Wednesday, 22 December 2010

Im-Personal reflections on the Medical Hypotheses Affair: Editors of major medical and scientific journals- The Dog that didn'tbark

A brief account of the Medical Hypotheses Affair may be found here:

But there is one general aspect which I learned from the experience, and which is - I think - worth further emphasis. 

This is the aspect of The Dog That Didn't Bark.


The Dogs whose silence throughout this episode was so highly significant were the editors of the major medical and scientific journals, indeed editors of all academic journals were silent.

Twenty five years ago there would, without any shadow of doubt, have been vigorous comment on the happenings at Medical Hypotheses from (say) the editors of Nature, Science, the New England Journal of Medicine, JAMA, the Lancet, the British Medical Journal and others.

And the gist of this would have been: publishers must keep their hands-off editorial independence.

Instead: silence.




The MeHy Affair was a very explicit and highly public example of a publisher intervening directly to over-ride the editor of an established scholarly journal.

This was not merely affecting the conduct of academic discourse, but directly shaping the content of published academic discourse.

In their actions towards Medical Hypotheses, the publishers (Reed-Elsevier - who publish about 20 percent of the world scholarly journals, and a higher proportion of those journals with high impact in their fields) decided what went into the scholarly literature and what did not.

More exactly, specific managers employed by a publishing corporation decided what went into the scholarly literature and what did not.


Precisely, the publishers of Medical Hypotheses acted unilaterally to withdraw two already-e-published  papers from a scholarly journal and delete them from the online records. 

And then (in the period of time leading up to the editor being sacked) Elsevier managers continued to filter-out papers that had been formally accepted for publication by the editor (in other words the papers were officially 'in the press') - but which these managers regarded as unacceptable in some way, and therefore withdrew from the publication process.

In other words, managers took direct control of the content of the published academic literature.


Why was The Silence of the Editors so significant?

In an abstract sense, Elsevier's behaviour contravened the basic established conduct of academic discourse - which is supposed to be independent of publishers and a matter decided between editors and scholars.

Indeed, this was, by a strict 'legalistic' definition, a direct breach of the principle of academic freedom.

So - even abstractly considered - it would be expected that leading journal editors would have raised objections to the corruption of academic discourse.


But there is a much more direct and personal reason to expect leading editors to comment.

Which is that condoning Elsevier's actions set a precedent for further instances whereby managers employed by publishers will simply over-ride editorial independence: managers will decide what gets into journals and what does not.

So, by remaining silent, each editor of each major journal made it more likely that in future their publisher would do the same to them as Elsevier did to me!


Why would leading editors of major journals condone such a thing?

There is a simple explanation: that they are afraid.

As in Vaclav Havel's Poster Test: the Silence of the Editors was a coded statement unambiguously (but deniably) meaning: "I am afraid and therefore unquestioningly obedient".


So now we know that the editors of leading scholarly journals are not independent.

That editors of leading journals are already doing what publishers want.

That the editors of leading journals have accepted this situation as a fait accompli.


This particularly applies to The Lancet, which is published by Elsevier.

In the past, the Lancet was a fiercely, indeed aggressively, independent journal.

Past editors of the Lancet would not have imagined for a moment acceding to managerial pressure from publishers.

Clearly things have changed, and the current Lancet is happy to operate as a smokescreen for the publishers influence on the medical science literature.


Yet the current Lancet editors went one step further than merely acceding to pressure from the publishers, they actually assisted the publishers in over-riding editorial independence in a quasi rational manner.

The Lancet arranged a 'show trial ' whereby the papers which Elsevier management had withdrawn from Medical Hypotheses were 'refereed' by a group of anonymous persons such that it could be claimed that for the papers had been rejected by peer review.

This sham process was implemented by The Lancet, despite the blazingly obvious paradox that the main point of Medical Hypotheses was that it was an editorially reviewed - not peer reviewed; on the rationale that MeHy provided a forum for papers which would probably be rejected by peer review, but which justified publication as hypotheses for other reasons.

There is only one coherent conclusion: that the modern Lancet is a lap-dog of its publisher.


What did I conclude from the Dogs That Did Not Bark?

I realized that science was in an even-worse state that I had previously recognized. That the level of corruption and deception went both deeper and further than I had previously recognized.

And that the role of major journals had moved beyond acquiescence with the forces of darkness and into actual collusion.

That, in fact, science was not just sick but in an advanced state of dissolution: and that indeed the head of the fish was by-now dead and already putrefied.


Note added: Glen P Campbell - who (seemed to be - the senior Elsevier manager responsible for the Medical Hypotheses Affair, (presumably) including over-riding of editorial autonomy, was subsequently appointed to be American director of the British Medical Journal in late 2013. This is consistent with the above argument.

From: International Association of Scientific, Technical & Medical Publishers- The Voice of Academic and Professional Publishing:

GLEN P. CAMPBELL, US Managing Director, The BMJ  Glen has been in STM publishing for more than 34 years, starting with Alan R. Liss in 1980. In 1984, he was appointed an Editor for books and journals in the life sciences, and continued at John Wiley & Sons after they acquired Liss. In 1990, Glen joined Elsevier as a Biomedical Journals Editor. Over more than 23 years at Elsevier, he held a number of positions with responsibility for setting strategies for the growth and development of biomedical journals in print and online. In his roles as EVP, Global Medical Research, he oversaw more than 435 journals in the health science, including The Lancet, and many premier society journals.  In his role as EVP, STM Society Publishing, Glen worked with many of the most prestigious societies in the health, life, physical, and social sciences. Glen joined BMJ late in 2013 as Managing Director the US, and is thrilled to be working on the development and growth of The BMJ, BMJ Journals, and BMJ Clinical Improvement Products in North America. Glen is a past Chair of the Executive Council of the Professional and Scholarly Publishing Division (PSP) of the Association of American Publishers (AAP). In addition, he serves on the American Medical Publishers Committee (AMPC) of the PSP and the AMPA/National Library of Medicine Subcommittee of that group. Glen is currently Chair of Board of Directors of the Friends of the National Library of Medicine.

Tuesday, 29 June 2010

This blog is complete


Since I am no longer the editor of Medical Hypotheses, I now regard this blog as complete, and do not intend to add to it.

I am continuing blogging at Bruce Charlton's Miscellany

Tuesday, 11 May 2010

RIP Medical Hypotheses

Just to note that I was sacked from the editorship of Medical Hypotheses today.

Medical Hypotheses was very much a 'one man band' as a journal - its content being selected by the editor (occasionally after seeking advice from a member of the editorial advisory board) over a period of some 35 years.

The journal's essence was that it was editorially reviewed (not peer reviewed), and favoured revolutionary science over normal science; that is, it favoured ideas on the basis that they were (for example) radical, interesting, dissenting, or sometimes amusing in a way likely to stimulate thought.

The journal had just two editors during its lifespan: the founder David Horrobin from 1975 to his death in 2003; and his chosen successor: myself from 2003-2010.

As a consequence of mergers, Medical Hypotheses fell into the hands of Elsevier in 2002.

Aside from a few issues still in the pipeline, the real Medical Hypotheses is now dead: killed by Elsevier 11 May 2010. RIP.

Thursday, 6 May 2010

The Medical Hypotheses Affair - Times Higher Education

"Without prejudice" - 6 May 2010 - Times Higher Education

Bruce G Charlton

"Bruce Charlton explains why he published a paper by 'perhaps the world's most hated scientist' and the importance of airing radical ideas"


On 11 May, Elsevier, the multinational academic publisher, will sack me from my position as editor of Medical Hypotheses. This affair has attracted international coverage in major journals such as Nature, Science and the British Medical Journal.

How did it come to this? Last year I published two papers on Aids that led to a complaint sent to Elsevier.

This was not unexpected. Medical Hypotheses was established with the express intent of allowing ideas outside the mainstream to be aired so that they could be debated openly. Its policy had not changed since its founding more than three decades ago, and it remained unaltered under my editorship, which began in 2003.

Nevertheless, managers at Elsevier sided with those who made the complaints and against Medical Hypotheses. Glen P. Campbell, a senior vice-president at Elsevier, started a managerial process that immediately withdrew the two papers - without consulting me and without gaining editorial consent. After deliberating in private, the management at Elsevier informed me of plans to make Medical Hypotheses into an orthodox, peer-reviewed and censored journal. When I declined to implement the new policy, Elsevier gave notice to kick me out before my contract expired and without compensation.

One of the papers, by Marco Ruggiero's group at the University of Florence, (doi:10.1016/j.mehy.2009.06.002) teased the Italian health ministry that its policies made it seem as if the department did not believe that HIV was the cause of Aids. The other paper, by Peter Duesberg's group at University of California, Berkeley (doi:10.1016/j.mehy.2009.06.024), argued that HIV was not a sufficient cause of Aids.

The Ruggiero paper seems to have been an innocent bystander that was misunderstood both by those who made a complaint and by Elsevier. The real controversy focused on Duesberg's paper.

Why did I publish a paper by Duesberg - perhaps the world's most hated scientist?

Peter Duesberg is a brilliant and highly knowledgeable scientist with a track record of exceptional achievement that includes election to the US National Academy of Sciences. However, his unyielding opposition to the prevailing theory that HIV is a sufficient cause of Aids has made Duesberg an international hate figure, and his glittering career has been pretty much ruined.

I published Duesberg's paper because to do so was clearly in line with the long-term goals, practice and the explicitly stated scope and aims of Medical Hypotheses. We have published many, many such controversial and dissenting papers over the past 35 years. Duesberg is obviously a competent scientist, he is obviously the victim of an orchestrated campaign of intimidation and exclusion, and I interpret his sacrifice of status to principle as prima facie evidence of his sincerity. If I had rejected this paper for fear of the consequences, I would have been betraying the basic ethos of the journal.

Medical Hypotheses was founded 35 years ago by David Horrobin with the purpose of disseminating ideas, theories and hypotheses relating to biomedicine, and of doing so on the basis of editorial review instead of peer review. Horrobin argued that peer review intrinsically tended to exclude radical and revolutionary ideas, and that alternatives were needed. He chose me as his editorial successor because I shared these views.

Both Horrobin and I agreed that the only correct scientific way to deal with dissent was to publish it so that it could be debated, confirmed or refuted in an open and scientific forum. The alternative - suppressing scientific dissent by preventing publication using behind-the-scenes and anonymous procedures - we would both regard as extremely dangerous because it is wide open to serious abuse and manipulation by powerful interest groups.

Did I know that the Duesberg paper would be controversial?

Yes. I knew that Duesberg was being kept out of the mainstream scientific literature, and that breaching this conspiracy would annoy those who had succeeded in excluding him for so long.

When I published the Duesberg article, I envisaged it meeting one of two possible fates.

In the first scenario, the paper would be shunned or simply ignored - dropped down the memory hole. This is what has usually happened in the past when a famous scientist published ideas that their colleagues regarded as misguided or crazy. Linus Pauling (1901-94) was a Nobel prizewinner and one of the most important chemists in history. Yet his views on the medical benefits of vitamin C were regarded as wrong. He was allowed to publish them, but (rightly or wrongly) they were generally ignored in mainstream science.

In the other scenario, Duesberg's paper would attract robust criticism and (apparent) refutation. This happened with Fred Hoyle (1915-2001), a Fellow of the Royal Society whose work on the "steady state" theory of the Universe made him one of the most important cosmologists of the late 20th century. But his views on the origins of life on Earth and the Archaeopteryx fossil were generally regarded as eccentric. Hoyle's ideas were published, attracted much criticism, and were (probably) refuted.

So I expected that Duesberg's paper either would be ignored or would trigger letters and other papers countering the ideas and evidence presented. Medical Hypotheses would have published these counter-arguments, then provided space for Duesberg to respond to the criticisms and later allowed critics to reply to Duesberg's defence. That is, after all, how real science is supposed to work.

What I did not expect was that editors and scientists would be bypassed altogether, and that the matter would be settled by the senior managers of a multinational publishing corporation in consultation with pressure-group activists. Certainly, that would never have happened 25 years ago, when I began research in science.

The success of Medical Hypotheses

Nor did I not expect that I would be sacked, the journal destroyed and plans made to replace it with an impostor of the same name. I did not expect this because I had been doing a good job and Medical Hypotheses was a successful journal.

Elsevier managers in the UK had frequently commended my work, I got a good salary for my work as editor, and I was twice awarded substantial performance-related pay rises. The journal was expanded in size by 50 per cent under my editorship, and a spin-off journal, Bioscience Hypotheses (edited by William Bains), was launched in 2008 on the same principles of editorial review and a radical agenda.

The success of Medical Hypotheses is evidenced by its impact factor (average citations per paper), which under my editorship rose from about 0.6 to 1.4 - an above-average figure for biomedical journals. Download usage was also exceptionally high with considerably more than 1,000 online readers per day (or about half a million papers downloaded per year). This level of internet usage is equivalent to that of a leading title such as Journal of Theoretical Biology.

But Medical Hypotheses was also famous for publishing some rather "eccentric" papers, which were chosen for their tendency to provoke thought, trigger discussion or amuse in a potentially stimulating way. Papers such as Georg Steinhauser's recent analysis of belly-button fluff have polarised opinion and also helped make Medical Hypotheses a cult favourite among people such as Marc Abrahams, the founder of the IgNobel Prizes. But they have also made it the subject of loathing and ridicule among those who demand that science and the bizarre be kept strictly demarcated (to prevent "misunderstanding").

It is hard to measure exactly the influence of a journal, but some recent papers stand out as having had an impact. A report by Lola Cuddy and Jacalyn Duffin discussed the fascinating implications of an old lady with severe Alzheimer's disease who could still recognise tunes such as Oh, What a Beautiful Mornin'. This paper, which was discussed by Oliver Sacks in his book Musicophilia: Tales of Music and the Brain, seems to have helped spark a renewed interest in music in relation to brain disease.

The paper "A tale of two cannabinoids" by E. Russo and G.W. Guy suggested that a combination of marijuana products tetrahydrocannabinol (THC) and cannabidiol (CBD) would be valuable painkillers. This idea has since been widely discussed in the scientific literature.

And in 2005, Eric Altschuler published in Medical Hypotheses a letter outlining his idea that survivors of the 1918 flu epidemic might even now retain immunity to the old virus. A few 1918 flu survivors were found who still had antibodies, and cells from those people were cloned to create an antiserum that protected experimental mice against the flu virus. The work was eventually published in Nature and received wide coverage in the US media.

What is my own position on the cause of Aids?

As an editor of a radical journal, my position was resolutely agnostic - in other words, I was not pursuing an agenda. I would publish papers presenting both sides of the debate. Most of the papers I published on Aids were orthodox ideas relating to HIV as the main cause. However, as well as Duesberg's article, I published some other papers challenging the HIV causal theory and proposing different mechanisms, such as work by Lawrence Broxmeyer arguing that some Aids patients actually have tuberculosis.

As for my personal opinions on the cause of Aids, these are irrelevant to real science because the subject is too far away from my core expertise and I do not work in that area. It is clear that Duesberg understands far more about HIV than I do, and more than at least 99 per cent of his critics do. Therefore, the opinions of most of Duesberg's critics, no matter how vehement, are just as irrelevant to real science as are mine.

But for me to collude with prohibiting Duesberg from publishing, I would have needed to be 100 per cent sure that Duesberg was 100 per cent wrong. Because even if he is mostly wrong, it is possible that someone of his ability may be seeing some kind of problem with the current consensus about Aids that other people of lesser ability (that is, most of us) are missing.

And if Duesberg may be even partially correct, it is extremely dangerous that the proper scientific process has been so ruthlessly distorted and subverted simply to exclude his ideas from the official scientific literature.

Bruce G. Charlton is professor of theoretical medicine, University of Buckingham.

Sunday, 25 April 2010

Some influential papers from Medical Hypotheses

Some influential papers from the history of Medical Hypotheses

I believe that a journal editor should be ‘agnostic’ about the truth of the papers he publishes, since truth in science is not something that editors ought to guess, but should only be determined after publication by evaluation and testing within the wider scientific community.

There is, at present, no objective method of evaluating a journal's relative or unique influence either quantitatively or qualitatively. To do this would require a great investment of intelligence, time and resources.

After all, papers published in very high impact journals like Nature, Science and PNAS would - if rejected from one of these - almost-certainly have been published in another of these, or elsewhere in a specialist journal with similar impact; and if this had happened the same paper may well have had identical impact.

What is hard to get-at is the _distinctive_ contribution of a _specific_ journal. At present, the best avaiable method may be biographical: asking scientists their opinion about the importance of particular papers in particular journals:

However the crude influence of publications can sometimes be estimated using citation analysis – this looks at the number of times a paper has been listed in the reference section by other scientists.

Citations build-up over several years, so that citation analysis is more reliable for older papers. But citations tend to reward mainstream 'methodological' papers - it is hard to estimate the importance of 'ideas' papers such as hypotheses and theories, especially as scientists do not feel obliged to cite the sources of their ideas even if they can remember them (whereas, by contrast, scientists must cite the source of any empirical data on which their own research depends).

Bearing in mind these methods and caveats, I have compiled a short list of some of the papers from Medical Hypotheses which seem to have been most influential.

There were just two editors of Medical Hypotheses in its 35 year history

1975-2003 – David L Horrobin as Editor

In the early days of Medical Hypotheses many of the papers reflected the first Editor’s interest in nutritional topics; and Medical Hypotheses published many ideas that helped launch some of today’s mainstream ideas about diet, such as the benefits of supplementation with ‘omega’ fatty acids and antioxidants.

In 1985 AJ Verlangieri and others outlined the now widely-accepted idea that eating plenty of fruit and vegetables helps prevent heart disease in a widely quoted paper: “Fruit and vegetable consumption and cardiovascular mortality”.

Through the 1980s in Medical Hypotheses, freelance US scientist Mark F McCarty was publishing many of the early and influential papers about the importance of antioxidants in the diet, and their possible role in preventing disease. Over some three decades McCarty has published more papers in Medical Hypotheses than anyone else, and together these papers have been cited thousands of times in the scientific literature.

In 1987 the Medical Hypotheses founding editor David Horrobin published a frequently-referenced paper on the ‘omega-3’ type of essential fatty acid, which so many people now use as dietary supplements: “Low prevalences of coronary heart disease (CHD), psoriasis, asthma and rheumatoid arthritis in Eskimos: Are they caused by high dietary intake of eicosapentaenoic acid (EPA), a genetic variation of essential fatty acid (EFA) metabolism or a combination of both?”

