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Benveniste affair

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Jacques Benveniste (March 12, 1935–October 3, 2004) was a French immunologist. In 1979 he published a well-known paper on the structure of platelet-activating factor and its relationship with histamine. He was head of INSERM's Unit 200, directed at immunology, allergy and inflammation.

Benveniste was at the center of a major international controversy in 1988, when he published a paper in the prestigious scientific journal Nature describing the action of very high dilutions of anti-IgE antibody on the degranulation of human basophils, findings which seemed to support the concept of homeopathy. Biologists were puzzled by Benveniste's results, as only molecules of water, and no molecules of the original antibody remained in these high dilutions. Benveniste concluded that the configuration of molecules in water was biologically active; a journalist coined the term water memory for this hypothesis. He also asserted that this "memory" could be digitized, transmitted, and reinserted into another sample of water, which would then contain the same active qualities as the first sample.

As a condition for publication, Nature asked for the results to be replicated by independent laboratories. After the article was published, a follow-up investigation by a team including Nature editor John Maddox and well-known skeptic James Randi, with the cooperation of Benveniste's own team, failed to replicate the original results. Subsequent investigations have not supported Benveniste's findings. His reputation was damaged, but he refused to retract his controversial article. He began to fund his research himself as his external sources of funding were withdrawn. In 1997, he founded the company DigiBio to "develop and commercialise applications of Digital Biology."

Benveniste died in Paris at the age of 69 after heart surgery. He was twice married and had five children.

Nature publication and investigation

Unusual conditions

Nature agreed to publish Benveniste's article in June 1988 with two conditions: first, that, contrary to standard scientific practice, Benveniste obtain prior confirmation of his results from other laboratories; second, that a team selected by Nature be allowed to investigate his laboratory following publication. Benveniste accepted these conditions; the results were replicated by four laboratories, in Milan, Italy; in Toronto, Canada; in Tel-Aviv, Israel and in Marseille, France.

Unusual disclaimer

Following replication, the article was then published in Nature, which printed an editorial titled "When to believe the unbelievable" in the same issue of the journal and attached the following disclaimer to the article:  :"Editorial reservation: Readers of this article may share the incredulity of the many referees. . . There is no physical basis for such an activity. . . Nature has therefore arranged for independent investigators to observe repetitions of the experiments." The last time such a disclaimer had been added was in 1974 on an article on Uri Geller.

A critical investigation

A week after publication of the article, Nature sent a team of three investigators to Benveniste's lab to attempt to replicate his results under controlled conditions. The team consisted of Nature editor and physicist Sir John Maddox, American scientific fraud investigator and chemist Walter Stewart, and skeptic and former magician James Randi.

The team pored over the laboratory’s records and oversaw seven attempts to replicate Benveniste’s study. Three of the first four attempts turned out somewhat favorable to Benveniste; however the Nature team was not satisfied with the rigor of the methodology. Benveniste invited them to design a double blind procedure, which they did, and conducted three more attempts. Before fully revealing the results, the team asked if there were any complaints about the procedure, but none were brought up. These stricter attempts turned out negative for Benveniste. In response to Benveniste’s refusal to withdraw his claims, the team published in the July 1988 edition of Nature[citation needed] the following critiques of Benveniste’s original study:

  1. Benveniste’s experiments were "statistically ill-controlled", and the lab displayed unfamiliarity with the concept of sampling error. The method of taking control values was not reliable, and "no substantial effort has been made to exclude systematic error, including observer bias"
  2. "interpretation has been clouded by the exclusion of measurements in conflict with the claim". In particular, blood that failed to degranulate was "recorded but not included in analyses prepared for publication". In addition, the experiment sometimes completely failed to work for "periods of several months".
  3. There was insufficient "avoidance of contamination", and, to a large extent, "the source of blood for the experiments is not controlled".
  4. The study had not disclosed 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."
  5. "The phenomenon described is not reproducible". "We believe that experimental data have been uncritically assessed and their imperfections inadequately reported."

