[sci.research] Strange results in Nature article

colvin@mahler.llnl.gov (Mike Colvin) (07/23/88)

	Has anyone read in the newsgroup read the article: "Human basophil
degranulation triggered by very dilute antiserum against IgE" in
the June 30 Nature on page 816?  It's also discussed in an editorial
entitled "When to Believe the Unbelievable" on page 787 of the same issue.

	The article reports an extremely weird result which would seen to 
have no sensible physical explaination.  The researchers set out to find the 
fractional cell degranualtion at various antibody concentrations. 
They found that there was *no* level of dilution at which the fraction
of cell degranulation went to zero.  EVEN WHEN THEY DILUTED THE SOLUTION
DOWN TO 1 x 10**120.  Since Avagadro's number is only about 6 * 10**23, this
means that there is not even a single antibody present in these solutions.
Note that degranulation is a very specific reaction which does not occur
spontaneously or in the presence of other proteins.  To futher rule out
contamination the diluted solution was run through an ultrafiltration system,
but the filtrate still caused degranulation.  Interestingly, this activity
can be inactivated by freeze-thawing or heating the solution above 70 C.
Of course the experiment has been rerun several times by 6 research groups 
in 4 countries using normal double blind procedures.  The authors have no 
explaination but hypothesize that the antibody is somehow leaving its 
"imprint" on the water molecules, but this explaination is unsatisfactory
for many reasons.  Nature is sponsoring an overview committee to monitor
repititions of this experiment.

	Anyway, I just wanted to point out this truly bizarre article and
would like to hear what other people have to say about it.
	
							-Mike Colvin

jackson@esosun.UUCP (Jerry Jackson) (07/23/88)

This sounds related to Rupert Sheldrake's Hypothesis of Formative
Causation -- Would anyone who knows more about Sheldrake's recent work
care to comment on this experiment?

(Briefly for anyone who hasn't heard of this work -- Sheldrake is a
developmental biologist who has taken a radical approach to explaining
morphogenesis -- He postulates the existence of 'morphogenetic fields'
that influence the development of forms.  For systems with a clear
lowest energy state, the energetic considerations leave no room for the
effects of these fields... That's why all hydrogen atoms look alike.

In complex systems, however, there may be an enormous number of states
with nearly equal energy -- this leaves some room for the
morphogenetic fields to influence the time development of the system..
For instance, proteins have very distinct patterns in which they fold;
so far, the rapid folding of identical proteins into identical shapes
is very difficult to explain.  Sheldrake suggests that the morpho. fields
direct the developmental path of the protein molecules...

A related suggestion is that crystals of a particular type should be
easier to form after they have been formed in the past.

Another suggestion is that an animal behavior may be easier to learn
when many other animals have already learned it e.g. the 100th monkey.

There is actually experimental evidence supporting this last conjecture
that was arrived at when testing the Lamarckian inheritance hypothesis
for rats.  The idea of the test was to teach a subset of a group of
rats a behavior then see if the descendants of the educated rats would
perform better on the behavior without training -- The actual results
did not support Lamarck (Big surprise :-). What did occur, however,
made no sense until years later -- *all* the new rats performed better
than the previous set.  Hmm..)

A caveat -- I know this sounds absurd... However, morphogenesis is 
such an incredibly difficult problem with no deep understanding in sight
that it seems worthwile to consider unusual ideas.  Until the standard
explanations actually *explain*, I don't think someone should be
discouraged from trying new approaches.  BTW: Sheldrake seems to be
far from a raving crackpot.. On the contrary, his book is very measured
and careful to avoid glossing over difficulties or pretending his
hypothesis is more than just that.


In any case, it would be very nice to hear more from someone in the know.

+-----------------------------------------------------------------------------+
|   Jerry Jackson                       UUCP:  seismo!esosun!jackson          |
|   Geophysics Division, MS/22          ARPA:  esosun!jackson@seismo.css.gov  |
|   SAIC                                SOUND: (619)458-4924                  |
|   10210 Campus Point Drive                                                  |
|   San Diego, CA  92121                                                      |
+-----------------------------------------------------------------------------+

dd@beta.lanl.gov (Dan Davison) (07/23/88)

In article <10465@lll-winken.llnl.gov>, colvin@mahler.llnl.gov (Mike Colvin) writes:
> 
> 	Has anyone read in the newsgroup read the article: "Human basophil
> degranulation triggered by very dilute antiserum against IgE" in
> the June 30 Nature on page 816?  It's also discussed in an editorial
> entitled "When to Believe the Unbelievable" on page 787 of the same issue.
>   [much description deleted] 
> 	Anyway, I just wanted to point out this truly bizarre article and
> would like to hear what other people have to say about it.

I've been surprised by the lack of comment on the article in this
newsgroup.  I had to read the thing over 5 times before being
comfortable with it.  The extensive testing and reproducibiliy
help a lot.

This case appears to fall in one of two categories: (1) the famous
"polywater" class, where some Russian scientists reported finding
a state of water with very unusual properties, which eventually
turned out to be contaminants.  (2) A major paradigm breakdown.
The latter would have impressively widespread consequences;
my general feeling that any result that breaks that much physics
and chemistry needs to be extremely carefully checked out.

We will now have to endure years of extravagant homeopathic claims
to the effect that mainline science now supports homeopathic
theories; it may well turn out that they do, but a lot more
evidence will have to be accumulated.

