Jacques Benveniste
Encyclopedia
Jacques Benveniste was a French immunologist
Immunology
Immunology is a broad branch of biomedical science that covers the study of all aspects of the immune system in all organisms. It deals with the physiological functioning of the immune system in states of both health and diseases; malfunctions of the immune system in immunological disorders ; the...

. In 1979 he published a well-known paper on the structure of platelet-activating factor
Platelet-activating factor
Platelet-activating factor, also known as a PAF, PAF-acether or AGEPC is a potent phospholipid activator and mediator of many leukocyte functions, including platelet aggregation and degranulation, inflammation, and anaphylaxis...

 and its relationship with histamine
Histamine
Histamine is an organic nitrogen compound involved in local immune responses as well as regulating physiological function in the gut and acting as a neurotransmitter. Histamine triggers the inflammatory response. As part of an immune response to foreign pathogens, histamine is produced by...

. 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
Scientific journal
In academic publishing, a scientific journal is a periodical publication intended to further the progress of science, usually by reporting new research. There are thousands of scientific journals in publication, and many more have been published at various points in the past...

 Nature
Nature (journal)
Nature, first published on 4 November 1869, is ranked the world's most cited interdisciplinary scientific journal by the Science Edition of the 2010 Journal Citation Reports...

describing the action of very high dilutions of anti-IgE
Immunoglobulin E
Immunoglobulin E is a class of antibody that has been found only in mammals. IgE is a monomeric antibody with 4 Ig-like domains...

 antibody
Antibody
An antibody, also known as an immunoglobulin, is a large Y-shaped protein used by the immune system to identify and neutralize foreign objects such as bacteria and viruses. The antibody recognizes a unique part of the foreign target, termed an antigen...

 on the degranulation of human basophils, findings which seemed to support the concept of homeopathy
Homeopathy
Homeopathy is a form of alternative medicine in which practitioners claim to treat patients using highly diluted preparations that are believed to cause healthy people to exhibit symptoms that are similar to those exhibited by the patient...

. 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
Water memory
Water memory is the claimed ability of water to retain a "memory" of substances previously dissolved in it to arbitrary dilution. No scientific evidence supports this claim. Shaking the water at each stage of a serial dilution is claimed to be necessary for an effect to occur...

 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.

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 in France. After the article was published, a follow-up investigation was set up by a team including physicist and Nature editor John Maddox
John Maddox
Sir John Royden Maddox, FRS was a British science writer. He was an editor of Nature for 22 years, from 1966–1973 and 1980-1995.-Career:...

, illusionist and well-known skeptic James Randi
James Randi
James Randi is a Canadian-American stage magician and scientific skeptic best known as a challenger of paranormal claims and pseudoscience. Randi is the founder of the James Randi Educational Foundation...

, as well as fraud expert Walter Stewart who had recently raised suspicion on the work of Nobel Laureate David Baltimore
David Baltimore
David Baltimore is an American biologist, university administrator, and Nobel laureate in Physiology or Medicine. He served as president of the California Institute of Technology from 1997 to 2006, and is currently the Robert A. Millikan Professor of Biology at Caltech...

. 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."

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

Unusual conditions

Nature agreed to publish Benveniste's article in June 1988 with two unusual conditions: first, that 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
Peer review
Peer review is a process of self-regulation by a profession or a process of evaluation involving qualified individuals within the relevant field. Peer review methods are employed to maintain standards, improve performance and provide credibility...

. . . 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
Uri Geller
Uri Geller is a self-proclaimed psychic known for his trademark television performances of spoon bending and other supposed psychic effects. Throughout the years, Geller has been accused of using simple conjuring tricks to achieve the effects of psychokinesis and telepathy...

.

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
John Maddox
Sir John Royden Maddox, FRS was a British science writer. He was an editor of Nature for 22 years, from 1966–1973 and 1980-1995.-Career:...

, American scientific fraud investigator and chemist Walter Stewart, and skeptic
Scientific skepticism
Scientific skepticism is the practice of questioning the veracity of claims lacking empirical evidence or reproducibility, as part of a methodological norm pursuing "the extension of certified knowledge". For example, Robert K...

 and former magician James Randi
James Randi
James Randi is a Canadian-American stage magician and scientific skeptic best known as a challenger of paranormal claims and pseudoscience. Randi is the founder of the James Randi Educational Foundation...

.

