[sci.med] Infinite dilutions revisited

werner@aecom.YU.EDU (Craig Werner) (07/22/88)

	Recently, both in this newsgroup and in the general scientfic and
popular press, there was a lot of discussion about a rather amazing 
experiment done in France by Jacques Benveniste of INSERM at the South
Paris University that suggests that certain compounds can be
diluted infinitely without necessarily losing biological activity.
	I will attempt to review the actual experiment, and explain why,
opinions to the contrary, it really doesn't much further the cause of
homeopathy all that much.

	The experiment:
	The experiment deals with the immunology of the allergic response,
namely the IgE-allergen induced degranulation of Mast Cells, which causes
the release of histamine and other allergic mediators.
	Normally, IgE is bound to the cell surface of mast cells via the
FcEI (pronounced F c epilson One ) receptor. Allergen cross-links the
IgE, and the "capping" of the IgE sets off allergic responses.  As a
universal allergen, one can use anti-IgE antibody, which cross-links all
IgE regardless of which antigen the IgE naturally binds. 

	If one does this, one finds that the results actually fall into
two parts.  The first is what you expect, an arbitrary 100% activity falls
to a very low value with dilution, i.e., the active component gets diluted
out.  However, with further dilution, the activity INCREASED to an 
intermediate value, and then decreased, and increased again in a periodic
fashion.  This pattern continued to a dilution of 10^-120, well beyond
the molecular limit where one would expect any molecules of the original
mixture to be remaining.  This periodic behavior was robust -- it replicated
on different trials -- although the phase was not constant between trials
(i.e., on one trial, peaks might be seen at dilutions 45 49 53 57 etc,
while on a later trial, no activity would be seen on those dilutions, but
would appear in dilutions 47 51 55 59 etc.)   All the relevant controls
seemed to behave as expected, the most telling being that when anti-IgG
serum (which has no initial activity) was used instead of anti-IgE, the
activity started at zero and stayed there.  This implies that one must
dilute active ingredient, even if it is to absurdly low concentrations.
	Another interesting phenomenon was that the handling of the
compounds was important. If following dilution, only gentle mixing was
applied, no activity wa recorded. Activity was only recorded if the
tubes were subjected to 10 seconds of vigorous vortexing.

	An interesting and intriguing experiment all around.
	Now here's why it is not all that relevant to homeopathy:  
First of all, dilution didn't really increase activity beyond what chemical 
principles would suggest.  The highest biological activity was noted at 
the lowest (Zero) dilution.  What the experiment noted was a cyclical 
fluctuation between low and moderate activity.
	Secondly, homeopathy purports to treat "like with like", which is
to say, that a little bit of a compound will prevent the symptoms that a
lot of the compound would cause.  In this experiment, all that "like" 
seemed to do was cause variable symptoms at the various low doses.
 	Thirdly, the fact that the parallel experiments had differences
phases means that predicting which dilution of a homeopathic preparation
contains active compound is impossible without a bioassay.  Since this
is just the sort of the thing that homeopaths disdain, there is no
way to predict the efficacy of a homeopathic preparation. Considering that
the number of dilutions are standardized, then this experiment still shows
that homeopathy is a hit or miss business (which is if you think about it,
an upgrading of status from a miss or miss business). This is reinforced
by the observation the the results of the experiment are dependent on sample
preparation, which in the absence of a bioassay, means there is even less
means of quality control.
	Fourth, homeopathy predicts that dilution will increase a substances
potency, not that its potency will vary cyclically between 0 and 40% 
effectiveness.  Thus the results of the experiment does not agree with either
the dogmas of homeopathy or the dogmas of pharmacology.

	The best popular science summary appears in New Scientist 14 July 1988
(p. 39).  The Newsweek and Science News articles are too superficial.  The
Nature article (333:816) is really thick reading, even by the standards of
scientific writing.


-- 
	        Craig Werner   (future MD/PhD, 4 years down, 3 to go)
	     werner@aecom.YU.EDU -- Albert Einstein College of Medicine
              (1935-14E Eastchester Rd., Bronx NY 10461, 212-931-2517)
               "Time flies when you're streaking out N. gonorrheae." 

sarima@gryphon.CTS.COM (Stan Friesen) (07/26/88)

In article <1907@aecom.YU.EDU> werner@aecom.YU.EDU (Craig Werner) writes:
>
>	Recently, both in this newsgroup and in the general scientfic and
>popular press, there was a lot of discussion about a rather amazing 
>experiment done in France by Jacques Benveniste of INSERM at the South
>Paris University that suggests that certain compounds can be
>diluted infinitely without necessarily losing biological activity.
>[Material deleted describing basic premise of experiment]
>
>  However, with further dilution, the activity INCREASED to an 
>intermediate value, and then decreased, and increased again in a periodic
>fashion.  This pattern continued to a dilution of 10^-120, well beyond
>the molecular limit where one would expect any molecules of the original
>mixture to be remaining.  This periodic behavior was robust -- it replicated
>on different trials -- although the phase was not constant between trials
>(i.e., on one trial, peaks might be seen at dilutions 45 49 53 57 etc,
>while on a later trial, no activity would be seen on those dilutions, but
>would appear in dilutions 47 51 55 59 etc.)
> [ Description of controls deleted ]
>	Another interesting phenomenon was that the handling of the
>compounds was important. If following dilution, only gentle mixing was
>applied, no activity wa recorded. Activity was only recorded if the
>tubes were subjected to 10 seconds of vigorous vortexing.
>
	Aha!! This looks like the key to the problem. This sounds like
a Chaotic Attractor. That is a complex, but deterministic, system which
shows apparently disorganized or unpredictable behavior. And mixing is
a known mechanism for producing Chaotic effects. I would suggest that the
vigorous mixing actually *increased* the "order" of the solution not
decreased it. That is the sample became internally heterogenous with the
antibody being relatively concentrated in small portions of the solution,
thus allowing moloecules to remain even at large "dilutions". Or at least
this is one possibility. A more thorough study of the dynamics of mixing
and the "reorganization" effect of some classes of mixing seems in order.
(Such effects are known, though I suppose my particular scenario is rather
simplistic and naive - still it may be something along these lines).

	If anyone out there has any more knowledge on Chaos Studies than
my beginner's knowledge, I would welcome more detailed discussion.

PS. Perhaps someone should suggest this to the researchers who are
working on this.
-- 
Sarima Cardolandion			sarima@gryphon.CTS.COM
aka Stanley Friesen			rutgers!marque!gryphon!sarima
					Sherman Oaks, CA