Wednesday, February 07, 2007

What You Want is What You Get

A few weeks ago, a reporter interviewed me about my research. During the interview, she asked me, “What do you want the result to be?” I was flabbergasted – it truly had never occurred to me to “want” an outcome to my research. I want to find out what really happens, what reality is – at least in the small world of my research project.

“Wanting” an outcome is what starts a lot of pseudoscience. The Holmes, et al paper is a great example of what happens when you “want” a certain result. Certain that mercury was the cause of autism, the authors took their very screwy results and spun a “Just So” story that, as it turned out, “Just Isn’t So”.

This is not always a conscious distortion of reality. Too often, it is the absolute certainty that their hypothesis is right that leads otherwise rational scientists over the edge and into the abyss. Just ask Stanley Pons and Martin Fleischman, “discoverers” of cold fusion . Neither of them was a “crackpot”, but they let their belief in their own hypothesis blind them to the flaws (major flaws) in the data.

Which leads us to the question of mercury and autism.

Let’s go ‘way back to the beginning of the hypothesis. Some folks thought that the apparent rise in autism prevalence (the “autism epidemic”) starting around 1985 could be due to the increase in thimerosal-containing vaccines that happened at about the same time. The timing wasn’t particularly close, but it wasn’t the worst hypothesis ever written. The known neurotoxicity of mercury made it biologically plausible (but didn’t prove that thimerosal could cause autism).

In real science, a hypothesis needs to explain the data – all the data – or it needs to be revised (or replaced). Things started to go wrong with the mercury-autism hypothesis when the Madsen, et al study failed to show a drop in Danish autism prevalence after Denmark removed thimerosal from its vaccines. There were some methodological problems with the study (which were spelled out by the authors), but it certainly raised a lot of doubt.

Before too long, more studies came out showing the lack of association between thimerosal dose and autism prevalence (Verstraeten, et al and Andrews, et al; Fombonne, et al). Rather than modifying (or abandoning) the mercury-causes-autism hypothesis, its proponents concentrated on attacking the motivations and ethics of the researchers.

A few studies using the thoroughly discredited VAERS database (see Goodman and Nordin) attempted to refute the better-designed studies, but were generally disregarded, except by those who were desperately trying to keep the mercury-causes-autism hypothesis alive. A report of declining autism prevalence (Geier and Geier) was not only poorly done but, as later data revealed, wrong.

Here is the crux of the matter: the autism prevalence data from the California Department of Developmental Services (CDDS) and the United States Department of Education (USDE) have not shown a decline in autism prevalence. That is not an issue in question – it is simple fact. Whether or not this data is valid (and there is some doubt about that, see Shattuck, Newschaffer and Laidler), it was what the original mercury-causes-autism hypothesis was based on.

The reason that the prevalence of autism is so critical to the mercury-causes-autism hypothesis is, of course, because thimerosal was removed from children’s vaccines in the US sometime between 2000 and 2001 (depending on which source you use). No matter when it was finally completely removed, the thimerosal dose received by children in their vaccines has [a] not risen since 1999 and [b] has significantly fallen since 2000.

Thus, even if thimerosal had remained in all children’s vaccines at its 1999 concentration – which it hasn’t – the autism prevalence should have reached a plateau by now. And it hasn’t.

Let me repeat that, for emphasis.

Even if the total amount of thimerosal that a child received in vaccines had remained at the 1999 level, the prevalence of autism would have reached a plateau by now if thimerosal was a major cause of autism.

Given that the thimerosal dose received by children born after 2001 (to allow an overly generous time for all the “on the shelf” doses to be used) has been significantly reduced, we should have seen a decline in autism prevalence by now, if thimerosal caused a significant fraction of autism cases. And we haven’t – decidedly not.

Now, the mercury-causes-autism proponents have been forced to resort to a variety of “bait and switch” tactics to keep their supporters’ eyes off of the poverty of their hypothesis. Mercury from power plants, China and crematoria has been invoked – despite the fact that mercury deposition rates have been declining since 1961 (Roos-Barraclough, et al ).