This reminds me of the time (yes, Dizzy and Sam, I'm that old) when
evidence was accumulating that DNA and RNA were not necessarily
colinear.  It seemed very unlikely, then just unlikely, then
yeah maybe, then obviously true.  Splicing, though *fit*; the
current state of knowledge about the infinite-dilutibility of
antibodies doesn't.

-- 
dan davison/theoretical biology/t-10 ms k710/los alamos national laboratory
los alamos, nm 875545/dd@lanl.gov (arpa)/dd@lanl.uucp(new)/..cmcl2!lanl!dd
"I think, therefore I am confused"

mayo@speedy.cs.wisc.edu (Bob Mayo) (07/23/88)

In article <10465@lll-winken.llnl.gov> colvin@mahler.llnl.gov.UUCP (Mike Colvin) writes:
] 
] 	Has anyone read in the newsgroup read the article: "Human basophil
] degranulation triggered by very dilute antiserum against IgE" in
] the June 30 Nature on page 816?  It's also discussed in an editorial
] entitled "When to Believe the Unbelievable" on page 787 of the same issue.
] [...] 
] The authors have no 
] explaination but hypothesize that the antibody is somehow leaving its 
] "imprint" on the water molecules, but this explaination is unsatisfactory
] for many reasons.  

One thing which struck me as odd is that they aren't diluting with water.
See the "methods" section in Figure 1.  The solution used for dilution
contains NaCl, KCl, HEPES, EDTA-Na4, glucose, heuman serum albumin (HSA),
and heparin).  I don't know what all of these are, but it seems like a complex
organic soup to me.  

I would think that no great leap is required to hypothesize
that the IgE anitserum catalyzed an as-yet-undiscovered reaction in this stuff.
And perhaps once the reaction gets going it doesn't really need IgE to be
around so dilution has no effect.

But the authors and nature hypothesize changes in the state of water molecules,
etc..  I am missing something?  Shouldn't we look at the complex organic stuff
before hypothesizing more radical things such as changes in the state of water?

--Bob Mayo

P.S.  I know nothing about immunology and biochemistry.  Please correct me if
my statements are wrong.


<Sorry for the repost, if any.  My article didn't appear on our machine so I
assume it was lost.>

blm@cxsea.UUCP (Brian Matthews) (07/24/88)

Dan Davison (dd@beta.lanl.gov) writes:
|In article <10465@lll-winken.llnl.gov>, colvin@mahler.llnl.gov (Mike Colvin) writes:
|> 	Has anyone read in the newsgroup read the article: "Human basophil
|> degranulation triggered by very dilute antiserum against IgE" in
|> the June 30 Nature on page 816?  It's also discussed in an editorial
|> entitled "When to Believe the Unbelievable" on page 787 of the same issue.
|>   [much description deleted] 
|> 	Anyway, I just wanted to point out this truly bizarre article and
|> would like to hear what other people have to say about it.
|
|I've been surprised by the lack of comment on the article in this
|newsgroup.  I had to read the thing over 5 times before being
|comfortable with it.  The extensive testing and reproducibiliy
|help a lot.

Forgive my ignorance, but could someone give a quick summary of what the
first paragraph above means?  The whole discussion sounds interesting,
but I don't know enough about biology or chemistry to understand why
everyone's up in arms.

-- 
Brian L. Matthews  blm@cxsea.UUCP   ...{mnetor,uw-beaver!ssc-vax}!cxsea!blm
+1 206 251 6811    Computer X Inc. - a division of Motorola New Enterprises

robiner@ganelon.usc.edu (Steve) (07/26/88)

>They found that there was *no* level of dilution at which the fraction
>of cell degranulation went to zero.  EVEN WHEN THEY DILUTED THE SOLUTION
>DOWN TO 1 x 10**120.  Since Avagadro's number is only about 6 * 10**23, this
>means that there is not even a single antibody present in these solutions.

I'm not a biologist, but I know something about organic material.  Isn't it
possible that these antibodies are reproducing themselves in solution? Perhaps
they're just splitting into smaller pieces.  Maybe the degranulation can 
occur with only a small part of the orginal present.

Why don't they try a better test for the presence of these antibodies, if that's
what they think is actually there.  Or, if it's *changed* the water, use a
filter which is so small that ONLY water moelcules can go through.

Just some thoughts on not believing the unbelievable.
=Steve=

pell@boulder.Colorado.EDU (Anthony Pelletier) (07/26/88)

In article <11063@oberon.USC.EDU> robiner@ganelon.usc.edu (Steve) writes:

[Account of the results on antibody dilution from Beneviste's lab]

>
>I'm not a biologist, but I know something about organic material.  Isn't it
>possible that these antibodies are reproducing themselves in solution? Perhaps

Well...no...that is I doubt it...that is to say, that would break more
rules than the explanation they suggest...but, wouldn't that turn some heads
(actually, it does not fit the data--see below).

