"It's better to light a candle than curse the darkness"

This can’t be for real…

March 11th, 2009

But it is.

Sometimes, I read about new “treatments” for autism that seem too wacky to be real. Unfortunately, most of the time they are all too real. What I am talking about today is the use of nicotine patches to “treat” autism.

No, I’m not kidding.

The history of this latest therapeutic misadventure in autism begins with a presentation on 17 November 2008 at the Society for Neuroscience meeting in Washington, D.C. by Dr. Rene Anand, an associate professor of Pharmacology at Ohio State University’s College of Medicine.

Dr. Anand’s presentation was about neurexin-1, a gene that has been implicated in nicotine addiction, schizophrenia and autism. In his research (not yet published), Dr. Anand has apparently found that one of the products of the neurexin-1 gene (neurexin-1 beta) is responsible for directing a specific type of acetylcholine receptor (nicotinic receptors) to the synapse.

Since abnormalities in acetylcholine receptors have been noted in autism (see here and here) and the neurexin-1 gene has also been implicated in autism, this seems like an promising line of inquiry into the etiology of autism. When asked, Dr. Anand was quoted as saying:

“If we were to use drugs that mimic the actions of nicotine at an early time in human brain development, would we begin to help those and other circuits develop properly and thus significantly mitigate the deficits in autism? This is a novel way of thinking about how we might be able to use drugs to approach autism treatment.”

So far, so good. It certainly sounds like an intriguing area for future research. But how did the “biomedical” community of practitioners respond to this information?

Well, Dr. Jeff Bradstreet, noted DAN! physician, has jumped on this news and is currently treating autistic children with nicotine patches (see here, esp. the last three slides). I’m sure he’s not the only one, but he’s been kind enough to put his……”practices” on the web for all to see.

And if Dr. Bradstreet is treating autistic children with the nicotine patch, there are sure to be several other “alternative” practitioners who are following his lead.

It is truly frightening to watch how a bit of speculative musing was “morphed” in a few short months into a full-blown “biomedical” treatment for autism. Without even a single piece of data supporting the use of nicotine in autism, “alternative” practitioners are slapping nicotine patches on autistic children across the country (and possibly all over the world).

In his usual fashion, Dr. Bradstreet has marshalled a number of tangentially relevant studies to support - after the fact - his decision to promote this “treatment”.  He cites the Potter and Newhouse (2008) study that showed the nicotine patch improved cognitive performance in young adults (18 - 22 years old) with ADHD [Note: ADHD is not the same as autism].

He also cites (but apprently does not comprehend) the Sacco et al (2004) review of  nicotinic receptor mechanisms and cognitive function (if he had understood it, he would have seen that it didn’t support the use of nicotine in autism - it doesn’t even mention autism).

Likewise, he makes liberal use of the graphics in the de Jonge and Ulloa (2007) article about the anti-inflammatory actions of the α-7 acetylcholine receptor without showing that autism is caused by neuroinflammation (although he seems fixated on that concept, the data supporting it is weak at best). His presentation also wanders into vagal nerve stimulation, which is a frightening window onto what he may be considering in the future.

I’d like to emphasise that I’m not picking on Dr. Bradstreet. He, at least, has made an attempt (largely negated by his use of scientific studies to “prove” what he already “believes”) to understand the science behind what he proposes to do to autistic children. Others haven’t even gone that far - they simply mimic what “everyone else is doing”.

But enough about Dr. Bradstreet and the parrot practitioners. What is the actual likelihood of the nicotine patch helping an autistic child? Let’s go back to Dr. Anand’s statement for a moment:

“If we were to use drugs that mimic the actions of nicotine at an early time in human brain development, would we begin to help those and other circuits develop properly and thus significantly mitigate the deficits in autism?”

“…at an early time in brain development…” does not mean six years old. Dr. Anand was probably speaking about intrauterine development. In fact, Dr. Anand doesn’t have any idea if this would work or not - he’s just speculating. Read the sentence again if you disagree with me.

In addition, the studies looking at acetylcholine receptor abnormalities in autism have shown problems with expression of the genes for the receptors themselves, not with neurexin-1-related proteins. In fact, even the study linking neurexin-1 disruption to autism found:

“A scan of the NRXN1 coding sequence in a cohort of ASD subjects, relative to non-ASD controls, revealed that amino acid alterations in neurexin 1 are not present at high frequency in ASD.”

