Here is a study I was reading today:
Original Research Papers
Histamine dilutions modulate basophil activation
P. Belon 1, J. Cumps 2, M. Ennis 3, P. F. Mannaioni 4, M. Roberfroid 5, J. Sainte-Laudy 6, F. A. C. Wiegant 7
© Birkhäuser Verlag, Basel, 2004
Inflammation Research
Inflamm. res. 53 (2004) 181–188
What it is about is doing a test involving the use of histamine to inhibit basophil activation.
Here is what is said in the Introduction:
Human basophils play a key role in allergic diseases. Activation of basophils via cross-linking of membrane bound IgE induces fusion of the cytoplasmic granules with the plasma membrane and the subsequent release of potent mediators including histamine. Histamine itself can inhibit the further degranulation of the basophil by acting on H2 receptors [1, 2]. A series of investigations, mainly by one group, has demonstrated that high dilutions of histamine are also capable of inhibiting basophil degranulation.
So what I get from this introduction is something like this:
Basophils are involved in allergy reactions — the do something to bring on allergy symptoms. The way they do that is that an antibody (IgE antibody, which is the one that allergic people produce) has combined with the cell and makes it do its basophil thing. One of the main things is releasing histamine which causes a big reaction in the tissues.
However, if histamine is already out there it prevents more of the basophil action — sort of sounds like a feedback system, doesn’t it?
Then they go on:
Although a biological action of ultra high dilutions has been shown, this is extremely controversial [5 – 8]. Indeed the paper published by Benveniste and colleagues in 1988 sparked a series of letters and investigations of various degrees of seriousness [7–15]. This group suggested that high dilutions of anti-IgE were able to stimulate human basophils. Ovelgönne et al. and Hirst et al. attempted to repeat these experiments but found no evidence for any periodic or polynomial change of degranulation as a function of anti-IgE dilution [7, 8]. The results did, however, contain a source of variation that could not be explained [8].
So now they are telling us why they are doing this study. The prior work that Benveniste did, that caused so much upset, was a similar study using basophils, etc., only they did it with a different angle, using highly diluted antibody (actually diluted and succussed but the critics like to leave the succussion part off because just dilution sounds so silly). They found the highly diluted antibody caused the basophils to be triggered and to release their stuff. (We might remember that many laboratories duplicated this work. I don’t remember how many, I want to say 6?).
However some other group said they did it as well and could find no evidence for “any periodic or polynomial change” of the basophil effect. What the hell does that mean?
Periodic I assume means some kind of variation related to the dilution of the antibody. I looked up “polynomial” in the dictionary and it gives this definition:
an expression of more than two algebraic terms, esp. the sum of several terms that contain different powers of the same variable(s).
So what the hell does this mean? Best I can come up with is that the research group reported they could not find some sort of correlation, even a mathematical one, related to the Benveniste dilution/succussion studies. It sort of implies a criticism doesn’t it? But why? I mean if there is no correlation then that means there is no correlation, right? Is there some sort of law that says there has to be a mathematical formula for an observation to be real? Maybe there is one but we don’t know it yet.
So then they say:
Our experiments began in the early 80’s and were initially based on examination of the activity of histamine dilutions on basophil activation measured by alcian blue staining. The first series of studies used specific allergen and leukocytes taken from allergic subjects and thereafter we employed anti- IgE. These data obtained between 1981–1994 [16–20] demonstrated inhibition of basophil activation by histamine dilutions which were always in the same dilution range (between 10–6 and 10–8 and 10–30 to 10–34 theoretical molar concentrations). The inhibition by histamine was reversed by an H2 receptor antagonist (cimetidine) and a structural analogue such as histidine showed no effect [21].
