The following is a letter and reply:
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Journal of Medical Virology 2017; 89:1125-1126
LETTER TO THE EDITOR
Homeopathy in disguise. Comment on Don et al.: Dose-dependent antiviral activity of released-active form of antibodies to interferon-gamma against influenza A/California/07/09(H1N1) in murine model
Evgenia V. Dueva(1,2), Alexander Y. Panchin(3)
1. Chumakov Institute of Poliomyelitis and Viral Encephalitides, Moscow, Russia
2. Department of Chemistry, Lomonosov Moscow State University, Moscow
3. Institute for Information Transmission Problems, Russian Academy of Sciences, Moscow
https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.24761(no abstract)
Excerpts:
“The actual doses of the alleged active substance of Anaferon for children (AC) administrated to the animals are not deducible from the article:”
“The authors state that «AC contained RAFof Abs to IFN-gamma is a mixture of 12, 30,and 50 centesimal dilutions of antibodies to IFN-gamma». RAF(release active form) of Abs (antibodies) is not an accepted scientific concept and the term appears only in the articles involving the commercial products of «MATERIA MEDICA HOLDING». According to Avogadro's law, 12 or more centesimal dilutions lead to a lack of any active substance in any amount of solution that a mouse can drink. It seems that AC is a disguised version of homeopathy and the authors have confused the reviewers with their vague description of AC.”
[various other criticisms of the methods and analysis deleted]
“Given the fact that there is no accepted mechanism of action for any treatment with such dilutions as in the case of AC and composition of initial AC solutions is unknown the simpler explanation for the observed antiviral effects is bias introduced by lack of proper randomization and blinding or the influence of undeclared contaminants.
“The authors state: «In this study, the dose-response effect of AC was demonstrated on mice for the first time». AC is a marketed drug in the Russian Federation. This implies that the drug was marketed without prior testing of the dose-response effect in animal studies.
“In addition, this statement contradicts itself: «The authors declare no conflict of interest. Four authors have an affiliation to the commercial funders of this research study (OOO [abbreviation for a Russian term for limited liability company] «NPF «MATERIA MEDICA HOLDING»)». «MATERIA MEDICA HOLDING» produces and markets AC, so the authors do have a conflict of interest. Even more, Oleg I. Epstein is the CEO of OOO «NPF «MATERIA MEDICA HOLDING».
“Given the severe concerns about the validity of the experimental procedures, conflict of interest, and a low prior probability that treatment so severely diluted can have any biological effect whatsoever, we recommend that the journal retracts the study «Dose-dependent antiviral activity of released-active form of antibodies to interferon-gamma against influenza A/California/07/09(H1N1) in murine model» by E. Don et al.”
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Journal of Medical Virology 2017; 89:1127-1130
LETTER TO THE EDITOR
The phenomenon of released-activity. Reply on comment on Don et al.: Dose-dependent antiviral activity of released-active form of antibodies to interferon-gamma against influenza A/California/07/09(H1N1) in murine model
Elena S. Don (1), Alexandra G. Emelyanova (1), Natalia N. Yakovleva (2), Nataliia V. Petrova (1), Marina V. Nikiforova (2), Evgeniy A. Gorbunov (2), Sergey A. Tarasov (2), Sergey G. Morozov (1), Oleg I. Epstein (1)
1. The Institute of General Pathology and Pathophysiology, Moscow, Russian Federation
2. OOO “NPF MATERIA MEDICA HOLDING”, Moscow, Russian Federation
Abstract
This text is aimed to provide the readers with detailed information about phenomenon of released-activity and reply on the specific risen questions.
https://onlinelibrary.wiley.com/doi/abs/10.1002/jmv.24759Excerpts:
“On the assumption of the letter title and the conclusion made, it follows that the only reason for concerns about our results is the fact that Drs. Dueva and Panchin designated tested product as homeopathic product and thus they considered all the results just as a bias. The product described in the article is not homeopathic.
“For 20 years, we have been focused on developing a new trend in pharmacotherapy step-by-step, namely the targeted (pharmacological) application of low doses.”
“Lack of confidence in homeopathy gives rise to mistrust in a large number of scientific articles, which have been appearing since the 1970s, on the biological and physicochemical activity of low doses identified by standard experimental methods.”
“We are neither followers nor opponents of homeopathy. However, 20 years ago we, using biological models, identified a new physical phenomenon, called ‘released-activity,’ enabling us to initiate the development of a new trend in pharmacology and a modern, scientific approach to low doses, homeopathy being a particular case of their application.
“We performed a number of paradoxical experiments with various medicinal products, for example prednisolone, haloperidol, cyclophosphane, diclofenac. Therapeutic or toxic doses of each product were co-administered to animals with a low dose of the same product. The results demonstrated that a low dose has a modifying activity, manifested as a reinforced effect of the pharmacological product and a reduction in its toxic effect.