In 1985, Clouston and Kerr published in Medical Hypotheses an influential paper called “Apoptosis, lymphocytotoxicity and the containment of viral infections”. This first described the now widely accepted idea that viruses may be fought by inducing suicide in virus-infected cells.

The most widely cited paper in Medical Hypotheses was published in 1991: The macrophage theory of depression by RS Smith. This is a key paper which argues that immune system chemicals may be a major cause of depression, and has been cited 242 times according to Google Scholar.

2004-2010 Bruce G Charlton as Editor

Here are some recent papers under my editorship which have already had an impact:

In 2005, Lola Cuddy and Jackie Duffin of Queens University Canada published an influential paper in Medical Hypotheses based on an elderly lady with several Alzheimer’s disease who still retained the ability to recognize music. They theorized that this might provide useful information on the nature of brain damage in Alzheimer’s, and suggested that dementia sufferers might benefit from a more musical environment. This paper was awarded the David Horrobin Prize for 2005 for the paper in Medical Hypotheses which best exemplified the intentions of the founding editor – the famous Cambridge transplant surgeon Sir Roy Calne was judge.

In “A tale of two cannabinoids” by E Russo & GW Guy from 2006, the authors presented the rationale for using a combination of marijuana products tetrahydrocannabinol (THC) and cannabidiol (CBD) as useful painkilling drugs and for the treatment of several other medical conditions. This idea has since been widely discussed in the scientific literature.

In 2005 Eric Altschuler published a letter in Medical Hypotheses outlining his idea that survivors of the 1918 flu epidemic might even now retain immunity to the old virus. A few 1918 flu survivors were found who still had antibodies, and cells from these people were cloned to create an antiserum that protected experimental mice against the flu virus. The work was eventually published in Nature and received wide coverage in the media.

Tuesday, 13 April 2010

The Cancer of Bureaucracy

Bruce G Charlton

The cancer of bureaucracy: how it will destroy science, medicine, education; and eventually everything else

Medical Hypotheses - 2010; 74: 961-5.


Everyone living in modernizing ‘Western’ societies will have noticed the long-term, progressive growth and spread of bureaucracy infiltrating all forms of social organization: nobody loves it, many loathe it, yet it keeps expanding. Such unrelenting growth implies that bureaucracy is parasitic and its growth uncontrollable – in other words it is a cancer that eludes the host immune system. Old-fashioned functional, ‘rational’ bureaucracy that incorporated individual decision-making is now all-but extinct, rendered obsolete by computerization. But modern bureaucracy evolved from it, the key ‘parasitic’ mutation being the introduction of committees for major decision-making or decision-ratification. Committees are a fundamentally irrational, incoherent, unpredictable decision-making procedure; which has the twin advantages that it cannot be formalized and replaced by computerization, and that it generates random variation or ‘noise’ which provides the basis for natural selection processes. Modern bureaucracies have simultaneously grown and spread in a positive-feedback cycle; such that interlinking bureaucracies now constitute the major environmental feature of human society which affects organizational survival and reproduction. Individual bureaucracies must become useless parasites which ignore the ‘real world’ in order to adapt to rapidly-changing ‘bureaucratic reality’. Within science, the major manifestation of bureaucracy is peer review, which – cancer-like – has expanded to obliterate individual authority and autonomy. There has been local elaboration of peer review and metastatic spread of peer review to include all major functions such as admissions, appointments, promotions, grant review, project management, research evaluation, journal and book refereeing and the award of prizes. Peer review eludes the immune system of science since it has now been accepted by other bureaucracies as intrinsically valid, such that any residual individual decision-making (no matter how effective in real-world terms) is regarded as intrinsically unreliable (self-interested and corrupt). Thus the endemic failures of peer review merely trigger demands for ever-more elaborate and widespread peer review. Just as peer review is killing science with its inefficiency and ineffectiveness, so parasitic bureaucracy is an un-containable phenomenon; dangerous to the extent that it cannot be allowed to exist unmolested, but must be utterly extirpated. Or else modernizing societies will themselves be destroyed by sclerosis, resource misallocation, incorrigibly-wrong decisions and the distortions of ‘bureaucratic reality’. However, unfortunately, social collapse is the more probable outcome, since parasites can evolve more rapidly than host immune systems.


Everyone in modernizing ‘Western’ societies (roughly the USA, UK, Western and Central Europe) will, no doubt, have noticed that there has been a long-term, progressive growth and spread of bureaucracy. Except during major war; this has not been a matter of pendulum swings, with sometimes less and sometimes more bureaucracy, but instead of relentless overall expansion – albeit sometimes faster and at other times slower.

The bureaucratic takeover applies to science, medicine, education, law, police, the media – indeed to almost all social functions. Such unrelenting growth implies either that 1. Bureaucracy is vital to societal functioning and the more bureaucracy we have the better for us; or that 2. Bureaucracy is parasitic and its growth is uncontrollable. Since the first alternative has become obviously absurd, I am assuming the second alternative is correct: that bureaucracy is like a cancer of modernizing societies – i.e. its expansion is malignant and its effect is first parasitic, then eventually fatal.

While it is generally recognized that modern societies are being bled-dry by the expense, delays, demoralization and reality-blindness imposed by multiple expanding and interacting bureaucracies, it is not properly recognized that bureaucratic decision-making is not merely flawed by its expense and sluggishness but also by its tendency to generate wrong answers. Modern bureaucracy, indeed, leads to irrational and unpredictable decisions; to indefensible decisions which are barely comprehensible, and cannot be justified, even by the people directly involved in them.

In what follows, I will make a distinction between, on the one hand, Weberian, functional, ‘rational’ bureaucracy which (in its ideal type, as derived from the work of Max Weber; 1864-1920) incorporated individual decision-making and was evaluated externally in terms of results and efficiency; and, on the other hand, modern ‘parasitic’ bureaucracy which (in its ideal type) deploys majority-vote committees for its major decision-making, is orientated purely towards its own growth, and which by means of its capacity to frame ‘reality’ - has become self-validating.

I will argue that parasitic bureaucracy evolved from rational bureaucracy in response to the rapidly changeable selection pressures imposed by modern society, especially the selection pressure from other bureaucracies having constructed a encompassing, virtual but dominant system of ‘bureaucratic reality’; and that the system of rational bureaucracy is by now all-but extinct – having been rendered obsolete by computerization.

The problem of parasitic bureaucracy

It is a striking feature of modern bureaucracy that nobody loves it, many loathe it (even, or especially, the bureaucrats themselves), yet it keeps growing and spreading. One reason is that bureaucracy is able to frame reality, such that the more that bureaucracy dominates society, the more bureaucracy seems to be needed; hence the response to any bureaucracy-generated problem is always to make more and bigger bureaucracies. It is this positive feedback system which is so overwhelming. Mere human willpower is now clearly inadequate to combat bureaucratic expansionism. Bureaucracy has become like The Borg on Star Trek: the next generation: it feeds-upon and assimilates opposition.

Bureaucracies are indeed no longer separable but form a linked web; such that to cut one bureaucracy seems always to imply another, and larger, bureaucracy to do the cutting. When the dust has settled, it is invariably found that the total sum and scope of societal bureaucratic activity has increased. And it is well recognized that modern bureaucracies tend to discourse-about, but never to eradicate, problems – it is as-if the abstract bureaucratic system somehow knew that its survival depended upon continually working-on, but never actually solving problems... Indeed, ‘problems’ seldom even get called problems nowadays, since problems imply the need and expectation for solutions; instead problems get called ‘issues’, a term which implies merely the need to ‘work-on’ them indefinitely. To talk in terms of solving problems is actually regarded as naïve and ‘simplistic’; even when, as a matter of empirical observation, these exact same problems were easily solved in the past, as a matter of record.

Over much of the world, public life is now mostly a matter of ‘bureaucracy speaking unto bureaucracy’. Observations and opinions from individual humans simply don’t register – unless, of course, individual communications happen to provide inputs which bureaucracies can use to create more regulations, more oversight, hence create more work for themselves. So individual complaints which can be used to trigger bureaucratic activity may be noted and acted-upon, or personal calls for more bureaucratic oversight may be amplified, elaborated and implemented. But anything which threatens the growth and spread of bureaucracy (i.e. anything simple that is also worryingly swift, efficient or effective) is ignored; or in extremis attacked with lethal intent.

The main self-defence of modern bureaucracy, however, is to frame reality. Since bureaucracies now dominate society, that which bureaucracies recognize and act-upon is ‘reality’; while that which bureaucracies do not recognize does not, for practical purposes, exist. Bureaucracy-as-a-system, therefore constructs a 'reality' which is conducive to the thriving of bureaucracy-as-a-system.

When a powerful bureaucracy does not recognize a communication as an input, then that communication is rendered anecdotal and irrelevant. Information which the bureaucracy rejects takes-on an unreal, subjective quality. Even if everybody, qua individual, knows that some thing is real and true – it becomes possible for modern bureaucracy implicitly to deny that thing's existence simply by disregarding it as an input, and instead responding to different inputs that are more conducive to expansion, and these are then rendered more significant and 'realer' than actual reality.

For many people, the key defining feature of a bureaucracy (as described by Weber) is that ideally it is an information-processing organization that has established objective procedures which it implements impartially. It is these quasi-mechanical procedures which are supposed to link aims to outcomes; and to ensure that, given appropriate inputs a bureaucracy almost-automatically generate predictable and specific outputs and outcomes.

However modern bureaucracies do not work like that. Indeed, such has been the breakdown in relationship between input and output that modern bureaucracies devote immense resources to change pure-and-simple; for example continually changing the recognition of input measures (i.e. continually redefining 'reality') and re-defining an organization’s mission and aims (i.e. rendering the nature of the organization different-from and incommensurable-with the past organization) and repeatedly altering the organizational outcomes regarded as relevant (re-defining making any decline in the efficiency of the organization formally un-measurable).

Such change may be externally- or internally-triggered: either triggered by the external demands of other bureaucracies which constitute the organizational environment, or triggered by the innate noise-generating tendencies of committees.

With endlessly-altering inputs, processes and outputs, bureaucratically-dominated organizations are impossible to critique in terms of functionality: their effectiveness is impossible to measure, and if or when they may be counter-productive (in terms of their original real world purpose) this will also be unknowable. Individual functional organizations disappear and all bureaucracies blend into a Borg-like web of interdependent growth.

The nature of bureaucracy: rational versus parasitic

What is bureaucracy? The traditional definition emphasises that bureaucracy entails a rational human organization which is characterized by hierarchy and specialization of function, and that the organization deploys explicit procedures or regulations that are impartially administered by the personnel. A rational ‘Weberian’ bureaucracy was probably, on the whole, performing a useful function reasonably efficiently – in other words its effectiveness was perceived in terms of externally-pre-decided criteria, and its growth and spread were circumscribed.
In medical terms, Weberian bureaucracy was therefore – at worst - a benign tumour; potentially able to overgrow locally and exert pressure on its surroundings; but still under control from, and held in check by, the larger host organism of society.

But, just as cancers usually evolve from benign precursors, so it was that modern parasitic and useless bureaucracies evolved from the rational and functional bureaucracies of an earlier era. Probably the key trigger factor in accelerating the rate of this evolution has been the development of computers, which have the potential to do – almost instantly, and at near zero cost – exactly the kind of rational information processing which in the past could only be done (much more slowly, expensively, and erratically) by Weberian bureaucracy. My contention is that large scale rational, functional bureaucracies are now all-but extinct, destroyed by computerization.

I assume that, when rational bureaucracy was facing extinction from computerization, there was a powerful selection pressure for the evolution of new forms of irrational bureaucracy – since rational procedures could be converted into algorithms, formalized and done mechanically; while irrational procedures were immune from this competition.

The outcome is that, despite retaining a vast structure of procedure and regulation, and the organizational principles of hierarchy and specialization, those powerful modern bureaucracies that survived the challenge of computerization and are still alive and growing nowadays are non-rational in their core attributes. Irrationality is indeed an essential aspect of a modern bureaucracy’s ability to survive and thrive. Those bureaucracies which remain and are expanding in this post-computerization era are neither rational nor functional.

This evolution towards pure parasitism – with no performance of a substantive real-world function - is only possible because, for any specific bureaucracy, its relevant environment now substantially consists of other bureaucracies. It is 'other bureaucracies' that are the main selection pressure: other bureaucracies pose the main threat to survival and reproduction. A modern bureaucracy therefore must respond primarily to ‘bureaucratic reality’ – and any engagement with ‘real life’ (e.g. life as it is perceived by alert and informed individual human beings) simply stands in the way of this primary survival task.

So, the best adapted modern bureaucracies are those which most efficiently play the game of satisfying the constantly-and rapidly-changing requirements of other major bureaucracies. Success brings expansion by local growth and metastatic spread. But, in contrast, satisfying the stable requirements of ‘real life’ and human nature, by contrast, brings a bureaucracy little or no rewards, and a greater possibility of extinction from the actions of other bureaucracies.

The role of committees in the evolution of bureaucracy

I will argue that the major mechanism by which irrationality has been introduced into bureaucracies is the committee which makes decisions by majority voting.

Committees now dominate almost all the major decision-making in modernizing societies – whether in the mass committee of eligible voters in elections, or such smaller committees as exist in corporations, government or in the US Supreme Court: it seems that modern societies always deploy a majority vote to decide or ratify all questions of importance. Indeed, it is all-but-inconceivable that any important decision be made by an individual person – it seems both natural and inevitable that such judgments be made by group vote.

Yet although nearly universal among Western ruling elites, this fetishizing of committees is a truly bizarre attitude; since there is essentially zero evidence that group voting leads to good, or even adequate, decisions – and much evidence that group voting leads to unpredictable, irrational and bad decisions.

The nonsense of majority voting was formally described by Nobel economics laureate Kenneth Arrow (1921-) in the 1960s, but it is surely obvious to anyone who has had dealings with committees and maintains independent judgement. It can be demonstrated using simple mathematical formulations that a majority vote may lead to unstable cycles of decisions, or a decision which not one single member of the committee would regard as optimal. For example, in a job appointments panel, it sometimes happens that there are two strong candidates who split the panel, so the winner is a third choice candidate whom no panel member would regard as the best candidate. In other words any individual panel member would make a better choice than derives from majority voting.

Furthermore, because of this type of phenomenon, and the way that majority decisions do not necessarily reflect any individual's opinion, committee decisions carry no responsibility. After all, how could anyone be held responsible for outcomes which nobody intended and to which nobody agrees? So that committees exert de facto power without responsibility. Indeed most modern committees are typically composed of a variable selection from a number of eligible personnel, so that it is possible that the same committee may never contain the same personnel twice. The charade is kept going by the necessary but meaningless fiction of ‘committee responsibility’, maintained by the enforcement of a weird rule that committee members must undertake, in advance of decisions, to abide by whatever outcome (however irrational, unpredictable, unjustified and indefensible) the actual contingent committee deliberations happen to lead-to. This near-universal rule and practice simply takes ‘irresponsibility’ and re-names it ‘responsibility’…

Given that committee decisions are neither rational nor coherent, and are therefore radically unpredictable, what is their effect? In a nutshell the short answer is that committees – overall and in the long term – generate random ‘noise’. Committees almost certainly increase the chances that a decision is wrong – but overall they probably do not have lead to any specifically biased direction of wrongness. While some committees using some procedures are biased in one direction, others are biased in other directions, and in the end I think the only thing that we can be sure about is that committees widen the range of unpredictability of decisions.

Now, if we ask what is the role of randomness in complex systems? - the answer is that random noise provides the variations which are the subject of selection processes. For example, in biology the random errors of genetic replication provide genetic variation which affects traits that are then subjected to natural selection. So, it seems reasonable to infer that committees generate random changes that generate variations in organizational characteristics which are then acted-upon by selection mechanisms. Some organizational variations are amplified and thrive, while other variations are suppressed and dwindle. Overall, this enables bureaucracies rapidly to evolve – to survive, to grow and to spread.

How much random noise is needed in a bureaucracy (or any evolving system)? The short answer is that the stronger is the selection pressure, the greater is the necessity for rapid evolution, then the more noise is needed; bearing in mind the trade-off by which an increased error rate in reproduction also reduces the ability of an evolving system accurately to reproduce itself. A system under strong selection pressure (e.g. a bureaucracy in a rapidly-changing modernizing society) tends to allow or generate more noise to create a wider range of variation for selection to act upon and thereby enable faster evolution – at the expense of less exact replication. By contrast, a system under weaker selection pressure (such as the Weberian bureaucracies of the early 20th century – for instance the British Civil Service) have greater fidelity of replication (less noise), but at the expense of a reduced ability to change rapidly in response to changing selection pressures.

I am saying here that committees using majority voting are responsible for the evolution of malignant bureaucratic growth in modern bureaucracies, and that this is why majority-vote decision-making permeates modern societies from the top to the bottom.

Although almost all major decision-making in the ‘Western’ world is now by majority voting there may be two significant exceptions: firstly military decision-making in time of war; secondly the personal authority of the Pope in the Roman Catholic Church. In both these types of organization there seems to be a greater emphasis on individual decision-making than on committee voting. Military command structures and the Roman Catholic hierarchy are therefore probably both closer to the ideal type of a Weberian rational bureaucracy than to the ideal type of a modern parasitic bureaucracy.

If so, the only major exceptions to majority rule decision-making at a world level, and probably not by coincidence, are the oldest and longest-enduring bureaucratic structures: that is, organizations which have retained functionality and have not themselves been destroyed by bureaucratic cancer.

Why are there committees at all?

Although they may nowadays be almost wholly damaging, committees cannot in their origins have been entirely useless or harmful; or else the form would never have survived its first appearance. If we acknowledge that individuals have the potential for better (i.e. more rational and coherent) decision-making than committees, then the decline of individual decision-making must not be due to the lack of advantages so much as the perceived problems of individual decision-making.

The problems of individual decision-making are the same as the problems of individual power: in essence these problems are self-interest (i.e. the observation that power will be deployed differentially to benefit the power-holder) and corruption (i.e. the observation that over time power will corrupt, making the individual progressively a worse-and-worse decision-maker until he us note merely self-interested but progressively driven mad: power mad).

