Дмитрий К.Юрьев

23 May 2003

Glaxo Conspiracy Against Discovery of Helicobacter Pylori

Glaxo(SmithKline) earns over 30 billion dollars on anti-ulcer drugs Zantac sales while the pair of most prestigious sci. journals Nature and Science kept dead silence about the discovery of a less profitable curative treatment. It caused an approximately 10-years-long delay in introduction of new treatment resulting in millions extra deaths during that period.
This is a well known controversy (e.g. New Yorker, 20 Sept. 1993; Economist, March 5, 1994; Fortune, June 9, 1997). There was always little doubt that some sort of Glaxo conspiracy against H.Pylori discovery exists. Though its mechanism was never exposed. No attention has ever been paid to participation of Nature/Science editorial boards in this story.
Meanwhile, in February 2003 Nature and Science released an open declaration that their editors are now officially entitled to use exactly this same method of banning publication in high profile academic journals in order to bury (under pretext of biosecurity) any biomedical work "regardless of its merits"

I hope, I am not alone who feels slightly annoyed in recent years by strange sequence of paranoid media campaigns accompanying basically fruitless scientific or near-scientific projects. Nuclear winter, AIDS, ozone holes, global warming, cloning, human genome, Year 2k bug, SARS ...  Importance of these themes and quality of science behind them is varying (slightly above nothing) yet, certainly, there is something else in common among them. In particular, it's hardly possible to get rid of an impression that all these campaigns are the result of tireless efforts of some groups of skilful imagemakers and public relations experts rather than that they were just spontaneous interest of independent press to some honest scientific publication.
Well, so what is wrong with this? Perhaps, the system of converting science into world news headlines is slightly corrupted today; but whether the problem is sufficiently important to talk about? Does it make much harm if influential academic gangs are so successful presenting their achievements, findings or just fantasies in this way?
The following story of 10-years-long misfortunes accompanying, perhaps, the most important practical breakthrough in medicine of the recent 20-30 years proves that it does. The trouble is that the opposite situation may occur. It may happen that a really important discovery of which the wide public really needs to be informed may fail to reach adequate publicity. Just because another gang does not need it...

full text in pdf >>


Highly recdommended additional reading:
big article"America's Other Drug Problem" in New Republic (December 16, 2002, p.27). Excellent overview of the wide spectrum of semi-criminal business practices in modern (American) drug industry. Yet, written by two former editors-in-chief of the New England Journal of Medicine this article failed to write a single word about corruption links of drug industry and top biomedical bureaucracy. Another omission - the word "Glaxo" appears in this text only thrice - always in most innocent context (timing of authors' NEJM editorship coincided with period of H.Pylori troubles).

Two latest exposures of recent Glaxo endeavours:

  • in May 2004 Italian police ended a 2-year long investigation into marketing practices of Glaxo in Italy. It was found that Glaxo spent $300m over four years on comparaggio - bribes to doctors, chemists etc. to get them to prescribe drugs produced by company. Over 4000 doctors and 273 Glaxo employees have criminal charges. Some face up to five years in jail if tried and convicted.
    links to articles on this scandal: in Guardian>>    in Economist>>
    Glaxo maintained that its promotional campaign was both legal and proper, "In parts of Europe, these things are absolutely rife". Indeed, it's an over $7 billion busines in USA today - see overview in New Republic article cited above, section Marketing: Where the Action Is,
  • In June 2004 New York attorney-general Spitzer filed a lawsuit against Glaxo accusing company in concealing information that its antidepressant Paxil (aka Seroxat) caused suicidal behaviour among children during clinical trials. Estimated up to 10 thousand deaths were caused by this drug.
    Obviously, this story resembles the IGFarben/Prontosil controversy. It is nice that such thing has reached the court today (apparently, first precedent in world history!?). Yet the outcome looks puzzling. Actually, I don't understand what it means. Glaxo refused to express any contrition and just "settled" the suit by paying $2,5m. No investigation has been conducted again.
    links on this theme:
    Press release of Eliot Spitzer office >>

    June 2004

    Comments


    I think, it is a purely criminal story. So I've sent letters to British police, US Attorney-General and to European fraud-fighting agency OLAF. Surprisingly, I failed to get a single response.