Benveniste fights back

In the same issue of the journal Nature, and in subsequent commentary, Benveniste derided the Nature team’s "mockery of scientific inquiry" and warned other scientists not to permit such investigations into their own labs.[citation needed] He claimed that such "Salem witchhunts or McCarthy-like prosecutions will kill science." Some of his criticisms included:

  1. "Lip service is paid to our honesty; yet accusation of cheating was rampant". For example, the Nature team implied that the lab’s partial funding from the homeopathy industry was cause for concern, even though industry funding - both homeopathic and non-homeopathic - of research is commonplace.
  2. The team of non-biologists displayed "amateurism", failed to "get to grips with our biological system", created an atmosphere of "constant suspicion", and their member James Randi played tricks and pulled stunts such as taping information to the ceiling to prevent tampering.
  3. The team arrived without a prior plan, and based on one week of work "would blot out five years of our work and that of five other laboratories".
  4. The blinded attempts likely failed due to "erratic controls", the excessive work-load, and the team’s experimental design.
  5. Benveniste totally rejected the team's allegations of unfamiliarity with sampling error, and of the unreliability of his control values.[1]

Attempts to replicate Benveniste's results

Academy of Sciences

In 1991, Benveniste found the French Academy of Sciences willing to publish his latest results, obtained under the supervision of a statistician, in its weekly Proceedings. Eric Fottorino writing in Le Monde relates how the remorseful Academy of Science noticed that an earlier edition contained a study critical of the memory of water. Seizing on this opportunity, the Academy ordered the printing to stop and the already printed copies destroyed, so that it could print a revised edition, in which Benveniste's article was labeled a mere "right of reply" - downgraded from the status of an article.

Although the new findings fell substantially short of confirming the patterns previously claimed by Benveniste, writer Yves Lignon quotes study co-author and statistician Alfred Spira, who said that "the transmission of information persisted at high dilution", and acknowledged that a "weakness in the experimental procedure was possible".

Ovelgonne et al

A group of Dutch researchers reported their failure to duplicate the results in Experientia in 1992:

"In fact, in our hands no effect of extreme dilutions was shown at all. We conclude that the effect of extreme dilutions of anti-IgE, reported by Davenas et al., needs further clarification and that in this process the reproducibility of results between experimenters should be carefully determined."

Hirst et al

A group of English researchers reported another failure to duplicate the results in Nature in 1993:

"Following as closely as possible the methods of the original study, we can find no evidence for any periodic or polynomial change of degranulation as a function of anti-IgE dilution."

However, Benveniste in a 1994 letter to Nature argued that the study neglected to faithfully follow his methods. The study has also been criticized on the grounds that its results were more favourable to Benveniste's claims than the study authors acknowledged in their conclusion.[2][3]

Josephson and the APS

Benveniste gained the public support of Brian Josephson, a Nobel physicist with a reputation for openness to paranormal claims. Time magazine reported in 1999 that, in response to skepticism from physicist Robert Park, Josephson had challenged the American Physical Society (APS) to oversee a replication by Benveniste, using "a randomized double-blind test", of his claimed ability to transfer the characteristics of homeopathically diluted water over the Internet. The APS accepted and offered to cover the costs of the test, and Benveniste wrote "fine by us" in his DigiBio NewsLetter in response to Randi’s offer to throw in the $1 million challenge prize-money if the test succeeded. However, Randi in his Commentary notes that Benveniste and Josephson did not follow up on their challenge.

Ennis et al

An article published in Inflammation Research in 2004 brought new media attention to the issue with this claim:

"it has been shown that high dilutions of histamine may indeed exert an effect on basophil activity. . . We are however unable to explain our findings and are reporting them to encourage others to investigate this phenomenon."[4]

Following up on a study they had published in 1999 in the same journal, the researchers concluded that an effect did exist. Some of the researchers had not been involved in homeopathic research before, while others had, such as former Benveniste collaborator Philippe Belon, Research Director at the homeopathic company Boiron. It was Madeleine Ennis who received the most attention in the media. Ennis led the activities at the British lab, with other labs in Europe, running a variation of Benveniste's water memory experiments. Ennis states that she began the research as a skeptic, but concluded that the "results compel me to suspend my disbelief and start searching for rational explanations for our findings."[5]

BBC Horizon

In 2002 BBC Horizon broadcast its failed attempt to win James Randi's $1 million prize to prove that a highly diluted substance could still have an effect. Prominent spokespersons on both sides of the debate were interviewed, including Benveniste. See water memory.