Since humans are self-centred beings living in an imperfect world, all individuals tend to be both self-interested and corruptible (albeit to widely-varying degrees!). Of course, self-interest and corruptibility applies equally to people 'serving' on committees - each of whom is wielding lesser but anonymous and irresponsible power. Nonetheless, it seems to me that committees are mostly favoured because they are seen as a solution to these intrinsic problems of individual power. The implicit assumption is that when a committee is run by majority voting then individual self-interests will cancel-out. Furthermore, that since power is spread-around more people on a committee, then the inevitably corrupting effect of power will be similarly diluted.

In reality, committees mostly solve the problems of power to the extent that they reduce the effective deployment of power. So that, if committees are indeed less self-interested and less prone to corruption than individuals, this is achieved mainly because the committee structure and procedures make decision-making so unpredictable and incoherent that committees are rendered ineffective: ineffective to such an extent that committees cannot even manage consistently to be self-interested or corrupt! Therefore, the problems of power are ‘solved’, not by reducing the biases or corruptions of power, but simply by reducing the effectiveness of power; by introducing inefficiencies and obscuring the clarity of self-interest with the labile confusions of group dynamics. Power is not controlled but destroyed…

Therefore, if committees were introduced to reduce the abuse of power, then instead of achieving this, their actual outcome is that committees reduce power itself, and society is made docile when confronted by significant problems which could be solved, but are not. And surely this is precisely what we observe in the West, on an hourly basis?

Because committee-based bureaucracy is predicated on an ethic of power as evil: it functions as a sort of unilateral disarmament that would be immediately obvious as self-defeating or maladaptive unless arising in a context of already-existing domination. And a system of committee-based bureaucracy can only survive for as long as it its opponents can be rendered even-weaker by even-more virulent affliction with the same disease: which perhaps explains the extra-ordinarily venomous and dishonest pseudo-moralizing aggression which committee bureaucracy adopts towards other simpler, more-efficient or more-effective organizational systems that still use individual decision-making.

If we assume that committees were indeed introduced as a purported solution to (real or imagined, actual or potential) abuses of individual power; then committees will therefore usually achieve this goal. So long as the quality of decision-making is ignored, then the committees seem to be successful. Committees can therefore be seen as a typical product of one-sided and unbalanced moralism that has discarded the Aristotelian maxim of moderation in all things. Bureaucracy adopts instead unilateral moralism which aims at the complete avoidance of one kind of sin, even at the cost of falling into another contrasting kind of sin (so pride is avoided by encouraging submission, and aggression is avoided by imposing sloth).

However the subject matter of ‘trade-offs’ is avoided; and the inevitable self-created problems of single issue moral action are instead fed-upon by bureaucracy, leading (of course!) to further expansion.

Hence, modern decision-making means that societal capability has declined in many areas. It has become at best slow and expensive, and at worst impossible, to achieve things which were done quickly, efficiently and effectively under systems based on individual decision-making. To avoid the corruption of individual authority, society has been rendered helpless in the face of threats which could have been combated.

Bureaucracy in science – the cancer of peer review

This situation can readily be seen in science. Although modern science is massively distorted and infiltrated by the action of external bureaucracies in politics, public administration, law, business and the media (for example), the major manifestation of bureaucracy actually within science is of course peer review.

Over the last half-century or so, the growth and metastatic spread of peer review as a method of decision-making in science has been truly amazing. Individual decision-making has been all-but obliterated at every level and for almost every task. The elaborateness of peer review has increased (e.g. the number of referees, the number of personnel on evaluating panels, the amount of information input demanded by these groups). And peer review or other types of committee are now used for admissions, appointments, promotions, grant review, project management, research evaluation, journal and book refereeing, the award of prizes… the list just goes on and on. Clearly, peer review fits the pattern of malignant expansion of bureaucracy that is seen in the rest of modern society.

And, as with the rest of society, the cancer of bureaucratic peer review eludes the immune system of science. It has now been widely accepted, by the other bureaucracies of modern society in particular, that peer review is intrinsically valid; and that any other form of decision-making is intrinsically corrupt or unreliable. This belief is not merely implicit, but frequently explicit: with ignorant and nonsensical statements about the vital and defining role of peer review in science being the norm in mainstream communication.

The irresistible rise of peer review can be seen most starkly in that any deficiencies in peer review triggers demands (especially from other bureaucracies) for more elaborate and widespread peer review. So that the endemic failure of increased journal peer review to maintain quality, or to eliminate what it is purported to detect; such as deliberate fraud, or multiple publication, or serious error - leads inevitably leads to plans for further increases in peer review. So there is peer review of greater elaborateness, with further steps added to the process, and extra layers of monitoring by new types of larger committees. The ultimate validity of peer review is simply an assumption; and no amount of contrary evidence of its stultifying inefficiency, its harmful biases, and distorting exclusions can ever prove anything except the need for more of the same.

Yet the role of peer review in the progress of science remains, as it always has been, conjectural and unverified. The processes of gathering and collating peer opinion as a method of decision-making are neither rational nor transparent – and indeed (as argued above) this irrationality and unpredictability is in fact a necessary factor in the ability of committee systems such as peer review to expand without limit.

In the past; the ultimate, bottom-line, within-science validation of science came not from the committee opinions of peer reviewers but from the emergent phenomenon of peer usage – which refers to the actual deployment of previous science (theories, facts, techniques) in the ongoing work of later scientists. This was an implicit, aggregate but not quantified outcome of a multitude of individual-decisions among peers (co-workers in the same domain) about what aspects of previous science they would use in their own research: each user of earlier work was betting their time, effort and reputation on the validity of the previous research which they chose to use. When their work bore fruit, this a validation of previous research (in the sense that having survived this attempt at refutation the old science now commanded greater confidence); but when previous research was faulty it 'sabotaged' any later research building upon it in terms of correctly predicting or effectively-intervening-in the natural world. Beyond this lies the commonsensical evaluation of science in terms of ‘what works’ – especially what works outside of science, by people such as engineers and doctors whose job is to apply science in the natural world.

But now that committee-based peer review has been explicitly accepted as the ‘gold standard’ of scientific validity, we see the bizarre situation that actual scientific usage and even what works is regarded as less important than the ‘bureaucratic reality’ of peer review evaluations. Mere opinions trump observations of objective reality. Since ‘bureaucratic reality’ is merely a construct of interacting bureaucracies, this carries the implication that scientific reality is now, to an ever-increasing extent, simply just another aspect of, and seamlessly-continuous-with, mainstream 'bureaucratic reality'. Science is merely a subdivision of that same bureaucratic reality seen in politics, public administration, law, the media and business. The whole thing is just one gigantic virtual world. It seems probable that much of peer reviewed ‘science’ nowadays therefore carries no implications of being useful in understanding, predicting or intervening-on the natural world.

In other words, when science operates on the basis of peer review and committee decision, it is not really science at all. The cancer of bureaucracy has killed real science wherever it dominates. Much of mainstream science is now ‘Zombie Science’: that is, something which superficially looks-like science, but which is actually dead inside, and kept-moving only by continuous infusion of research funds. So far as bureaucratic reality is concerned, i.e. the reality as acknowledged among the major bureaucracies; real science likely now exists at an unofficial, unacknowledged level, below the radar; only among that minority of scholars and researchers who still deploy the original scientific evaluation mechanisms such as individual judgement, peer usage and real-world effectiveness.

What will happen?

The above analysis suggests that parasitic bureaucracy is so dangerous in the context of a modernizing society that it cannot be allowed to exist; it simply must be destroyed in its entirety or else any residuum will re-grow, metastasize and colonize society all over again. The implication is that a future society which intends to survive in the long-term would need to be one that prevents parasitic bureaucracy from even getting a toe-hold.

The power of parasitic bureaucracy to expand and to trigger further parasitic bureaucracies is now rendered de facto un-stoppable by the power of interacting bureaucracies to frame and construct perceived reality in bureaucratic terms. Since bureaucratic failure is eliminated by continual re-definition of success, and the since any threats of to bureaucratic expansion are eliminated by exclusion or lethal attack; the scope of bureaucratic takeover from now can be limited only by collapse of the social system as a whole.

So, if the above analysis is correct, there can be only two outcomes. Either that the cancer of modern bureaucracy will be extirpated: destroyed utterly. In other words, the host immune system will evolve the ability to destroy the parasite. Maybe, all majority voting committees will coercively be replaced by individuals who have the authority to make decisions and responsibility for those decisions.
Or that the cancer of bureaucracy will kill the host. In other words, the parasite will continue to elude the immune system. Modernizing societies will sooner-or-later be destroyed by a combination of resource starvation plus accumulative damage from delayed and wrong decisions based on the exclusions and distortions of ‘bureaucratic reality’.

Then the most complex rapidly-growing modernizing Western societies will be replaced by, or will regress into, zero-growth societies with a lower level of complexity - probably about the level of the agrarian societies of the European or Asian Middle Ages.

My prediction is that outcome two – societal collapse - is at present the more probable, on the basis that parasites can evolve more rapidly than host immune systems. Although as individuals we can observe the reality of approaching disaster, to modern parasitic bureaucracies the relevant data is either trivial or simply invisible.


Further reading: Although I do not mention it specifically above, the stimulus to writing this essay came from Mark A Notturno’s Science and the open society: the future of Karl Popper’s philosophy (Central European University Press: Budapest, 2000) – in particular the account of Popper’s views on induction. It struck me that committee decision-making by majority vote is a form of inductive reasoning, hence non-valid; and that inductive reasoning is in practice no more than a form of ‘authoritarianism’ (as Notturno terms it). In the event, I decided to exclude this line of argument from the essay because I found it too hard to make the point interesting and accessible. Nonetheless, I am very grateful to have had it explained to me.

I should also mention that various analyses of the pseudonymous blogger Mencius Moldbug, who writes at Unqualified Reservations, likely had a significant role in developing the above ideas.

This argument builds upon several previous pieces of mine including: Conflicts of interest in medical science: peer usage, peer review and ‘CoI consultancy' (Medical Hypotheses 2004; 63: 181-186); Charlton BG, Andras P. What is management and what do managers do? A systems theory account. (Philosophy of Management. 2004; 3: 3-15); Peer usage versus peer review (BMJ 2007; 335: 451); Charlton BG, Andras P. Medical research funding may have over-expanded and be due for collapse (QJM 2005; 98: 53–55); Figureheads, ghost-writers and pseudonymous quant bloggers: the recent evolution of authorship in science publishing (Medical Hypotheses. 2008; 71: 475–480); Zombie science’ (Medical Hypotheses 2008; 71:327–329); The vital role of transcendental truth in science’ (Medical Hypotheses. 2009; 72: 373–376); Are you an honest scientist? Truthfulness in science should be an iron law, not a vague aspiration (Medical Hypotheses. 2009; Volume 73: 633-635); and, After science: has the tradition been broken? Medical Hypotheses, in the press.

Sunday, 4 April 2010

Covert drug dependence

Covert drug dependence should be the null hypothesis for explaining drug-withdrawal-induced clinical deterioration: The necessity for placebo versus drug withdrawal trials on normal control subjects

Bruce G. Charlton

Medical Hypotheses. 2010; 74: 761-763.



Just as a placebo can mimic an immediately effective drug so chronic drug dependence may mimic an effective long-term or preventive treatment. The discovery of the placebo had a profound result upon medical practice, since it became recognized that it was much harder to determine the therapeutic value of an intervention than was previously assumed. Placebo is now the null hypothesis for therapeutic improvement. As David Healy describes in the accompanying editorial on treatment induced stress syndromes [1], an analogous recognition of the effect of drug dependence is now overdue. Drug dependence and withdrawal effects should in future become the null hypothesis when there is clinical deterioration following cessation of treatment. The ideal methodology for detecting drug dependence and withdrawal is a double-blind placebo controlled and randomized trial using disease-free normal control subjects. Normal controls are necessary to ensure that the possibility of underlying chronic disease is eliminated: so long as subjects begin the trial as ‘normal controls’ it is reasonable to infer that any clinical or psychological problems (above placebo levels) which they experience following drug withdrawal can reasonably be attributed to the effects of the drug. This is important because the consequences of failing to detect the risk of covert drug dependence may be considerably worse than failing to detect a placebo effect. Drug dependent patients not only fail to receive benefit and suffer continued of inconvenience, expense and side effects; but the drug has actually created and sustained a covert chronic pathology. However, the current situation for drug evaluation is so irrational that it would allow chronic alcohol treatment to be regarded as a cure for alcoholism on the basis that delirium tremens follows alcohol withdrawal and alcohol can be used to treat delirium tremens! Therefore, just as placebo controlled trials of drugs are necessary to detect ineffective drugs, so drug withdrawal trials on normal control subjects should be regarded as necessary to detect dependence-producing drugs.


Just as a placebo can mimic an immediately effective drug, so chronic drug dependence may mimic an effective long-term or preventive treatment

The discovery of the placebo had a profound result upon medical practice. After the placebo effect was discovered it was recognized that it was much harder to determine the therapeutic value of an intervention than previously assumed. As David Healy describes in the accompanying editorial on treatment induced stress syndromes [1], an analogous recognition of the effect of drug dependence is now overdue, especially in relation to psychoactive drugs.

Therefore, just as placebo controlled trials of drugs are regarded as necessary to detect ineffective drugs, so drug withdrawal trials on normal control subjects should be regarded as necessary to detect dependence-producing drugs.

Determining the specific benefit of a drug

Throughout most of the history of medicine it was naively assumed that when a patient improved following a specific therapy, then this positive change could confidently be attributed to the beneficial effects of that specific therapy. But it is now recognized that clinical improvement may have nothing to do with the specific treatment but may instead have general psychological causes to do with a patient’s expectations. So that when a drug treatment is begun and the patient gets better, the change may not be due to the drug but some or all of the observed benefit could be due to the placebo effect.

Indeed, nowadays the placebo effect is routinely assumed to be the cause of patient improvement unless proven otherwise. Placebo effect is therefore the null hypothesis used to explain therapeutic improvements.

This tendency to regard the placebo effect as the default explanation for clinical improvement has led to major methodological changes in the evaluation of putative drug therapies; because the first aim of drug evaluation is now to show that measured benefits cannot wholly be explained by placebo. This has led to widespread adoption of placebo controlled trials which compare the effect of the putative drug with a placebo. Only when the drug produces a greater effect than placebo alone, is it recognized as a potentially effective therapy.

The effect of withdrawing a drug upon which a subject has become dependent can be regarded as analogous to the placebo effect, in the sense that drug dependence resembles the placebo effect in being able to mislead concerning clinical effectiveness.

It may routinely be assumed that if a patient gets worse when drug treatment is stopped, then this change is due to the patient losing the beneficial effects of the drug, so that the underlying disease (for which the drug was being prescribed) has re-emerged. That is, when a patient does better when taking a drug than after cessation, it seems apparent that the patient benefits from this drug. So the naïve assumption would be that worsening of a patient’s condition on withdrawal implies that the patient had a long-term illness which was being treated by the drug, and the chronic illness was revealed when drug treatment was withdrawn.

However, this naïve assumption is certainly unjustified as a general rule because drug dependence produces exactly the same effect. When a patient has become dependent on a drug, then adverse consequences following withdrawal may have nothing to do with revealing an underlying, long-term illness. Instead, chronic drug use has actually made the patient ill, the drug has created a new but covert pathology; the body has adapted to the presence of the drug and now needs the drug in order to function normally such that the covert pathology only emerges when the drug is removed and body systems are disrupted by its absence.

In other words, the drug dependent patient may have had independent pathology which has disappeared, or else drug treatment may have been the sole cause of pathology. But either way, clinical deterioration following withdrawal is mainly or wholly a consequence of drug dependence and not a consequence of underlying independent chronic pathology.

So, before assuming that the patient benefits from a drug the possibility of covert drug dependence must first be eliminated as an explanation. Healy’s argument is that drug dependence and withdrawal effects should in future become the null hypothesis in evaluating the chronic need for therapy in the same way as placebo is now a null hypothesis for clinical improvement following drug therapy. Worsening of the patient’s condition following cessation or dose reduction of a drug should therefore be assumed to be caused by withdrawal unless otherwise proven.

However, current methods of therapeutic evaluation cannot reliably detect stress induced drug dependence. This implies that a new kind of clinical trial is required explicitly to test for covert drug dependence and withdrawal effects in a manner analogous to the placebo controlled therapeutic trial.

Assumptions about the cause of post-withdrawal clinical deterioration

It has not yet been generally recognized that eliminating drug dependence as an explanation for withdrawal effects cannot be achieved in the context of normal clinical practice, nor by the standard formal methodologies of controlled clinical trials.

Just as eliminating the possibility of placebo effects requires specially designed placebo controlled therapeutic trails, so eliminating the occurrence of covert drug dependence requires also specially designed withdrawal trials on normal control subjects.

At present, it is usual to assume a drug does not cause dependence, except when it is proved that a specific drug does cause dependence. This means that when no information on dependence is available, or when the information about dependence on a particular drug is either incomplete or inconclusive, then the standard accepted inference is that the drug does not cause dependence. In effect, the onus of proof is currently upon those who are trying to argue that a drug causes dependence.

The situation for withdrawal trials testing for dependence is therefore exactly the opposite of that applying to therapeutic trials and the placebo effect. Consequently, as Healy describes, prevailing clinical evaluation procedures may systematically be incapable of detecting withdrawal effects. Even worse, current procedures systematically tend to misattribute the creation of dependence and harm following withdrawal, as instead being evidence of drug benefit with implication of the necessity for continued treatment of a supposed chronic illness.

The currently prevailing presumption therefore favours new drugs about which little is known; and it favours a perpetuation of the state of ignorance, since no evidence of dependence is almost invariably being interpreted as evidence of no dependence. In other words, as things stand; a drug that actually creates chronic dependence is instead credited with curing a chronic disease; despite that the chronic disease is actually a stress syndrome disease state which that same drug has actually caused.

The current situation is equivalent to chronic alcohol treatment being regarded as a cure for alcoholism on the (warped) basis that delirium tremens follows alcohol withdrawal and alcohol can be used to treat delirium tremens!

When to suspect covert dependence

The almost-total lack of awareness of covert drug dependence and withdrawal problems need not be accidental, but could be a consequence of the fact that unrecognized drug dependence is financially advantageous for the pharmaceutical companies who fund and conduct most clinical trials.