    Nevertheless, I have got several informative comments from a number of scentists and major participants of Helicobacter Pylori story.
    At first, I even received a pretty kind note from Barry Marshall ("Maybe you are a little harsh but no doubt it will get people thinking."). Apparently, it was an ill-considered premature letter - reanimating this scandal does not look today profitable to H.Pylori industry. So, very soon Dr.Marshall expressed a more reasonable loss of interest to my work ("I have so much work on-line from emails that I have set your letter aside...").
    Significantly more interesting comment came from David Graham - major opponent of H.Pylori discovery who made at late stages of H.pylori story a very serious positive contribution promoting H.pylori discovery to final official recognition (he was the author of the first editorial in NEJM on H.Pylori in 1993 and it was him who told to senator Kennedy that there is at last sufficient data to say that ulcers is caused by H.Pylori [1] ). Naturally, his comments on my findings were clearly negative ("I think you have made a spurious correlation... Your correlation is retrospective and misses the actual flavor of the issue... I think that your hypothesis deserves to be neglected...") Yet he also appended to his letter a file with his own interpretation of Helicobacter pylori history which contained a so obvious falsification that on the aggregate his letter definitely strengthened confidence in appropriateness of my allegations against Glaxo.
    I also greatly appreciate other comments. Further, I group them by major points of my investigation that seem to be worth discussing.

    1. Whether Nature/Science did publish nothing on Helicobacter Pylori discovery?

    As a silly cowardly (and not too diligent) scientist I was slightly afraid to commit a trivial mistake declaring that there were no publications in Nature/Science on H.Pylori theme for so many years. Obviously, this risky claim might be easily disproven by pointing to a pair significant articles. Now I can sigh with relief - I have not received a single objection or even doubt concerning this statement. So, this question is closed now.

    2. Why Nature/Science published nothing on Helicobacter Pylori?

    Searching for all possible answers to this question was not primary objective of my article. My explanation of Nature/Science silence by corruption links with drug industry is plainly obvious. It is based on the common knowledge that if some "independent" institution (or govt. official, or local policeman, or anything else ) for many year shows some activity (or inactivity)  significantly favouring some commercial organization it is usually explained by corruption and NEVER by mere coincidence. I have just wild guesses what specific sort of corruption link might exist between Glaxo and Nature/Science editors. It is clearly indicated in the main text.
    Nature/Science editorial boards might try to present an alternative decent explanation for their dead silence on H.pylori discovery. I have asked Nature/Science editors for any comments on my investigation; naturally, they vouchsafed me no answer.

    Of course, it is easy to make a nice nelly explanation that Nature/Science did not publish anything on HP theme because somehow it was not exactly their theme. Yet it seems pretty hopeless. From one viewpoint HP discovery is identical to discovery of AIDS virus (to which Nature/Science printed paranoid amounts of publications) and from another viewpoint it is identical to discovery of H2 blockers on which the original article by Sir James Black was also published in Nature (236:385-90, 1972). Perhaps, here I also ought to quote some grounding documents with mission statements of Nature/Science proving that disseminating objective information on HP discovery was their basic duty, yet it seems plainly obvious and, again, I am not a too diligent scientist. Help would be greatly appreciated.

    I don't know significant anecdotal stories on rejections HP articles from Nature/Science. Though Dr.Marshall informed me that his HP article was rejected from NEJM in 1987 - it also proves the point.

    3. How great was the contribution of Nature/Science silence to H.pylory discovery misfortunes?

    The "antiterrorist initiative" of sci.journals consortium lead by Nature, Science and PNAS is an undisputable proof that the service of covert stifling of "unpalatable" scientific research is presented in their pricelist.
    The fact that this service was activated against HP discovery also does not deserve any discussion.
    The question remains whether boycott of HP discovery by Nature/Science was the primary cause of HP discovery troubles. Perhaps, there were other more important factors.

