The Benveniste affair French: [bɛnvənist]; is a major international controversy in 1988, when Jacques Benveniste 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. As a condition for publication, Nature asked for the results to be replicated by independent laboratories. The controversial paper published in Nature was eventually co-authored by four laboratories worldwide, in Canada, Italy, Israel, and France. After the article was published, a follow-up investigation was set up by a team including physicist and Nature editor John Maddox, illusionist and well-known skeptic James Randi, as well as fraud expert Walter Stewart who had recently raised suspicion of the work of Nobel Laureate David Baltimore. With the cooperation of Benveniste's own team, the group failed to replicate the original results, and subsequent investigations did not support Benveniste's findings either. Benveniste refused to retract his controversial article, and he explained (notably in letters to Nature) that the protocol used in these investigations was not identical to his own. However, his reputation was damaged, so he began to fund his research himself as his external sources of funding were withdrawn.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."
Jacques Benveniste (12 March 1935 – 3 October 2004) was a French immunologist, born in Paris. 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 died in 2004 in Paris following heart surgery.
Nature publication and investigationEdit
Benveniste 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. 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. Much later, in the nineties, Benveniste 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.
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 to an article on Uri Geller.
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 W. 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. The samples were randomized, and Randi wrapped the codes which identified the samples in tinfoil before fixing it on to the ceiling with adhesive tape. 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. Since multiple readings of the samples were closer than statistically expected for the non-double blind tests, the team argued that unintentional bias was the culprit.
On 3 September 1988 Channel 4 broadcast an After Dark television discussion featuring Benveniste, James Randi and Walter Stewart among others (including Jonathan Miller), reviewed the following week by Sean French in the New Statesman.
Attempts to replicate Benveniste's resultsEdit
Academy of SciencesEdit
In 1991, Benveniste found the French Academy of Sciences willing to publish his latest results, obtained under the supervision of Alfred Spira, 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. The study is a replication of early high dilution experiments, in collaboration with Inserm U292.
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.Edit
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.Edit
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.
Josephson and the APSEdit
After the Nature controversy, Benveniste gained the public support of Brian Josephson, a Nobel laureate physicist with a reputation for openness to paranormal claims. Experiments continued along the same basic lines, culminating with a 1997 paper claiming the effect could be transmitted over phone lines. This was followed by two additional papers in 1999 and another, in the controversial non-peer reviewed Medical Hypotheses, on remote-transmission in 2000 by which time it was claimed that it could also be sent over the Internet.
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. This challenge was to be "a randomized double-blind test", of his claimed ability to transfer the characteristics of homeopathically altered solutions over the Internet:
- "[Benveniste's] latest theory, and the cause of the current flap, is that the 'memory' of water in a homeopathic solution has an electromagnetic 'signature.' This signature, he says, can be captured by a copper coil, digitized and transmitted by wire--or, for extra flourish, over the Internet--to a container of ordinary water, converting it to a homeopathic solution."
The APS accepted the challenge and offered to cover the costs of the test. When he heard of this, Randi offered to throw in the long-standing $1 million prize for any positive demonstration of the paranormal, to which Benveniste replied: "Fine to us." in his DigiBio NewsLetter. Randi later noted that Benveniste and Josephson did not follow up on their challenge, mocking their silence on the topic as if they were missing persons.
Ennis et al.Edit
An article published in Inflammation Research in 2004 brought new media attention to the issue with this claim:
- "In 3 different types of experiment, it has been shown that high dilutions of histamine may indeed exert an effect on basophil activity. This activity observed by staining basophils with alcian blue was confirmed by flow cytometry. Inhibition by histamine was reversed by anti-H2 and was not observed with histidine these results being in favour of the specificity of this effect. We are however unable to explain our findings and are reporting them to encourage others to investigate this phenomenon."
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."
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.
A report was published in 2005 on the prestigious journal of Statistics Significance by the statesman John Martin Bland, professor at the University of York.
With the support of Brian Josephson, the experiments continued, culminating in a 1997 paper claiming a water memory effect could be transmitted over phone lines. This culminated in two additional papers in 1999 and another on remote-transmission in 2000.
Intrigued by Benveniste's claims that biological interactions could be digitized, the US Defence Advanced Research Projects Agency (DARPA) asked 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 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. 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".
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".
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." Despite its critics, Nobel Laureate Luc Montagnier who is credited with identifying the AIDS virus has subsequently taken up Benveniste's work on water memory and he and a number of other scientists claim to have successfully replicated Benveniste's experiments (Ref: the 2014 documentary on Luc Montagnier titled "Water Memory").
- Davenas E, Beauvais F, Amara J, et al. (June 1988). "Human basophil degranulation triggered by very dilute antiserum against IgE". Nature. 333 (6176): 816–8. Bibcode:1988Natur.333..816D. doi:10.1038/333816a0. PMID 2455231.
- Maddox J (June 1988). "Can a Greek tragedy be avoided?". Nature. 333 (6176): 795–7. Bibcode:1988Natur.333..795M. doi:10.1038/333795a0. PMID 3133566.
