research in their review articles. Many non-specialists and textbook writers will rely upon review articles to keep them up to date in areas outside their own specialism.

In 2013, I found more than fifty review articles by RK Chandra available in the literature, nine reviews from record breaking fraudster Yoshitaka Fujii and twenty from another fraudulent anaesthesiologist Joachim Boldt. The inquiry into the fraudulent activities of Dutch social psychologist Diederik Stapel found that 4 reviews or book chapters co-authored by Stapel were partly based upon material in his fraudulent papers. Perhaps most worrying is that several reviews by disgraced South African oncologist Werner Bezwada remained in the literature. He used fabricated clinical trial data to support the benefits of aggressive high dose chemotherapy for some breast cancer patients. His fabricated data helped to increase and prolong the use of this dangerous and expensive treatment even though it offered no measurable benefits for patients.

Finally these fraudsters can influence scientific and public opinion through writing books, popular articles and through media interviews. It is claimed, for example, that Ranjit Chandra has authored or edited 22 books.

Many fraudsters are serial offenders and have been allowed to pollute the scientific record for decades even when suspicions were raised much earlier – did secrecy and the desire not to make concerns public protect fraudsters and allow them to continue? The failure to publicly expose several prolific fraudsters like Fujii, Chandra and Heslop Harrison despite credible evidence of fraud found many years before their final unmasking has already been discussed. It is very difficult even with the benefit of hindsight to see how these people were able to carry on forging very successful careers despite this suspicion and evidence – sometimes pretty incontrovertible evidence.

One telling addition to the discussion about how fraudsters are able to flourish for so long is a comment made in book review by the distinguished immunologist and Nobel laureate Sir Peter Medawar. He recalls being shown a rabbit which had purportedly had its whole cornea transplanted from a human cadaver after this cornea had undergone a period of incubation. William Summerlin claimed that this pre-incubation of skin, corneas and other tissues prevented tissue rejection even when transplants were between different species. The eye of the rabbit showed no signs of surgery and. Medawar said that he did not believe that the rabbit had undergone any surgery to its cornea (which it had not) but admits that he lacked the moral courage to say that he believed that the distinguished audience were being made victims of a hoax. If someone with a Nobel Prize and a worldwide reputation as an eminent authority in their field felt inhibited from pointing out what he believed to be an obvious fraud then it is not surprising that others without such a reputation are also tempted to say nothing:

All it takes for evil to succeed is for a few good men to do nothing…”

Bibliography

Ahluwalia J, Tinker A, Clapp LH, Duchen MR, Abramov AY, Pope S, Nobles M and Segal AW (2004 RETRACTED) The large-conductance Ca2+– activated K+ channel is essential for innate immunity. Nature 427, 853-859. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2099462/

Bezwoda, WR, Seymour, L and Dansey, RD (1995 RETRACTED) High dose chemotherapy with haematopoietic rescue as primary treatment for metastatic breast cancer: a randomized trial. Journal of Clinical Oncology 13, 2483-9.

Carlisle, JB (2012a) The analysis of 168 randomised controlled trials to test data integrity. Anaesthesia 67, 521-37. http://www.anesth.or.jp/news2012/pdf/20120501_2-1.pdf

Carlisle, JB (2012b) A meta-analysis of postoperative mausea and vomiting: randomised controlled trials by Fujii et al compared with other authors. Anaesthesia 67, 1076-90. http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.370.2379&rep=rep1&type=pdf

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Chandra, RK 1992 Effect of vitamin and trace-element supplementation on immune responses and infection in elderly subjects.  Lancet 340, 1124-1126.

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Jain AL (2002) Influence of vitamins and trace-elements on the incidence of respiratory infections in the elderly. Nutrition Research 22, 85-87. http://media.sethroberts.net/chandra/Jain_article.pdf

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Kranke, P, Apfel, C and Norbert, R. (2000) Reported data on granisetron and postoperative nausea and vomiting by Fujii et al. are incredibly nice! Anesthesia and Analgesia 90, 1004-6. Available at: http://journals.lww.com/anesthesia-analgesia/Fulltext/2000/04000/Reported_Data_on_Granisetron_and_Postoperative.53.aspx

McLaren, DS (1974) The great protein fiasco. Lancet ii, 93-96.

McLaren, DS (2011) The legacy of a life (interview by Jonathan Steffen). Sight and Life 25(3), 50-53. http://www.sightandlife.org/fileadmin/data/Magazine/2011/25_3_2011/donald_s_mclaren_the_legacy_of_a_life.pdf

Medawar, P (1996) The Strange Case of the Spotted Mice and other classic essays on science. Oxford: Oxford University Press.

Meguid, MM (2005) Retraction Nutrition 21, 286. http://media.sethroberts.net/chandra/2005_01_Nutrition_retraction.pdf

O’Neill-Yates, C (reporter) and Burgess, L (producer) (2006) The secret life of Ranjit Chandra. Broadcast January 30th 2006 The National, Canadian Broadcasting Corporation. Text version available at: http://www.infactcanada.ca/Chandra_Jan30_2006.htm Broadcasts available at: https://www.youtube.com/watch?v=gKYr1VerT4A (part1) https://www.youtube.com/watch?v=2R7-QM8eKCM (part2) https://www.youtube.com/watch?v=YbQNlm7sw5A (part 3).

Preston, CD (2004) John Raven’ report on his visit to the Hebrides, 1948. Watsonia 25, 17-44. http://archive.bsbi.org.uk/25-1-PrestonRaven.pdf

Sabbagh, K (1999) A Rum Affair. The Exposure of Botany’s Piltdown Man. Penguin Books: London.

University College London (2010) UCL procedure for investigating and resolving allegations of misconduct in academic research: Dr Jatinder Ahluwalia. Available at: https://www.ucl.ac.uk/srs/governance-and-committees/resgov/UCL-Statement-26-November-2010.pdf

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