These facts together suggest that treating autistic children with nicotine patches is not likely to help them at all.

And what are the risks of treating young children with nicotine?

Well, for starters, nicotine is an addictive drug. Parents who recoil at the thought of giving their children Ritalin (methylphenidate) because it is addictive should contemplate this fact carefully.

Secondly, nicotine withdrawal causes anxiety, irritability and aggressive behaviors. Will this lead parents to believe that the nicotine patch is “working” because their children are so much worse when they don’t get their “fix”? I suspect it will.

Thirdly, we don’t have a lot of information about how nicotine affects childhood development, largely because few children - prior to now - have become addicted to nicotine before their early teens. Once again, parents of autistic children are queing up to have their kids turned into guinea pigs.

The chance of benefits is extremely low and the risk of bad outcomes is significant (nearly a certainty, given what we know about nicotine in adults). In addition, the symptoms of withdrawal in nicotine-addicted autistic people are likely to be misinterpreted by parents (and many “alternative” practitioners) as signs that the nicotine patch “works” to treat autism.

We should ”just say no” to giving nicotine to autistic children. Not just because nicotine is an addictive drug, but also because it’s a poorly thought-out idea with no data to support it.

Prometheus

Filed under: Autism Practitioners, Autism Treatments | 30 Comments »

Jabberwocky revisited

March 8th, 2009

‘Twas brillig, and the slithy toves
Did gyre and gimble in the wabe;
All mimsy were the borogoves,
And the mome raths outgrabe.

“Beware the Jabberwock, my son!
The jaws that bite, the claws that catch!
Beware the Jubjub bird, and shun
The frumious Bandersnatch!”

He took his vorpal sword in hand:
Long time the manxome foe he sought—
So rested he by the Tumtum tree,
And stood awhile in thought.

And as in uffish thought he stood,
The Jabberwock, with eyes of flame,
Came whiffling through the tulgey wood,
And burbled as it came!

One, two! One, two! and through and through
The vorpal blade went snicker-snack!
He left it dead, and with its head
He went galumphing back.

“And hast thou slain the Jabberwock?
Come to my arms, my beamish boy!
O frabjous day! Callooh! Callay!”
He chortled in his joy.

‘Twas brillig, and the slithy toves
Did gyre and gimble in the wabe;
All mimsy were the borogoves,
And the mome raths outgrabe.

Lewis Carroll, 1871

 

The recent Autism Omnibus decisions in the Cedillo, Snyder and Hazelhurst test cases have brought into sharp relief the differences between the “experts” on the vaccines-cause-autism “side” and the true experts who testified for the respondents.  Kathleen Seidel at Neurodiversity Weblog has done her usual masterful job summarizing the decisions, if you’re not up to reading them in their entirety.

However, I think that the people who continue to blindly support the allegation that vaccines cause autism should read every word of these decisions, if only to counter the wild and conspiratorial stories spread by those people who have a financial and emotional stake in not letting this hypothesis die a quiet and well-deserved death.

This information has been covered - in greater depth - by other ‘bloggers (see above as well as here and here ), but what got me motivated to write this piece was a comment from a distraught parent (not one of the three families in the test cases). She said:

“I can’t see how we lost. I listened to all the testimony and I thought that our side had better experts and better science.”

Before I give my views, let me quote a few sentences from the legal decisions.

In Cedillo vs. HHS, Special Master Hastings had this to say about the evidence presented:

“…I concluded that the evidence was overwhelmingly contrary to the petitioners’ contentions. The expert witnesses presented by the respondent were far better qualified, far more experienced, and far more persuasive than the petitioners’ experts, concerning most of the key points. The numerous medical studies concerning these issues, performed by medical scientists worldwide, have come down strongly against the petitioners’ contentions.”

He also made some specific comments, which show that he understood what many of the “vaccines-cause-autism” promoters do not:

“Dr. Corbier, like Dr. Kinsbourne and many of the respondent’s witnesses, did explain that the measles virus can in some instances cause injury or death in humans, in the form of disorders such as measles encephalitis, SSPE, etc. He seemed to then jump from that evidence to the conclusion that the MMR vaccine-strain form of the measles virus is capable of causing autism in a person with genetic susceptibility. But Dr. Corbier never persuasively explained how he can reasonably make that startling jump, in light of the fact that autism is a disorder quite different from measles encephalitis, SSPE, and the other disorders that are known to be caused by the measles virus.”