>Why don't they try a better test for the presence of these antibodies, if that's
>what they think is actually there.  Or, if it's *changed* the water, use a
>filter which is so small that ONLY water moelcules can go through.
>
>Just some thoughts on not believing the unbelievable.
>=Steve=

Well Steve, you may not be a biologist, but you are a scientist (or you
should be).
Actually, the experiments you suggested were among the controls they did.
You might like to read the paper for yourself, though the writing style makes
it pretty hard going.  
They did pass it through a milipore filter and the activity did come through.
They also ran it over a column and it came out in the void (buffer only)
volume while the antibody would be retained in both cases.
They establish also that sensitivity to heat and freeze- thawing of the dilute
activity is different then that of the starting material (antibodies or
ionophores, which also show the same effect).
The thing having the effect in the dilute solution is NOT the antibody.
As for what it is...the water idea is no less crazy then any other I have
heard or thought of.

In fact, the controls done by these people were about as thorough as
I have ever seen.  And, the experiments were repeated in 6 different labs.
All of the easy "you-missed-this-obvious-point" explanations have been
ruled out.
Two things seem clear:
1.that the paper accurately reports a strange-but-true phenomenon unless there
is a big hoax being perpetrated by the French on the uncivilised portion of the
world;

2.there is almost certainly no hoax.  Beneviste seems to HATE this result.
One gets the impression that he really wishes there was be a simple
explanation.  He is not touting it as some great discovery.  I don't think
he believes it anymore than we do.

Nature is planing a follow-up report in a couple of weeks.  This will be based
on investigations currently being conducted by a group of "experts."
This group includes not only other immunologists but also "The Amazing
Randi" (No joke, they really are sending him).  I rather doubt Beneviste is
sending secret messages to the cells through a radio transmitter, but,
perhaps he can help.  Beneviste is cooperating fully in the investigation
(which is more than Uri Geller ever did).

Oh well, there may be a missed control somewhere, but I doubt it.
If I were of a different religious inclination, I would suggest that this
is God's way of saying to us scientists "Hey, don't get cocky!"

-tony

mayo@speedy.cs.wisc.edu (Bob Mayo) (07/26/88)

In article <2444@cxsea.UUCP> blm@cxsea.UUCP (Brian Matthews) writes:
>Forgive my ignorance, but could someone give a quick summary of what the
>first paragraph above means?  The whole discussion sounds interesting,

Ultra condensed summary:  

    Substance A causes effect Y on substance B.  When substance A is
    diluted to the point where *none* of it remains, it still has effect Y
    on substance B.  Experiment is repeated at other laboratories and with
    all conceivable controls, yielding the same results.

ethan@ut-emx.UUCP (Ethan Tecumseh Vishniac) (07/27/88)

> |In article <10465@lll-winken.llnl.gov>, colvin@mahler.llnl.gov (Mike Colvin) writes:
> |> 	Has anyone read in the newsgroup read the article: "Human basophil
> |> degranulation triggered by very dilute antiserum against IgE" in
> |> the June 30 Nature on page 816?  It's also discussed in an editorial
> |> entitled "When to Believe the Unbelievable" on page 787 of the same issue.
> |>   [much description deleted] 
> |> 	Anyway, I just wanted to point out this truly bizarre article and
> |> would like to hear what other people have to say about it.
> |

I see in today's newspaper that an investigation by Nature  discovered
that there were at least two problems (fatal problems) with the
laboratory protocol.  First, the experimenters knew at all times
which solutions were which (i.e. control and experiment) and
this is well known to produce biased results.  Second, the laboratory
notebooks revealed a large number of cases that produced negative
results but were not included in the statistics.  In other words,
the experimental setup allowed for unconcious bias, and the data reduction
included a fair amount of concious bias.  This is all supposed to come
out in Nature in the near future.  The author (Benveniste ?) is
standing by the work and has denounced the investigation as sloppy
and unprofessional.

As with any truly startling result, the sensible thing is to believe it
only when such questions have been cleared.  Far firmer and more
believable results have collapsed under examination.

-- 
 I'm not afraid of dying     Ethan Vishniac, Dept of Astronomy, Univ. of Texas
 I just don't want to be     {charm,ut-sally,ut-ngp,noao}!utastro!ethan
 there when it happens.      (arpanet) ethan@astro.AS.UTEXAS.EDU
    - Woody Allen            (bitnet) ethan%astro.as.utexas.edu@CUNYVM.CUNY.EDU

dgary@ecsvax.uncecs.edu (D Gary Grady) (07/27/88)

It is claimed that a biologically active substance diluted in solution
retains its bilogical activity even when effectively diluted out of
existence.  The author of the Nature paper suggests that the solution
has somehow retained a memory of its previous contents.  Well, maybe.
I try to keep an open mind, but...

It seems to me there's a logical problem here.  Suppose the results are
valid.  Was the water used in these experiments somehow primordial
(i.e., was it perhaps created by burning hydrogen)?  Otherwise, it would
seem, it might carry with it the memory of some past contaminants,
unless dionization or distillation produced aquatic amnesia..

Also, if the results are true, it bodes ill for wastewater treatment.
Once contaminated, always contaminated might be the rule, barring (say)
distillation or electolysis.

Where *do* homeopaths get their water, by the way?
-- 
D Gary Grady
(919) 286-4296
USENET:  {seismo,decvax,ihnp4,akgua,etc.}!mcnc!ecsvax!dgary
BITNET:  dgary@ecsvax.bitnet

eddy@boulder.Colorado.EDU (Sean Eddy) (07/27/88)

article <4520@ut-emx.UUCP> ethan@ut-emx.UUCP (Ethan Tecumseh Vishniac) writes:
>I see in today's newspaper that an investigation by Nature  discovered
>that there were at least two problems (fatal problems) with the
>laboratory protocol.  First, the experimenters knew at all times
>which solutions were which (i.e. control and experiment) and
>this is well known to produce biased results.  Second, the laboratory
>notebooks revealed a large number of cases that produced negative
>results but were not included in the statistics.  