Whew! OK. Since the 1980′s they have been doing some studies of this. They used a test that stained the basophils which was the way they determined if the cells had discharged or not. Presumably the dye showed granules or something. The first tests they did involved mixing what they thought was the thing causing the allergy in a person (the allergen) and white blood cells from people with allergies. They mixed the two together and added diluted histamine to see what would happen. They apparently had an effect from the diluted histamine even in dilutions as high as 10 to the 34th dilution (they don’t say if they did succussion, presumably they did it like Benveniste). Well, a 10 to the 34th dilution is equivalent to a remedy potency of histamine of 17c, not super high but high enough that it is beyond any physical substance being present. If you remember that Avogadro’s number is the number of molecules of histamine in a (more or less) quart of water (or whatever) and that number is 10 to the 23rd molecules being present, then a dilution to 10-34 is way beyond that. How far beyond? Well, 34-23 = 11, which is then a dilution beyond the last molecule of histamine done 11 more times (assuming a 1:10 dilution). Pretty darn likely there is no more histamine around (unless one really sticky molecule somehow hung on!).
So you can see why they say:
Given the controversial nature of these results, a multi-centre blind investigation of the inhibition of basophil degranulation by high dilutions of histamine was performed. In order to further investigate the effect, using a flow cytometric assay of basophil activation, further studies were performed in three of the participating laboratories. Part of this work has been published in the form of refereed extended abstracts [21–23].
They start out saying what they found out before is controversial (well, hey! it is not always predictable what you are going to find). Having been in science myself I can tell you what this means. “Controversial” means that some people just don’t like the results. Tough noodles, guys, that is the way science comes down.
Anyway, they are going to really go for it now. A “multi-centre” investigation means they are going to do the experiments in more than one laboratory. Presumably this reduces cheating or maybe some particular investigator from controlling it with their mind. That it is spelled “centre” instead of “center” means this is really high level stuff.
Then they use a new assay method, the “flow cytometric assay”. I have no idea what this is, but sounds really impressive. I mean it is flowing…
I think “cytometric” must mean that they are counting the cells so maybe the cell broth is flowing through some sort of counting apparatus? I like it.
Then they finish up by letting us know that what they have already published was “refereed”. What does this mean? Well, means they got some other people to agree with them, that their studies were done OK. This is important because we all know that there can’t be anything new found in science that others will not agree with, right? I mean what if you were the ONLY ONE! Like maybe Einstein, or Galileo or one of those radicals.
Anyway, I digress…
So then they do their study, get some of the same effects, tell us how terribly careful they were this time (had the solution prepared someone else and had the people preparing wearing eye patches — oops! I mean “blinded” so they didn’t know what they were preparing, and so on. They go on to justify the “flow” way of evaluating, how people were trained to be accurate and so on — actually quite impressive. They were able to see positive effects in multiple laboratories and they put the conclusions (and, yes, there are detailed tables and charts if you want to study them) like this:
It is clear from Figure 1 that ultra-high dilutions of histamine inhibit basophil activation (CD63) without any dose-response relationship. It is equally clear from Figure 4 that high dilutions of histamine inhibit the immunological release of histamine without any dose-response relationship.
Did you get it? They are saying YES the high dilutions DID have action on the cells. This is amazing, isn’t it? But they put it in a way that you would hardly notice it. Like when you read it, sort of seems like they are saying they couldn’t really show any dose relationship, like that is the point of the sentence. I think that means they could not correlate the effect with what dilution they used BUT THERE WAS STILL AN EFFECT SEEN ANYWAY. Wouldn’t you think they would really get excited about this?
Well, to my eye they are actually embarrassed by it because they take the trouble to sort of justify what they found. Usually in a scientific report the beginning of it will have the history so to speak, the work that others have done that leads up to this. In this report they actually insert the positive results of others in the Discussion part, at the end. Odd, and not typical but I think because they are trying to say “See, we’re sorry we got these results but these other guys did first…”).
Here is what they put in:
Other biological models have examined the effects of high dilutions:
– Doutremepuich and co-workers [6, 31, 32, 33] demonstrated that, in the rat, high dilutions of aspirin (15 C 10–30 g/l) have pro-aggregant and prothrombotic activity. They showed that the effect of an injection of 100 mg/kg aspirin is totally inhibited by the extemporaneous injec- tion of aspirin 15 C.