Digital Biology

Benveniste gained the public support[6] of Brian Josephson, a Nobel Prize-winning physicist with a reputation for openness to paranormal claims. Increasingly odd experiments continued, culminating in a 1997 paper claiming a water memory effect could be transmitted over phone lines.[7] This culminated in two additional papers in 1999[8] and another on remote-transmission in 2000.[9]

Intrigued by Benveniste’s claims that biological interactions could be digitized, the US Defence Advanced Research Projects Agency (DARPA) asked Dr. Wayne Jonas, homeopath and then director of the US National Center for Complementary and Alternative Medicine, to organize an attempt at independently replicating the claimed results. An independent test of the 2000 remote-transmission experiment was carried out in the USA by a team funded by the US Department of Defense. Using the same experimental devices and setup as the Benveniste team, they failed to find any effect when running the experiment. Several positive results were noted, but only when a particular one of Benveniste's researchers was running the equipment. Benveniste admitted to having noticed this himself, and offered a variety of reasons to explain away what appeared to be another example of experimenter effect. The experiment is also notable for the way it attempted to avoid the confrontational nature of the earlier Maddox test.[10] The study implemented “A social and communication management process that was capable of dealing with conflicting interpersonal dynamics among vested parties in the research effort.” One of Benveniste’s machines was used, and, in the design and pilot project phase in 2001, Benveniste and other members of his DigiBio lab participated as consultants. Interviews at the time indicated study participants were satisfied with the way the study was being conducted. In the end, the authors reported in the FASEB Journal in 2006 that "Our team found no replicable effects from digital signals".

INSERM

The July 1989 edition of Nature reported that INSERM placed Benveniste on probation following a routine evaluation of his lab. Although INSERM found that his laboratory activities overall were exemplary, it expressed severe discomfort with his high dilution studies, and criticized him for "an insufficiently critical analysis of the results he reported, the cavalier character of the interpretations he made of them, and the abusive use of his scientific authority vis-à-vis his informing of the public".[11]

Benveniste and homeopathy

Nearly all legitimate scientists believe that credible evidence to support claims that homeopathic remedies actually work does not exist, nor that a plausible mechanism exists to explain how homeopathy could work.[12] Indeed, skeptics often dismiss homeopathy out of hand, citing the fact that biological reactions require the presence of chemicals, whereas homeopathic remedies are so diluted that they are equivalent to pure water. Homeopaths respond that this is a straw man argument, since they have long acknowledged the absence of chemicals in their products. Homeopaths have instead based their claims on some other yet-to-be-discovered mechanism.

Benveniste’s 1988 article attracted attention in large part because it hinted at a potential mechanism that could be used by proponents of homeopathy to explain how homeopathy might work. This is the idea that water may somehow retain a memory of a substance that it no longer contains.

Conventionally, pure water is pure water, regardless of whether it once contained a substance in the past. Benveniste flouted this convention by claiming that water that had once contained antibodies but had had them removed could affect a basophil just as if the water still contained antibodies.