If the first part is true, someone is in big trouble. The Nature
article describes an elaborate set of double (or triple, even?)
blind experiments involving multiple experimenters and coded tubes.

As for the second part, newspaper reporters may have a hard time
accepting the fact that experiments quite often fail for reasons
quite distinct from refutation of a hypothesis (for instance, the
grad student performing the experiment had one too many cups
of coffee that morning). Manipulation of a complex biological system
can be more art then science at times. The ability to reproduce
a positive result in biology can be much more telling than even
a series of inexplicable experimental failures.

(Not that I believe the result, you understand...)

- Sean Eddy
- Molecular/Cellular/Developmental Biology; U. of Colorado at Boulder
- eddy@boulder.colorado.EDU		!{hao,nbires}!boulder!eddy	
-
- "Just as the locusts, once they are through with a field, have simplified
-  it horribly, could we not say that this is also true of some of the
-  great generalizations of biology?"
-                       - biochemist Erwin Chargaff

pell@boulder.Colorado.EDU (Anthony Pelletier) (07/27/88)

In article <4520@ut-emx.UUCP> ethan@ut-emx.UUCP (Ethan Tecumseh Vishniac) writes:
>I see in today's newspaper that an investigation by Nature  discovered
>that there were at least two problems (fatal problems) with the
>laboratory protocol.  First, the experimenters knew at all times
>which solutions were which (i.e. control and experiment) and
>this is well known to produce biased results.

This does not sound right.  I hate to suggest that you do someting radical
like read the original paper, but they state in the paper that each initial
tube was coded with two different codes by two different pairs of observers
(not actually doing the experiment).  They do point out that, not long after
the experiments were begun, it was possible for the experimenter to tell
which was which from the results.  This is a problem that is hard to overcome,
believe me.  Even if someone else labels your samples in code, the experimental
sample can have an appearance so distict that you can tell which it is.
From that point on, you know which tube is which.

>Second, the laboratory
>notebooks revealed a large number of cases that produced negative
>results but were not included in the statistics. 

This could be a big problem; or it could be that it does not work all the time.
Do your expermints work all the time?  Unless you have never tossed a
data point, don't be too quick to judge.  
But, this requires some explanation.

>This is all supposed to come
>out in Nature in the near future.  The author (Benveniste ?) is
>standing by the work and has denounced the investigation as sloppy
>and unprofessional.
>
>As with any truly startling result, the sensible thing is to believe it
>only when such questions have been cleared.

No argument there.  I am a bit surprised that someone who seems to be proud
of his skepticism has assumed that "the Amazing Randi" and Co. have
the definitive, final word on the accuracy of a scientific work.
What did they have to say about the fact that 6 independent labs got the
same result?  Or, does that mot matter?  


> I'm not afraid of dying     Ethan Vishniac, Dept of Astronomy, Univ. of Texas
> I just don't want to be     {charm,ut-sally,ut-ngp,noao}!utastro!ethan
> there when it happens.      (arpanet) ethan@astro.AS.UTEXAS.EDU
>    - Woody Allen            (bitnet) ethan%astro.as.utexas.edu@CUNYVM.CUNY.EDU


Let's wait until all the data are in--I don't think they are yet.

-tony

ethan@ut-emx.UUCP (Ethan Tecumseh Vishniac) (07/28/88)

In article <2301@boulder.Colorado.EDU>, pell@boulder.Colorado.EDU (Anthony Pelletier) writes:
> In article <4520@ut-emx.UUCP> ethan@ut-emx.UUCP (Ethan Tecumseh Vishniac) writes:
> >I see in today's newspaper that an investigation by Nature  discovered
> >that there were at least two problems (fatal problems) with the
> >laboratory protocol.  First, the experimenters knew at all times
> >which solutions were which (i.e. control and experiment) and
> >this is well known to produce biased results.
> 
> This does not sound right.  I hate to suggest that you do someting radical
> like read the original paper, but they state in the paper that each initial
> tube was coded with two different codes by two different pairs of observers
> (not actually doing the experiment).  They do point out that, not long after
> the experiments were begun, it was possible for the experimenter to tell
> which was which from the results.  This is a problem that is hard to overcome,
> believe me.  Even if someone else labels your samples in code, the experimental
> sample can have an appearance so distict that you can tell which it is.
> From that point on, you know which tube is which.

I have read the original paper.  My statement was based on the article
in the NY Times.  I am aware of the conflict between the two.  I don't
see any way for me to judge who is telling the truth except by the
credibility of the sources, in this case a group of fairly credible people
on all sides.


> 
> >Second, the laboratory
> >notebooks revealed a large number of cases that produced negative
> >results but were not included in the statistics. 
> 
> This could be a big problem; or it could be that it does not work all the time.
> Do your expermints work all the time?  Unless you have never tossed a
> data point, don't be too quick to judge.  
> But, this requires some explanation.

I'm a theorist.  My experiments never work (or they always do) :-)
I have also listened to a large number of very impressive experimental
talks whose results have evaporated in subsequent years.  I try to
be both slow to believe and slow to disbelieve any particular result.