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 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
    Sampling error
    -Random sampling:In statistics, sampling error or estimation error is the error caused by observing a sample instead of the whole population. The sampling error can be found by subtracting the value of a parameter from the value of a statistic...

    . The method of taking control values was not reliable, and "no substantial effort has been made to exclude systematic error
    Systematic error
    Systematic errors are biases in measurement which lead to the situation where the mean of many separate measurements differs significantly from the actual value of the measured attribute. All measurements are prone to systematic errors, often of several different types...

    , 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
    Boiron
    Boiron is a manufacturer of homeopathic products, headquartered in France and with an operating presence in 59 countries worldwide. It is the largest manufacturer of homeopathic products in the world. In 2004, it employed a workforce of 2,779 and had a turnover of € 313 million...

    ."
  5. "The phenomenon described is not reproducible". "We believe that experimental data have been uncritically assessed and their imperfections inadequately reported."

Response

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. He claimed that such "Salem witchhunts
Salem witch trials
The Salem witch trials were a series of hearings before county court trials to prosecute people accused of witchcraft in the counties of Essex, Suffolk, and Middlesex in colonial Massachusetts, between February 1692 and May 1693...

 or McCarthy
McCarthyism
McCarthyism is the practice of making accusations of disloyalty, subversion, or treason without proper regard for evidence. The term has its origins in the period in the United States known as the Second Red Scare, lasting roughly from the late 1940s to the late 1950s and characterized by...

-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.

After Dark

On 3 September 1988 Channel 4
Channel 4
Channel 4 is a British public-service television broadcaster which began working on 2 November 1982. Although largely commercially self-funded, it is ultimately publicly owned; originally a subsidiary of the Independent Broadcasting Authority , the station is now owned and operated by the Channel...

 broadcast an After Dark television discussion featuring Benveniste, James Randi
James Randi
James Randi is a Canadian-American stage magician and scientific skeptic best known as a challenger of paranormal claims and pseudoscience. Randi is the founder of the James Randi Educational Foundation...

 and Walter Stewart among others, reviewed the following week by Sean French
Nicci French
Nicci French is the pseudonym of English husband-and-wife team Nicci Gerrard and Sean French, who write psychological thrillers together.-Personal life:...

 in the New Statesman
New Statesman
New Statesman is a British centre-left political and cultural magazine published weekly in London. Founded in 1913, and connected with leading members of the Fabian Society, the magazine reached a circulation peak in the late 1960s....

.

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.

Josephson and the APS

Benveniste gained the public support of Brian Josephson
Brian David Josephson
Brian David Josephson, FRS is a Welsh physicist. He became a Nobel Prize laureate in 1973 for the prediction of the eponymous Josephson effect....

, a Nobel
Nobel Prize
The Nobel Prizes are annual international awards bestowed by Scandinavian committees in recognition of cultural and scientific advances. The will of the Swedish chemist Alfred Nobel, the inventor of dynamite, established the prizes in 1895...

 physicist with a reputation for openness to paranormal claims. Time magazine reported in 1999 that, in response to skepticism from physicist Robert Park
Robert L. Park
Robert Lee Park , also known as Bob Park, is an emeritus professor of physics at the University of Maryland, College Park and a former Director of Public Information at the Washington office of the American Physical Society...

, Josephson had challenged the American Physical Society
American Physical Society
The American Physical Society is the world's second largest organization of physicists, behind the Deutsche Physikalische Gesellschaft. The Society publishes more than a dozen scientific journals, including the world renowned Physical Review and Physical Review Letters, and organizes more than 20...

 (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:
"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
Madeleine Ennis
Madeleine Ennis is a pharmacologist and researcher at Queen's University in Belfast, Northern Ireland. She generated controversy by publishing results that seemed to show that ultra-dilute solutions of histamine, diluted to the levels used in homeopathic remedies, could affect cells just as the...

 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."

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
Water memory
Water memory is the claimed ability of water to retain a "memory" of substances previously dissolved in it to arbitrary dilution. No scientific evidence supports this claim. Shaking the water at each stage of a serial dilution is claimed to be necessary for an effect to occur...

. In 2003, George Vithoulkas
George Vithoulkas
George Vithoulkas is a teacher and practitioner of homeopathy.He studied homeopathy in South Africa and received a diploma in homeopathy from the Indian Institute of Homeopathy in 1966...

 claimed that he had taken up this challenge but that Randi had withdrawn.