- Watts, Geoff (2004-11-27). "Jacques Benveniste". BMJ : British Medical Journal. 329 (7477): 1290. doi:10.1136/bmj.329.7477.1290. ISSN 0959-8138. PMC 534457.
- L. Rousseau, Denis (January–February 1992). "Case Studies in Pathological Science". American Scientist. 80 (1): 54–63. Bibcode:1992AmSci..80...54R.
- Maddox, John; James Randi; Walter W. Stewart (28 July 1988). "'High-dilution' experiments a delusion". Nature. 334 (6180): 287–290. Bibcode:1988Natur.334..287M. doi:10.1038/334287a0. PMID 2455869.
- List of After Dark editions
- 'Diary', New Statesman, 9 September 1988
- Benveniste en mémoire, La chronique d'Eric Fottorino, Eric Fottorino, Le Monde 6 octobre 2004.
- J. H. Ovelgönne et al., “Mechanical Agitation of Very Dilute Antiserum against IgE Has No Effect on Basophil Staining Properties,” Experientia 48, no. 5 (May 15, 1992): 504–8, https://doi.org/10.1007/bf01928175.
- Experiments past and future Some remarks on the Memory of Water Controversy
- ÉTUDE CRITIQUE ET PROJETS D'AVENIR Dr B. POITEVIN Archived 2004-12-09 at the Wayback Machine
- Brian Josephson, molecule memories, New Scientist letters, 1 November 1997
- J. Benveniste; P. Jurgens; W. Hsueh; J. Aissa (21–26 February 1997). "Transatlantic Transfer of Digitized Antigen Signal by Telephone Link". Journal of Allergy and Clinical Immunology. 99 (1): S175. doi:10.1016/S0091-6749(97)81064-0.
- J. Benveniste; Aissa, J.; Guillonnet D. "The molecular signal is not functional in the absence of "informed water"". FASEB Journal. 13 (A163).
- J. Benveniste; Thomas Y; Schiff M; Belkadi L; Jurgens P; Kahhak L (2000). "Activation of human neutrophils by electronically transmitted phorbol-myristate acetate". Medical Hypotheses. 54 (1): 33–39. doi:10.1054/mehy.1999.0891. PMID 10790721.
- Leon Jaroff, Homeopathic E-Mail, Time Magazine, May 9, 1999
- Jacques Benveniste and Didier Guillonnet, DigiBio - NewsLetter 1999.2, "Demonstration challenge, etc." section
- James Randi, Computer problems, a Nobel Laureate reneges, more magnetic shoes, the metric system, and ..., Commentary, 26 January 2001
- Belon P, Cumps J, Ennis M, Mannaioni PF, Roberfroid M, Sainte-Laudy J, Wiegant FA (21 April 2004). "Histamine dilutions modulate basophil activation". Inflammation Research. Birkhäuser Basel. 53 (5): 181–188. doi:10.1007/s00011-003-1242-0. PMID 15105967.
- Milgrom, Lionel (March 15, 2001). "Thanks for the memory". Guardian Unlimited.
- Bland, Martin (2005). "TheHorizonhomeopathic dilution experiment". Significance. 2 (3): 106–109. doi:10.1111/j.1740-9713.2005.00109.x.
- Jonas, Wayne B.; John A. Ives; Florence Rollwagen; Daniel W. Denman; Kenneth Hintz; Mitchell Hammer; Cindy Crawford; Kurt Henry (January 2006). "Can specific biological signals be digitized?". FASEB J. 20 (1): 23–28. doi:10.1096/fj.05-3815hyp. PMID 16394263. — this paper includes an excellent references list.
- Coles, Peter (1989). "Benveniste under review". Nature. 340 (6229): 89. Bibcode:1989Natur.340...89C. doi:10.1038/340089b0. PMID 2739750.
- Benveniste, J.; P. Jurgens; W. Hsueh; J. Aissa (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. Archived from the original on 2012-09-21. Retrieved 2011-02-08.
- BBC Horizon (2002) Homeopathy: The Test, first broadcast November 26, 2002. Summary and transcript. Rebroadcast on ABC Catalyst in 2003.
- Beauvais, Francis (2016) Ghosts of Molecules - The case of the "memory of water", Coll. Mille-Mondes , Ed. Lulu.com, ISBN 978-1-326-45874-4.
- Belon, P.; Cumps, J.; Ennis, M.; Mannaioni, P. F.; Sainte-Laudy, J.; Roberfroid, M.; a. c. Wiegant, F. (1999). "Inhibition of human basophil degranulation by successive histamine dilutions: Results of a European multi-centre trial". Inflammation Research. 48: 17–18. doi:10.1007/s000110050376. PMID 10350142.
- 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.; Beauvais, F.; Arnara, J.; Oberbaum, M.; Robinzon, B.; Miadonna, A.; Tedeschi, A.; Pomeranz, B.; Fortner, P.; Belon, P.; Sainte-Laudy, J.; Poitevin, B.; Benveniste, J. (1988). "Human basophil degranulation triggered by very dilute antiserum against IgE". Nature. 333 (6176): 816–18. Bibcode:1988Natur.333..816D. doi:10.1038/333816a0. PMID 2455231.