> 
> >This is all supposed to come
> >out in Nature in the near future.  The author (Benveniste ?) is
> >standing by the work and has denounced the investigation as sloppy
> >and unprofessional.
> >
> >As with any truly startling result, the sensible thing is to believe it
> >only when such questions have been cleared.
> 
> No argument there.  I am a bit surprised that someone who seems to be proud
> of his skepticism has assumed that "the Amazing Randi" and Co. have
> the definitive, final word on the accuracy of a scientific work.
> What did they have to say about the fact that 6 independent labs got the
> same result?  Or, does that mot matter?  

I never said that the Amazing Randi has had the last word.  I implied
his criticisms need to be convincingly answered.  Surely this is a modest
request.

As for the independent labs, again there seems to be conflicting information.
The investigation team from Nature ascribed almost all the positive results
to a single researcher working in two different labs.

> Let's wait until all the data are in--I don't think they are yet.

They never will be.  However, I remain quite willing to alter my stance
in light of further information.
F
 i
  l
   l
    e
     r

      F
       o
        r

         t
          h
           e 
              machine
-- 
 I'm not afraid of dying     Ethan Vishniac, Dept of Astronomy, Univ. of Texas
 I just don't want to be     {charm,ut-sally,ut-ngp,noao}!utastro!ethan
 there when it happens.      (arpanet) ethan@astro.AS.UTEXAS.EDU
    - Woody Allen            (bitnet) ethan%astro.as.utexas.edu@CUNYVM.CUNY.EDU

dkhusema@faui44.UUCP (Dirk Husemann) (07/28/88)

From article <2263@boulder.Colorado.EDU>, by pell@boulder.Colorado.EDU (Anthony Pelletier):
> [A lot of stuff deleted ...]
> ...
>
> Nature is planing a follow-up report in a couple of weeks.  This will be based
> on investigations currently being conducted by a group of "experts."
> This group includes not only other immunologists but also "The Amazing
> Randi" (No joke, they really are sending him).  I rather doubt Beneviste is
> sending secret messages to the cells through a radio transmitter, but,
> perhaps he can help.  Beneviste is cooperating fully in the investigation
> (which is more than Uri Geller ever did).

	At the begining of the week I read the results of this in the papers
here (Sueddeutsche Zeitung). The publisher of Nature was reported as being
really rejective about Beneviste's work now. Beneviste himself was quoted 
with a rather low opinion of the investigators.

	What I can't understand is why they sent it those people as in-
vestigators in the first place. After all, what *is* Nature, the Sun (Na-
tional Enquirer) of the sciences? At least it seems like a pretty weird
practise to send in a *magician* ("The Amazing Randi") to investigate an
issue which has been verified by other labs also ...

	But - after all, I'm *not* a biologist either ...

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---------------------------------------------------------------
> 
> Oh well, there may be a missed control somewhere, but I doubt it.
> If I were of a different religious inclination, I would suggest that this
> is God's way of saying to us scientists "Hey, don't get cocky!"
> 
> -tony

bph@buengc.BU.EDU (Blair P. Houghton) (07/29/88)

In article <4520@ut-emx.UUCP> ethan@ut-emx.UUCP (Ethan Tecumseh Vishniac) writes:
>
>I see in today's newspaper that an investigation by Nature  discovered
>that there were at least two problems (fatal problems) with the
>laboratory protocol.
[...]
> The author (Benveniste ?) is
>standing by the work and has denounced the investigation as sloppy
>and unprofessional.
[...]
>
>-- 
> I'm not afraid of dying     Ethan Vishniac, Dept of Astronomy, Univ. of Texas
> I just don't want to be     {charm,ut-sally,ut-ngp,noao}!utastro!ethan
> there when it happens.      (arpanet) ethan@astro.AS.UTEXAS.EDU
>    - Woody Allen            (bitnet) ethan%astro.as.utexas.edu@CUNYVM.CUNY.EDU

This is funny.  That denial is worded almost identically to the one
given by [something] Methodist University [something] in the Daily
Free Press (the B.U. paper) about a report one of _its_own_ comittees
gave which confirmed reports of much unprofessionalism in the B.U. School
of Theology.  It seems those hoping for a biased result are in the
same groove when it comes to supporting thair suspect actions.
Or it could be E.S.P.

				--Blair

ayermish@athena.mit.edu (Aimee Yermish) (07/29/88)

It's extremely unlikely that the antibodies would reproduce
themselves, considering that they don't have the machinery around to
do it with.  I don't know enough about the structure of the molecules
involved to answer the splitting issue, but I will suggest that if
you're diluting to 10**120, whether you started with 100 molecules or
500 molecules is really pretty immaterial.  I vote for a combination
of some loosening up by the organic gunk and some mechanical shear
provided by the vortexing (they did say vigorous, right?), will have
to really pick at their protocols in my copious free time.  It would
be really good to find something that answers the IgG control...

If they filtered it such that only water molecules could get through,
and the results turned out believable again, don't you think *someone*
would suggest that they filtered out the somehow changed water
molecules that were responsible for the effect in the first place. (grin)

--Aimee

------------------------------------------------------------------
Aimee Yermish		ayermish@athena.mit.edu
MIT couldn't care less about anything I say. 
(as long as I finish that last paper...)

diaz@aecom.YU.EDU (Dizzy Dan) (07/29/88)

Look, these degranulation results with Beneviste's infinitely diluted
antibody are certainly funky.  What's just as funky are the explanations
people will come up with when such a mystery arises.

