Tuesday, January 4, 2011

Jacques Benveniste - Fallen Hero of Homeopathy


Jacques Benveniste
(1935 - 2004) 
Any sane person knows that there is no shortcut to research, study and trial and error as far as the application of medicines are concerned. Homeopathy runs counter to the established scientific wisdom and the breach with science starts from its three basic tenets. Running counter to the established wisdom is no crime as many revolutionary scientific concepts such as general relativity and quantum mechanics attest to it. Many of the principles of quantum mechanics runs contrary to common sense even, but the accuracy of that theory is proved so conclusively that we know them to be true. Moreover, these ideas overturned or complemented the existing theories as is the case with general relativity which went against Newton’s theory of gravity. We still use Newton’s theory for most of the cases and use Einstein’s theory when greater precision is required or very large quantities come into the picture. But no such analogy holds good in the case of homeopathy, which has been around for more than two centuries, but still stands at the same place where it began its toddling journey. The basic ideas of homeopathy are explained in an earlier post.

In these circumstances, it is only natural that homeopaths would be greatly rejoiced at a research paper, which somehow appears to vindicate any of the unscientific concepts of homeopathy. Doubly so, if the paper appeared in reputed science journals like Nature or Science. One such incident occurred in the 1980s which was greatly trumpeted upon by its propagandists. The following incident is a very much condensed synopsis of a brilliantly written chapter in the equally brilliantly written book H2O – A Biography of Water written by Philip Ball who was also one of the editors of Nature. The subject matter of the controversial paper has long been identified as unreliable - if not fraudulent - by the academia. This episode is still hailed as a victory by some homeopathy propagandists who are either not aware of the full story, or has decided to submerge the true facts. It is good to remove doubts from the unsuspecting public.

The French medical research organization, INSERM runs an institute called Unit 200 in Paris devoted to the study of immune response and allergy. Jacques Benveniste became director of the unit in 1981 and his laboratory acquired good reputation for its work in the succeeding seven years till 1987 in which year his team discovered something peculiar while studying the response of basophils, a type of human white blood cells to antibodies. Basophils patrol the bloodstream for harmful foreign particles and are triggered by the presence of allergens. When these encounter the allergens, they release granules containing histamine in a process called degranulation. This is part of the human defence mechanism, but histamine produce effects such as hay fever, asthma, irritation and inflammation. So, anti-allergy medications contain an antihistamine ingredient that controls the level of histamine. The interaction of basophils with allergens is mediated by a protein called immunoglobulin E (IgE for short). These molecules take up position at specified locations of basophils and their interaction with allergens stimulates degranulation.

Benveniste’s team were studying the allergenic response in test tubes. Instead of employing typical allergens, they were using ‘fake allergens’ which are produced in animal bodies as a response to IgE injection into their bodies. Antibodies designed to bind to human IgE, called anti-IgE antibodies can be generated in this way. The team used commercially available anti-IgE from goats in their experiments. They noticed that sometimes degranulation was triggered by concentrations of anti-IgE that should be too low to have any effect. Intrigued, they decided to look systematically at how the degranulation response varied as the concentration is reduced to zero, with the expectation that it would gradually fall to zero. They claimed that as they diluted the anti-IgE, degranulation would first fall but then rise again – and keep falling and rising repeatedly as the dilution increased. It continued well past the point at which the number of molecules of anti-IgE in the solution reached zero. The water, it seemed, retained a memory of the molecule’s presence. Benveniste’s team did serial anti-IgE dilutions of 120 orders of magnitude and still reported the effect of anti-IgE on degranulation. And significantly, the team declared that vigorous mixing – ‘vortexing’ – of the solutions was essential for this effect to be revealed. Here, it seemed, was scientific vindication of the assertions that homeopaths have made for two hundred years!

