" High - dilution " experiments a delusion

THE remarkable claims made in Nature (333,816; 1988) by Dr Jacques Benveniste and his associates are based chiefly on an extensive series of experiments which are statistically ill-controlled, from which no substantial effort has been made to exclude systematic error, including observer bias, and whose interpretation has been clouded by the exclusion of measurements in conflict with the claim that anti-IgE at "high dilution will degranulate basophils. The phenomenon described is not reproducible in the ordinary meaning of that word. We conclude that there is no substantial basis for the claim that anti-IgE at high dilution (by factors as great as 10) retains its biological effectiveness, and that the hypothesis that water can be imprinted with the memory of past solutes is as unnecessary as it is fanciful. We use the term "high dilution" reluctantly; these solutions contain no molecules of anti-IgE, and so are not solutions in the ordinarv sense. "Solute-free solution" would similarly be illogical. Our conclusion is based on a week-long visit to Dr Benvenistes laboratory, the INSERM unit for immunopharmacology and allergy (otherwise INSERM 200) at Clamart, in the western suburbs of Paris, during the week beginning 4 July. Among other things, we were dismayed to learn that the salaries of two of Dr Benveniste's coauthors of the published article are paid for under a contract between INSERM 200 and the French company Boiron et Cie., a supplier of pharmaceuticals and homoeopathic medicines, as were our hotel bills. Benveniste's results are being widely interpreted as support for homoeopathic medicine. In the light of our investigation, we believe that such use amounts to misuse. Our visit and investigation were preconditions for the publication of the original article. We acknowledge that we are an oddly constituted group. One of us (J.R.) is a professional magician (and also a MacArthur Foundation fellow) whose presence was originally thought desirable in case the remarkable results reported had been produced by trickery. Another of us (W.W.S.) has been chiefly concerned, during the past decade, in studies of errors and inconsistencies in the scientific literature and with the subject of misconduct in science. The third (J.M.) is a journalist with a background in theoretical physics. None of us has first-hand experience in the field of work at INSERM 200. We acknowledge that we might well have found ourselves unable to get to grips 'with the work of the laboratory. But, on the basis of our experience, we are confident that the design of the experiments reported by INSERM 200 is inadequate as a basis for the claims made last month and that the defects we shall catalogue are a sufficient explanation of the remarkable results then reported. We believe that experimental data have been uncritically assessed and their imperfections inadequately reported. We believe that the laboratory has fostered and then cherished a delusion about the interpretation of its data. We are grateful to Dr Jacques Benveniste for his openness in discussing most of the questions we raised with him. He allowed us to borrow and to photocopy the relevant laboratory notebooks, which were invaluable for our investigation. We have every reason to believe that Dr Benveniste was (and, perhaps, still is) convinced of the reality of the phenomena reported in his article. We are also in the debt of several of Dr Benveniste's colleagues, especially to Dr Elisabeth Davenas. On her fell most of the burden of demonstrating the standard dilution experiments and of repeating them in a blinded protocol under our scrutiny. We know that our report will be a disappointment to the laboratory. We are sorry. What follows is a narrative account of our visit and a summary of our conclusions. Our investigations concentrated exclusively on the experimental system on which the publication was based. During our week in Paris, we resisted several proffered opportunities to examine other systems in which high dilution is claimed