X-ray diffraction of polypeptides and polynuclotides has shown that
water molecules associated with amino acids and nucleotides will often
order themselves in a regular pattern, detectable using
crystallographic methods.  Such ordered water can also be seen with
nuclear magnetic resonance.  Such ordered molecules are either directly
in contact with a macromolecular component or another water which is
itself associated with the protein or nucleic acid.  In all cases, such
ordered water shells are no more than 1-2 molecules thick to my
knowledge.  Despite the great electrostatic fields generated by
macromolecules they usually do not influence the structure of water more
than a few Van der waals radii beyond their surfaces.

What I'm leading to is the fact that aside from its association with
solutes and self-association in the solid phase, water usually takes on
a random structure.  If we've got some water "ghost" of the
immunoglobulin degranulating the basophils then how did we get it?  The
structure of the antibody is presumably complementary to the structure
of its binding site on the surface antibodies on the basophil.  So first
we have to have an ordered water matrix which is complementary to the
degranulating antibody, right?  We then have to make a complementary
ordered matrix of this first impression in order to regenerate the
antibody combining site of the degranulating antibody.  Sounds as
complicated as protein synthesis to me!  We've got some serum albumin
and salts in the diluent.  Are these components sufficient to induce
this primary and secondary antibody impression duplication system?

What I wonder is whether whatever is degranulating the basophils is
working by the same mechanism as the antibody.  Before we start this
physically and biochemically dubious game of postulating ordered water
ghosts, we'd better find out whether the observed degranulation has
anything to do with the surface antibodies on the basophil.  If there's
some ordered water matrix that mimics the antibody combining site then
it seems to me that this ghost should bind to an Fab fragment of the
antibody on the basophil.  If we study the binding of water by
diffraction or NMR we should see something different when using first
deionized water and secondly infinitely diluted antibody solution. 

My guess is that it's all a curious artifact we'll all be telling our
graduate students about in a few years.

-- 
      dn/dx      Dept Molecular Biology   diaz@aecom.yu.edu
     Dizzy Dan   Al Einstein's Med School  Big Bad Bronx, NY

dmark@cs.Buffalo.EDU (David Mark) (07/30/88)

In article <575@faui44.informatik.uni-erlangen.de> dkhusema@faui44.UUCP (Dirk Husemann) writes:
>From article <2263@boulder.Colorado.EDU>, by pell@boulder.Colorado.EDU (Anthony Pelletier):

>                                After all, what *is* Nature, the Sun (Na-
>tional Enquirer) of the sciences? At least it seems like a pretty weird
>practise to send in a *magician* ("The Amazing Randi") to investigate an
>issue which has been verified by other labs also ...
>

I think my source for this is Canadian radio, but I recall that "The Amazing
Randi" is a leading (founding?) member of SICOP (Society for the Investigation
of Claims Of the Paranormal"), and has a terrific record of exposing hoaxes
involving mediums (media??), hauntings, spoon-bendings, etc.  I think he is
well qualified to investigate experimental methods, possible biases, etc.
Any SICOP members read this group?  (BTW, SICOP publishes The Skeptical
Enquirer.)

dmark@joey.cs.buffalo.edu

gwyn@brl-smoke.ARPA (Doug Gwyn ) (07/30/88)

In article <575@faui44.informatik.uni-erlangen.de> dkhusema@faui44.UUCP (Dirk Husemann) writes:
>At least it seems like a pretty weird practise to send in a *magician*
>("The Amazing Randi") to investigate an issue which has been verified by
>other labs also ...

It not only seems like a sensible thing to do to me, I wish they had
done some investigation like that before publishing such an article.

I seem to recall that "polywater" was also verified by other labs.

tneff@dasys1.UUCP (Tom Neff) (08/01/88)

From what I read about this in SCIENCE and elsewhere, the real sticky
part is that NATURE sent its investigating team out before publication,
but then went ahead and published anyway before the team reported.  The
editor defended this by saying that the results were already being
reported in the French press and he didn't want to look like he was
sitting on a discovery.  This after delaying 2 years from receipt.  Now
isn't that a HELL of a way to run a railroad?

It seems clear to me that what prompted NATURE to send in a team
featuring Randi and his intrepid band of spoon-straighteners was the
presence of homeopathic doctors on the French team, not to mention that
it WAS a French team to begin with.  Homeopathy, for those who aren't
familiar with it, believes (among other things) that you can administer
microscopically tiny doses of harmful agents (infectious and otherwise)
to a patient and by doing so counteract or immunize against the
deleterious effects the harmful things would cause in normal doses.
Obviously a result that showed you could dilute an antibody infinitely
but retain its effect, would be music to the ears of homeopaths the
world over.  I'm sure that's why the homeopathic foundation supported
Beneviste's research, and why those h.p. doctors themselves were on the
team.  The discipline is far more popular in Europe than it is in the
US or the UK, which is one potential source of cultural bias when an
Anglo-American journal tries to deal with h.p. funded results.

