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Favorite Scientific Paper?

T'ai Chi

Penultimate Amazing
T
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May 20, 2003
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Hi,

What is your favorite scientific paper?

(by that I mean a paper, published in a respected peer-reviewed scientific journal)
 
To cross-reference a moment to Geni's thread on homoeopathic excuses, I sent a copy of the abstract of that paper to the homoeopath who kept challenging me to take 30C belladonna and be amazed. He has chosen not to reply. (To be fair, I have chosen not to respond to some fan-mail papers he sent to me, because there's only so often you can say "no evidence is presented that these patients actually had the disease in question in the first place" before it gets boring.)

Assuming you want a serious answer rather than amusement value, I'll need to think about it.

Rolfe.
 
Rolfe:

I assume you have read the full paper since it is your favorite scientific paper of all time so I have a
few questions.

Since balladonna gives rise to psychoactive and hallucinatory effects , I would be
interested in knowing if the subjects were told they were taking belladonna and if they were
told what to expect. Did they look just at psycho/hallucinatory symptoms
or did they consider the presence, at no appreciable difference between placebo and the homeopathic prep, of the physical effects as well?

What were the predefined criteria for comparing the subjects' diary entries against?

thanks.....



http://chemweb.calpoly.edu/chem/bailey/377/PapersF2000/Rebecca/


The following excerpted from the above website: The leaves contain 0.3-0.5% total alkaloids and the root contains 0.4-0.7% total alkaloids. (2) The tropane alkaloids are antimuscarinics that block the acetylcholine receptors that are muscarinic, not nicotinic. (9) Both the central nervous system and peripheral nervous system (11) are affected by giving anticholinergic effects. The muscarinic receptors affected, M1, M2, and M3 are part of the parsympathetic pathway. Scopolamine is thought to be more psychoactive because it crosses the blood-brain barrier more readily. (9) Most humans, are poisoned from the ingestion of the least toxic part of the plant, the berries, containing the lowest percentage of the alkaloids. (3) Handling when cuts or abrasions are present can also cause poisoning. (15)

Sytmptoms


Free-falling.....Psychoactive effects are seen by large doses of the tropane alkaloids such as disorientation, confusion, hallucinations, delusions, and panic. But, these hallucinogens tend to make people really feel like they are real which can become very dangerous. The distortion of position/ kinetic sense can cause a person to feel like they are flying or free-falling. (9) The symptoms can vary depending on the amount Belladonna eaten or the concentration of alkaloids present. As seen above different parts of the plant contain higher risks. The symptoms include dry skin, dry mucous membranes, dilated pupils, flushing, hyperpyrexia, tachycardia, restlessness, coma, respiratory failure, and convulsions. (5) There is an old english rhyme, showing the symptoms for "anticholinergic syndrome" that is caused by the tropane alkaloids of the Solanaceous family going something like this:(snipped) "
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Steve the stuff they were taking was at 30C that is 1*10^60

Avogadro's constant is 6.022*10^23

But sice you ask. Form the paper:

Ethical approval was sought and granted by Southampton and South-west Hampshire Ethics Committee (LREC 363/00) and the East Dorset Local Research Ethics Committee (LREC 97/01/S). Student volunteers were recruited locally (November 2000 to December 2001).
Click to expand...
 
SteveGrenard said:
Rolfe:

I assume you have read the full paper since it is your favorite scientific paper of all time so I have a
few questions.

Since balladonna gives rise to psychoactive and hallucinatory effects , I would beinterested in knowing if the subjects were told they were taking belladonna and if they weretold what to expect. Did they look just at psycho/hallucinatory symptoms or did they consider the presence, at no appreciable difference between placebo and the homeopathic prep, of the physical effects as well?

What were the predefined criteria for comparing the subjects' diary entries against?
Click to expand...

It might help to read the post, Steve. You might note it was from geni, not Rolfe.

It might help to read the abstract, Steve. You might note the "diaries" were structured questionaires. That might have some relevance for your question about "predefined criteria."
 
It might help to note that Rolfe considers this paper so great he has circulated it to a homoepathic contact.
I guess I'll have to get the full text myself to determine if any aspect skewers the results. What if all the questions to the following structured questions were answered "no"? Is the conclusion then going to be : active versus placebo, no difference?

It might help to illuminate for us what the structured questions were, or pre-defined criteria which is "their words," er, not mine.