    I have not found such factors. There is only one available alternative explanation that delay in recognition of HP discovery was just a natural way of diffusion alien ideas in a traditionally conservative environment of medical profession. Apparently, this interpretation of HP story originates from David Graham and, in the absence of any definitive ideas on what actually happened with their works from Warren/Marshall it should be considered an official version of HP story.
    As I wrote in the main text, I can well believe that this "natural obscurantism" inerpretation of HP troubles may be valid only for first several years of HP story. Extending this explanation for the whole 10-year-long period of HP misfortunes requires rather awkward falsifications. The most important one may be seen in the following listing [by D.Graham, ref.2] of requirements for establishing the cause of stomach ulcers:

    Table1.
    Some requirements before the hypothesis that Helicobacter pylori could be accepted as the cause of peptic ulcer disease
    Ability of reliably culture the organism
    Reliable diagnostic tests to confirm its presence
    Reliable treatments
    Randomized clinical trials showing benefits of treating the infection
    Integration of the new knowledge into the established data base
    Dr.Graham was quite consistent in saying that reliable treatment is a requirement for establishing infectious nature of ulcers; here is what he advised to senator E.Kennedy, (obviously, publication was on "reliable treatment"):
    "The world changed with a January 1993 paper in JAMA" says Graham. "It had no new information but enough data to say that if you cure HP, you cure ulcers" [ref.1]
    This is a classical "sentence first - verdict afterwards" trick. Establishing the infectious etiology of ulcer disease and finding a reliable treatment for it are absolutely different problems! It is the most fundamental paradigm of medicine: at first the cause of the disease should be identified and then the knowledge of this cause draws more researchers and money, facilitates and accelerates further search and evalauting effective treatments. Identification of infectious etiology of stomach ulcers failed to get adequate publicity and therefore official recognition and THAT was the primary trouble in HP story.
    Of course, there were also lot of troubles with official approving the effective antibacterial treatment. Actually these are the troubles whose existence Dr.Graham tries to deny.

    In this paragraph, I should also express great thanks to Peter Hinkle and to Michael Wynne for pointing to an error in the original version of my work. I wrote that practising doctors were also underinformed on HP theme thanks to Nature/Science silence. Of course, I was wrong. Practising doctors rarely read Nature or Science, much more often they get professional information from other sources. So, the silence of these two journals on HP theme did not influence significantly the supply of information on H.Pylori to this group of people. I was misled by statements that in early 90-es only about 5% of ulcers patients get antibacterial treatment. At first glance, this number means that only slightly above 5% of doctors knew about this treatment. Surely, if 5% of doctors practically use the new therapy which is tainted by some vague discussions and which is not approved officially, of course it means that closer to 100% of them should have been informed about it.
    It is not an important error. Conclusive confirmation of antibacterial treatment required conducting long-term statistical study. And though hypothetically every practising gastroenterologist might decide for himself whether he should use antibacterial treatment (read the HP publication - and the drugs were on the market) it could be just a sort of gambling. In reality, practitioners could not influence the fate of HP discovery regardless of whether they were informed about it or not. They had to wait for an "officially" approved approaches.

    4. Helicobacter Pilory Vaccine

    This is an off-topic for the present investigation, yet, quest for HP vaccine seems to be today the most important practical problem in HP research. Than, I also have some special interest to vaccines because of my old iconoclastic works on basic theory of vaccines. So, I've sent 20 e-mails to authors of sci.publications on Helicobacter pylori vaccine asking for comments yet, alas, I have got nothing in response to speak of. Unfortunately, it supports again my old sneaking suspicions that vaccinology is governed by idiots.
    Perhaps, I may express my disappointment in a form of trivial opinion that HP vaccine research has collapsed into the same meaningless parasitic form as it happened with AIDS vaccine. Here is a short qoute from a big 6-year-old review on HP vaccine. I guess, nothing changed since that time. (Note a striking similarity to AIDS rhetoric):
    A convincing body of data now exists supporting the potential for successful immunization against H pylori. However, we are still at a preliminary stage in clinical development. The best immunogens, the best mode of presentation, the number of doses needed, optimal age at immunization, expected benefit, cost-effectiveness, and other factors involved in vaccine development require further study.
    The complex pathogenesis of this infection, including the presence of antigens on H pylori shared with the host (a mechanism for immune evasion), demands novel approaches to the development of a final vaccine formulation. [ref.3]

    References

    1. Brian O'Reilly - Why doctors aren't curing ulcers -- Fortune (June 9, 1997)
    2. Graham DY. Overview of Helicobacter pylori infection: History, epidemiology, diseases and future.  In: Helicobacter pylori infection in gastroduodenal lesions. The second decade. JM Pajares Garcia, P Correa, GI Perez Perez (Eds), Prous Science, Barcelona, 2000; pp 1-11.
    3. Thomas P. Monath et.al.- Infect Med 15(8):534-546, 1998 (http://www.medscape.com/viewarticle/417377)