“Newly identified modifying activity is technogenic and depends on the manufacturing method by a multiple reduction in initial substance concentration, or even trituration, rather than concentration of the initial substance .
“Therefore, the historical term ‘low doses’ does not reflect the new positive properties of the products generated by the technique. To underline the technogenic nature of the modifying activity, we proposed calling it ‘released-activity’ and the products— ‘released-active’ ones.
“The obtained experimental data enabled us to formulate the principal issue of ‘low doses’ in a new way: it is not about the way in which high dilutions retain the activity of the initial substance; rather it is about the way in which they acquire entirely new activity. Using routine pharmacological methods, we managed to detect released-activity, investigate both its molecular mechanisms, and a number of peculiarities...At present the manuscripts dedicated to explanation of the phenomenon's mechanisms are under preparation for being submitted.
“The modifying activity of released-active dilutions offers the opportunity to exert a targeted and simultaneously ‘have mercy effect on’ any target-molecules in an organism.
“We have investigated various fields of application for released-active products, for example, we have clinically and experimentally demonstrated that they may be used for detoxifying or reinforcing the principal effect of pharmacological products. We had concluded that high dilutions of antibodies have the highest therapeutic potential.”
“Thus, investigations of released-active antibodies to interferon-gamma using nuclear magnetic resonance spectroscopy demonstrated their modifying effect on the conformational characteristics of the interferon-gamma molecule causing a shift in the equilibrium between the monomer and dimer forms of this cytokine (transformation from inactive into active form of the protein).”
“The pathogenetic application of released-active products does not need any special conditions. The efficacy and safety of our products under development are verified by routine non-clinical methods and clinical trials, predominantly double blind, placebo-controlled ones.”
“Released-active forms enabled the use of antibodies to treat of infectious and somatic diseases and develop a group of original drugs, which were awarded with the Russian Federation Government Prize in 2005 and 2006. To date, our innovative products have been authorized in Russia and abroad and have been used by various medical specialists.
“Since 2010, more than 30 clinical trials have been carried out in 328 sites involving 6256 subjects.”
“We have been in cooperation with scientific centers in Russia and 20 countries worldwide, including France, the United Kingdom, Belgium, Germany, the Netherlands, Norway, and the USA.
“More than 100 PhD theses have been defended in our field, more than 75 monographs and more than 1000 scientific articles have been published...”
“We believe that the body of experimental and clinical data obtained in dozens of countries shows that the detected activity of high dilutions is an objective reality and not the consequence of operator's error. However, sometimes we face opinions claiming that the results of our studies might be erroneous. For example, since the United Kingdom Intellectual Property Office (UKIPO) does not normally issue patents for homeopathic products, it had a preconceived opinion of our results. Therefore, we had to file an appeal in the High Court of Justice of England and Wales the ruling of which rendered such an approach as unjust and obliged the UKIPO to reconsider its negative decision.
“The discovery of the released-active phenomenon brings ‘low doses’ from alternative medicine to the field of natural sciences. The modifying effect of high dilutions (unlike the individual hyperergic reactions used in homeopathy) is reproducible and may be investigated and applied in various fields of science and technology.”
“Our long-term efforts have verified that released-active dilutions may generate pharmacological products with generally accepted body of evidence and scientific (pathogenetic) approaches.”
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Comment: as I was getting ready to post this item, I was also reading a new post by David Gorski on Science-Based Medicine:
https://sciencebasedmedicine.org/plos-one-peer-review-and-a-crappy-acupuncture-study/Included is the following section:
“...as James Coyne has noted, it took PLOS ONE a long time to retract a more obviously dubious study...Here’s the retraction notice:
“‘Following publication of this article [1], concerns were raised about the scientific validity of the study as well as a potential competing interest that was not declared. The PLOS ONE Editors discussed the concerns with the authors and consulted external experts. In light of our editorial assessment and advice received in the expert consultations, we are retracting this article due to concerns about the scientific validity of the research question, study design, and conclusions.
“‘Specifically, we are concerned about the overall design of the study, which aims to detect effects of a reagent diluted to such a degree that the solution is not expected to contain biochemically relevant levels of antibody. The consulted experts also raised concerns about the validity and rigor of the immunoassay system used in the study. The enzyme-linked immunosorbent assay (ELISA) used was adjusted to give barely detectable signals, which renders the assay particularly susceptible to interference. In light of these issues, we consider that the article does not present sufficient or reliable evidence to support the conclusions.’
“Stealth homeopathy paper indeed. I note that this paper was first published in 2014. PLOS ONE also notes undisclosed conflicts of interest.”
The link to the retraction is:
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0197086and the paper is another one by Oleg Epstein and coworkers on “release-active” forms of antibodies.