Let's put it this way, if Beneviste had been working at Johns Hopkins
with a bunch of Texans and Bostonians on his team, and Pfizer paying, I
doubt Randi would have paid that call. :-)  Of course, had the above
been the case perhaps the result wouldn't have been obtained.  We'll
find this out when more people try to reproduce the results.

But sending Randi was an insult.  The man is a macrophage.  He makes
his living from charlatanism as surely as Madame Zolana and her
palmistry shop down the street.  Madame Z produces it, Randi debunks
it.  It's a neat ecology.  Research does not take place in a vacuum,
political or economic.  Sending "The Amazing Randi" [sheesh] after a
serious experimenter is like sending the Child Abuse Squad to visit
your bachelor uncle. Sure, it's easy to say "if nothing is amiss, they
won't be able to prove anything."  But tell that to the neighbors!  Tell
it to the grants board next time around.  Beneviste is not claiming to
be able to bend spoons for crissake, he's claiming to be able to dilute
an antibody astronomically but still detect activity via a special
staining technique.  What's Randi's job, to look for an Algerian midget
under the lab table?  Maybe a trick microscope?  Disappearing ink in
the notebooks, perhaps.

I fault NATURE on two counts: putting a professional debunker and
showman like Randi on its team, and then publishing anyway before the
team had reported.  Beneviste undoubtedly laid himself open to this
trouble by taking homeopath money and emplying homeopath assistants
*ON A PROJECT* so likely to be dear to their hearts.  Regardless of
whether the results bear out, I hope he learned a lesson.
-- 
Tom Neff			UUCP: ...!cmcl2!phri!dasys1!tneff
	"None of your toys	CIS: 76556,2536	       MCI: TNEFF
	 will function..."	GEnie: TOMNEFF	       BIX: t.neff (no kidding)

res@ihlpe.ATT.COM (Rich Strebendt, AT&T-DSG @ Indian Hill West) (08/01/88)

In article <5826@dasys1.UUCP>, tneff@dasys1.UUCP (Tom Neff) writes:
> But sending Randi was an insult.  The man is a macrophage.  He makes
> his living from charlatanism as surely as Madame Zolana and her
> palmistry shop down the street.  Madame Z produces it, Randi debunks
> it.  It's a neat ecology.

This is a gross misrepresentation of the man and his works.  Randi has
never advertised himself as anything other than a professional magician
and illusionist.  From his life-long study of the performance of magic
tricks and illusions, he has become an expert in how tricks and
illusions can be performed, and an expert in spotting such things.
Unfortunately, it turns out that scientists in general are very poor
themselves at spotting trickery, since a true scientist HAS to BELIEVE
that the results reported are being reported accurately and in a manner
consistent with the ethical code true scientists follow.  Scientists
are easy picking for a "medium" (or whatever the current stylish nom de
fraud is) or an unscrupulous collegue.

> Research does not take place in a vacuum, political or economic.

Very true.  Unfortunately, neither does unethical activity or self
delusion.

> Sending "The Amazing Randi" [sheesh] after a
> serious experimenter is like sending the Child Abuse Squad to visit
> your bachelor uncle.

Not quite.  What was done was more akin to sending a chemist to the
biology investigation to examine the chemical basis for the claims.
Randi is an expert in an area that none of the other investigators is
an expert, the art and science of illusion.  I am only surprized that
the people forming the team were smart enough to include him!!

> Sure, it's easy to say "if nothing is amiss, they
> won't be able to prove anything."  But tell that to the neighbors!  Tell
> it to the grants board next time around.  Beneviste is not claiming to
> be able to bend spoons for crissake, he's claiming to be able to dilute
> an antibody astronomically but still detect activity via a special
> staining technique.  What's Randi's job, to look for an Algerian midget
> under the lab table?  Maybe a trick microscope?  Disappearing ink in
> the notebooks, perhaps.

I cannot presume to guess what he might look for in this investigation.
I do recognize him as an expert in illusion and trickery, and assume
that his role was to be alert for such during the course of the
investigation.  Certainly, one could not expect trusting scientists to
spot such things!!

				Rich Strebendt
				...!att![iwsl6|ihlpe|ihaxa]!res

gordonl@microsoft.UUCP (Gordon Letwin) (08/02/88)

  In article <5826@dasys1.UUCP>, tneff@dasys1.UUCP (Tom Neff) writes:

  > But sending Randi was an insult.  The man is a macrophage.  He makes
  > his living from charlatanism as surely as Madame Zolana and her
  > palmistry shop down the street.  Madame Z produces it, Randi debunks
  > it.  It's a neat ecology.  

Randi doesn't receive much, if any, income from debunking.  He's a professional
magician and earns his keep that way.  

  > Beneviste is not claiming to
  > be able to bend spoons for crissake, he's claiming to be able to dilute
  > an antibody astronomically but still detect activity via a special
  > staining technique.  What's Randi's job, to look for an Algerian midget
  > under the lab table?  Maybe a trick microscope?  Disappearing ink in
  > the notebooks, perhaps.

Beneviste is claiming a result "impossible" under the existing view of
reality, a result caused by something which would have dramatic impact
on a great deal of science.  This is equivalent to spoon bending.  The
only difference is that Geller claims to be causing the spoon bending
whereas Beneviste doesn't claim to be personally causing his result.
Geller says that it's Mind Power, Beneviste says that its "unknown".