Digital Biology

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 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.
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 2010 Ennis Review

In 2010, a review of the attempts to replicate studies into the activation and inhibition of human basophils with homeopathic dilutions was published in the journal Homeopathy. Entitled, Basophil models of homeopathy: a sceptical view, and written by Madeleine Ennis of The Queen’s University
of Belfast, the paper reviewed a list of studies to find out what can be confidently said about the 20 years of research into the subject.

Ennis concludes,
"The methods are poorly standardized between laboratories – although the same is true for conventional studies as described above. Certainly there appears to be some evidence for an effect – albeit small in some cases – with the high dilutions in several different laboratories using the flow cytometric methodologies. How much of the effect is due to artifacts remains to be investigated."


Ennis believes that in order to draw the "never-ending story" of homeopathic inhibition of basophils to a close then a new multi-centre trial would be required. Before such a trial could take place there would need to be agreement about how best to undertake the experiment, including how to source donor cells, how to prepare histamine solutions and how to detect activation. Importantly, independent laboratories should prepare the solutions and encode to ensure proper blinding and randomization. Independent statisticians should analyze the results. Such an approach might provide a definitive result.

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".

Benveniste and homeopathy

Nearly all scientists believe that there is no credible evidence to support claims that homeopathic remedies actually work, nor is there a plausible mechanism to explain how homeopathy could work. Indeed, skeptics often dismiss homeopathy, citing internal inconsistencies in the hypothesis, and the fact that biological reactions require the presence of chemicals, whereas homeopathic remedies are so diluted that they are equivalent to pure water.

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. The idea of "water memory
Water memory
Water memory is the claimed ability of water to retain a "memory" of substances previously dissolved in it to arbitrary dilution. No scientific evidence supports this claim. Shaking the water at each stage of a serial dilution is claimed to be necessary for an effect to occur...

" remains controversial and is not generally accepted by scientists.

Miscellaneous

Benveniste has been awarded two Ig Nobel Prize
Ig Nobel Prize
The Ig Nobel Prizes are an American parody of the Nobel Prizes and are given each year in early October for ten unusual or trivial achievements in scientific research. The stated aim of the prizes is to "first make people laugh, and then make them think"...

s in Chemistry
Chemistry
Chemistry is the science of matter, especially its chemical reactions, but also its composition, structure and properties. Chemistry is concerned with atoms and their interactions with other atoms, and particularly with the properties of chemical bonds....

. They are a parody
Parody
A parody , in current usage, is an imitative work created to mock, comment on, or trivialise an original work, its subject, author, style, or some other target, by means of humorous, satiric or ironic imitation...

 of the Nobel Prize
Nobel Prize
The Nobel Prizes are annual international awards bestowed by Scandinavian committees in recognition of cultural and scientific advances. The will of the Swedish chemist Alfred Nobel, the inventor of dynamite, established the prizes in 1895...

s. 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."

See also

  • Experimental errors and frauds in physics
  • Junk science
    Junk science
    Junk science is a term used in U.S. political and legal disputes that brands an advocate's claims about scientific data, research, or analyses as spurious. The term may convey a pejorative connotation that the advocate is driven by political, ideological, financial, or other unscientific...

  • Pathological science
    Pathological science
    Pathological science is the process in science in which "people are tricked into false results ... by subjective effects, wishful thinking or threshold interactions". The term was first used by Irving Langmuir, Nobel Prize-winning chemist, during a 1953 colloquium at the Knolls Research Laboratory...

  • Protoscience
    Protoscience
    In the philosophy of science, a protoscience is an area of scientific endeavor that is in the process of becoming established. Protoscience is distinguished from pseudoscience by its standard practices of good science, such as a willingness to be disproven by new evidence, or to be replaced by a...

  • Topics characterized as pseudoscience
  • Scientific misconduct
    Scientific misconduct
    Scientific misconduct is the violation of the standard codes of scholarly conduct and ethical behavior in professional scientific research. A Lancet review on Handling of Scientific Misconduct in Scandinavian countries provides the following sample definitions: *Danish definition: "Intention or...

  • Water memory
    Water memory
    Water memory is the claimed ability of water to retain a "memory" of substances previously dissolved in it to arbitrary dilution. No scientific evidence supports this claim. Shaking the water at each stage of a serial dilution is claimed to be necessary for an effect to occur...


External links

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