– Jonas and co-workers [34] demonstrated that preincubation of neuronal cells with high dilutions of glutamate (10–22 and 10–30 g/L) protects against subsequent exposure to toxic levels of glutamate. High dilutions of cycloheximde (10–27 M) also protected against the effects of glutamate exposure [35].
– Using a radioactive tracer method high dilutions of As2O3 (10–14 g/l) enhanced the elimination of orally administered arsenious anhydride [36].
So they are saying that other studies showed similar results with highly “diluted” substances:
1. diluted aspirin affected clotting.
2. diluted glutamate protected nerve cells from damage from toxic doses of the same (isopathy).
3. diluted cyclohexamide also protected nerve cells from toxic doses of glutamate (I don’t know why but that is not the point).
4. diluted arsenic enhanced elimination of arsenic when (rats?) poisoned by mouth with it.
So they are trying to say they are not alone in this. Still they bury the results as much as they can. When you read it, however, they do say that they had positive results, even dramatic results, in all 3 laboratories.
They do have the gumption to say they can’t explain it (doesn’t matter that we homeopaths can cause we’re wrong, right?)
We are not yet able to propose any theoretical explanation of these findings. Despite searching for artefacts, we have been unable to find any. Taking into account the ultralow concentration of molecules in such dilutions, we hypothesize that biological information must come from solvent which is pure water in our experiments. Thus we have investigated not only biological models but also physical models.
They are buying into the whole fictitious “water structure” model as a way of sneaking around it. I mean why not just say they don’t have the slightest idea how to explain it from their understanding of biology and chemistry? They go on to quote some of the “water structure” ideas. This unfortunately is being promulgated in the homeopathic community and I predict it will backfire — badly. Why? There may be changes in water, could be, but a side effect and irrelevant.
Why do I say that? Simply because if this is how remedies act (through restructuring water) then water is necessary in the preparation of remedies. This has been well shown not to be the case, therefore water is not the necessary ingredient.
Evidence?
1. Trituration = remedies made without water, in milk powder.
2. Benveniste’s experiments = remedies made into potency with no water whatsoever. He used two kinds of alcohol.
3. Experiments reported by Hahnemann (1836 if I remember right) in which 1 dry medicated pellet added to 13,500 dry unmedicated pellets, the whole lot shaken together and the remedy potency transferred to all the pellets.
That these 3 examples show ipso facto that water is not necessary means that water is not necessary in making remedies. Therefore, it is not the way in which the information is transferred or carried to the patient.
I pointed this out in the lecture. In discussion afterwards with the homeopath sitting next to me, he said that even if this is not the way remedies act it may be convincing to non-homepaths — hardly a reason to spread the error to my mind.
Anyway, I digress. In this paper, the authors are reluctantly grabbing the water ship as it leaves the harbor. I mean, by God, it can’t be something that is not physical, right? If it were then those damn homeopaths would be right and there are people that would rather die than have homeopaths be right.
The last paragraph in the paper:
The findings presented in this paper suggest that high dilutions may indeed exert an effect on cellular activity. We are however unable to explain our findings and are reporting them to encourage others to investigate this phenomenon. On the basis of previous results, we plan to test with the flow cytometric technique the effect of other agents such as H1 agonists and antagonists and autocoïds.
Don’t you love it? I understand this because I used to be in academia and write papers like this. You can’t say “WE FOUND THAT HIGH DILUTIONS HAVE BIOLOGICAL ACTIVITY, LIKE IN HOMEOPATHY!” No, you have to tone it down. You say “the findings in this paper suggest…” Do you get it? They didn’t do it — THE FINDINGS DID IT! Those damn findings.
Not only that but they “may” indeed exert an effect. Duh! What did your experiment show? Did the flow counter say “maybe”? But this is the way you are supposed to write scientific papers. No one actually did the work, the findings came out on their own, and what they tell you may or may not be correct — I mean who am I to say, the lowly scientist.
Anyway, they are plunging ahead with more studies.
Will be interesting.
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