They have also proposed mercury in dental amalgams, Rho-Gam shots and flu shots as potential sources of mercury.

The basic problem with all this “bait and switch” is that they are acting as though the core assertion of their hypothesis – that mercury can cause autism – has been proven, which it decidedly has not!

The failure of US, UK, Danish, Swedish and Canadian autism prevalence to fall following the removal of thimerosal from children’s vaccines has not supported their claim – in fact, it has weakened it. In addition, showing that mercury can cause autoimmune disorders, “oxidative stress” and neuronal injury is not the same as showing that it can cause autism.

Pretty much everybody knows that mercury is not a good thing for you. This is not the question. The question at hand is whether it can cause autism. And the answer to that question – at least so far – has been “No.”

So, asking if I’m in favor of exposing kids to mercury or if I think that mercury is a good thing for kids is simply a ploy to shift attention away from the glaring absence of data supporting the mercury-causes-autism hypothesis.

And pointing out that flu shots have mercury, or that there is mercury in our food, water and air is just more of the same. The onus is on those who propose that mercury causes autism to bring sufficient data (data, not testimonials, stories about “recovered” children or wild fantasies about governmental conspiracies) to the table to show why their hypothesis is a better explanation of how the universe (and neurobiology) works than the “null hypothesis” (that mercury doesn't cause autism).


A few ground rules:

As a personal pre-condition (a promise made to myself) of returning to ‘blogging, I have elected to moderate all comments. I do this to prevent the sort of free-for-all insult-fests that are all too common from certain individuals (who need not be named).

I expect people to behave themselves in a civilized fashion. Do not bring fights from other ‘blogs into this one simply because you have been banned somewhere else. Fore Sam has already gotten himself banned for a day for doing just that. And because he has already used up his lifetime allotment of second chances. Fore Sam, consider yourself on permanent probation – you’ve earned it.

If it upsets you that your commentary is not appreciated here, then you are free to set up your own ‘blog and rant about my arbitrary justice to your heart’s content. You are free to say what you want here, as long as you remain within the bounds of civilized discourse.

Finally, do not be surprised or upset if your assertions ("It's right because I say it's right! Are you callin' me a liar!?!"}, anecdotes ("It worked for me!"), unsupported hypotheses ("I don't have any data! I don't have time to get data - I'm busy saving lives!") and conspiracies ("It's a guv'mint plot!") fail to convince. That's just the way science works.


Enjoy!



Prometheus

22 Comments:

Blogger Fore Sam said...

If mercury didn't cause the problem, will you explain why chelation works?
Suppose you're right. Then ADD numbers should not be going down either. Does anyone know if they are?
Granted, you guys can keep knocking me until I cure Sam since the progress is very slow. However, I knocked out my younger son's ADD in a couple of months with chelation. He went from struggling with every subject to getting 100% on all his tests and breezing through his homework.
So, if you can show me that mercury didn't cause the ADD, I think some science guys should be able to explain why the chelation worked.

07 February, 2007 05:55  
Blogger Estee Klar-Wolfond said...

Very illuminating.

There is one thing we can all want, however, which is respect and dignity for all persons and everything can branch from that.

07 February, 2007 08:33  
Blogger Prometheus said...

To Fore Sam:

Have you or anyone else shown data that chelation "works" for autism? Not that I'm aware of.

Remember, anecdotes like "It worked for my kid!" aren't data. I might point out that secretin was once thought to "work" for autism (and is still used by many "autism doctors") - study after study has shown that it doesn't work. This includes several major studies by a company (Repligen) that had a significant economic incentive to see secretin "work" for autism. In the end, even Repligen had to admit that it didn't do squat.

This is why controlled studies are so important in medicine - even more so than in any other branch of biology. People want to get better (or they want their kids to get better) and so will "emphasize the positive, eliminate the negative...", as the old song goes.

Sorry, Fore Sam, but asserting that "chelation works" will not make it so. Show us the data.

Now, if chelation were to be shown to improve autism, that might be a tiny bit of data in favor of the mercury-causes-autism hypothesis. However, you would still have to show that it wasn't some other effect of these drugs (they DO have more than one effect) that caused the improvement.