Its a very simple request that is not answered by the abstract or by you:

Were the pre-defined questionnaire or, sure, ok, "structured diary questions" dealing only with psychoactive or hallucinatory effects of belladonna or did they also include tachycardia, xerostoma, cardiac arrest, coma...?

Part two of the question: were the study subjects told the drug being tested was belladonna and were they told what the effects of belladonna are? Presumably they could look up the latter if they were told the former like anybody else. You see some big problems here? What informed consent subject is going to take a drug, one effect of which is cardiac arrest? Nobody. On the other hand, if they are told they are being given homeopathic belladonna (no chance of a cardiac arrest) and a placebo of pure water, they'd be safe, then the whole experiment is a sham ...


This also goes to the question of the diary questions?

i.e.:

(physical example)

Did you suffer from a dry mouth?"

Did you have a cardiac arrest?

Did you develop a fever?

Did you go into a coma?

Did you develop respiratory failure?


OR: (hallucinatory example)


Did you have feelings that you were flying through the air?

Did you feel you were free-falling through space?
 
5 of the questions related to true Belladonna proving symptoms. 5 of them were false belladonna proving symptoms and two were for internal consistancy.
 
SteveGrenard said:
Rolfe:

I assume you have read the full paper since it is your favorite scientific paper of all time so I have a few questions. ....
Click to expand...
Sorry? What the **** are you talking about?
Assuming you want a serious answer rather than amusement value, I'll need to think about it.
Click to expand...
I'm considering something in my own field, rather than a world-shattering discovery. Possibly a paper by Robertshaw and Taylor on the different mechanisms of inducing sweating in the donkey. But it's a big question T'ai Chi has asked, and it deserves some thought.

Edited to remark: Where did I say I thought the paper was so great? A homoeopathic colleague told me that if I took 30C belladonna I'd be so struck by the unmistakable things I'd inevitably feel that I'd be instantly convonced of the efficacy of homoeopathic remedies.

There are about four published papers (including two by committed homoeopathic devotees) which state categorically that groups of volunteers, when blinded to what they were taking, couldn't distinguish 30C belladonna from placebo. As these findings were so extremely relevant to my colleague's challenge, I sent him copies of the abstracts. What's so odd about that?

Then Geni happened to mention one of these papers as his current favourite. I remarked that I'd recently had that contact with a colleague regarding that publication.

And Steve goes ballistic. Wow.

Rolfe.
 
Still can't get an answer to some simple questions from people who take a study as gospel and don't ask any questions themselves.

Nice diversions. I guess this means thisstudy refuting homeopathy is garbage.

I did not go ballistic....... Hoyt did. As usual.
 
Steve, just a simple question. Do you understand that there are no molecules of belladonna in a 30C preparation?

By the way, I loved your "nutball" recipe. Looks delicious. But maybe rather a lot of Calories, no? :)

Rolfe.
 
I know there are no molecules of belladona in 30C Belladona. I also know there aren't any molecules of Belladona in the placebo either.

What I don't know is:

1. Were the study subjects told this was belladona being tested?

2. Were they told the effects of belladona, even the so-called hmeopathic proving effects expected?

3. Were the defined criteria or structured questions in their daily dairies covering the psychoactive symptoms of belladona, the physical symptoms of belladona or both?

4. What was the conclusion based on: that there was no difference between placebo and the molecule-free (they say "ultramolecular") 30C prep:

1. Both: No psychoactive symptoms
2. Both: . No physical symptoms
3. Both: psychoactive symptoms
4. Both: physical symptoms.

where the term "both" means the so-called active substance + the
placebo.

Rolfe...admit it, there is a serious methodological flaw with this type of experiment.

I not arguing the validity of homeopathy which you seem to think I am, and you repeatedly misattrib about what I have said on this. I am arguing the methodology of the studies to date which both refute and support the discipline.

Yes, my nutball recipe is yummy.
 
SteveGrenard said:
I know there are no molecules of belladona in 30C Belladona.
Click to expand...
Good, that clarifies the discussion. I'm anxious not to misattribute you, but you do make it difficult sometimes.
SteveGrenard said:
Rolfe...admit it, there is a serious methodological flaw with this type of experiment.

I not arguing the validity of homeopathy which you seem to think I am, and you repeatedly misattrib about what I have said on this. I am arguing the methodology of the studies to date which both refute and support the discipline.
Click to expand...
I never even claimed to have read the whole paper. Have you? However, based on what I have read, I have a couple of comments on your comments.

