Positive Health Online

A study recently published in the journal Inflammation Research may mark the beginning of a resolution to the so-called 'Benveniste affair'. The study in question was a multi-centre experiment on the inhibition of degranulation human basophils by ultra-molecular dilutions of histamine.[1] In order to understand the background and significance of this work, we need to go back eleven years.

A series of experiments reported by the research group lead by Dr Jacques Benveniste in Nature in June 1988 caused euphoria in the homeopathic world.[2] Certainly, the implications were amazing, particularly to those unfamiliar with homeopathy. In Benveniste's own words, 'it was like shaking your car keys in the Seine at Paris and then discovering that water taken from the mouth of the river would start your car!' But euphoria soon gave way to dismay and disarray with the publication of a report by a team nominated by the editor of Nature, which described the work as a 'delusion' and 'pseudo-science'. Benveniste responded indignantly, accusing the inspection team of witch hunting and McCarthyism.[3],[4]

The experimental method concerned was the Human Basophil Degranulation Test (HBDT). Basophils are leucocytes which play an important role in the anaphylactic reaction. Their cytoplasm contains granules containing histamine and other immune mediators which, when released, produce an allergic reaction. Basophils can be provoked to degranulate by various stimuli. This can be observed in vitro and is the basis of the HBDT.

Various stimuli provoke basophil degranulation, for instance the basophils of hayfever sufferers degranulate when mixed with pollen extract in vitro. This is a specific allergen – the basophils of non-sensitive individuals do not react. But there are also non-specific stimuli which provoke degranulation of all basophils, sensitised or not. These include the antiserum anti-IgE. IgE is an antibody found on the outside of basophils which recognises and binds to allergens. It is this binding which triggers degranulation. Anti-IgE is an IgG antiserum produced by inoculating goats with human IgE; it binds to IgE on the basophil surface triggering degranulation. Benveniste's group claimed that degranulation can be triggered by anti-IgE at dilutions far into the ultramolecular range – up to 10-120. However, these results proved irreproducible in the hands of two independent groups.[5],[6]

Irreproducibility

Some of Benveniste's key collaborators have tacitly conceded that these results are indeed irreproducible, while insisting that related experiments do give valid and reproducible results. Others contend that he is a victim of scientific censorship.[7] Meanwhile, Benveniste himself has moved on and is now interested mainly in what he calls Digital Biology: the recording and transmitting of specific biological signals. He claims that he can record specific biological signals using electromagnetic coils and amplifier, then play the signal back via a computer sound card to sensitised biosystems, mimicking the effect of the original molecule. He has established a company called Digibio to promote this research (website: www.digibio.com).

But the 'Benveniste Affair' cast a long shadow over in vitro research in homeopathy; not only was the scientific scandal damaging, but the prospect of an in vitro method which could be reproduced in any suitably equipped laboratory was raised, only to be snatched away. The recent publication may mark the end of this unhappy chapter. The researchers include some of Benveniste's former key collaborators: Philippe Belon, Director of Research of the homeopathic pharmaceutical company, Boiron (Lyon, France) and Jean Sainte-Laudy of the CERBA Laboratory (near Paris, France); an author of one of the negative attempted repetitions, Fred Wiegant (University of Utrecht, Netherlands); and other workers with no previous involvement, Madeleine Ennis (Queen's University of Belfast, UK), PF Mannaioni (University of Florence, Italy), Marcel Roberfroid and Jean Cumps of the Catholic University of Louvain, Belgium.

Inhibition of Degranulation

As in the Benveniste experiments, the experimental method was the HBDT. But instead of degranulation triggered by high dilutions of anti-IgE, inhibition of degranulation by high dilutions of histamine was measured. Histamine in substantial concentrations is known to inhibit basophil degranulation, a negative feedback effect. In these experiments, degranulation was provoked with substantial doses of IgE, a concentration of 0.04 µg/ml was found to be best. The test treatments were 15, 16, 17, 18 and 19 centesimal dilutions of histamine hydrochloride in distilled water, prepared with vortexing. Comparison was made, blind, with distilled water control. The experiments were conducted in parallel at 4 independent laboratories. Coordination, coding, randomisation and statistical analysis were done by the Belgian group. Participants received preliminary training in the method and all reagents came from the same source.

The pooled results from the 4 laboratories yielded a total of 772 valid data points with anti-IgE 0.04 µg/ml. Mean degranulation with control was 48.8%, with highly diluted histamine 41.8%, P < 0.0001. Results from the individual laboratories were similar: 3 of the 4 laboratories' results taken alone were statistically significant, although those from the lab with the largest number of observations were not (n = 312, P = 0.065).

The presentation of this paper was low-key, perhaps not surprisingly in view of the preceding controversy, and Benveniste's Nature paper was not even cited. The authors comment that they are developing this work further, using an automated method (flow cytometry). Clearly more work is needed, but it seems that the Benveniste affair may yet have a happy ending.

Certainly congratulations are due to the researchers who persisted in this work despite discouraging circumstances.

References

1 Belon P, Cumps J, Mannajoni PF, Ste-Laudy J, Roberfroid M, Wiegant FAC. Inhibition of human basophil degranulation by successive histamine dilutions: results of a European multi-centre trial. Inflamm res. 48 supplement 1: S17-18. 1999.
2 Davenas E, Beauvais F, Amara J et al. Human basophil degranulation triggered by very dilute antiserum against IgE. Nature. 333: 816-818. 1988.
3 'High-dilution' experiments a delusion. Nature. 334: 287-290. 1988.
4 Benveniste J. Reply. Nature. 334: 291. 1988.
5 Ovelgonne JH, Bol AWJM, Hop WCJ, van Wijk RL. Mechanical agitation of very dilute antiserum against IgE has no effect on basophil staining properties. Experientia. 48: 504-508. 1992.
6 Hirst SJ, Hayes MA, Burridge J, Pearce FL, Foreman JC. Human basophil degranulation is not triggered by very dilute antiserum against IgE. Nature. 366: 525-7. 1993.
7 Schiff M. The Memory of Water. London. Thorsons. 1995.

This article is reprinted with permission. It was first published in The British Homeopathic Journal, Volume 88, Number 4, October 1999. To subscribe contact Stockton Press, Houndmills, Basingstoke, Hampshire, RG21 6XS. Tel: 01256 329242. Information on the Journal is available on the publisher's website at www.stockton-press.co.uk