Although there are signs which may warn of dependence on a drug, and the possibility of withdrawal effects (e.g. dwindling effects of a drug, or the need for escalating doses in order to maintain its effect) – none of these are easy to discriminate from therapeutic effects.

But dependence may be suspected when what was perceived as an acute and self-limiting illness requiring a time-limited course of treatment, gradually becomes perceived as a chronic disorder requiring long-term drug treatment. This has been a pattern observed for several psychiatric conditions including depression and acute psychosis. Naturally, there can be rationalizations for this – for example, that the disease was previously unrecognized or under-treated.

Nonetheless, the difficulty of resolving such disputes serves to make clear the need for establishing a presumption of drugs being dependence-producing, and the necessity that this possibility be eliminated by withdrawal trials at an early stage in the evaluation of the drug.

Covert dependence generates a long-term demand for drugs by converting acute into chronic disease among the legitimate therapeutic target community. For example, acute and self-limiting depressive illness can be made into an apparent chronic disease if antidepressants create dependence such that drug withdrawal provokes depressed mood – such that a lifetime of antidepressant treatment can then be justified as ‘preventing’ a supposed chronic recurrent depressive disorder which is actually itself a product of drug administration.

Another way in which covert dependence is advantageous for pharmaceutical companies happens when the inclusiveness of diagnostic criteria are expanded. Because the more patients that are treated (on whatever excuse), the more dependence is produced and the more people who then require chronic drug administration.

Possible examples are when the threshold sensitivity for prescribing is reduced for a dependence-producing drug, such as the suggestion that early or preventive treatment of psychosis is beneficial, using an ‘atypical’ or traditional antipsychotic/neuroleptic. And because withdrawal of antipsychotics causes an increased likelihood of psychotic breakdown, preventive drug treatment is an apparently self-fulfilling prophesy. Or when a new and allegedly high prevalence disease category such as ‘bipolar disorder’ is created along with indications for treatment by dependence-producing drugs; this will tend to generate a new cohort of drug dependent patients whose long-term dependence on drugs can be disguised as a newly-discovered and previously-unsuspected type of severe and chronic psychiatric pathology.

In other words, under currently prevailing research standards, mass creation and exploitation of drug dependence may actually be spun as evidence of medical progress!

The necessity for drug-withdrawal trials on normal control subjects

Drug dependence needs a level of recognition comparable to the placebo effect because it is more damaging than the placebo effect. The main problem of failing to detect a placebo effect is that patients may be unnecessarily exposed to the expense and side effects of a drug. So the placebo effect may be clinically desirable, so long as the placebo is inexpensive and harmless.

But the consequences of failing to detect covert drug dependence may be considerably worse than this. When dependence is a problem, patients who receive chronic drug treatment may not only fail to receive any benefit (and thereby suffer unnecessary risk of side effects and expense) but the drug may actually create increasingly severe covert pathology. If a patient is prescribed a drug inappropriately, then they may become drug dependent even when ineffectiveness, inconvenience, expense or treatment side effects mean that they wish (or need) to stop.

In a nutshell, the problem with placebos is merely that a drug fails to treat pathology, but the problem with dependence is that a drug has created pathology.

Clearly, the ideal – and perhaps indispensable – methodology for detecting covert drug dependence is a double-blind placebo controlled and randomized trial using disease-free normal control subjects. Normal controls are necessary to ensure that the possibility of chronic disease is eliminated: since controls begin the trial as ‘normal’ it is reasonable to infer that any clinical or psychological problems (above placebo levels) which they experience following drug withdrawal can reasonably be attributed to the effects of the drug.

A withdrawal trial needs to be prolonged to include not just sufficient chronicity of treatment by the active drug or placebo; but also a sufficient follow-up period after stopping the drug or placebo, during which it can be discovered whether there is any worsening of conditions following withdrawal and an increase in new pathologies. Specifically, what needs to be measured is a comparison of the frequency of post-withdrawal problems in the two randomly-assigned placebo and active drug groups.

Since the nature of withdrawal effects will not be known in advance, such a trial cannot rely upon highly focused and pre-specified questionnaires but would need to include very general questioning about more general feelings of well-being and quality of life; and any signs of problems as perceived by observers. Follow-up could include measures such as all-cause mortality, all source morbidity; and measures of the frequency of adverse events such as suicide, accidents, medical contacts and hospital admissions.

In conclusion, covert drug dependence should be the null hypothesis explanation for post-withdrawal clinical deterioration, especially for new drugs and even more so for drugs acting on the brain. A default assumption is required that lack of evidence concerning drug dependence implies that a drug is dependence-producing.

Because unless covert drug dependence becomes a default assumption, then it remains advantageous for pharmaceutical companies self-servingly to maintain the current state of ignorance in which recommendations for chronic drug treatment are enforced by drug dependence that is systematically misinterpreted as therapeutic effectiveness.


[1] Healy D. Treatment induced stress syndromes. Med Hypotheses, in press. doi:10.1016/j.mehy.2010.01.038.

Sunday, 21 March 2010

After science: Has the tradition been broken?

After science: Has the tradition been broken?

Bruce G. Charlton

Medical Hypotheses. 2010; 74: 623-625


The majority of professional scientists make use of the artefacts of science but lack understanding of what these mean; raising the question: has the tradition of science been broken? Explicit knowledge is only a selective summary but practical capability derives from implicit, traditional or ‘tacit’ knowledge that is handed on between- and across-generations by slow, assimilative processes requiring extended human contact through a wide range of situations. This was achieved mainly by prolonged apprenticeship to a Master. Such methods recognize the gulf between being able to do something and knowing how you have done it; and the further gap between knowing how you have done something and being able to teach it by explicit instructions. Yet the ‘Master–apprentice’ model of education has been almost discarded from science over recent decades and replaced with bureaucratic regulation. The main reason is probably that scientific manpower has expanded so rapidly and over such a long period as to overwhelm the slow, sure and thorough traditional methods. In their innocence of scientific culture, the younger generation of scientists are like children who have been raised by wolves; they do not talk science but spout bureaucratic procedures. It has now become accepted among the mass of professional ‘scientists’ that the decisions which matter most in science are those imposed upon science by outside forces: for example by employers, funders, publishers, regulators, and the law courts. It is these bureaucratic mechanisms that now constitute the ‘bottom line’ for scientific practice. Most of modern science is therefore apparently in the post-holocaust situation described in A canticle for Liebowitz and After Virtue, but the catastrophe was bureaucratic, rather than violent. So, the tradition has indeed been broken. However, for as long as the fact is known that the tradition has been broken, and living representatives of the tradition are still alive and active, there still exists a remote possibility that the tradition could be revived.


After science: has the tradition been broken?

Imagine that the natural sciences were to suffer the effects of a catastrophe. A series of environmental disasters are blamed by the general public on the scientists. Widespread riots occur, laboratories are burnt down, physicists are lynched, books and instruments are destroyed. Finally a know-nothing political movement takes power and successfully abolishes science teaching in schools and universities, imprisoning and executing the remaining scientists. Later still there is a reaction against this destructive movement and enlightened people seek to revive science, although they have largely forgotten what it was. But all that they possess are fragments: a knowledge of experiments detached from any knowledge of the theoretical context which gave them significance; parts of theories unrelated either to the other bits and pieces of theory which they possess or to experiment; instruments whose use has been forgotten; half-chapters from books, single pages from articles, not always fully legible because torn and charred. Nonetheless all these fragments are re-embodied in a set of practices which go under the revived names of physics, chemistry and biology. Adults argue with each other about the respective merits of relativity theory, evolutionary theory and phlogiston theory, although they possess only a very partial knowledge of each. Children learn by heart the surviving portions of the periodic table and recite as incantations some of the theorems of Euclid. Nobody, or almost nobody, realizes that what they are doing is not natural science in any proper sense at all. For everything that they do and say conforms to certain canons of consistency and coherence and those contexts which would be needed to make sense of what they are doing have been lost, perhaps irretrievably.

From After Virtue – Alasdair MacIntyre [1]

The classic science fiction novel A canticle for Liebowitz by Walter Miller [2] portrays a post-nuclear-holocaust world in which the tradition of scientific practice – previously handed-down from one generation of scientists to the next – has been broken. Only a few scientific artefacts remain, such as fragments of electronic equipment. It turns out that after the tradition has been broken, the scientific artefacts make no sense and are wildly misinterpreted. For instance a blueprint is regarded as if it was a beautiful illuminated manuscript, and components such as diodes are regarded as magical talismans or pills.

I will argue that modern science may have entered a similar state in which for the majority of professional scientists the artefacts of science remain – such as the academic hierarchy, laboratory techniques and machines, statistical methods, and the peer review mechanism – but understanding of what these mean has apparently been lost; raising the question: has the tradition been broken?

A theme associated with philosophers such as Polanyi [3] and Oakeshott [4] is that explicit knowledge – such as is found in textbooks and scientific articles – is only a selective summary that misses that the most important capability derives from implicit, traditional or ‘tacit’ knowledge. It is this un-articulated knowledge that leads to genuine human understanding of the natural world, accurate prediction and the capacity to make effective interventions.

Tacit knowledge is handed on between- and across-generations by slow, assimilative processes which require extended, relatively unstructured and only semi-purposive human contact. What is being transmitted and inculcated is an over-arching purpose, a style of thought, a learned but then spontaneous framing of reality, a sense of how problems should be tackled, and a gut-feeling for evaluating the work or oneself, as well as others.

This kind of process was in the past achieved by such means as familial vocations, prolonged apprenticeship, co-residence and extended time spent in association with a Master – and by the fact that the Master and apprentice personally selected each other. The pattern was seen in all areas of life where independence, skill and depth of knowledge were expected: crafts, arts, music, scholarship – and science.

Although such methods sound a bit mysterious, not to say obscurationist, to modern ears – in fact they are solid realism and common sense. Such methods for ensuring the transmission of subtle knowledge recognize the gulf between being able to do something and knowing how you have done it; and the further gap between knowing how you have done something and being able to teach it by explicit instructions.

Such systems as apprenticeship recognize that the most important aspects of knowledge may be those which are not known or understood to be the most important, or may even be in opposition to that which is believed or supposed to be important. The educational ‘method’ was that an apprentice should spend a lot of time with the Master in many situations; and as for educational evaluation, the best way for a Master to know that his skill really has been passed-on, is for him to spend a lot of time with the apprentice in many situations.

Imperfect as it inevitably was, traditions were maintained and often improved over centuries by means of apprenticeship – which was regarded as the safest and surest way of ensuring that the knowledge and skills could be sustained and developed.

However, priorities have changed. The preservation and development of high-level human skills and expertise is no longer regarded as a priority, something to which many other concerns will inevitably need to be subordinated. And the ‘Master–apprentice’ model of education, which stretches back in human history as far as we know, has been all-but discarded from science (and much of mainstream culture) over recent decades. Indeed the assumptions have been reversed.

It is important to recognize that the discarding of traditions of apprenticeship and prolonged human contact in science was not due to any new discovery that apprenticeship was – after all – unnecessary, let alone that the new bureaucratic systems of free-standing explicit aims and objectives, summaries and lists of core knowledge and competencies etc. were superior to apprenticeship. Indeed there is nothing to suggest that they are remotely the equal of apprenticeship. Rather, the Master–apprentice system has been discarded despite the evidence of its superiority; and has been replaced by the growth of bureaucratic regulation.

The main reason is probably that scientific manpower, personnel or ‘human resources’ (as they are now termed) have expanded vastly over the past 60 years – probably about tenfold. So there was no possibility of such rapid and sustained quantitative expansion (accompanied, almost-inevitably, by massive decline in average quality) being achieved using the labour-intensive apprenticeship methods of the past. The tradition was discarded because it stood in the path of the expansion of scientific manpower.

Among the mass of mainstream professional scientists, science – as a distinctive mode of human enquiry – now has no meaning whatsoever. Among these same scientists, who dominate the social system of science both in terms of power and numbers, the resolution of scientific disputes and disagreements is a matter of power, not reason – and relevant ‘evidence’ is narrowly restricted to bureaucratically-enforced operational variables. The tradition seems to have been broken.

I first observed this when I worked in epidemiology, and I realized that most epidemiologists did not understand science and were not scientists – but they did not realize it [5]. They believed that what they did was science, since it had many of the explicit characteristics of science, it involved making measurements and doing statistics, it was accepted as science by many other people, and (most importantly!) epidemiology got funded as science. But most epidemiology was not science, as any real scientist could easily recognize – it was no more science than were those market researchers with clipboards who question pedestrians on the high street. I saw a similar picture in almost all the vast amount of ‘functional brain imagining’ which was the dominant and most prestigious type of Neuroscience. And again in the people who were mapping the average human genome – then (presumably) going on to map the genome of every individual human, then perhaps every creature on the planet?

As Jacob Bronowski once remarked: science is not a loose leaf folder of ‘facts’; not the kind of thing which can be expanded ad infinitum – simply by iterative addition of ever-more observations. Science is instead the creation of structured knowledge, with the emphasis on structure [6]. The modern scientific literature is ballooning exponentially with published stuff and ever-inflated claims about its significance – but, lacking structure, this malignantly-expanding mass adds-up to less-and-less. Meanwhile, understanding, prediction and the ability to intervene on the natural world to attain pre-specified objectives all dwindle; because real science is a living tradition not a dead archive.

The younger generation of scientists are like children who have been raised by wolves. They have learned the techniques but have no feel for the proper aims, attitudes and evaluations of science. What little culture they have comes not from science but from bureaucrats: they utterly lack scientific culture; they do not talk science, instead they spout procedures.

It has now become implicitly accepted among the mass of professional ‘scientists’ that the decisions which matter most in science are those imposed upon science by outside forces: by employers (who gets the jobs, who gets promotion), funders (who gets the big money), publishers (who gets their work in the big journals), bureaucratic regulators (who gets allowed to do work), and the law courts (whose ideas get backed-up, or criminalized, by the courts). It is these bureaucratic mechanisms that constitute ‘real life’ and the ‘bottom line’ for scientific practice. The tradition has been broken.

A minority of young scientists have, by dedication or luck, absorbed the tradition of real science, yet because their wisdom is tacit and is not shared by the majority of the bureaucratically-minded, they will almost-inevitably be held back from status and excluded from influence. It is bureaucracy that now controls ‘science’, and that which bureaucracy cannot or will not acknowledge might as well not exist, so far as the direction of ‘science’ is concerned.

Most of modern science is therefore apparently in pretty much the post-holocaust situation described in A canticle for Liebowitz and After Virtue – the transmission of tacit knowledge has been broken. But the catastrophe was bureaucratic, rather than violent – and few seem to have noticed the scale of destruction.

But, it might be asked, supposing the tradition had indeed been broken; if this was true, then how would we know it was true? – given that the point of MacIntyre’s and Miller’s fables was that when a tradition is broken people do not realize it. The answer is that we know at the moment that the tradition has been broken, but this knowledge is on the verge of extinction.

The sources of evidence are at least fourfold. If we judge the rate of scientific progress by individualistic common sense criteria (rather than bureaucratic indices), it is obvious that the rate of progress has declined in at least two major areas: physics and medical research [7], [8] and [9]. Furthermore there has been a decline in the number of scientific geniuses, which is now near-zero [10]. If geniuses are vital to overall scientific progress, then progress probably stopped a while ago [11].

In addition, the actual practice of science has transformed profoundly [12] – the explicit aims of scientists, their truthfulness, what scientists do on a day by day basis, the procedures by which their work is evaluated… all of these have changed so much over the past 50 years that it is reasonable to conclude that science now is performing an almost completely different function than it was 50 years ago. After all, if modern science neither looks nor quacks like a duck, why should we believe it is a duck? Just because science has the same name, does not mean it is them same thing when almost-everything about it has been transformed!

And finally we might believe that the tradition has been broken because this has been a frequently implicit, sometimes explicit, theme of some of the most original and informed scientists for several decades: from the Feynman and Crick through to Brenner – take your pick. It seems to me that they have for many years been warning us that science was on a wrong track, and the warnings have not been heeded.

So: the tradition has been broken. However, for as long as the fact is known that the tradition has been broken, and representatives of the tradition are still alive and active, there still exists a remote possibility that the tradition could be revived.


Some of these ideas emerged in conversations with Jonathan Rees, and quite a few were derived from him.


[1] A. MacIntyre, After virtue: a study in moral theory, Duckworth, London (1981).

[2] W.M. Miller, A canticle for Liebowitz, Weidenfeld and Nicholson, London (1960).

[3] M. Polanyi, Personal knowledge: towards a post-critical philosophy, University of Chicago Press, Chicago, USA (1958).

[4] M. Oakeshott, Rationalism in politics and other essays, Methuen, London (1962).

[5] B.G. Charlton, Should epidemiologists be pragmatists, biostatisticians or clinical scientists?, Epidemiology 7 (1996), pp. 552–554. View Record in Scopus | Cited By in Scopus (8)

[6] J. Bronowski, Science and human values, Harper Colophon, New York (1975).

[7] L. Smolin, The trouble with physics, Penguin, London (2006).

[8] D.F. Horrobin, Scientific medicine – success or failure?. In: D.J. Weatherall, J.G.G. Ledingham and D.A. Warrell, Editors, Oxford textbook of medicine (2nd ed.), Oxford University Press, Oxford (1987), pp. 2.1–2.3.

[9] B.G. Charlton and P. Andras, Medical research funding may have over-expanded and be due for collapse, QJM 98 (2005), pp. 53–55. Full Text via CrossRef | View Record in Scopus | Cited By in Scopus (15)

[10] B.G. Charlton, The last genius? – reflections on the death of Francis Crick, Med Hypotheses 63 (2004), pp. 923–924. Article | PDF (209 K) | View Record in Scopus | Cited By in Scopus (2)

[11] C. Murray, Human accomplishment. The pursuit of excellence in the arts and sciences 800 BC to 1950, HarperCollins, New York (2003).

[12] J. Ziman, Real science, Cambridge University Press, Cambridge, UK (2000).

Friday, 19 February 2010

Authors' letters of support for Medical Hypotheses

I have received more than one hundred and fifty individual letters of support for Medical Hypotheses in its current form, mostly from scholars who have published in the journal in the past.

I am extremely grateful to all of these scholars for their support – I have answered all the letters individually, and the majority of these letters have been forwarded to Elsevier (the publishers of Medical Hypotheses).