Benveniste’s results flew in the face of well established theories in chemistry, one of them being the ‘Law of mass action’. This says in essence that the outcome of a chemical process is determined by the amounts of substances present. If two chemical reagents, A and B, come together and react to produce two others, C and D in a sealed environment and in equilibrium, such a reaction never consumes every last scrap of A and B, although it may seem like it. When it reaches the equilibrium point, all four reagents A, B, C and D are present in it and the reaction can go either way depending on which of the reagents are more in the solution. If we add A and B, more C and D will be produced, whereas if C and D are added, more A and B will result. Benveniste’s results negated this well proved fact discovered in the early 1800s by French chemist Claude Berthollet.

The paper was submitted to Nature in August 1987, but the magazine was unwilling to publish such an outlandish piece. Careful scrutiny couldn’t find any glaring errors, either. The INSERM 200 team had went to some pains to show that their results were not the consequence of poor technique or self-delusion. The pressure was mounting on the journal for the publication of the paper and the magazine carried it several months later with bold disclaimers from referees. The contributors explained the effect as “We propose that….specific information must have been transmitted during the dilution/shaking process. Water could act as a ‘template’ for the anti-IgE molecule, for example, by an infinite hydrogen-bonded network or electric and magnetic fields”. The authors cautioned that “any such hypothesis was unsubstantiated at present”. But in reality, there was no hypothesis at all, as water was indeed full of hydrogen bonds which is the result of electromagnetic forces between molecules. Also, they couldn’t explain why the response alternated between high and small values like a sine wave as the dilution steadily increased.

Several scientists around the world tried to repeat the experiments proposed. Henry Metzger and Stephen Dreskin from the National Institutes of Health in USA. In blind tests, so that one person analysed the samples in ignorance of how the other had coded the dilutions, they saw nothing but the expected sharp drop-off of basophil response with increasing dilution. Jean Clare Seagrave from the University of New Mexico School of Medicine conducted similar experiments and saw nothing in particular, while the three teams arranged by Benveniste in Israel, Canada and Italy obtained results supporting his argument! Benveniste countered the opposing teams with the argument that “our exact experimental design was not reproduced”. In science, this broad-brush argument will not wash. As arguments heated up, Nature constituted a team assist the editor John Maddox, to superrvise the experiments in person at the INSEM Lab. The team was composed of Walter Stewart, a biologist and James Randi, a professional magician! The latter was included in the team to detect any forgery or sleight of hand which was not entirely unexpected.

Benveniste’s team bristled with distrust as the mere inclusion of James Randi carried the unspoken accusation of fraud so as to insist that he be kept away from the samples when blind tests were being set up! The investigators spent a week in the laboratory, during which time they conducted or supervised many more experiments than the French team would normally have managed in that space of time. Four runs were conducted, of which Benveniste remarked the first three to be supporting his argument though they indicated that peak responses showed no sign of being either periodic or reproducible – they appeared in different places each time. Strictly speaking, the “repetitive, reproducible waves” claimed in Benveniste’s paper justified neither adjective! The fourth experiment was different. Oddly, this one was coded by the investigators! It showed very strong degranulation peaks at roughly repeating dilutions of 10,000. Unenlightened and concerned about the way the group were handling sampling errors, the investigators devised three more runs, with an elaborate coding procedure for blind testing, recording the procedure on video. The results of these ‘true’ blind tests were unambiguous. The anti-IgE at conventional dilutions caused degranulation, but at ‘high dilution’, there was no effect. The effects reported by the INSERM team was considered to be delusion.

The team tried to discredit the investigators’ competence, but the die was already cast. Following a routine evaluation of Unit 200 in 1989, Benveniste was put on a six-month probationary period during which he was expected to establish ‘the full guarantee of his peers’ and to adopt the ‘critical and reserved attitude’ expected of a scientist.The evaluation committee recommended that he stop the work on high dilutions, which they considered Benveniste had interpreted ‘out of proportion with the facts’. Thus ended the storm in the tea cup which tried to vindicate the outdated ideas of homeopathy.

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