In Snyder vs. HHS, Special Master Vowell said:

“To conclude that Colten’s condition was the result of his MMR vaccine, an objective observer would have to emulate Lewis Carroll’s White Queen and be able to believe six impossible (or, at least, highly improbable) things before breakfast. The families of children with ASD and the court have waited in vain for adequate evidence to support the autism-MMR hypothesis.”

She also said:

“The evidence presented was both voluminous and extraordinarily complex. After careful consideration of all of the evidence, it was abundantly clear that petitioners’ theories of causation were speculative and unpersuasive. Respondent’s experts were far more qualified, better supported by the weight of scientific research and authority, and simply more persuasive on nearly every point in contention.”

So, the Special Masters - who listen to this sort of testimony all the time - weren’t convinced. In fact, Special Master Vowell had this to say about the petitioners “experts”:

I am convinced that the reports and advice given to the Cedillos by Dr. Krigsman and some other physicians, advising the Cedillos that there is a causal connection between Michelle’s MMR vaccination and her chronic conditions, have been very wrong. Unfortunately, the Cedillos have been misled by physicians who are guilty, in my view, of gross medical misjudgment. Nevertheless, I can understand why the Cedillos found such reports and advice to be believable under the circumstances. I conclude that the Cedillos filed this Program claim in good faith. [emphasis added]

The question then is why the parents continue to be misled by the “experts”.

I am in frequent contact with parents who “believe” that vaccines - in one way or another - caused their children’s autism. From this, I have come to realise that it is the presentation of the information - rather than the information itself - that has led to (and continued) their belief. 

A lot of parents who are involved in “alternative” or “biomedical” autism treatments mention that they were told by the diagnosing physician that “nothing can be done” about autism. Whether or not their recollection of the discussion is accurate, their perception is that “mainstream” medicine didn’t offer “answers” that were satisfactory to them. All too often, the “alternative” practitioners have the “answers” these parents are looking for. The problem is that the “answers” aren’t correct - as the Special Masters noted above.

What it comes down to is that most people can’t tell when they are hearing the “straight scoop” on science and when they are hearing “Jabberwocky”. There is no shame in this. Everyone has their own areas of expertise and not everyone has the necessary education and experience to tell when they are being fed a line of…..fertiliser about biology and medicine.

The average citizen cannot tell the difference between real science and something that merely sounds like science. Some doctors cannot tell the difference, having been unable or unwilling to keep up with scientific developments. But rather than admit to themselves that they don’t understand a word of what they are hearing, people fall back on their secondary method of telling if something is true or not - their feelings about how trustworthy the speaker is; how persuasive they are.

The problem is that some people are very persuasive even when they aren’t being trustworthy.

Think of all the rich people - presumably very “smart” about financial matters - who invested money with Bernie Madoff. It wasn’t his investment strategy that convinced them to give him billions to invest - he didn’t tell them his investment strategy - it was his personality that convinced them (and his reputation). He persuaded them - against what had to be their better judgement - to trust him.

Likewise, it is the personality - and the apparent confidence - of the “alternative” practitioners that leads people to “believe” in them, even when they don’t really understand what they say. The irony is that these same practitioners often tell the parents to not “believe” what anyone else says. This is what makes it so hard to convince the parents that they’ve been misled.

When I read the transcripts of the expert testimony during the Autism Omnibus Proceedings, it was clear to me that the petitioners’ experts were not just unpersuasive, they were uninformed. Many of them are intelligent people who have done good work in their fields (some are not), but their conclusions were at odds with the data and what we know about biology.

For people who know biology and/or medicine, the nonsense and contradictions in the petitioners’ experts’ testimonies were as obvious as if someone had talked about a “touchdown” during a baseball game or if they said, “The square root of orange is turquois.”

That’s why they lost.

They lost because the Special Masters could tell the difference between real science and Jabberwocky.

 

Prometheus

Filed under: Autism Practitioners, Autism Science, Autism Treatments, Critical Thinking | 24 Comments »