Below I have published (with authors' permission) a selection of these supportive letters.

These published letters were mainly chosen from among those which contained relatively detailed personal information about how Medical Hypotheses has ‘made a difference’ to the career and work of these specific people.


78 Barrie St
Kingston, Ontario
Canada K7L 3N6

Chris Lloyd
Vice-President of Health Sciences Journals

Dear Chris Lloyd

We write in support of maintaining the status quo at Medical Hypotheses. This fascinating journal fills an important function in the world of medical science. It offers a forum for scientific ideas—hypotheses--, which spark new questions and perceptions to orient future enquiry. The scientific community has been ably served by editors David Horrobin and Bruce Charlton.

Long aware of the journal as a dignified space for theoretical ideas, we were fortunate to have our paper on music memory and dementia published in Medical Hypotheses in 2005. This paper presented two hypotheses related to evidence that may have been familiar to caregivers of people with dementia, but it had been little problematized by the scientific community. The publication helped to draw attention and funding to a new research project for us that has since resulted in controlled trials, leading to several other peer-reviewed research papers, collaborations, and conference presentations.

Our Medical Hypotheses paper was one of the first scientific publications on this topic. It preceded the recent, dramatic rise in popular interest in music and the brain, exemplified by the famous book Musicophililia of Oliver Sacks, who cited our MH paper. We were honoured to have been selected for the David Horrobin prize and will continue to acknowledge this award with gratitude and pride regardless of your future decision concerning the editor and the journal.

Regarding the controversy that has led to your deliberations: one of us (JMD) is a hematologist and medical historian, long aware that Peter Duesberg has been a denier of the HIV hypothesis of AIDS etiology for two decades or more. His views are provocative and extremely useful in teaching students. It is not necessary to agree with him to heartily defend his right to air his reasoning in a courteous manner and in appropriate fora. We feel that the opinionated responses of readers who disagree with an author are not a reason to alter the trajectory of the entire journal.

If it emerges that Duesberg’s paper erred beyond his minority viewpoint to actual errors—be they deliberate or accidental, a signal comparison can be made to two leading medical journals. Medical Hypotheses would have been no less a victim or a wrongdoer than the distinguished entities The Lancet and the New England Journal of Medicine.

Earlier this month, Elsevier’s flagship journal The Lancet withdrew a 1998 paper by Andrew Wakefield et al. that helped foster the now discredited theory linking autism and MMR vaccines. No one has called for the alteration of Lancet. Indeed, the issue has drawn attention to the preeminent leadership role that The Lancet plays in the dissemination of knowledge and ideas.

Similarly, in 2000 the New England Journal of Medicine published a peer-reviewed paper that strongly supported the use of rofecoxib (known as Vioxx®). Later it emerged that the paper had suffered improper industry interference and failed to declare a treatment-related death. The drug was taken off the market in 2004. Considerable discussion surrounded the editorial responsibilites for the 2000 article when the flaws came to light in 2005. But no one called for the New England Journal of Medicine to be altered in any way. Jeffrey Drazen is still its editor-in-chief.

The scientific world is a global epistemic community where ideas should be openly expressed and debated. Elsevier can be proud of the record of Medical Hypotheses and the unique theoretical contributions it offers to this community; and it should be grateful to the fine tradition established and maintained by its editors.

Lola L. Cuddy, Ph.D.
Department of Psychology

Jacalyn M. Duffin, M.D., F.R.C.P.(C), Ph.D.
Hannah Chair in the History of Medicine

cc Bruce Charlton

AJ Wakefield, SH Murch, A Anthony, J Linnell, DM Casson, M Malik, M Berelowitz, AP Dhillon, MA Thomson, P Harvey, A Valentine, SE Davies, JA Walker-Smith. Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children. The Lancet 351 (1998), p. 637-641.
Claire Bombardier, Loren Laine, Alise Reicin, Deborah Shapiro, Ruben Burgos-Vargas, Barry Davis, et al., for The VIGOR Study Group, “Comparison of Upper Gastrointestinal Toxicity of Rofecoxib and Naproxen in Patients with Rheumatoid Arthritis,” NEJM, 343 (2000), p. 1520-1528.
Gregory D. Curfman, Stephen Morrissey, Jeffrey M. Drazen, “Expression of Concern: Bombardier, et al., N Engl J Med 2000: 343: 1520-8,” NEJM, 353 (2005), p. 2813-2814; Gregory D. Curfman, Stephen Morrissey, Jeffrey M. Drazen, “Expression of Concern Reaffirmed,” NEJM, 354 (2006), p. 1193; Jeffrey M. Drazen, “COX-2 Inhibitors--a Lesson in Unexpected Problems,” NEJM, 352 (2005


Subject: Medical Hypotheses under threat
Date: Tuesday, 19 January, 2010, 14:02

Dear Professor Charlton,
I am sad to hear that Medical Hypotheses is under threat.

I published my first article in Medical Hypotheses in 1987

"Morris JA, Haran D, Smith A. Hypothesis: common bacterial toxins are a possible cause of the sudden infant death syndrome. Medical Hypotheses 1987; 22: 211 - 222."

This is now the leading theory to explain SIDS (see my leader in the Lancet 2008: Morris JA, Harrison LM Sudden unexpected death in infancy: evidence of infection. Lancet 2008; 371: 1848 - 53.) The Medical Hypotheses paper and the idea were quoted and were influential in four high profile cases at the Court of Appeal i.e Sally Clark, Angela Cannings, Donna Anthony and Lorraine Harris. The idea is about to be played out once more at the Court of Appeal in March when the conviction of Karen Henderson is under review.

In 2007 I extended and refined the idea, also published in Medical Hypotheses (Morris JA, Harrison LM, Biswas J, Telford DR. Transient bacteraemia: a possible cause of life threatening events. Medical Hypotheses 2007; 69: 1032 - 1039).

We are now in a position to prove or disprove the idea using the new science of proteomics. The proof or the disproof will depend on data and will appear in a conventional peer review journal. But the idea comes before the proof, in this case many years before the proof, and we need journals that will publish at the idea stage.

I should also add that the only time my work has been quoted in Minerva (BMJ,most read bit) is when I have published in Medical Hypotheses.

My rule is if you want to enhance your CV and research score go for a conventional journal with a high impact factor but if you want to say something important, interesting and exciting which is likely to be noticed - go for Medical Hypotheses.


Professor J A Morris
Consultant Pathologist
Education Centre
Royal Lancaster Infirmary


From: John Spangler
Subject: RE: Medical Hypotheses is under threat
Date: Friday, 15 January, 2010, 15:53

Dear Dr. Charlton,

I am alarmed to find out that Medical Hypotheses is under threat of dramatic, and in my mind, destructive changes. As a four-time author in this journal, I know first-hand how useful it is in generating new hypotheses that other journals would not publish.

Medical Hypotheses sits at the cutting edge of science, because it announces to the broader scientific community original ideas that may be worthy of further investigation. The papers I wrote generated much publicity, both scientifically and in the lay press.

For example, if you google the following words you will receive over 9000 hits: spangler, manganese, shower. These Google postings relate to the study I published that received world-wide publicity, and encouraged manganese scientists and regulatory agencies to rethink the safety of manganese in public water supplies (Elsner R, Spangler JG. Neurotoxicity of Manganese: Public Health Danger in the Shower? Medical Hypotheses 2005; volume 65; e-release May 21, 2005.)
I feel quite certain, because of the radical nature of my hypothesis—one that is difficult to test but needs to be considered globally since manganese is increasing in the environment from its addition to gasoline—no other journal would have been willing to accept it.

Indeed, this study has led to other peer reviewed studies which I have written regarding environmental manganese (Spangler JG, Reid JC. Environmental Manganese and Cancer Mortality Rates by County in North Carolina: An Ecological Study. Biol Trace Elem Res. 2009 Jun 4. [Epub ahead of print]; Spangler AH and Spangler JG. Groundwater manganese and infant mortality in North Carolina Counties. Ecohealth, 2010; in press).

Science needs radical hypotheses, forward thinkers, scientific risk-takers. This is how science has always made its greatest advances (think: Einstein). While I am no Einstein, nonetheless the articles which I have published have sparked interest in a wide variety of disciplines. The same is true for other articles in Medical Hypotheses.

Peer reviewed journals are by nature conservative. They worship at the altar of p<0.05, at the throne of the randomized placebo controlled clinical trial. However, innovative ideas are often difficult to test readily. Peer reviewed journals demand data, even when data cannot be obtained. In fact, data might never be obtained unless someone publishes the novel idea in the first place. Clearly, an editorially-reviewed outlet—willing to take risks—is very much needed in science. I hope the publishers will recognize the jewel they have in this remarkable journal. I hope they will continue to publish it in its current editorial format. This simply is a matter of scientific advancement. Sincerely, John Spangler, MD, MPH Professor of Family Medicine Wake Forest University School of Medicine Winston-Salem, North Carolina 27157 Phone: 336-716-2238 * On Sat, 16/1/10, Paul W. Sherman wrote:

From: Paul W. Sherman
Subject: Re: Medical Hypotheses is under threat
Date: Saturday, 16 January, 2010, 18:56
Re: Medical Hypotheses is under threat

Dear Dr. Charlton,

Under your editorship, Medical Hypotheses has become an important vehicle for publishing exciting new ideas and information that is helping to shape the directions of medical research.

My own special interest is in Darwinian medicine. This exciting, new, interdisciplinary field takes an evolutionary perspective on human health and disease. Practitioners ask whether behaviors and symptoms that traditionally are considered pathological might have evolved to serve useful purposes. Whereas traditional medicine focuses on how symptoms are brought about (their underlying mechanisms) and designs more effective ways to eliminate them, Darwinian medicine focuses on why the symptoms occur in the first place (their reproductive consequences) and whether it is advisable to eliminate them. These approaches are complementary, not mutually exclusive. The promise of Darwinian medicine is that it will lead to better-informed medical practices because, to fix something as complex as the human body, it is essential to know what each of its parts was "designed" (by natural selection) to do.

Medical Hypotheses is - literally - the only journal where Darwinian hypotheses for medical phenomena are routinely presented for rigorous evaluation. Cancelling the journal, or massively altering its focus and editorial policies, would potentially deprive both the medical and biological communities of their only existing forum for interaction. I hope that such a serious loss can somehow be averted.

Sincerely, Paul W. Sherman (Professor)


From: Resia Pretorius
Subject: Re: Medical Hypotheses is under threat
Date: Monday, 18 January, 2010, 5:57

Dear Prof Charlton,

It is with great regret that I learn of the plans to change Medical Hypotheses. I have the most highest regard for your process and a few years back, as young researcher with little experience, you gave me the change to publish my ideas. Now, more than 130 peer reviewed articles in ISI rated journals further, I think back and have to thank you for giving a young, wide-eyed researcher a huge opportunity!

Hope you succeed to keep the journal as it is!

Kind regards, Resia

Prof Resia Pretorius (PhD)
Director: Applied Morphology Research Centre
Faculty of Health Sciences, University of Pretoria
P.O. Box 2034, Pretoria 0001
South Africa
Tel: +27 12 319 2533
Fax: +27 12 319 2240
Cell: +27 82 929 5041


On Sat, 16/1/10, Matt Bianchi wrote:

From: Matt Bianchi
Subject: MH
Date: Saturday, 16 January, 2010, 15:53
Dear Drs Charlton and Lloyd,

As a young clinician-scientist beginning my career, I wanted to extend my personal thanks to you and to Medical Hypotheses for the unique service I feel it extends to the scientific and medical community. As I built upon my graduate work on ion channel physiology to explore a realm of possible drug design strategies (known as rational promiscuity), I discovered that journal after journal would respond to my submissions with "...interesting, but too theoretical, and we do not take unsolicited hypothesis papers". I estimated that I had read for this project about 1000 papers over 10 years collecting the data necessary to put forth a series of 4 hypothesis manuscripts. This work was mainly undertaken over the years of medical school, internship, and residency, when there is little time for experimental science. This "gap" in the training of MD-PhDs is the continued subject of debate, a limbo in which we are often too junior to have a broad reputation required for hypothesis publishing, but we are also ripe with ideas that may bridge clinical and basic sciences.

I am deeply thankful that the first 3 of these papers have been published through Medical Hypotheses, the only dedicated publication for hypothesis in medicine. I have received many contacts from around the world for reprints, but more importantly, the ideas are now easily available through PubMed and other databases, for anyone to consider. Having a platform to construct and share these thoughts has proven invaluable, and has laid the groundwork for finally initiating experiments (which are very costly) to generate data of my own to begin testing the hypothesis. I am as proud of these papers as any experimental paper I've published, and in many ways they were in fact more challenging.

I can think of no better evidence for the lack of understanding of the importance of this Journal than the demands for restructuring based on a visceral response to an unpopular hypothesis. Science is uniquely poised to remain agnostic to politics - at least in theory. Unlike any other endeavor on the face of the earth, doubt and uncertainty are the foundations of progress, and diversity of experimental and theoretical approaches are the currency driving this progress. It is by no means a perfect process, and the road is littered with countless examples of "proof" later considered folly - and vice versa. But any thoughtful academic will understand that this is part of the magic of science. Perhaps the outspoken critics would do well to read some of the history of science and medicine, in particular the cogent accounts provided by Ramon y Cajal or Kuhn or Feynman. While I think there is little room for the censorship proposed by critics, I do understand that this is an area of uncertainty crossing boundaries into public policy and public health. But as much as I dislike cliches, images of babies and bathwater are unavoidable when the response to a disagreeable topic is to completely abolish the journal as we know it. One alternative approach would be to claim that the Journal should have formal peer review or else be removed from PubMed listing - but by this logic, every PNAS paper directly submitted (ie not reviewed externally) should be removed as well (and some might agree with that; I would not). Another approach would be that the format remains intact, save that certain topics should be censored, but surely proponents of this angle would concede the impossibility of deciding on the special list of prohibited topics. But anyone submitting the argument that peer review somehow prevents "bad science" from being published simply hasn't ever attended a journal club meeting. That certain topics could be used for nefarious reasons by ill-intentioned individuals is, in my view, completely irrelevant, as there is quite literally no prevention against that possibility in this information age. Unfortunately, those easily fooled by such devious efforts are not likely to be among those who understand the difference between good and bad science (which is not always straightforward even for seasoned investigators). Perhaps a format in which public comments (positive and negative) could be attached to articles via the MH website would be a reasonable compromise.

My intention is to offer neither a philosophical "it's-all-relative-so-leave-us-alone" argument, nor an existential "all-human-thought-is-absurd-so-leave-us-alone" argument, nor an aloof confidence that "science-will-work-itself-out-so-leave-us-alone" (although I admit personally to all 3 feelings). What we have are very tangible and very practical arguments in favor of maintaining the status quo of MH. The transparent policies, long history, and unique platform for sharing ideas with a community hungry for new and imaginative vistas of investigation, are all evidence that Medical Hypotheses stands alone in serving a critical (and largely unmet) need in the research community: the dissemination of medical hypotheses.

With kindest regards,

Matt Bianchi MD PhD
Instructor, Department of Neurology
Massachusetts General Hospital
Assistant in Neurology
Harvard Medical School


From: Jenny Shen
Subject: Support of the policies of Medical Hypotheses
Date: Saturday, 30 January, 2010, 11:10

Dear Professor Charlton,

From what I have been through as an author struggling to publish my work, I strongly and fully support the policies of the journal Medical Hypotheses, which was established 34 years ago by Dr. David F. Horrobin.

During my time at the Oxford University, UK, I formulated my hypothesis of the pathogenesis of Alzheimer disease in 1992. I submitted the work to eight journals including Nature, Science, NEJM, Trends in Neuroscience, J Alzheimer's disease, Brain Research. However, not one journal after peer review was willing to accept my work for publication because the expert reviewers favored the prevailing hypotheses in the field at the time (please see one of the comments from the editorial office of NEJM as evidence in the attachment.)

I finally submitted the piece of work to Medical Hypothesis, encouraged by the policies that the founder and editor Dr. David F. Horrobin established in 1975. It reads: “Scientific progress depends on the existence of creative tension between ideas and observations…There is neither free presentation of new ideas nor open criticism of old ones. Outdated concepts can persist for prolonged periods because the evidence against them is scattered through hundreds of papers and no one is allowed to gather it together in one article to mount a sustained attack.” “I will publish papers from anyone regardless of whether they have done experimental work in the field, and regardless of the reputation of the authors or the institutions from which they come.”

I didn’t receive any response from the Journal for three months after my submission, and I assumed the reviewers were unwilling to say yes or no. I have been ever so grateful to Dr. Horrobin who reviewed my manuscript himself and accepted it for publication in the journal Medical Hypotheses. This hypothesis has been later refereed as one of the four leading hypotheses in the field (Progress in Neurobiology 52(6):511-535, 1997).

Invigorated by the policies of the Journal Medical Hypotheses, I’ve published a total of seven hypotheses which were rejected by other journals. One hypothesis of the possible cause of Gulf war syndrome received special attention after the publication from the Pentagon in the US (please see attachment) and has been proved completely correct ten years later in an article published in PNAS, 2008, 105(11):4295-300. Scientists all over the world have cited my hypotheses published in Medical Hypotheses up to this day of 2010. I’ve received a considerable amount of invitations to contribute articles, and have been regarded as an opinion leader and rising star whose ideas would influence drug development and management in the field in the next five to ten years (please see attachment). The issue of the unsatisfactory outcome of the use of AChE inhibitors in the treatment of patients with Alzheimer’s disease was raised by me in my first and subsequently published hypotheses and now has become one of the most popular medical news stories of 2009 in MedscapeCME (information is enclosed in the attachment.)

Like most authors and medical scientists I truly wish my painstaking research to be known and to have a positive impact on the care of patients and on medical science. However as a matter of fact, it will not be possible for researchers like me to imagine and to hope that my hypothesis will be published and disseminated in the world, if there were no such journal with policies like those of Medical Hypotheses.

In the name of science I believe it will be a shameful and unforgivable mistake, if the publishers change the unorthodox journal of Medical Hypotheses into an orthodox one.

Sincerely yours,

ZhengXuan Shen
Professor of Department of Pharmacology
School of Pharmacy
Fudan University,
Shanghai, China


From: Georg Steinhauser
Subject: Medical Hypotheses
Date: Friday, 15 January, 2010, 15:55

Dear Dr Lloyd,

I have been informed that Elsevier is currently thinking about destroying the fundamental idea – editorial review – of the renowned journal Medical Hypotheses. PLEASE DO NOT!