I know that a number of the doctors providing chelation for autistic children have promised that they have data. Unfortunately, they always seem to get too busy saving lives (or giving talks) to publish their data.

This is a real shame - if they had data showing that chelation really was helpful, publishing it would mean that more autistic children would be able to get this therapy.

But they don't publish. And I am left wondering why.


Prometheus

07 February, 2007 10:08  
Blogger clone3g said...

FS: I think some science guys should be able to explain why the chelation worked.

It wasn't ADD, yer other son was suffering from a DMSA deficiency.

07 February, 2007 10:11  
Blogger Joseph said...

I wasn't aware ADHD was diagnosed or undiagnosed based on school grades. Either way, it's hard to believe anything Fore Sam says. I have to wonder where the exaggeration and where the omissions are.

07 February, 2007 11:59  
Blogger Prometheus said...

I completely missed Fore Sam's ADD/ADHD comments - my bad!

Fore,

You've gotten it all backwards. It's your job to explain why mercury can cause ADD and/or ADHD, not my job to explain why it can't.

Come on, man! I'm sitting here willing to be convinced! All you have to do is show me the data! And you're holding out on me! Show me the data! You've GOT to have data, as confident as you are.

Right?

Don't you?

Or have you simply lept to the conclusion that, since someone told you that mercury can cause one developmental disorder, that it can cause them all? In THAT case, you can rest easy; mercury has not been shown to cause autism, so ADD and ADHD are probably also not caused by mercury.


Prometheus

07 February, 2007 13:25  
Blogger David N. Andrews MEd (Distinction) said...

Ah, Prometheus.....

But you forget.... John isn't really interested in the science. He doesn't understand it. He doesn't want to understand it. He just wants to get some money.

And he daren't have a go at my credentials anymore, so he's taken to having a go at other people...

Pretty sad, really.

07 February, 2007 14:49  
Anonymous anonimouse said...

John Best prefers his arguments to be data-free and logic-free.

07 February, 2007 15:24  
Anonymous isles said...

Jim Adams, the engineering professor, was, when last heard from, undertaking a study of the efficacy of chelation. That was quite some time ago. No triumphant study-waving has ensued. Could it be that the results were not what the anti-mercury campaigners hoped? They wouldn't have tried to bury an unfavorable result, would they?

07 February, 2007 18:30  
Blogger mcewen said...

those "'x' cured my child" are so tantalizing initially when you first have a diagnoses and no nothing.
Cheers

07 February, 2007 18:36  
Blogger Fore Sam said...

All I asked was for you to show me why the chelation worked to get rid of the ADD. You claim it isn't mercury so tell me what happened to solve the problem. Show me you know more about all of this than Andy Cutler.

07 February, 2007 19:19  
Blogger Prometheus said...

Fore Sam:

I think that before anyone - including me - spends any time or effort "investigating" why chelation "works" for ADD, we should have some indication that it actually does work.

Sorry, but having you say "Chelation cured my kid of ADD (or autism)!" a thousand times doesn't make it a fact (or data. Not even if you shout it.

Here is the data you have provided:

[1] Your child showed behaviors that you felt were consistent with ADD.

You have not established yourself as a qualified psychiatrist or psychologist, nor have you stated that the diagnosis of ADD was made by a qualified psychiatrist or psychologist, so this "data point" remains in question.

[2] Your child received chelation of an unspecified type, dose and duration.

[3] At some time after [2], the behaviors mentioned in [1] decreased. This change was not confirmed - per your posts to date - by anyone other than yourself.

Doesn't that pretty much describe what you've told us?

Now, let's go on to what I've told you:

[1] You have not provided sufficient data for me to conclude that your child had (or has) ADD or ADHD. Poor school performance can have a variety of causes, so an improvement in grades is diagnostic of precisely zip.

I make no claims about "...what happened to solve the problem..", since you have not provided enough data to show what the "problem" was or that your "intervention" (chelation) "solved" it.

[2] I have not said that "...it isn't mercury..."; what I've said is that you haven't shown that it is mercury.

