Well, well, well, well.
Sometimes science and ethics do win out after all:
CHICAGO (AP) -- A government agency has dropped plans for a study of a controversial treatment for autism that critics had called an unethical experiment on children.
The National Institute of Mental Health said in a statement Wednesday that the study of the treatment -- called chelation -- has been abandoned. The agency decided the money would be better used testing other potential therapies for autism and related disorders, the statement said.
The study had been on hold because of safety concerns after another study published last year linked a drug used in the treatment to lasting brain problems in rats.
Chelation (kee-LAY'-shun) removes heavy metals from the body and is used to treat lead poisoning. Its use as an autism treatment is based on the fringe theory that mercury in vaccines triggers autism -- a theory never proved and rejected by mainstream science. Mercury hasn't been in childhood vaccines since 2001, except for certain flu shots.
But many parents of autistic children are believers in the treatment, and NIMH agreed to test it.
The researchers had proposed recruiting 120 autistic children ages 4 to 10 and giving half a chelation drug and the other half a dummy pill. The 12-week test would measure before-and-after blood mercury levels and autism symptoms.
The study outline said that failing to find a difference between the two groups would counteract "anecdotal reports and widespread belief" that chelation works.
Except that it wouldn't have.
Antivaccinationists would never have believed this study if it were negative, and because there was no plausible biological mechanism by which it was even possible that chelation therapy could work, the the chances that any child would benefit were slim and none while the chances of a child being injured were not inconsequential. I've already discussed in detail why the proposed study represented both bad science and bad ethics, as has Steve Novella.
Overall, it was an excellent decision to kill this misbegotten and ill-conceived study. Just because a lot of quacks have convinced parents of autistic children that chelation therapy does anything more than line their pocketbooks is not in and of itself adequate justification to do a clinical trial. Certainly it's no reason to bypass the usual series of studies necessary to justify and lead up to a clinical trial, including basic science, cell culture models, and animal models, required to provide scientific justification before testing a therapy in humans. And, once again, no matter what the results of the study, the true believers wouldn't believe it anyway. In fact, they'd declare it a conspiracy, just as the antivaccinationists at Age of Autism will no doubt soon be calling it.
Still, sometimes science wins out, and yesterday was just such a day. Autistic children will not be subjected to risk with almost certainly no potential for benefit, and the money that would have funded this study can be spent elsewhere.
I'm not sure "science wins out" when research is halted.
I don't understand the context of your statement "no plausible biological mechanism by which it was even possible that chelation therapy could work". There is no doubt that chelation does indeed "work" in removing metals from the body. There is no doubt that this effect can be therapeutic (which is why it is indicated for lead poisoning). Is removing toxic metals therapeutic for autism? I'm not sure how one could contend that this is not possible and should not be looked at.
It's one thing to disagree with chelation as a therapy, it's clear ignorance to say it does not work or that we understand the effect it has in treating autism - we don't.
Who said "research is halted"? It's not. It's just that one badly conceived and unethical clinical trial has been halted because the proposed treatment is highly implausible and that makes there in essence no potential benefit but a real risk.
Chelation can go through the same stages of research that all ethical clinical research goes through: Basic science, cell culture, and animal studies. If advocates of chelation therpay can provide preclinical evidence supporting the use of chelation therapy for autism, then I'd be all for a trial. There is no such preclinical data. Get the data first, then come back and propose a clinical trial. This trial was unethical because it in essence put the cart before the horse and started a human study before there was adequate preclinical evidence to justify one.
As for the context that there is no "plausible" mechanism for chelation to "work," I suspect you know what I meant. I meant that there is no evidence that mercury, be it from thimerosal-containing vaccines or from other sources, causes autism. So even if chelation therapy removes mercury it's not going to do anything for autistic symptoms. There is only one indication for chelation therapy that's supported by science is acute heavy metal poisoning. For that, chelation is effective.
David,
You know who wins out when stupid studies like this are halted? Kids. Kids who don't need chelation because they are not mercury poisoned.
There is not a single credible study that shows a relationship between the amount of mercury one gets and their risk of becoming autistic. Not one. At the absolute bare minimum, you need to illustrate that heavy metal poisoning plays a role in autism before you subject kids to treatment.
The study had been on hold because of safety concerns after another study published last year linked a drug used in the treatment to lasting brain problems in rats.
So the chelation fans treat autism by using a drug that really is linked to brain damage - that's some fine medical care, there, fellas.
For chelation to have any possible effect, even assuming the mercury-autism hypothesis, there would have to be mercury in autistic children. Possibly more than in healthy children. Anyways, I'm curious, how much mercury is there in a typical child?
I'm glad this study was stopped before someone was hurt. I think that sometimes these people dehumanize these kids by grouping them as sub-standard "auties" and forget that they are human beings, not lab rats.