- Fisher, Peter (1999). "The End of the Benveniste Affair?". British Homoeopathic Journal. 88 (4): 186–7. doi:10.1054/homp.1999.0327. PMID 10582651. Archived from the original on 2005-12-24. Retrieved 2005-11-23.
- Fottorino, Eric (1997) Le Monde, January 21, 22 & 23, 1997.
- Hammer, M.; Jonas, W. (2004). "Managing Social Conflict in CAM Research: The Case of Antineoplastons". Integr. Cancer Therapy. 3 (1): 59–65. doi:10.1177/1534735404263448. PMID 15035877.
- Hirst, S.J.; Hayes, N.A.; Burridge, J.; Pearce, F.L.; Foreman, J.C. (1993). "Human basophil degranulation is not triggered by very dilute antiserum against human IgE". Nature. 366 (6455): 525–7. Bibcode:1993Natur.366..525H. doi:10.1038/366525a0. PMID 8255290.
- 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
- Jonas, W. B.; Ives, J. A.; Rollwagen, F.; Denman, D. W.; Hintz, K.; Hammer, M.; Crawford; Henry, K. (2006). "Can Specific Biological Signals be Digitized?". FASEB J. 20 (1): 23–28. doi:10.1096/fj.05-3815hyp. PMID 16394263.
- 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". Nature. 335 (6193): 760–3. Bibcode:1988Natur.335..760M. doi:10.1038/335760a0. PMID 3185705.
- Maddox, John (1988). "When to believe the unbelievable". Nature. 333 (6176): 787. Bibcode:1988Natur.333Q.787.. doi:10.1038/333787a0.
- Milgrom, Lionel (1999) "The memory of molecules", The Independent, March 19. Full text
- Ovelgonne, J.H.; Bol, A.W.; Hop, W.C.; Van Wijk, R (1992). "Mechanical agitation of very dilute antiserum against IgE has no effect on basophil straining properties". Experientia. 48 (5): 504–8. doi:10.1007/BF01928175. PMID 1376282.
- 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[permanent dead link]
- Randi, James. Commentary. January 26, 2001 "a Nobel Laureate reneges". September 5, 2003 "Benveniste and Josephson on Abandoning Science".
- Targ, Russel; Puthoff, Harold (1974). "Information transfer under conditions of sensory shielding". Nature. 251 (5476): 602–7. Bibcode:1974Natur.251..602T. doi:10.1038/251602a0. PMID 4423858.
- Thomas, Y.; Schiff, M.; Belkadi, L.; Jurgens, P.; Kahhak, L.; Benveniste, J. (2000). "Activation of Human Eurtrophils by Electronically Transmitted Phorbol-Myristate Acetate". Medical Hypotheses. 54 (1): 33–39. doi:10.1054/mehy.1999.0891. PMID 10790721.
- 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)
- Benveniste, Jacques (2005) Ma vérité sur la 'mémoire de l'eau', Albin Michel. ISBN 2-226-15877-4
- Benveniste, Jacques, and Peter Jurgens. On the Role of Stage Magicians in Biological Research The Anomalist 1998
- Benveniste, Jacques. Electromagnetically Activated Water and the Puzzle of the Biological Signal INSERM Digital Biology Laboratory (March 10., 1999)
- Benveniste, Jacques. "Put a match to pyre review" Nature 396 Dec 10 1998
- Benveniste, Jacques. "Further Biological Effects Induced by Ultra High Dilutions: Inhibition by a Magnetic Field", In P.C. Endler, ed.,Ultra High Dilution: Physiology and Physics. Dordrecht: Kluwe academic, 1994
- Benveniste, Jacques, "Transfer of Biological Activity by Electromagnetic Fields." Frontier Perspectives 3(2) 1993:113-15.
- Benveniste, Jacques (1993). "Molecular signaling at high dilution or by means of electronic circuitry". Journal of Immunology. 150: 146A.
- Benveniste, Jacques (1994). "Transfer of the molecular signal by electronic amplification". FASEB Journal. 8: A398.
- Benveniste, Jacques (1995). "Electronic transmission of the cholinergic signal". FASEB Journal. 9: A683.
- Benveniste, Jacques (1995). "Direct transmission to cells of a molecular signal via an electronic device". FASEB Journal. 9: A227.
- Benveniste, J.; Ducot, B.; Spira, A. (1994). "Memory of water revisited". Nature. 370 (6488): 322. Bibcode:1994Natur.370..322B. doi:10.1038/370322a0. PMID 8047128.
- Benveniste, J., Davenas, E. & A. Spira (1991) Comptes Rendus de l'Académie des Sciences, January.
- Association Jacques Benveniste pour la Recherche (in French), including an obituary (in English)
- Obituary from the Guardian, 2004
- Obituary, British Medical Journal, 27 November 2004