There is a huge difference between those two statements - and I think that you know that. You're the one making the claim - you support it. If you don't want to support it (for whatever reasons you might have), then don't be surprised when I assert that you haven't supported your claims.

Clear enough so far?

As to Andy Cutler - I've read his books and I feel confident that I know more about the topic than he does. But you don't have to take my word for it, since I don't expect you to believe my unsupported claims any more than I believe yours.

If you want to believe what Andy Cutler says about mercury, I wouldn't dream of standing in your way. I suspect that his explanation of reality fits your world-view far better than anything I could provide.

To Everybody Else:

I want to reiterate that Fore Sam is not a "sock puppet" I created to act as my "straight man". As far as I know, he is a real person, writing under a pseudonym. Frankly, I don't think I would have the patience to do the job he's doing for me.


Prometheus.

08 February, 2007 08:55  
Blogger David N. Andrews MEd (Distinction) said...

"I want to reiterate that Fore Sam is not a 'sock puppet' I created to act as my 'straight man'. As far as I know, he is a real person, writing under a pseudonym."

'Fore Sam' is John Frederick Best, of Londonderry, New Hampshire (at least, that is what I was able to find out).

John claims to have a Bachelor of Arts degree in Psychology, although I have found very little evidence of a sound knowledge of psychological principles in his postings on the internet and in his - rather abusive - e-mails that he is wont to send out from time too time. He claims to have - in addition to the BA in Psychology - a Master of Public Administration degree.

Prometheus (to JBJr/FS): "You have not established yourself as a qualified psychiatrist or psychologist, nor have you stated that the diagnosis of ADD was made by a qualified psychiatrist or psychologist, so this 'data point' remains in question."

He is not, on the basis of his claimed qualifications, a suitably qualified person to make such a diagnosis. Assuming that the BA claim is genuine, even that is not qualification enough to be making this diagnosis. Your note about the data point being 'in question' is a somewhat kind way of describing the ADD issue claimed regarding his son.

Prometheus (to JBJr/FS): "[2] I have not said that '...it isn't mercury...'; what I've said is that you haven't shown that it is mercury."

In my capacity as Associate International Editor of the journal Good Autism Practice, I myself have offered John the chance to demonstrate his point. He was offered a chance to put into practice the skills one would ordinarily learn in a BA degree in psychology, in the form of a practitioner-research study on his son. The study, which would have been a typical way of publishing practitioner-research results, would (subject to it having conformed to certain standards - such as those used by the APA or the BPS - in terms of quality of research, writing and referencing) have been assessed on how well it demonstrated the effectiveness of chelation as a treatment option in autism.

He didn't just decline this opportunity: he refused it (this is all documented on (I believe) Joseph's blog). Better still, he actually demanded that I do the study... notwithstanding that he is the one wanting people to accept what he says! As far as I am concerned (and as far as Good Autism Practice would be concerned... I would have to run this notion past the main editors, but I can pretty much guarantee an agreement here), he makes the claims and he wants the world to take them seriously... so he should be the one doing the study, not me. His refusal, in my view, is an admission that he does not know for certain that this 'treatment' is actually working: anyone who was certain of that would actually go ahead and do the study anyway - just to find out if their idea was right! Refusal is also a likely sign that he knows that the 'treatment' is not the 'active ingredient' in Sam's (or in Sam's brother's) life that is bringing about the changes JBJr actually claims are occurring.

He is not interested in demonstrating anything; he merely wishes to rile people. That's the impression I get.

Prometheus: "Frankly, I don't think I would have the patience to do the job he's doing for me."

Thankfully, none of us has to, since he is perfectly happy to go on record saying obviously errant things (and I myself am being very kind here about what he says).

08 February, 2007 10:07  
Blogger Fore Sam said...

As usual, you call me a liar and do some tap dancing. We're not in court here. See ya.

08 February, 2007 18:01  
Blogger Prometheus said...

Fore Sam,

You are so terribly predictable. In your reply, you stated:

"As usual, you call me a liar and do some tap dancing."

This is very similar to the part of my post where I describe ineffective responses to constructive criticism of your ideas:

"It's right because I say it's right! Are you callin' me a liar!?!"