First, the design of the experiments seems to be to make up a questionnaire which is given to all the participants. Half the symptoms listed are those associated with belladonna in a homoeopathic proving. The other half are things not so associated. The participants were blinded as to whether they were in the test group or the placebo group. They were then asked to record which of the symptoms on the questionnaire they experienced.

You seem to be asking, quite reasonably, whether the participants were blinded as to what they were possibly taking. Also as to whether they were blinded as to which symptoms on the list were associated with belladonna and which weren't. These two points being related inasmuch as anyone who knew it was belladonna being tested could have gone to the homoeopathic literature and looked up the symptoms.

I haven't read the full paper, so I don't know. I was making the (reasonable, I think) assumption that the scrutineers for the British Journal of Clinical Pharmacology were smart enough to have queried that point before accepting it for publication. The point is almost certainly clarified in the full text. I find it hard to understand why you would categorically dismiss the whole thing as "garbage" without reading this. Now I think Geni must have read the whole thing, so maybe he could enlighten you. Since, despite your constant directing of these posts at me, it is Geni's favourite paper, after all.

But it gets more subtle than that. You are quite reasonably referring to the known symptoms of real quantities of belladonna (atropine). However, when you take this line with actual homoeopaths they will tell you that you have an incomplete understanding of homoeopathy and that this thinking is invalid. (Believe me, I've had some.)

You see, the provings themselves are done using ultramolecular preparations, and the results need have no connection to the effects of the real substance. Just as well, really, as they have proved things like the blood of an AIDS patient. The only way the findings may correlate to the original substance is that these studies themselves are usually not done blind, so the provers may be inclined to imagine relevant things, and more importantly the master prover may choose to select apparently relevant things from the slew of self-obsessed drivel that these diaries consist of.

To satisfy homoeopathic criticism, when doing a scientific study of this subject, it is necessary to follow their very odd "proving" protocols, where experienced homoeopaths examine the questionnaires and determine by their own criteria whether an individual is considered to have "proved" or not. When the abstract states:
Symptom diaries were analysed blind to determine if each subject had proved or not (based on predefined criteria). The main outcome was the proportion of subjects who had proved in each treatment group.
Click to expand...
this is what they are referring to. They're trying to do it the homoeopaths' way.

This isn't simple, because such a study has to satisfy both normal scientific criteria and the homoeopaths' own rather eccentric criteria in order to be accepted as valid by both camps. And I'm afraid the homoeopaths are rather good at moving the goalposts.

You do state rather sweepingly that all (or many or most, I'm not sure) studies of this nature have serious methodological flaws. I don't know how you can say that without looking at the full text. And while you're at it, as I said, there are several more papers on the very same subject. The others (links to abstracts) are:

G<FONT SIZE="-1">OODYEAR</FONT>, K., L<FONT SIZE="-1">EWITH</FONT>, G. & L<FONT SIZE="-1">OW</FONT>, J. L. (1998) Randomized double-blind placebo-controlled trial of homoeopathic 'proving' for Belladonna C30. J. R. Soc. Med. 91(11), 579-82.

V<FONT SIZE="-1">ICKERS</FONT>, A. J., <FONT SIZE="-1">VAN</FONT> H<FONT SIZE="-1">ASELEN</FONT>, R. & H<FONT SIZE="-1">EGER</FONT>, M. (2001) Can homeopathically prepared mercury cause symptoms in healthy volunteers? A randomized, double-blind placebo-controlled trial. J. Altern. Complement. Med. 7(2), 141-8.

W<FONT SIZE="-1">ALACH</FONT>, H. (1993) Does a highly diluted homeopathic drug act as a placebo in healthy volunteers? Experimental study of Belladonna 30C in a double blind crossover design - a pilot study. J. Psychosomatic Res. 37(8), 851-860.

W<FONT SIZE="-1">ALACH</FONT>, H., K<FONT SIZE="-1">OSTER</FONT>, H., H<FONT SIZE="-1">ENNIG</FONT>, T., & H<FONT SIZE="-1">AAG</FONT>, G. (2001) The effects of homeopathic belladonna 30CH in healthy volunteers - a randomized, double-blind experiment. J. Psychosomatic Res. 50(3), 155-160.

Note that Walach is a committed homoeopathic proponent, but even he finds no difference between placebo and control. He does question whether this is therefore an appropriate method of evaluating the effect, but not because he thinks his method had holes in it, simply because he's so convinced it's for real that he won't accept no for an answer.