Please do not regard my message not just as another email from a Medical Hypotheses-author: My research topic is technical sciences and I work in a nuclear physics institute.

It is “Publish or Perish” in the scientific world today. This forces researchers to submit hundreds of papers during their career. This, on the other hand, forces peer-reviewed journals to be more and more strict about accepting the researchers’ papers. This leads us into the completely wrong direction, because reviewers will only recommend papers for publication that are fully consistent with their view and only, if the study is absolutely complete or even overcomplete. Sometimes it is not a question of laziness to complete a study, sometimes it is simply impossible due to a lack of instrumentation, personnel or money. Medical Hypotheses is the ONLY high-class forum for making a good idea accessible to a broader audience – especially those ideas that could not be completed for some of the mentioned reasons.

Medical Hypotheses papers are read by the entire scientific community, not only by the medical one. And, of course, some of them make us laugh. Others make us shake our heads. So what? In a recent issue of Chemical & Engineering News (C&EN), which is the number one news platform for chemistry, my Medical Hypotheses paper of last year has been highlighted. I concluded the interview with C&EN with the following sentence.

"I truly regret that technical sciences do not have a forum for radical and cutting-edge ideas on a comparable level as Medical Hypotheses," Steinhauser says. "If we fail to investigate something, our best ideas often remain unpublished."
In fact, Elsevier should not cease Medical Hypotheses (neither completely nor in its present form) but launch MORE journals of this kind! Start with chemistry today, not tomorrow!

Kind regards
Georg Steinhauser


From: Allen, Stephen
Subject: RE: Medical Hypotheses is under threat
Date: Friday, 15 January, 2010, 11:52

Dear Dr Charlton,

I am surprised to hear about the proposed changes for MH. I have published 2 papers in the journal. These would probably have been blocked by peer review carried out in the current peer reviewing culture, which tends to discourage lateral thinking and inventiveness. I say this as a clinician and researcher who is involved in peer review both as an author and a reviewer, so I have no particular axe to grind. There needs to be a respected medium for hypothetical papers, and in my opinion MH meets the need very effectively. I am entirely happy for you to hand these comments on to the publishers.


Stephen Allen

Professor SC Allen
Consultant Physician and Professor of Clinical Gerontology
Tel: 01202 704539


From: Eva Zerovnik
Subject: at these times
Date: Thursday, 14 January, 2010, 19:59
Dear Vice Precident of Elsevier

Dear Editor BG Charlton

I think reading what Mr. Charlton says that Elsevier aims to make a new type of journal from the old "Medical Hypotheses", changing rigour and peer review requests - that this is not very wise.

The times are such that the communication between different disciplines is necessary and not every idea could be initially strictly founded. It could develop.

I myself published in Medical Hypotheses just once and my idea was well received (perhaps somewhere else it would be rejected as non-founded). It over years has proven to be in the right direction.

By my opinion, at least, the original founders would have to stay and the openess of the journal to get published new ideas.


Eva Žerovnik

Dr. Eva Žerovnik, Ass.Prof.
Senior Researcher
Dept. Biochem. Mol. & Struct. Biology
Jožef Stefan Institute, Jamova 39
1000 Ljubljana, Slovenia
tel + 386 1 477 3753


From: Biermann, Teresa
Subject: AW: Medical Hypotheses is under threat
Date: Friday, 15 January, 2010, 13:41

Dear Prof. Charlton

The idea that Medical Hypotheses will turn into a peer reviewed mainstream journal saddens me extremely. I wish I had a good idea to prevent such and if you have a good idea what to do, please let me know. There were times I felt i should leave research alone as there is no reviewer without hidden thoughts so far. Publishing your research is too complicated and it should be left to the reader to judge the manuscripts in the end. A "quality assessment" by peer review by anonymous reviewers would be poison for a highly constructive journal as Medical Hypotheses.

I hope you will be able to carry on!

Yours sincerely
Teresa Biermann

Dr. med. Teresa Biermann
Fachärztin für Psychiatrie und Psychotherapie

Universitätsklinikum Erlangen
Psychiatrische und Psychotherapeutische Klinik
Schwabachanlage 6
91054 Erlangen

Tel: 09131-85-44773 (direkt)
Fax: 09131-8534105


An open letter to Elsevier
Medical Hypotheses and its editorial policy: stet

Dissent is also a meaningful contribution to discussion: there can be no debate if there is no ‘against’ to the ‘for’. The medical world has always been and in the light of the ‘attack’ on Medical Hypotheses’s editorial policies, will continue to remain cocooned in its own ivory tower of supercilious self righteousness, using its arm-twisting others into kowtowing to its own definitions on journalistic ethics and privileges. The general and all-pervading intolerance to opinions or dissent or different from ‘acceptable’ self-proclaimed norms’

Merely because someone pronounces something unpalatable or contrary to popular trend about an infectious disease, and finds an appropriate forum to air his views, does not make his opinion gospel. Yet, to single out the editor or the journal for daring to open its pages to such radical views, is not ethical or cricket. Of recent development is the exposure of how really different the ground situation actually was during the so-called pandemic H1N1. While me-too editors were going overboard to touting dire straits, wily- nily jumping into the welcome home net spread wide by avaricious drug cartels.

Much brouhaha and tomtoming on the infallibility and merits of peer review and its absence in MH has accompanied the stifling and strangling of free and fearless editorial practices of MH, autocratic though they may appear at times – the fact is, there is nothing much that is sacrosanct about peer reviewing as a quality check for publishing: I myself have had my submissions politely rejected by anonymous reviewers of one journal, only to see that very paper published in yet another’ peer reviewed’ journal a while later. How may in the medial world will honestly declare they too haven’t experienced this irony? Do editorial boards of the so-called peer reviewed journals know how many of the papers their own reviewers ‘passed’ had been outright rejected by their own ilk elsewhere?

If a paper is lacking in conviction or content then it should be unsuitable for exposure to a wider audience. Yet, time and again, all of us know, that being rejected by one set of reviewing ‘peers, implies resubmission and acceptance in another equally popular or patronized journal: If the much vaunted peer review system was as holy a cow as assumed to be, how come there so difference and disparity in submission quality assessment between one journal and another?

If your name is Casca then you will be hanged for your bad verse: Strange logic this in a world moving towards open access along the free information. I myself, as author or co-author have had the mortification of having ‘accepted peer reviewed’ articles kept in permafrost by editors, neither seeing them in print nor having them released from the copyright transferred clause I readily agreed to sign. The only reason for the cold storage of at least one among such papers in question is, I deduce, because it says something at variance with ‘acceptable’ regimens and presents radical observations on lowering viral loads in HIV patients. Could is be that too many megabuck toted apple-carts would go cart-wheeling by new and effective cost-friendly initiatives on AIDS control.

Medical Hypotheses and its Editor has allowed me, at no price, to present a few observations and theories over the years, many of which I could not pursue meaningfully to conclusion for want of infrastructure and funding. That some of my publications in MH have even been cited or referred to in indexed journals is itself a telling commentary on how hollow the sanctity of peer review actually is ( incredibly a few editors even request the submitting author to suggest reviewers or choose tem from a panel provided: how much lower can the system go?.

As a novice editor of a nascent third world based open access journal, I humbly implore Elsevier to leave Medical Hypotheses and its editor/s pursue their goal of providing space to new, novel, controversial or dissenting opinions. Stet is a term that editors often use, maybe it is time publishers used it to. Stet, leave it as it was.

Prof. Arunachalam Kumar
Dean, Faculty of Medicine, Nitte University
K. S. Hegde Medical Academy
Mangalore 5785018, India


From: Mark McCarty
Subject: RE: Medical Hypotheses is under threat
Date: Friday, 15 January, 2010, 19:13

Dear Bruce – This is outrageous! I have posted a comment on the Times Higher Education website stating, among other things, that I will never again submit a manuscript to “Medical Hypotheses” if Dr. Horrobin’s original intent is dishonored and you are replaced as Editor. People who believe that the Medical Literature should be Holy Writ, purged of all Error , evidently have no understanding of the scientific process, and don’t merit our respect.

Ironically, an old scientific friend of mine, who died this last year, was a friend of Duesberg and respected his views on HIV. I could never agree with him on this, of course, but I respected the courage of his contrarian convictions, and I didn’t let it ruin our friendship. It took guts to publish Duesberg’s perspective, and I admire that. The people who took exception to this should have simply sent cogently argued rebuttals to MH, which you no doubt would have been pleased to publish as well. In my view, people like Duesberg and my late friend perform a service by emphasizing that our understanding of HIV’s physiological impact remains far from complete.

I suppose I have a hatred of all Dogma – scientific, religious, or otherwise. The last thing we need is for all editors of medical journals to function as Mini-Popes!

Please keep us updated on the evolution of this controversy, and I will do what I can to make my views known.

All best wishes, Mark


From: Susan Sheridan
Subject: Re: Medical Hypotheses is under threat ---
Cc: "Susan Sheridan"
Date: Friday, 15 January, 2010, 15:13


I have been one of the extremely lucky people to be published by you, essentially put on the map intellectually by you, for which I can never thank you enough. Dr. Walter J. Freeman, even though now in his 80's, has been corresponding with me for at least 15 years, and his comments in support of my new book for professional caregivers of young children, including teachers and therapists, provide the imprimature for the book, just as your journal provided support for my papers: The Scribble Hypothesis and A Theory of Marks and Mind. The book Saving Literacy itself, of course, rests upon my two papers published via Medical Hypotheses Journal. I am also publishing a companion book at the same time for parents, HandMade Marks.

Your publishing of my theories and research was critical to my confidence and to my authority as an innovative theorist and practitioner around children's intentional marks.

It would be a terrible shame for Medical Hypotheses Journal to be destroyed after 34 years of important support and publication.

I will also write Chris Lloyd in support of the journal.

Sincerely, concernedly, gratefully,

Dr. Susan Rich Sheridan


Subject: Medical Hypotheses
Date: Friday, 15 January, 2010, 23:26

Dear Bruce G Charlton,

It's a shame that this unique journal has to face these problems. I would like to say that I consider it very important for the scientific community as it s one of the few dealing with theoretical issues in the biomedical sciences

While nobody questions theoretical physics eg radical ideas in cosmology(that can not be experimentally tested),seems that this is not the case in the biosciences.

In my particular case I published one paper dealing with a model of cellular aging that was selected as suggested readings in GeneReviews. This is an honour in such a competitive field.

I am very proud of it, and Medical Hypotheses gave me the opportunity
to publish it.

Of course I also believe that how to evaluate the best possible way special papers related to public health problems will be a challenge for the editors in the future .

To summarize I believe that Medical Hypotheses is a very important journal and its phylosophy should be kept intact.

I really wish the best for Medical Hypotheses, and I hope we can celebrate its 100th aniversary

Yours sincerely

Ruben Agrelo

Dr Ruben Agrelo
IMP Research Institute of Molecular Pathology
Dr Bohr Gasse 7 1030
+43 (1) 797 30


From: Dr O. Walusinski
Subject: med hypo
Date: Saturday, 16 January, 2010, 8:17

Dear colleague,

I am a French physician and work about yawning.(see scholarpedia :

In 2006, you agreed to publish my article :

Walusinski O. Yawning: unsuspected avenue for a better understanding of arousal and interoception. Medical Hypotheses 2006;67(1):6-14

It was a fundamental step for me.

Since, I have had the opportunity to publish in other medical peer review journals (see piece joint)

I hope you can manage ever in the same manner Medical Hypotheses

with best regards

Dr. Olivier Walusinski


From: Robert Whitaker
Subject: Re: Medical Hypotheses is under threat
Date: Friday, 15 January, 2010, 14:25

Dear Bruce,

This is extremely discouraging news. As you know, you published The Case Against Antipsychotic Drugs, and no peer-reviewed journal (often supported by drug-company ads) would have publshed that article. Yet I know that article made an impact, including on some who teach psychopharmacology. Peer reviewed journals allow for scientific reviews to proceed along narrow corridors, and they generally exclude truly novel and fresh thinking. Your journal made that possible.

Please pass on my comments to Elsevier. If they change Medical Hypotheses into one more peer-reviewed journal, science, medicine and the public will all suffer a loss.

With best wishes,

Bob Whitaker


From: Mark Germine
Subject: RE: Medical Hypotheses is under threat
Date: Friday, 15 January, 2010, 19:51

Dear Dr. Charlton:

I have published two papers in Medical Hypotheses. I have also published in journals like the New England Journal of Medicine, JAMA, Biological Psychiatry, Psychiatry Research, and Journal of Nervous and Mental Diseasee, and many other highly reputed journals. I am a physician and a scientist with a solid publication history. I am editor of three e-journals in the field of mind/brain science. In my publications in Medical Hypotheses, Consciousness and Synchronicity, was the first publication to describe quantum evolution of brain states by collapse of the wave function, now a leading theory of consciousness and the subject of at least 3 books. The second, Virtual Brain States and Non-locality of the ERP, was a seminal paper and has lead to a number of subsequent investigations, and was state-of-the-art data driven. Unfortunately, these papers have been rarely cited, although many have used the ideas. You can't copyright ideas, so there is nothing I can do.

Medicine needs an outlet for new ideas, however radical they may be, as long as they are supported by evidence or are logical solutions to theoretical problems. I would hate to see us lose this valuable outlet. Science, in my opinion, has a philosophical bias towards untrenched ideas and paradigms, which may be incorrect. The history of science is replete with revolutionary and paradigm changing ideas that have been scorned and rejected in their own time. A hypothesis is, by definition, unproven, and for every new hypothesis that proves to be correct there are many that do not. It is difficult to publish purely theoretical work, especially if they are interdisciplinary, although I have published many such papers in reputable journals. If there is no outlet for new medical hypotheses, all of medicine and science will suffer as a result.

I hope that Medical Hypotheses can continue with its mission unabated.

Mark Germine, MD, MS


From: Pall, Martin L
Subject: RE: Medical Hypotheses is under threat
Date: Friday, 15 January, 2010, 22:10

RE: Medical Hypotheses is under threat

Dear Dr. Charlton:

Thank you for your email. Please forward my comments to Elsevier.

I published my first paper in Medical Hypotheses in January 2000, after having published many other scientific papers in many journals, all of which were peer reviewed. These included six Elsevier Journals. I have reviewed hundreds of papers for many journals, including various Elsevier journals.

That first paper has been cited 57 times during the past nine years, according to Google Scholar. It has led to my publishing a series of 22 papers and a book, entitled "Explaining 'Unexplained Illnesses'" most of which have also attracted substantial numbers of citations. The area of research that I have been pursuing over the past decade, all derived from that original paper in Medical Hypotheses has attracted much attention. I am currently scheduled to give 12 invited talks in the U.S. and in five European Countries between March and June of this year. Quite a number of these are prestigious talks, including an all day workshop for German physicians in Berlin scheduled to correspond to my visit; a talk at a special meeting on multiple chemical sensitivity in Paris also scheduled to correspond to my European visit; a 4 1/2 hour series of talks at the Royal Society of Medicine in London, also scheduled to correspond to my European visit. I have been asked to write a review, I would argue the definitive review, on multiple chemical sensitivity, a review that came out 2 months ago, in a prestigious multivolume reference work for professional toxicologists. All of this and much more is essentially derived lineally from that first Medical Hypotheses paper.

There is a need for a journal like Medical Hypotheses and it would be tragic, in my view, to destroy a journal that is performing a valuable function for the science of medicine, by converting it into something very different from what it is now. Medicine is a field that is dominated by vested interests, typically by well funded pharmaceutical industries, and is much less scientific than it should be because of this. This has been clearly documented in books written by Dr. Jerome Kassirer and also Dr. Marcia Angell, both former editors of the New England Journal of Medicine, who should certainly know this area well from their periods as editors of the most prestigious medical journal. The dominant role of vested interests in medicine has led to a world wide crisis in medical care, and while this crisis is most evident in the U.S., as shown by the recent debates on medicine in this country, it is a major problem all over the world. In this type of situation, a forum for documented opinions that is more open to those who hold views that dissent from those of the dominant vested interests is essential. If Medical Hypotheses is converted into a journal where there is a list of excluded topics, that would be unacceptable censorship by Elsevier, in my judgment.

I would like to add a comment on the issue of peer review. I published my first paper in 1968, some 42 years ago (in an Elsevier journal, by the way) and have been observing the functioning of peer review over that extensive period of time. Over that time, the peer review system has deteriorated substantially for two distinct but interrelated reasons, both related to the pressures and difficulties of maintaining research funding on the part of potential reviewers. One is that individual scientists have become highly focused on very narrow areas of science, with such narrow focus being viewed by many as essential to maintain funding. As a consequence of this, scientists are much less able to peer review papers that are outside their very narrow range of expertise. The second is that with much pressure on the time of scientists to maintain funding, they are much less willing to spend their time researching a paper in order to provide a competent peer review. Rather papers are much more often reviewed by peer reviewers who have a vested interest in determining whether the paper is published or not, rather than providing a scientifically objective peer review. This is a great challenge for editors who are trying to keep their journals truly scientific, as opposed to simply reflecting some vested interest position. There have been, as I think you know, whole journals that openly or covertly state that they are journals supporting some industrial line, rather than genuine scientific journals. There is some stunning junk published in peer reviewed journals, things that should never have been published if the paper had been properly reviewed. And this happens in the most prestigious journals as well as in more pedestrian ones. The fact is that peer review has very substantial flaws and there is an advantage to having some journals that are editorially reviewed - at least then you know who to blame when something slips through the cracks. The flaws of the peer review system are likely to impact a journal like Medical Hypotheses more than other journals - how do you get people to effectively peer review a paper that is truly novel?

I think that for all of these reasons, Medical Hypotheses should be viewed as a successful journal that is currently performing a valuable function to the scientific and medical communities and should be left to pursue further successes with its current structure. If Elsevier feels otherwise, then I would ask Elsevier to email me directly and tell me why.


Martin L. Pall

Professor Emeritus of Biochemistry and Basic Medical Sciences

Washington State University


Re: Medical Hypotheses is under threat
Friday, 15 January, 2010 14:14
"Sven Kurbel"

Osijek, Croatia, 14/01/2010

Dear Sir:

After reading reactions regarding the publication of a paper by Prof. Peter Duesberg on Aids in Medical Hypotheses I have found myself in a deja-vu situation. Humans are alike everywhere. All is the question of scale. Anyone playing not with us, ought to be an enemy.