An article I recently read explained why this result gets so much attention
wheras a proposal of a 5th fundimental force hasn't generated a visit from
Randi.  The "5th force" proposal is an enhancement to current theory,
something that if true can enhance and extend stuff that's today considered
"well proven".  Whereas Beneviste's result contradicts, or at least invalidates,
most biological and organic chemistry results that have been obtained since
the fields began.  (Toss out ALL those results because the experimenters
didn't control the previous uses of their water!  ANd because dilution
can *strengthen* the effect of a substance!)

When someone proposes an enhancment, it may or may not be true, but most
people take it calmly.  But when someone says, "Electricity doesn't work"
or "magic does work", then *that* generates a large interest, and
attempting to prove it's not so is the best way to go.  Note that I didn't
say "denying it's true", I said "proving it's not true".  When the one-in-
ten thousandth case comes up where it *is* true, those debunking attempts
will fail.  Sure, the poor discoverer gets hassled for a few years.  But
his Nobel prize will make up for it.  Much better than opening the
floodgates to the endless crazy ideas that folks, misguided or fraudulent,
propose.

And as for Randi's job, you betcha he was looking under tables for
Algerian midgets.  And not disappearing ink in notebooks, but for alterations.
Remember, Beneviste might not be the trickster himself; there have been
many cases where legitimate scientists were fooled by associates,
employees, subjects, etc.  In fact, Randi's role in these things is usually
as an aid to the experimenter to keep the subject(s) from cheating.
I recall a relatively recent case of a girl who claimed ESP which was
expressed through card tricks (forget the details).  She impressed a lot
of "scientists", but with Randi, an expert on card tricks, controlling
the protocol she couldn't perform anymore.  (Well, just once she managed
to perform.  They had an "official" camera and a hidden one.  They
conspiciously turned off the official camera and left the room for
coffee after she'd failed a series of trials.  When they went back in,
she suddenly succeeded a trial!  Of course, the hidden camera showed
her cheating.

  > -- 
  > Tom Neff			UUCP: ...!cmcl2!phri!dasys1!tneff
  > 	"None of your toys	CIS: 76556,2536	       MCI: TNEFF
  > 	 will function..."	GEnie: TOMNEFF	       BIX: t.neff (no kidding)
  
Gordon Letwin
Microsoft
  

stolfi@jumbo.dec.com (Jorge Stolfi) (08/03/88)

Doug Gwyn writes:

    I seem to recall that "polywater" was also verified by other labs.

Indeed, for a couple of years at least a few hundred scientists all
around the world worked on polywater, and published papers on it,
before this mysterious and wonderful new kind of water turned out
to be a mixture of roughly equal parts of dissolved silica, sweat,
and wishful thinking.

"Polywater!" by Felix Franks tells in great detail this embarassing
chapter in the story of chemistry.  Before you give too much credence
to Benaviste's claims, you should read this little book.

                Jorge Stolfi @ DEC Systems Research Center
                stolfi@src.dec.com, ...!decwrl!stolfi

sierch@well.UUCP (Michael Sierchio) (08/03/88)

Beneviste is not making a claim for something "impossible" in the
context of current theory.  He is making a claim for an effect for
which the current theory has no explanation.  Like Maxwell. Or
Semmelweiss. 

Remember that the Royal Society said that meteorites were the products
of over-active imaginations -- as Lavoisier said (or whomever) --
there are no stones in the sky -- therefore, no stones can fall from the sky.

It may be that the effect he is describing IS the product of self-delusion
and systematic fraud.  But your notions about the purpose of science and
the state of theory I find objectionable.  Whenever someone says something
is impossible, put yer hand on yer wallet!
-- 
	Michael Sierchio @ Small Systems Solutions

	sierch@well.UUCP
	{pacbell,hplabs,ucbvax,hoptoad}!well!sierch

dgary@ecsvax.uncecs.edu (D Gary Grady) (08/04/88)

In article <1666@microsoft.UUCP> gordonl@microsoft.UUCP (Gordon Letwin) writes:
>Randi doesn't receive much, if any, income from debunking.  He's a professional
>magician and earns his keep that way.  

Randi's current main source of income is a MacArthur Foundation
"genius" grant.  He also gets funding from CSICOP and from lecture fees
about pseudoscience.

>. . .  In fact, Randi's role in these things is usually
>as an aid to the experimenter to keep the subject(s) from cheating.

Agree completely.  Even when, sometimes, the experimenter doesn't want
to be helped!
-- 
D Gary Grady
(919) 286-4296
USENET:  {seismo,decvax,ihnp4,akgua,etc.}!mcnc!ecsvax!dgary
BITNET:  dgary@ecsvax.bitnet

srt@romeo.cs.duke.edu (Stephen R. Tate) (08/08/88)

In article <5826@dasys1.UUCP>, tneff@dasys1.UUCP (Tom Neff) writes:
> But sending Randi was an insult.  The man is a macrophage.  He makes
> his living from charlatanism as surely as Madame Zolana and her
> palmistry shop down the street.  Madame Z produces it, Randi debunks
> it.  It's a neat ecology.

You must be kidding....  If I understand your argument correctly, then
the police are no better than criminals -- the criminals breaks laws,
the police enforce laws.  "It's a neat ecology."  Sounds just like
what you were saying......


Steve Tate			ARPA:  srt@cs.duke.edu
				CSNET: srt@duke
				UUCP: ..!{ihnp4,decvax}!duke!srt