Miscellaneous

Benveniste has been awarded two Ig Nobel Prizes in Chemistry. They are a parody of the Nobel Prizes. The first in 1991 describes Jacques Benveniste as a "prolific proselytizer and dedicated correspondent of Nature, for his persistent belief that water, H2O, is an intelligent liquid, and for demonstrating to his satisfaction that water is able to remember events long after all trace of those events has vanished." The second in 1998 cites "his homeopathic discovery that not only does water have memory, but that the information can be transmitted over telephone lines and the Internet."[13]

Bibliography

See also

Notes

  1. ^ Maddox, John (28 July 1988). "'High-dilution' experiments a delusion" (PDF). Nature. 334: 287–290. doi:10.1038/334287a0. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  2. ^ Experiments past and futureSome remarks on the Memory of Water Controversy
  3. ^ ÉTUDE CRITIQUE ET PROJETS D'AVENIRDr B. POITEVIN
  4. ^ Cumps, J. (Received: 11 December 2002 Accepted: 12 November 2003 Published online: 21 April 2004). "Histamine dilutions modulate basophil activation". Inflammation Research. Volume 53, Number 5 / April, 2004. Birkhäuser Basel: 181–188. doi:10.1007/s00011-003-1242-0. {{cite journal}}: |volume= has extra text (help); Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  5. ^ Milgrom, Lionel (Thursday March 15, 2001), "Thanks for the memory", Guardian Unlimited {{citation}}: Check date values in: |date= (help)CS1 maint: date and year (link)
  6. ^ molecule memories: Letter to New Scientist
  7. ^ J. Benveniste (February 21-26, 1997). "Transatlantic Transfer of Digitized Antigen Signal by Telephone Link". Journal of Allergy and Clinical Immunology. {{cite journal}}: Check date values in: |date= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)
  8. ^ J. Benveniste. "The molecular signal is not functional in the absence of "informed water"". Medical Hypotheses. 54 (A163 (abstr.)). {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  9. ^ J. Benveniste. "Activation of human neutrophils by electronically transmitted phorbol-myristate acetate". FASEB Journal. 13 (1): 33–39. Retrieved 2007-06-05. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help)
  10. ^ Jonas, Wayne B. (2006). "Can specific biological signals be digitized?". FASEB Journal. 20 (1): 23–28. doi:10.1096/fj.05-3815hyp. PMID 16394263. Retrieved 2007-06-05. {{cite journal}}: Unknown parameter |coauthors= ignored (|author= suggested) (help); Unknown parameter |month= ignored (help)CS1 maint: unflagged free DOI (link) — this paper includes an excellent references list.
  11. ^ Coles, Peter (1989). "Benveniste under review". Nature. 340: 89. doi:10.1038/340089b0.
  12. ^ Report 12 of the Council on Scientific Affairs (A-97), American Medical Association. Downloaded 10 April 2006
  13. ^ Benveniste, J. (1997). "Transatlantic Transfer of Digitized Antigen Signal by Telephone Link". Journal of Allergy and Clinical Immunology - Program and abstracts of papers to be presented during scientific sessions AAAAI/AAI.CIS Joint Meeting February 21-26, 1997. Poster. {{cite journal}}: External link in |volume= (help); Unknown parameter |coauthors= ignored (|author= suggested) (help)