Anyway, I've rabbited on too long. Steve, you declare that there is a serious methodological flaw in Geni's favourite paper, apparently without reading the paper, but based on assuming that points not mentioned in the abstract were not addressed in the full text.

Over to Geni, I think.

Rolfe.
 
SteveGrenard said:


What I don't know is:

1. Were the study subjects told this was belladona being tested?

2. Were they told the effects of belladona, even the so-called hmeopathic proving effects expected?

3. Were the defined criteria or structured questions in their daily dairies covering the psychoactive symptoms of belladona, the physical symptoms of belladona or both?

4. What was the conclusion based on: that there was no difference between placebo and the molecule-free (they say "ultramolecular") 30C prep:

1. Both: No psychoactive symptoms
2. Both: . No physical symptoms
3. Both: psychoactive symptoms
4. Both: physical symptoms.

where the term "both" means the so-called active substance + the
placebo.
Click to expand...
All of these are addressed in the paper which makes it clear that it follows homeopathic proving principles. The paper is avaible online however it is subsception only.

Remeber I said at the moment this is my favroit paper. This can change quite often as my defintion of favroit in this context is "one I am finding the most useful" mabey in a few weeks time it will be some obscure analytical paper maybe something else.
 
this is a must read for anyone who complains about scientific studies not being real world.

Prolly the best journal article I've ever read.

Mook, Douglas G. (1983) In Defense of External Invalidity, American Psychologist, 38, 279-
 
Well I was trying to find the proving for Belladona and came across the following piece of history in a British on-line textbook on homeopathy (URL given below). Correct me if I am wrong, but doesn't old Sam use cinchona in detectable doses in his first proving?

Hahnemann conducted the first proving on himself in 1790 with Cinchona [Peruvian Bark]:

'Hahnemann having, by his simple and rational experiment with Cinchona bark in 1790, conclusively established the great therapeutic law, that to cure diseases medicines must be used which possess the power of exciting similar diseases, at once perceived that the whole edifice of the old Materia Medica must be rebuilt from the very foundation, as that Materia Medica furnished nothing positive regarding the [true] pathogenetic actions of drugs.' [Dudgeon, 1853, p.176]


Dr William Cullen

Disagreeing with Cullen about the action of Cinchona upon the stomach, Hahnemann resolved to take a little of the powdered bark himself as an experiment to observe its effects more closely. To his astonishment he began to manifest symptoms broadly similar to malaria itself. Symptoms which increased as he repeated the dose, and which subsided once he discontinued the doses. This first proving was followed in quick succession by many more and increasingly included his co-workers. He noted down the mental and physical effects of drugs in increasing detail. For modern examples, see Meinden, 1997, pp.37-38; L Klein, Helodrilus Proving, 1999, pp.36-38; Klein Proving of Dinosaur Bone, 1999, pp.10-13.
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excerpted from:

http://www.homeoint.org/morrell/british/provings.htm





from the same site, regarding Belladona which causes fever and flushing, I found the following:

"The law of similars was originally used in homeopathy almost exclusively for acute, specific disorders, like Belladonna for scarlet fever."
Click to expand...

So the question is: did the active homeopathic substance and the placebo both cause fever and flushing or did they both produce nothing of the kind? My original questions regarding what the test subjects knew and what other defined criteria or structured questions were asked remain? As does whether the agreement between the 30C belladona and the placebo was a negative one or not: e.g. no symptoms whatsoever between both groups is agreement just as symptoms between both groups is agreement.

Treating a group of patients with nausea, vomiting and gastroenteritis with Belladona 30C versus placebo double blinded would be a more rational approach.

The abstract leaves much to be desired. It touts the conclusions, is vague about how they were derived and of course is selective in its reporting. Clearly one needs to see the full paper before we can determine if it is open to criticism.

Geni, please don't ask us to appeal to authority regarding the validity of this study and let it stand or fall on its own. After all, it appeared in a journal dedicated to conventional pharmacology and the last thing these editors would publish would be any paper that does NOT repudiate homeopathy. Let's not be naive here also.
 
Both the group being treated with the homeopathic remedy and the group taking the placebo contained pepole that proved. There was no significant difference between the two. As I said read the paper then critisise.

Your last statement is 100% wrong as can been seen in the British Medical Journal August 19, 2000;321:471-476.
 
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