In fact, Fore Sam, if you read my comment, you will see that I take great pain to not call you a liar. That is because I am giving you the benefit of the doubt. If you have some data that would support your claims, please let us know about them.

From what you have posted here (I cannot account for information you might have posted on other 'blogs), your son's diagnosis of ADD/ADHD was made solely by you. It may be that you forgot to mention that he was diagnosed by someone qualified to make that diagnosis, or that you simply felt that you had all the information you needed to presume the diagnosis of ADD/ADHD.

Either way, you have not established your son's diagnosis as ADD/ADHD in any real way.

As for "tap dancing", I suppose that I am doing a bit of a dance in order to keep from bringing your veracity into question. I avoid that for exactly the same reason that I question your diagnosis of your youngest son - because I have no data to support it.

There may be other people who would have called you a "liar" by now, Fore Sam, but I'm not one of them. I think that you are immature, bullying and almost certainly very mistaken, but I have no data to support calling you a liar.

So, why don't you drop the wounded dignity pose and either show us the data or quietly let the matter drop?

It's your choice.


Prometheus

09 February, 2007 09:15  
Blogger María Luján said...

Prometheus
I have sent a post yesterday. Please let me know if you received it because I did not see it approved.
Thanks

09 February, 2007 10:38  
Blogger Fore Sam said...

My younger son was diagnosed by a neurologist after having been seen by a psychologist. The MD prescribed concerta which I never gave him. I chelated him and his schoolwork improved. I'm not giving you his name or his medical records and if that's not good enough for you, I don't care.
The only important thing to me is that mercury is not screwing up his life. I don't care to write details for publication anyplace. I'm happy to share the information with other parents who want to help their kids.

09 February, 2007 19:57  
Blogger Prometheus said...

Fore Sam,

See, that wasn't so hard.

I don't want or need to know your son's name and I certainly don't expect you to send his medical records (were those "straw man" arguments? I never asked for either his name or his medical records).

That certainly makes your case that chelation cured your son's ADD a bit stronger, now that we can know the diagnosis with confidence.

When I assess claims of a "cure" for any disorder, there are four "confounding factors" I look for:

[1] Errors in diagnosis. This is a big problem with both autism and ADD/ADHD - even with professional diagnosis - because there are no consistent objective findings in either condition. (However, I will accept the diagnosis of ADD as "confirmed" in Fore Sam's son because he made the effort).

[2] Assessment of improvement. Without an objective measure to follow, disorders like autism and ADD/ADHD are subject to errors in assessing improvement, especially if the assessment involves parental (or any other third party) report of behaviors.

[3] Simultaneous therapies. A lot of the "clinical research" in autism therapies (and ADD/ADHD therapies) is compromised because the therapy under study is not the only therapy used. This makes it impossible to attribute any improvement to one therapy.

[4] Hidden variables. The single most common hidden variable overlooked in many autism studies is aging. Behaviors change rapidly in children - especially young children - and disabled children are no exception. All too often overlooked is the fact that autism is a syndrome of developmental delay, not developmental stasis.

I want to commend Fore Sam for providing some data to support his claims. I hope that this won't be the last time this happens. It's a small step, but the journey of a thousand miles begins with a single step.


Maria,

I never got your post, which is why it wasn't approved.

Bazooka Joe,

I think you and Ian Parker should take your discussion off this blog, since it seems to be related to your personal differences of opinion. You're both welcome to post comments here, but only if you stay a bit closer to the subject.


That's all for now,


Prometheus

10 February, 2007 12:47  
Blogger Prometheus said...

Wade Rankin,

I realize now that approving Bazooka Joe's comment was a mistake, which is why I allowed Ian Parker to have a go. I do not intend to allow every aggrieved party a chance to vent their spleen at Bazooka Joe (or to allow him to reply to all of them in turn).

I have removed both Bazooka Joe's original comment and Ian Parker's reply. I suggest that anyone who feels a need for "satisfaction" find a more suitable venue (how about http://www.mudwrestling.blogspot.com ?).

In other words, why don't you boys (and/or girls) take it outside?