References

  • BBC Horizon (2002) Homeopathy: The Test, first broadcast November 26, 2002. Summary and transcript. Rebroadcast on ABC Catalyst in 2003.[2]
  • Beauvais, Francis (2007) L'Âme des Molécules - Une histoire de la mémoire de l'eau, Coll. Mille-Mondes[3], Ed. Lulu.com, Text in French, ISBN 978-1-4116-6875-1.
  • Belon, P., J. Cumps, M. Ennis, P.F. Mannaioni, M. Roberfroid, J. Sainte-Laudy, & F.A. Wiegant (1999) "Inhibition of human basophil degranulation by successive histamine dilutions: results of a European multi-centre trial", Inflammation Research, 48(13):17-8. Reference:[4]
  • Burridge, Jim (1992) "A Repeat of the 'Benveniste' Experiment: Statistical Analysis", Research Report 100, Department of Statistical Science, University College London, England. (early version of Hirst et al)
  • Chaplin, Martin (2000-2006) “Water Structure and Behavior London South Bank University
  • Davenas, E., F. Beauvais, J. Arnara, M. Oberbaum, B. Robinzon, A. Miadonna, A. Tedeschi, B. Pomeranz, P. Fortner, P. Belon, J. Sainte-Laudy, B. Poitevin & J. Benveniste (1988) "Human basophil degranulation triggered by very dilute antiserum against IgE", Nature, 333(6176):816-18. Full text (source 1)(2)(3)(4)
  • Fisher, Peter (1999) "The End of the Benveniste Affair?", British Homeopathic Journal, 88(4). Full text
  • Fottorino, Eric (1997) Le Monde, January 21, 22 & 23, 1997.
  • Hammer, M. & W. Jonas (2004) “Managing Social Conflict in CAM Research: The Case of Antineoplastons, ‘’Integr. Cancer Therapy’’, 3(1)59-65.Full text
  • Hirst, S.J., N.A. Hayes, J. Burridge, F.L. Pearce & J.C. Foreman (1993) "Human basophil degranulation is not triggered by very dilute antiserum against human IgE", Nature, 366(6455):527. Abstract
  • Ives, John (2002) "Evaluating Unusual Claims and Devices Using a Team Approach: A Case Study," Subtle Energies & Energy Medicine, 13(1):39-59, based on Dr. Ives Keynote Address made at the Twelfth Annual ISSSEEM Conference The Co-Creation Process in Energy Medicine: A Synergy of the Sciences and the Healing Arts, June 14-19, 2002. Abstract, Full text
  • Jaroff, Leon (1999) "Homeopathic E-Mail: Can the 'memory' of molecules be transmitted via the Internet?", Time, May 17. Full text
  • Jonas, W. B., J. A. Ives, F. Rollwagen, D. W. Denman, K. Hintz, M. Hammer, C, Crawford & K. Henry (2006) "Can Specific Biological Signals be Digitized?", The Federation of American Societies for Experimental Biology (FASEB) Journal, 20(1):23-28.Full text
  • Jonas, W. B. & J. Jacobs (1996) Healing with Homeopathy, Warner.
  • Lignon, Yves (1999) "L’Homéopathie et la mémoire de l’eau", Les dossiers scientifiques de l'étrange, Chapter 21, Michel Lafon Publishing. ISBN 2-84098-482-2. Full text in French
  • Maddox, John (1988) "Waves caused by extreme dilution", News and views, Nature, 335(6193):760-3.
  • Maddox, John (1988) "When to believe the unbelievable", Nature, 333:787.
  • Milgrom, Lionel (1999) "The memory of molecules", The Independent, March 19. Full text
  • Ovelgonne, J.H., A.W. Bol, W.C. Hop & R. van Wijk (1992) "Mechanical agitation of very dilute antiserum against IgE has no effect on basophil straining properties", Experientia, 48(5):504-8. Abstract
  • Park, Bob (1999) "The Challenge: Homeopathy Via the Internet", What’s New, May 14. Full text (source 1)(2)
  • Park, Bob (1997) "Alternative Medicine and the Laws of Physics", Skeptical Inquirer, 9/1/1997.Full text
  • Randi, James. Commentary. January 26, 2001 "a Nobel Laureate reneges"[5]. September 5, 2003 "Benveniste and Josephson on Abandoning Science"[6].
  • Targ, Russel & Harold Puthoff (1974) "Information transfer under conditions of sensory shielding", Nature, 251:602-7. Abstract
  • Thomas, Y., M. Schiff, L. Belkadi, P. Jurgens, L. Kahhak & J. Benveniste (2000) "Activation of Human Eurtrophils by Electronically Transmitted Phorbol-Myristate Acetate", Medical Hypotheses, 54(1),33-39.Abstract
  • Schiff, Michel. The Memory of Water: Homoeopathy and the Battle of Ideas in the New Science (Thorsons, 1995)
  • Vithoulkas, George (2003) The controversy with the BBC program Horizon. Full text
  • Walker, Martin (1993) "Dr Jacques Benveniste: The Case of the Missing Energy", Chapter in Dirty Medicine, Slingshot Publications, London. Chapter full text (source 1) (2)

External links

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