First, regarding my conflict of interest. As a young person trying to become a scientist in a war thorn country, I have published first papers outside Croatia in Medical Hypotheses in 1995. Since then I have published in several other journals with IF from 0.2 (papers in Colegium Anthropologicum) to 4.9 (a recent e-letter in The Oncologist), but at least annually I have always prepared something for Medical Hypotheses.

The reason for my loyalty to this Journal is simple. I find the basic concept intriguing for any free thinking person. During last years, as a reviewer for several Croatian and European journals, I have read several very malicious reviews aiming not to help the authors, but to make them realize just how pathetic was their submission. So, I believe that both the peer review approach and the editor review do have their limitations. The peer review can be im proved only with a large number pool of well-categorized reviewers, random assignment of papers to three reviewers and gradual exclusion of those reviewers that are repeatedly opposite to other two reviews. Nobody does that, since it would take to much money and time.

If the only real fuss regarding the content of a published paper in this Journal happened only once in 34 years, it would mean that we are talking about an extraordinary accurate journal with a respectable citation rate. People are reading, some of them are even citing the papers from it and there seems to be no problems. The reason for this smoothness is the journal name, evident in any citation: Medical Hypotheses. With this name no false argument is being made, authors are speculating on
available facts and anyone can take it as plausible or not. Nevertheless, often the papers are interesting to be read. Readers recognize it and no hard feeling can normally develop.

So, it must be the topic in the paper, not the Journal itself. I have no detailed knowledge regarding AIDS, but the idea in the paper must be an important taboo, otherwise more than 10% of papers in Medical Hypotheses would be considered controversial. With so much attention, it has to do something with the money, at least this is the way in the part of Europe I live.

Since this journal is unique by its profile, impact and tradition, every intervention in its concept would move as one step further to Lysenkoism, or other, more modern type of orthodoxy in science. Without this Journal, a not so small tribe of free thinkers in biomedicine would have to go elsewhere or to stop theorizing and think only on routine. Is this a future that we want, or is it made for us by those who know better? I hope not.

Sincerely Yours

Sven Kurbel MD, PhD

Prof. Sven Kurbel MD, PhD
SUNCE Health Centre, Osijek, Croatia
Dept. of Physiology, Osijek Medical Faculty
J. Huttlera 4, 31000 Osijek, Croatia
web page: e-mail:


From: Ginsburg Isaac
Date: January 16, 2010 9:19:27 PM IST
Subject: Medical Hypotheses

Jerusalem, January 16, 2010

Dr. Chris Llloyd
Vice president of Health journals

Dear Sir,

I have just received an e - mail from Dr. Bruce G Charlton regarding the " Unclear outlook for radical journal as HIV/Aaids deniers " which evoked an outrage of protests/ support views on whether or not to decide that Medical Hypotheses be changed to a new formate, this time including peer evaluations of scientific articles submitted to the Editor of the Journal. Many of the comments made expressed concern that establishing a peer review system might be counter productive since " wild and innovative ideas " which are not in line with the dogmas set by investigators who believe they " hold the ultimate truth in science ", will never be published.

As a contributor to " Medical Hypotheses ", I strongly believe that at least ONE out of the thousands of regular peer evaluated journals which exist today, should be left alone to serve as a spokesman for those articles which will definitely be rejected if submitted to a peer evaluated journal.

Let me brief you about the ordeal I had gone through during my long academic career which will clarify why I think that Medical Hypotheses should not be touched.

First, I highly recommend reading my invited overview article in the Scientist 2001 Volume 15(24):51 entitled " The disregard syndrome, a menace to the future of science ? " "which speaks for itself .

The following is a clear example why ideas which are not in line with accepted dogmas should have an appropriate independent forum of expression.

For years I have been struggling with Editors trying to convince them to instruct authors working on the mechanisms by which cationic peptides kill bacteria, to cite a large numbers of my publications on the subject. The accepted dogma today is that cationic peptides kill bugs by permeabilizing their outer and inner membranes rendering them non -viable. On the other hand we have argued that cationic peptides might ALSO kill bacteria by activating their endogenous autolytic wall enzymes ( muramidases) causing bacteriolysis and cell death. Furthermore, although one of the leading investigators finally mentioned in his peer reviewed article that the bacteriolysis concept, is valid, but surprisingly ignored any of my publications on the subject. Only " God " knows what had motivated this author to intentionally ignore the bacteriolysis concept, and why, the Editor of the journal had failed to deal with this issue. Such an INTENTIONAL suppression of " non orthodox" ideas is a setback to honest SCIENCE and the only crime the dissenter had committed, was that he " thought differently " !!

To my rescue came the Editor of Medical Hypotheses who in 2004 ( volume 62 : 367 - 374 ) had accepted my overview article entitled :
" Bactericidal cationic peptides can also function as bacteiolysis- inducing agents mimicking beta- lactam antibiotics ? it is enigmatic why this concept is consistently disregarded" . As of today, this article had been cited 33 times.

More recently, I have been invited to comment on a key review article on bacterial killing by cationic peptides submitted to Experts Rev Anti Infective Therap. Once more I found out that although the same author had again mentioned bacteriolysis as a possibility, he failed to cite our papers on the subject. Justifying my criticism, the editor of the journal invited me to compile a large polemic essay on the subject in order to bring to the attention of readers that there might be an additional mechanism of bacterial killing Please refer to : Are cationic antimicrobial peptides also " double - edged " swords ? Ginsburg I and Koren E, 2008 Volume 6:453- 462.

Taken together, in order to avoid either unintentional or intentional disregard for publications which do not coincide with the main stream of thoughts, we badly need " watch dogs " who will allow those authors whose papers might either be abused or rejected by PEER EVALUATORS , to present their ideas. This is why I strongly oppose to any attempt to change the current policy of the Editorial Board of Medical Hypotheses. Needless to say that any paper submitted for publications to any journal should be supported by convincing experimental data.

I shall greatly value your comments and suggestions and am looking forward to hear from you soon.

Sincerely yours

Isaac Ginsburg ( Emeritus Professor of Microbiology )

Institute for Dental Research
The Hebrew University Hadassah Faculty of Dental Medicine
Jerusalem, Israel
Phone 972- 2 6757073
Fax 972- 2 6758583


January 15, 2010

Mr. Chris Lloyd
Vice President of Health Science Journals

Dear Mr. Lloyd:
The editor of Medical Hypotheses recently made me aware that Elsevier had intended to radically alter the way he would be able to select articles for publication. Recently, two controversial, politically-sensitive, and probably scientifically inaccurate articles were withdrawn from the journal by your publishing company. No journal is immune from such errors and even the prestigious peer-reviewed journals Science and Nature have had to withdraw published articles because of fraudulent data or conclusions.
The basic tenants for article selection by Medical Hypotheses are unique in that they permit the dissemination of new paradigms of thought, more or less supported by real data, but nevertheless thought-provoking. Since Dr. Charlton has become editor, the quality of articles has progressively improved from those that were largely nutraceutical in content to those with more diverse subjects and authors from many disciplines. The progressive increase in the Impact factor has supported this statement.
It would be eminently sad to see the one of the very few beacons that welcomes radically new hypotheses and often serves as the only opportunity for such ideas to be widely shared by the world’s scientists to disappear from the publishing scene. Of course some of the articles might be considered trivial or even outrageous, but these are certainly not the rule. There are others that offer real food for thought and have stimulated new paradigms between disciplines of science and medicine.
I, and many of my colleagues, implore you and Elsevier to resist political pressure and maintain a steady support of Medical Hypotheses in its current form for the selection of articles. The editorial comments by Dr. Charlton have been particularly stimulating and we look forward to any issue that contains them.

Sincerely and very best wishes,
George E. Davis, Jr., MD, FACP. FACG
28 Eastern Ave.
Augusta, Maine, USA


On Sat, 16/1/10, velimir altabas wrote:

From: velimir altabas
Subject: letter of support
Date: Saturday, 16 January, 2010, 14:21
Dear Bruce Charlton,

First, it has always been a challenge writing articles for Medical Hypotheses, as well as we had a great satisfaction enjoying the attention we had here in our local community.

So, we were pretty upset, when we have heard about the troubles You are going through.

We are a small group of people trying to make science, from a small country, with small resources. It is crucial for us to publish hypotheses which are we cannot investigate alone, sometimes there is a positive echo from abroad – and among others - Medical Hypotheses made it possible.

It would be wrong to change the editorial policy of this journal because it is unique. The feeling of freedom while expressing our ideas was priceless, reading the articles of others was rather an inspiration, and invitation to reconsider what is known, and what is not in a particular topic. We had never the feeling we were fooled by others with some so called - pseudoscience.

Of course, there are people who have a different opinion. Maybe they are afraid their ideas could lose their public ? Well, if those ideas are wrong - it will surely happen, but that is just the pure nature of science - checking ideas and concepts in the search for the truth.

We are just afraid how dangerous those people are, if they want to destroy a journal just because it has published some ideas out of present dogmas. Well, it seems to us that we all were fooled at school when we learned that the times of inquisition, Nazism, communism etc were behind us ...

Suppressing different ideas is a way straight into dark ages, and we hope You will find many allies in Your fight for the right thing.

Sincerely Yours,

Velimir and Karmela Altabas
University Clinic "Sisters of Charity"


--- On Fri, 15/1/10, Huping Hu wrote:

From: Huping Hu
Subject: Re: Medical Hypotheses is under threat
To: "Chris Lloyd"
Cc: "Bruce G Charlton"
Date: Friday, 15 January, 2010, 21:32

Dear Sir Chris Lloyd, Vice President of Health Science Journals at Elsevier:

I am an author who over the recent years published two papers in Medical Hypotheses. I and my co-author of these two papers highly valaue the editorial review policy of this journal and the importance of this journal.

I'm shocked to learn from Dr. Bruce G. Charlton, the Chief Editor of Medical Hypotheses, that Elsevier are considering major editorial changes to this unique and proven journal (over 34 years) which makes money for Elsevier, apparently due to one or two allegedly inappropriate papers appeared in Medical Hypotheses.

The vitality and longevity of this journal depends on the editorial review policy (choice)instead of peer-review. The latter process often suppresses new ideas and hinders scientific process.

I urge that the leadership of Elsevier weighs very carefully about the issues in front of them, be far-sided and tolerant.

I am confident that the readers of this innovative journal and the general public are smart enough to recognize an "inappropriate" article which now-and-then may appear in the journal. Throwing the baby out with the bath water would be a tragedy.

Very truly yours,

Huping Hu, Ph.D., J.D.


From: Johnson, Bruce D., Ph.D. [RO CON]
Subject: RE: Medical Hypotheses is under threat
Date: Friday, 15 January, 2010, 16:31
Re: plan to alter the general format of the Medical Hypothesis Journal.

To whom it may concern,

I have submitted a number of papers to the Medical Hypothesis journal Usually the approach has been for my students to learn to articulate their ideas in a publication prior to diving into a new study and then to follow with the results of their study and describe whether their hypotheses were correct. It has been a valuable learning tool and forum where ideas can be transparently proposed without the politics and games that are typically associated with the usual journals. Changing this format would be a shame and we would cease to submit manuscripts to this journal if it did change.

Bruce D. Johnson, PhD
Professor of Medicine
Mayo College of Medicine.


On Sat, 16/1/10, Dr Kostas N Fountoulakis wrote:

From: Dr Kostas N Fountoulakis
Subject: medical hypothesis
Date: Saturday, 16 January, 2010, 12:16

Dear Mr Lloyd

It recently came to my attention that there was a crisis concerning the journal ‘Medical Hypothesis’ because of the publication of an anti-HIV article without peer review.

My field of expertise is not HIV and AIDS, since I am a psychiatrist myself, so my opinion is based on principal values and not by specific events and facts.

My view is that although peer review is and should be the mainstream for scientific publishing (I am editor-in-chief of a peer-reviewed journal myself), it is today more than ever necessary to have a parallel open system (a minority of journals within the publishing system) who will function in a different way (no matter whether this would be 'arrogant', 'selfish' or 'fatally problematic').

The peer review system has the advantage of choosing 'good science' papers and acts as a quality filter. The same time it has the important problem that it suppresses radical and revolutionary and it tends to support the current view and interpretation of things and precludes breakthrough.

As an editor-in-chief myself, I know how difficult it is today to find reliable peer reviewers; as an author I often find myself in the position to respond to impossible comments by reviewers who obviously have limited knowledge of the subject they were asked to review. The publishing of a paper is based on the assumption that the authors are honest and have not fabricated the data (I think that this can not be verified for most of the papers submitted to a journal) and that the reviewers have no conflict of interest, they have sufficient knowledge of the subject (I doubt for most cases) and that they will invest much time to do a proper review (I also doubt they will). For prestigious journals these are often the case but there are important problems for the majority of journals.

Another important problem is that although innovation today can come from a limited sources, and one of these sources is interdisciplinary collaboration and carrying of innovations achieved in one field of science to another, most scientists and reviewers are either super-expert prominent scientists or undereducated technicians (I know first names in prominent journals who can discuss nothing more than the very papers they have published, they have no more than 2-3 years of formal training and they are asked to review papers on a regular basis because their general credentials are never shown anywhere).
I often wonder what happens to papers accepted with bonfire by the highest ranking journals; the vast majority disappear from the scientific thinking and their results are proved mistaken and misleading after only a few years.

To cut a long story short, the above are inherent problems of the peer-review system and the way research is conducted today. We don’t have a better way to regulate things and we are indeed not allowed to let the field of science to become chaotic; a field where any charlatan can do whatever he wishes and cause harm to humanity.

However, we also need to keep a small door open; we need to let new ideas and proposals to circulate uncensored. The word UNCENSORED is important. There are not many journals in the publication business that are serving this goal, and Medical hypothesis is one of them. Their function is important for the future of science, no matter whether there are problems from time to time. Science is a dynamic procedure. Its not only a matter of democracy in expression, it is a matter of keeping the horizon open for the future development.

In this frame, I consider an honor for Elsevier to have such a journal, the Medical Hypothesis, and I hope that in the future it will continue to serve the same goal and need of the scientific community.

All the best

Dr. Kostas N. Fountoulakis M.D., Ph.D
Assistant Professor of Psychiatry
3rd Department of Psychiatry, Division of Neurosciences
School of Medicine, Aristotle University of Thessaloniki,
Editor-in-Chief, Annals of General Psychiatry
tel +30 2310 994622 (Hosp. AHEPA)
fax +30 2310 266570
mobile: +30 6945776935
Post address:
6, Odysseos street (1st Parodos, Ampelonon str.) 55535
Pournari Pylaia Thessaloniki Greece


From: MericAdil Altinoz
Subject: On Medical Hypotheses and Dr Bruce Charlton

Date: Monday, 18 January, 2010, 0:01

Dear Dr Bruce Charlton / Editorial Members of Elsevier,

I am a 34-years old medical doctor from Istanbul in Turkey, who published twice in Medical Hypotheses. My first publication was during the editorial period of Dr Horrobin in 2002 and my second publication was accepted by the editorial of Dr Charlton in 2007. My first publication gained attention of Professor Gerald F Joyce working on RNA evolution at the world-prestigious Scripps Institute with positive comments. My second paper gained attention of Bayer International and they decided to support a research study for testing aspirin effects to elevate fetal hemoglobin in attenuating the severity of thalassemia (** see below). Currently, I am giving lectures in a Molecular Biology Department of a private university and mainly interesting with molecular physiopathology of cancer, thalassemia and psychiatric disease; I wish to say couple words about the Elsevier's attempt to change the style of "Medical Hypotheses".

People often say that the worst thing, which could ever happen to a researcher is sacrifying a good idea to a bad experiment. I thing the worse probability is frequently happening to researchers from less-developed countries due to a simple fact: They could barely find equipments to test their idea. This can lead to several possibilities: I- Researchers from developed countries could reach to the searched fact in a short manner. II- The searched fact could be reached far later, since it might be overseen or neglected by researchers with more resources. III- A hypothesis, which might lead global benefits could never be tested, since it was the brain fruit of less-lucky geographies.

If "Medical Hypotheses" will be made a more orthodox journal, this could only lead to monotonization of scientific voice and opinion. Please let a journal to allow papers with little less orthodoxy, please let it to allow "more flying of ideas more freely". We have hundreds and thousands of journals of same style, same seriousness and same strictness. Diversity is the magic of nature and biomedical journal-dealing people are aware of "biodiversity", yet if they could have applied this principle to their own practice, this would very much change the pace of research benefits and its daily applications.

Dr Charlton (Charlton BG) seemed to contribute far enough to global research with an impact of 185 publications and 1109 citations in a 20 years period until 2010.

I support of his editorialship and I decline any strictness-type change in publication policy of Medical Hypotheses.


Meric A Altinoz, MD

Medroxyprogesterone - valproic acid - aspirin. MVA regime to reduce transfusion associated mortality in late-term hemoglobinopathies. Hypothesis and rationale. Altinoz MA, Ozdilli K, Carin MN, Gedikoglu G. Med Hypotheses. 2007;68(6):1342-7. Epub 2006 Dec 11.PMID: 17161547

Hypothetical clues suggesting that 'AU' and 'UA' were the first 'beginning' and 'end' codons: is their ancient polymerase extant present as a protein domain fossil in reverse transcriptase and telomerase? Altinoz MA. Med Hypotheses. 2002 Jul;59(1):63-7.


From: Sue Llewellyn
Subject: Re: Medical Hypotheses is under threat
Date: Saturday, 23 January, 2010, 17:31
Dear Bruce Charlton

I write in support of Medical Hypotheses as a non-peer reviewed journal.

Peer review works well for papers which seek to add to an existing body of knowledge. Peers are reviewing work which extends incrementally an accepted paradigm. Any radically new idea, however, by definition, breaks with conventional wisdom. Hence, there will not be a ready made group of peer reviewers conversant with the approach and easily able to assess the contribution. Moreover, ideas and interests go together. Established ideas which are gaining momentum attract large research grants, dominate conferences and can make careers. So radical hypotheses can struggle to be heard - they challenge the existing mind-set, at least at first can be difficult to understand and can, potentially, upset the on-going money/status/power apple cart.

