‘All that glisters is not gold’
William Shakespeare. The Merchant of Venice.
Most people are probably familiar with this statement although it is commonly misquoted and the word ‘glisters’ is often written as ‘glitters’. What has this got to do with blood? Many of us who are haematologists rely heavily on accurate reports in prestigious medical journals in order to inform our clinical practice or knowledge about haematological disorders. With the plethora of haematology journals and the difficulty in recruiting expert reviewers, the question should be asked: is such reliance justified or should we exercise a greater degree of healthy skepticism? Are all editors unbiased and/or do reviewers sometimes favour research communications from well-known investigators over the less well-known?
A widely held view among practitioners and academics is that a prospective, randomized, clinical trial is the only way of assessing the efficacy of a therapeutic intervention. Recently however, Gale and colleagues [1,2] have cast some doubt on this belief, albeit, in investigations of bone marrow transplantation treatment or its complications.1
James Lind (1716-1794), a Scottish physician, has a reputation, among physicians, for being the first medical doctor to carry out a ‘clinical trial’ and his name will be forever linked with the prevention of scurvy in British sailors in the 18th century. However, like many historical beliefs, the situation is somewhat more complicated. Although the beneficial effect of fresh fruit on the incidence of the ailment was known for centuries, it was not utilized. While Lind successfully prevented and treated scurvy in sailors, his published research was largely ignored and it was more than 100 years before the British Navy introduced a source of vitamin C as a preventative measure against scurvy. Once again, the water was somewhat muddied by the substitution of limes (hence the name ‘limey’ for British sailors) for lemons, although limes contain only a fraction of vitamin C compared with lemons. This decision was a ‘colonial’ preference as most of the limes came from the colonized West Indies. I do not intend to delve, in detail, into the story of vitamin C and scurvy but for those who are interested there is an excellent and detailed account of the saga by Baron,2 who writes:
I do not consider Lind’s report entirely reliable. Nevertheless, Lind’s book stimulated Thomas Trotter and Gilbert Blane to persuade the British Navy in 1793 to abolish scurvy by compulsory lemon juice, only for it to reappear after 1860. especially in polar regions, when lime juice was substituted.
Two annoying expressions have recently crept into the English lexicon: ‘research shows’ and ‘there is science behind this’. Both are beloved by politicians and journalists. There seems to be an implicit belief that all ‘research’ is conducted correctly and I am sure there is certainly no justification for implying a scientific logic to most political decisions. We know that in order to add veracity to research published in medical journals, a system known as ‘peer-review’ was instituted. The peer-review procedure was meant to ‘objectively’ evaluate research results but this is not always fool-proof.
Could it be that some editors of prestigious journals are prepared to publish unverified ‘research’ or/and show favour to authors from elite universities over authors from little-known institutions? It seems so. The editor of the Lancet, Richard Horton, claimed that perhaps 50% of published research could not be verified, implying intellectual fraud.3 Dr Marcia Angell, former editor-in-chief of the New England Journal of Medicine is credited with saying in 2014:
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. I take no pleasure in this conclusion, which I reached slowly and reluctantly over my two decades as editor of the New England of Medicine.
The infamous publication in 1998 by Wakefield and colleagues linking the MMR vaccine to autism has been widely discredited but not before it contributed to preventable morbidity and perhaps mortality.4 In 2010 Eggertson [6] wrote in the Canadian Medical Association Journal:
12 years after publishing a landmark study that turned tens of thousands of parents around the world against the MMR vaccine because of an implied link between vaccination and autism, The Lancet retracted the paper.
Eggertson also claimed that:
In the UK, the Health Protective Agency attributed a large measles outbreak in 2008 and 2009 to a concurrent drop in the number of children receiving the MMR vaccine. Pockets of measles – which can be fatal-have also cropped up in Canada and the United States as a result of parents’ refusal to vaccinate.
Further comment was made on behalf of UNICEF by epidemiologist Senad Begic:
The MMR vaccine does not cause autism. Dr. Wakefield had a financial interest in pursuing this topic and a few months before the study had registered his own vaccine against the very disease he was blaming for the condition. The article was removed from the Lancet and labelled as dishonest and fabricated, and Wakefield lost his license to work in the UK due to dishonest behaviour, violation of the moral code and non-compliance with the code of ethics of the honourable medical profession, and damage to the health of children around the world. Today he is considered the leading ‘fake expert’ who still makes a significant profit from publicity and public appearances that have nothing to do with medicine or science.
This sort of publication undoubtedly helps the ‘anti-vaccers’ and conspiracy theorists, coupled with the fact that many young physicians have never seen a case of measles, which may lead to a delay in diagnosis. Overall, a disease with significant morbidity and mortality, which had been eradicated in many countries, made a deadly comeback.
What is of major interest to haematologists are the egregious publications by Obokata and colleagues.5 Admittedly neither of these publications had major public health implications but their egregiousness shocked the haematology community as both publications had been favourably peer-reviewed and published in a prestigious journal. Their claim was that committed cells could be retro-programmed to become pluripotent cells (the ‘holy grail of cell biologists and haematologists) using relatively simple laboratory techniques, Unfortunately, not true! Although the research was subsequently withdrawn, sadly one of the co-authors subsequently committed suicide.
Therefore, several issues need to be examined urgently. Steps need to be taken to ensure that editors of prestigious journals are prevented from institutional, racial, gender or geographical bias. The pressure to publish or perish remains rampant in many academic institutions while the growth of ‘predatory’ journals makes the likelihood of publishing fraudulent or irrelevant research more likely. As Rawat and Meena pointed out in their article ‘Publish or perish: where are we heading’?:6
Frequent publication is one of the few powerful methods at scholar’s disposal to demonstrate academic talent to peers.
They also point out that there has been a proliferation of scientific/medical journals and that:
Publication has now become obligatory, however equal importance should be given to the education of students.
Reviewer bias is a closely related issue as editors often rely heavily on reviewers’ comments and recommendations. In a recent review of possible peer review bias, Haffar and colleagues conclude by saying:7
Double-blind peer review may be necessary. An open peer review system may be beneficial to authors and reviewers. We must improve the quality, transparency, and accountability of the peer review system.
Although the evidence of reviewer-bias is inconclusive, many authors have a hunch (sometimes totally incorrect) that research communications from prestigious, well-known authors or from famous institutions have an enhanced chance of being favourably reviewed. Clearly more research needs to be undertaken.
In conclusion, although I do not believe that research should always be ‘functional’, there are clearly some problems. With the plethora of new medical journals being published weekly it will become more difficult to recruit high quality reviewers. Methods other than peer review should be investigated to ensure that bias is not an issue for editors and reviewers. Funding bodies and universities should pay more attention to the quality of the research rather than the quantity and equal credit should be given to other talents, such as teaching students.
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About the author
Shaun Richard McCann received his M.B. from University College Dublin. He became a Member of The Royal College of Physicians in Ireland (MRCPI), by examination, in 1973. He was a specialist medical fellow at the University of Minnesota from 1974-76. The main focus of his research then was red cell structure and function, especially in hereditary spherocytosis. Click here to learn more.