You are all welcome to post on the topic, but try to keep the personal attacks to a minimum. I don't expect everyone to sit arm in arm and sing "Kumbaya", but at least make your personal attacks relate to the subject at hand.

For people who are expecting absolute consitency in my moderation choices, I have some sad new: I am but human (despite the name). My decisions may be questionable or even arbitrary but - on this 'blog, at least - they are final.


Prometheus

10 February, 2007 13:07  
Blogger Wade Rankin said...

No problem on my end, Prometheus. The only reason I felt the need to respond was that the horse was already out of the barn, and it did not appear that you were going to recapture it before closing the door. I'm happy to see that I was wrong.

10 February, 2007 13:36  
Blogger María Luján said...

Hi Prometheus

Thank you for your answer. The previous post was a candidate for deletion- it was an aswer to Mr "Bazooka Joe".

Personally, I do not think that a non-autistic child will become autistic because of vaccination- and the epi tells us this, even with its problems. I do think that a genetically susceptible child (not only autistics) can have very negative reactions to vaccination (especially when vaccines are given in combination or in high numbers, mainly if there are familiar antecedents of susceptibility- autoimmunity, adverse previous reactions, herpes zoster in parents/relatives, unknown, Alzeheimer, etc) and this is a different world.

In this sense, all the trials I have read have been done on healthy children in the long term of the cases that reach a Phase III trial (beyond the testing on specifically ill children such as asmathic in the case of influenza or transplanted and others, but meny times these patients have not adverse reactions to vaccination).

Therefore , IMHO, to the question
“Can postnatal total amount of thimerosal in vaccines be linked as an unique CAUSE of autism”
For the majority of the population the answer, with the data/science available it seems it is no.
“Can postnatal vaccines be linked as an unique CAUSE of autism”
For the majority of the population the answer, with the data/science available, it seems it is no.
And I agree with BOTH NO, with the constraints I included (majority, data available).

Now, let´s go to do different questions
Can thimerosal in vaccines produce adverse reactions in genetically susceptible children? What kind of and what extension and why?
Can vaccines (in particular or in Whole schedule, whole composition –including neomycin, Aluminium, others-including known contamination) produce adverse reactions in genetically susceptible children? What kind of and what extension and why?

Please note that I AVOID CAREFULLY the word CAUSE/S.I am talking of the potential of concomitant problems to an ASD diagnosis and a very much complicated picture, being this ONE part in a long list.

And the questions for me are how we detect them? How do we prevent them?

The study/studies proposal of the CDC is important, IMHO.
Study or Studies Regarding the Potential Association of Vaccine Adverse Events and Human Genetic Variations
I am really interested on the last questions and the results of this study. There are several reports on the HLA polymorphisms and adverse reactions to HepB and measles, and also reports of the same polymorphisms on a subgroup of autistic children, for example.
Link

10 February, 2007 14:36  
Blogger David N. Andrews MEd (Distinction) said...

John: "My younger son was diagnosed by a neurologist after having been seen by a psychologist. The MD prescribed concerta which I never gave him. I chelated him and his schoolwork improved. I'm not giving you his name or his medical records and if that's not good enough for you, I don't care."

Thanks for the info, John. However, this caveat at the end should also apply to you with regard to the diagnoses of adult autistics against whom you have made nasty attacks. I'm thinking in particular about Amanda and how you have allowed yourself to remain 'not convinced that she is autistic'. You want use to be satisfied with your say-so here, and I'll go with it like Prometheus will. But there is a flipside to this. You have the same obligation to Amanda if you want everyone else to abide by what you say about your sons and their diagnoses: you have to accept that Amanda is autistic and stop trying to make her out to be the fraud that she definitely is not. It's called reciprocal courtesy. In other words, treating people with the respect with which you want them to treat you.

This is where you demonstrate that you are indeed an officer and a gentleman.

"The only important thing to me is that mercury is not screwing up his life. I don't care to write details for publication anyplace. I'm happy to share the information with other parents who want to help their kids."

I'm with Prometheus on his reservations about this.

Nonetheless, well done on the letting go a bit and providing at least something.

11 February, 2007 04:06  

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