Medical Hypotheses is one of the very few places where revolutionary medical views can be published. Based on the arguments above, this is a strong reason, in itself, for continuing the present policy of editorial choice of well argued, coherent, new and/or radical hypotheses. But, there are other reasons that Medical Hypotheses is an important conduit. From my perspective as a social scientist, the medical field is surprisingly a-theoretical, research is super-specialised, analysis is valued over synthesis and methods are more or less restricted to the experimental approach. I don’t imply that social science is more open, merely that the exclusions differ. In any science, theory and empirical evidence, analysis and synthesis, in-depth specialization and interdisciplinary cross fertilization should all matter. And the pursuit of knowledge through a variety of methods is fundamental, dependent, obviously, on the nature of the problem under investigation. The present state of play in medical science results in the exclusion of theoretical ideas through heavy emphasis on experimental methods. Surely any theory should first be assessed on the basis of coherence and capability to explain observed phenomena? I refer to the email extract below, the result of submitting work to a conventional, highly regarded peer reviewed medical journal.

‘I regret to inform you that we are unable to accept your paper for publication. Your proposals are interesting, but very speculative without empirical testing of derived hypotheses. A journal such as Medical Hypotheses is better suited for these two articles. I did not want to delay you in moving forward.’

I took this advice and Medical Hypotheses published the work. I wish to do empirical testing but as someone from outside the medical field I will be reliant on working with others. They are unlikely to take me seriously if I cannot get my work published. Also it is rare for any experiment to produce incontrovertible results, experiments rest on assumptions and results have to be interpreted. Without theories that make assumptions explicit and enable results to be interpreted experimental research becomes fragmented and goes nowhere. Theoretical and empirical work should go hand in hand – they are reliant on each other.

Medical Hypotheses provides a possibility for new, radical, theoretical and/or interdisciplinary work to be published. David Horrobin established the journal as non-peer review specifically to support ‘speculative’ work. It will be a travesty if this founding principle is overturned.

Sue Llewellyn
Professor, Faculty of Humanities
The University of Manchester


From: Arthur Kümmer
Subject: RE: Medical Hypotheses is under threat
Date: Friday, 15 January, 2010, 11:37

Dear Prof. Bruce Charlton,

Medical Hypotheses is a great journal which significantly influenced my carreer choice and research projects that I have conducted. I became really upset after reading your email.

Medical Hypotheses is a revolutionary journal which questions frequently the status quo. The fact that the journal is editorially-reviewed reinforces this point of view. In other words, when most journals are peer-reviewed, Medical Hypotheses questions if every journal should be like that.

I truly believe that the current review process of the journal is the one which best fits its purpose. If this will change, the journal name should also change and the publisher should give Medical Hypothesis a chance to look for another publisher. I am sure that there are plenty of publishers eager to be a partner of Medical Hypothesis.


Arthur Kummer

Professor of Childhood and Adolescent Psychiatry
School of Medicine
Federal University of Minas Gerais.


From: Alan C. Logan
Subject: Re: Medical Hypotheses is under threat
Date: Thursday, 14 January, 2010, 21:21

Dear Dr Charlton

Your recent communication concerning the future of Medical Hypotheses is beyond disturbing. Our group from the University of Toronto published two papers in Medical Hypotheses related to the potential of oral microbes (so called probiotics) to influence the human mental state. As a result of publication, the hypotheses have generated bench and clinical studies by various international investigators.

These hypotheses papers would not have seen the light of day in any traditional peer-review format - or at least not in a journal with a long history of credibility such as Medical Hypotheses. Under your leadership the current format Medical Hypotheses strikes a delicate balance between scientific integrity and out-of-the-box, thought provoking ideas. Any transition to a strict peer-review process will disturb this balance. Researchers, including our group, will be forced to look to less reputable journals for the mere publication of ideas.

A decision to make a transition to strict peer-review will be a decision to destroy one of the most remarkable journals ever to be printed.

With Respect

Dr. Alan C. Logan
Edgewater, NJ


From: Takahiro Mezaki
Subject: Re: Medical Hypotheses is under threat
Date: Saturday, 16 January, 2010, 12:01

Dear Bruce G Charlton:

I love the current policy of the Medical Hypotheses. It is a unique journal, and it is unique because it is not peer-reviewed.

1. Science never progresses without imagination, and academic breakthrough often begins from an immature idea. It is very important that we have a place to open our imagination, unproven idea, or non-evidence-based belief as an expert, and the Medical Hypotheses is probably the only forum for them. It is the editorial-review system that allows the submission of potentially revolutionary but unproven ideas without constraint, because all we have to do is to convince only the editor to accept our opinions. On the other hand, authors have to submit their articles far more prudently under the peer-review system, because they never hope their article be rejected by part-time reviewers not realizing the policy of the journal, by the reason that it is not logically “perfect”. The authors may avoid submitting logically “imperfect” opinions, but it is, I think, against the original policy of the journal.

2. Nowadays we have so many medical journals that we can find no time to follow those with similar concepts. The impact factor of the Medical Hypotheses is only 1.416, higher than average but never in the highest rank, and therefore if the Medical Hypotheses changes its style to nothing but a moderate and ordinary journal, I will prefer to save time the New England Journal of Medicine or the Lancet based on my own opinion that all the articles actually discuss their “hypotheses”. We do not want lower priority journals with similar contents. To survive, the Medical Hypotheses must not lose their originality as a free forum of candid discussion.

Takahiro Mezaki MD PhD
Department of Neurology
Sakakibara Hakuho Hospital
5630 Sakakibara-cho, Tsu City, Mie 514-1251
Tel: +81-59-252-2300
Fax: +81-59-252-2301
E mail: tamezaki@kuhp,


From: Thelma C. Chavez
Subject: Review process for Med Hypotheses
To: "Bruce Charlton"
Date: Friday, 22 January, 2010, 17:45
Dear. Dr. Charlton:

I am dismayed to learn of possible alteration in the review procedure for Medical Hypotheses. The journal is unique in providing an important service in the medical field. In order for your current method to work, it is important to have well qualified and versatile people in the editorial office. Results over the years have amply demonstrated that this is the case. Your journal displays high standards and the ability to competently review a variety of subjects, and recognize frontier areas. In my own case, our hypotheses, which would not have seen the light of day via the conventional route, are enjoying ever increasing acceptance and recognition over the years.

Please forward my comments to the appropriate authorities. I strongly urge that the proposed change does not occur.

Pete Kovacic

Pete Kovacic
Adjunct Professor
SDSU Dept. of Chemistry & Biochemistry
5500 Campanile Drive
San Diego, CA 92182-1030


From: M. Oskar van Deventer
Subject: Re: Medical Hypotheses is under threat
To: "Charlton, Bruce"
Date: Saturday, 16 January, 2010, 11:44
Dear Dr. Charlton,

Thank you for your message, which is rather alarming. Here is my vision, which you may share with Elsevier.

Hypotheses are the basis of science. Good research involves experiment that test a hypothesis. The more data points found that don't contradict the hypothesis, the more useful it becomes for building a theory. Or the hypthesis is invalidated. Well, we all know Poppers and science philosophy.

Peer review is a good thing. Scrutiny is needed in the validation of hypotheses before accepting them in a theoretical framework. But it does not work the other way around. A hypothesis should not be rejected, because it does not fit in an existing theoretical framework. As long as a hypothesis has not been tested, it is just that, a hypothesis. The value of hypotheses is that they provoke discussion. Is there existing data that supports or contradicts the hypothesis? What tests can you perform to which the hypothesis should hold up?

The Medical Hypotheses magazine is a valuable source for medical science. Medical hypotheses are very expensive to validate. It is good to openly discuss these hypotheses and contemplate their potential impact and ways to validate them. This is true especially for radical and revolutionary scientific ideas, which will never pass peer review. Some other sectors of science could well use their own Hypotheses magazine, for example Climate Science Hypotheses. This is a good way to keep discussions on hypotheses clearly separated from their peer-reviewed scientific validation.

Of course any published idea can be abused. My own publication in Medical Hypotheses was cited with a product, something that I am not too happy about. But it was a correct reference: "if van Deventer's hypothesis is true, then ...". And when people check the reference, they can exactly read where the uncertainties are with the hypothesis.

From my own experience I know that the editorial staff scrupulously checks submitted hypotheses. My own article was only accepted when I provided sufficient arguments why my hypothesis could be true and how the hypothesis could be put to the test.

In summary, I think that Medical Hypothesis should remain what it is, that is, a platform to present and discuss medical hypotheses.

Yours sincerely,

M. Oskar van Deventer

Hannie Schaftstraat 62
2264 DL Leidschendam
+31 70 3204454


From: Steven Bodovitz
Subject: In support of the current format for Medical Hypotheses
Date: Thursday, 14 January, 2010, 20:00

Dear Lloyd,

I understand that Elsevier is considering changing Medical Hypotheses from editorial review to peer review. While I am completely in favor of the peer review system in general, I believe that editorial review has an important role to play in advancing biology and medicine. In my particular case, I have been studying human consciousness. This is a fascinating subject, and also quite daunting. Without Medical Hypotheses, I likely would not have been able to publish my early work, which likely would have been discouraging enough to prevent me from accomplishing as much as I have. I consider Medical Hypotheses to be a key partner in my progress.


Steven Bodovitz

Steven Bodovitz, PhD
Principal, BioPerspectives
1624 Fell Street
San Francisco, CA 94117


From: Richard Hellstrom
Sent: Thursday, January 14, 2010 7:18 PM
Subject: Medical Hyotheses

Mr. Chris Lloyd
Vice President of Health Science Journals at Elsevier

Mr. Lloyd:

I write in defense of keeping Medical Hypotheses exactly as it is. I write as an individual who has been published more than a dozen times by Medical Hypotheses when nobody else would publish me.

I think that the situation of Medical Hypotheses should be considered in context to Thomas Kuhn's description of the scientific process (he can be googled). Kuhn said that normal science has accepted a paradigm usually from scientific forebearers, and has the exclusive job of improving this paradigm by "puzzle-solving" studies.

Kuhn asserted that normal science rather invariably is negative to competing paradigms destructive of conventional wisdom. Also, normal scieance can be boxed into faililng to see problems with the accepted paradigm because nature is seen not as it is, but through the distorting lens of the accepted paradigm.

Kuhn said that major improvements in science come not from accumulation of studies, but by paradigm-change.

Unfortunately, medical scientists do not "see" the scientific process as defined by Kuhn. In my experience, medical operates by the inductive model. As current major positions are based on studies, only more studies can improve the current position.

This position essentially describes science as performance of studies - and does not allow for the possibility that a new paradigm might better explain a segment of science.

The story of Galileo is supposedly well known, and I suspect that most people believe that a Galileo problem can not occur today because the scientific process is well understood. I also suspect that most people do not understand why Galileo pushed the Copernican position. (Venus' full set of phases falsified the geocentric Ptolemaic theory - google this.)

I must admit that I speak from somebody with an unappreciated paradigm which challenges the basic conceptualization of heart attacks. Standard (PEER REVIEWED) journals invariably reject my papers, usually promptly and without outside reviews.

Incredibly, when rare outside reviews are obtained, they fail to evaluate the papers. Reviewers "think" in context to the accepted paradigm, and can not "see" the subject matter in context to the new paradigm. Kuhn said that those who believe in different paradigms live in different worlds, and sometimes the gulf between worlds is too great to allow understanding of the competing model.

If Medical Hypotheses, as presently constituted dies, they those with radical ideas are at the mercy of conventional thinkers.

Of course, there is nothing wrong with conventional thinking in context to reviewing results of studies. But I do insist that normal scientists fail to understand the nature of alternate paradigms, and do not understand how paradigms are evaluated - by verification/falsification techniques.

I knew David Horribin. I sent a paper to Medical Hypotheses, and David said he liked it, and invited me to lunch. As I live in the US, it was a while before I could take up the offer.

David Horribin knew full well that when radical hypotheses are published, there is a chance that some end up as "flat earth" ideas. But he was convinced that the more important issue was allowing publication of radical ideas unacceptable to "conventional wisdom."

Unfortunately, I was not surprised that the reaction of the "establishment" was to try to get Medical Hypotheses out of Medline because of a paper unacceptable to the establishment.

What is the difference of suppressing Medical Hypotheses and suppressing Galileo. In both cases, the suppressors were doing something "noble."

Those who believe that the AIDS article was nonsense should have written a paper which showed the foolishness of the article. If Medical Hypotheses would not publish a solid article which shows the imperfections of the AIDS paper, I would be quite unhappy with Medical Hypothses.

As I do not accept the standard paradigm for heart attacks, I have literally decades of experience in dealing with "normal science's" negativity to competing paradigms.

I have two goals: First to get an open and fair evaluation of my ideas by cardiology - which has not happened.

Secondly, to use my experience to make the point that Kuhn's description of the scientific process is valid. While most radical ideas might end up in the trashcan, they should not be suppressed!

I truly hope that Elsevier will not act in a manner similar to a pope of the early 17th century.

H. Richard Hellstrom, MD
Emeritus Professor of Pathology
SUNY Upstate Medical University


From: Leo Sher
Subject: "Medical Hypotheses"
Date: Monday, 18 January, 2010, 0:43
Dear Dr. Charlton,

I hope this note finds you well.

I was distressed to find out that there is an intention to transform “Medical Hypotheses” into an orthodox peer review journal. For many years, “Medical Hypotheses” has been a lighthouse of academic freedom.

I am sure that dishonest bureaucrats who run many academic institutions, departments, and centers around the world have been irritated by the fact that there is a journal that truly supports academic freedom and that they cannot control what is published in this outstanding Journal.

“Medical Hypotheses” is a great journal that has played a crucial role in the dissemination of scientific and medical information. “Medical Hypotheses” makes a fundamental contribution to biomedical progress and provides a voice that might otherwise never be heard. Any decision to change the format of manuscript review because of political considerations cannot be excused and can only lead to a higher level of censure than is already inherent within classical peer review. Peer review is problematic. Peer review makes the ability to publish vulnerable to control by elites, to personal jealousy, etc.

I sincerely hope that the leadership of Elsevier will make the right decision, and you will be able to continue doing your wonderful job as the Editor of this remarkable journal.

With deep respect and best regards,

Leo Sher, M.D.
Associate Professor
Department of Psychiatry
Columbia University
1051 Riverside Drive, Unit 42, Suite 2917
New York, NY 10032, USA
Tel: 212-543-6240
Fax: 212-543-6017


From: Alan C. Logan
Subject: Re: Medical Hypotheses is under threat
Date: Thursday, 14 January, 2010, 21:21
Dear Dr Charlton

Your recent communication concerning the future of Medical Hypotheses is beyond disturbing. Our group from the University of Toronto published two papers in Medical Hypotheses related to the potential of oral microbes (so called probiotics) to influence the human mental state. As a result of publication, the hypotheses have generated bench and clinical studies by various international investigators.

These hypotheses papers would not have seen the light of day in any traditional peer-review format - or at least not in a journal with a long history of credibility such as Medical Hypotheses. Under your leadership the current format Medical Hypotheses strikes a delicate balance between scientific integrity and out-of-the-box, thought provoking ideas. Any transition to a strict peer-review process will disturb this balance. Researchers, including our group, will be forced to look to less reputable journals for the mere publication of ideas.

A decision to make a transition to strict peer-review will be a decision to destroy one of the most remarkable journals ever to be printed.

With Respect

Dr. Alan C. Logan
Edgewater, NJ

Medical Hypotheses should retain its current format
Friday, 15 January, 2010 0:29
"Gad Saad"
View contact details
To Whom It May Concern,

I recently became aware of the fact that Elsevier is thinking of altering the unique format of Medical Hypotheses (or perhaps closing it down). In my opinion, it would be a mistake to alter MH's unique format. Whereas I cannot speak to the contentious issues surrounding the AIDS-related papers (as I have not read them), I strongly value a journal that provides a forum for truly innovative (and at times speculative) ideas that might not find an appropriate outlet otherwise.

I have published two papers in Medical Hypotheses, both of which have received some attention. In one of my papers, I provided a Darwinian account of how economic conditions might affect global male-to-female suicide ratios. In a second paper, I highlighted sex-specific instantiations of OCD and argued that these are rooted in sex-specific problems of evolutionary import. I suppose that these works could have been published elsewhere but under the able editorial guidance of Dr. Bruce Charlton, I was able to publish them in a highly-read prestigious outlet in a quick time period. As someone who has published in journals in the social sciences (where the review process is exceptionally long and tedious), I can truly appreciate a journal that promotes such a rapid dissemination of novel ideas.

I hope that the relevant parties at Elsevier will reconsider their decision and keep MH as is. Why alter something that has worked well for 34 years? Many thanks for attending to this matter.


Gad Saad

Dr. Gad Saad, Associate Professor

Concordia University Research Chair in Evolutionary Behavioral Sciences and Darwinian Consumption
John Molson School of Business
Concordia University
1455 de Maisonneuve Blvd. West
Montreal, QC, CANADA
H3G 1M8

Phone: (514) 848-2424 ext. 2900
Fax: (514) 848-4554





From: Mark A. Smith
Subject: Re: Medical Hypotheses is under threat
To: "Bruce Charlton" ,
Date: Thursday, 14 January, 2010, 18:53


I share your sentiments. Scientific publishing needs more than the meat and potatoes of peer-review. My own publications in Medical Hypotheses would never have seen the light of day through peer (i.e., consensus) review. Note, all have subsequently been well cited and in at least one case led to a whole new area of investigation. You are to be applauded for your work with the journal.


Mark A. Smith, Ph.D., Professor of Pathology
Wolstein Research Building, Room 5125, Department of Pathology
Case Western Reserve University
2103 Cornell Road, Cleveland, Ohio 44106
Tel: 216-368-3670; Fax: 216-368-8964;

Executive Director, American Aging Association

Editor-in-Chief, Journal of Alzheimer’s Disease


Medical Hypotheses
Sunday, 17 January, 2010 14:06
From: "Judith Harris"
To: "Chris Lloyd"
Cc: "Bruce Charlton"

Dear Chris Lloyd,

If you want to create another peer reviewed journal, go right ahead. But don't call it Medical Hypotheses.

Medical Hypotheses serves an important purpose that a peer reviewed journal cannot fill.

Leave it alone.

Sincerely, Judith Rich Harris

(Author of The Nurture Assumption and No Two Alike)