I'm curious now (total ignoramus here): what's thimerosal? How does/did it work in vaccines? Why was it discontinued in vaccines and what do vaccines contain nowadays and how much mercury can you have built up? I ask this just for interest's sake. Vaccination, the ethical and practical consequences around it and the recent and baffling anti-vaccination attitudes springing up are fascinating subjects that I'd like to learn more about.
Thimerosal is a preservative. It was used in bottles that contained more then one vaccination shot.
Gets converted into another form of mercury that the body can metabolize.
Discontinued due to the increase in knowledge of the danger of mercury. There are a few exceptions but those are not in the standard schedule.
Mostly replaced by single shot vaccinations.
Who Cares: My understanding is that thimerosal was phased out of vaccines not because (your words) "Discontinued due to the increase in knowledge of the danger of mercury", but as a precaution. All reports I've read state that there is/was no evidence that thimerosal caused harm, beyond local swelling at the site of the injection. One issue would have been that if an alternative exists, why not use it to be on the safe side. While not stated explicitly, another issue would have be the risk of return of disease as a result of reduced vaccination because of unwarranteed fears about thimerosal being promoted by various anti-vaccine parties, not because of medical concerns about the thimerosal itself. Neither of these are saying that thimerosal was shown to be an issue, but rather that larger issues suggested the better move to vaccines not using it as a precaution.
This article discusses some aspects of the issue: http://content.nejm.org/cgi/content/full/357/13/1278
The author of this article is also the author hosted the next book club shown in the post below this on this website (in the thread It lives! The ScienceBlogs Book Club has risen from the grave!).
brightbluelizard asked...
How does/did it work in vaccines?
Its a preservative, to prevent bacteria from contaminating the vaccine.
Why was it discontinued in vaccines
To assuage the paranoid fears of some parents who thought that thiomersal may cause autism. As of today there are 13 scientific studies monitoring autism rates as thiomersal was removed from childhood vaccines in their jurisdiction.
All 13 studies saw the exact same thing - absolutely no change in autism rates.
and what do vaccines contain nowadays
Other preservatives. Formaldehyde is one replacement preservative; others may be used.
and how much mercury can you have built up?
None. Thiomersal is metabolized to ethyl mercury, which our bodies readily excrete (half-life of about 6 days, meaning its all gone 3 months post-vaccination). Toxic forms of mercury - metallic mercury and methylmercury build up in neurological tissues (hence why small doses are toxic). They have half-lives in our bodies of 60-90 days, meaning that they take years to eliminate.
Well, what happened with Secretin is an indication that it is possible for science to counter autism testimonials, for the most part. There were maybe 10 or 15 studies, though.
This is a little off-topic, but there is a statutory provision that allows drug makers to get a 6-month extension on a patent if they conduct a clinical trial in kids. You've probably heard about the controversy over whether ezetimibe (Vytorin, Zetia) works to reduce atherosclerosis and heart disease, and whether it increases cancer risk.
Well, you guessed it, a clinical trial was conducted in kids with heterozygous familial hypercholesterolemia of Vytorin (ezetimibe/simvastatin) to test its effect on LDL and other lipids and its (short-term) safety. As a result, Schering-Plough was granted "pediatric exclusivity" and an extension on its patent. How did this help the kids? I don't know, because many clinical trials have already been conducted using statins in kids with heterozygous FH with very good results. Therefore, ezetimibe really isn't needed, IMO. In addition, as long as there is doubt about its safety and efficacy in adults, I don't think it should be used in kids.
Granted, the results of ENHANCE and SEAS hadn't been announced when the pediatric trial was started, but the lack of data on safety and efficacy in adults still applied.
I admit to being a little obsessed with this topic, because my teenage daughter has heterozygous FH.
Actually, pretty much all of the knowledge has increased confidence that the tiny bit of mercury in the vaccines was completely harmless. For example, we now know that the form of mercury in thimerosal is eliminated from the body even more efficiently than previously thought. And the lack of any impact of the removal of mercury on autism rates in multiple countries has definitively eliminated the notion that thimerosal has anything to do with autism.
Basically, mercury was eliminated because the hysteria about it made many people nervous about it. Given the importance of widespread vaccination to public health, this is a sufficient reason to eliminate it, even though probably the only net effect is to increase the cost of vaccination.
Actually, formaldehyde is not used as a preservative in vaccines. Small amounts remain from its use in producing the vaccines, but it's not a preservative. Mostly preservatives aren't used because we don't do multi-dose vials any more, but some use antibiotics.
bigbluelizard, there is more information here:
http://www.fda.gov/cber/vaccine/thimerosal.htm
Marilyn,
These patents are granted as an incentive to do research on children for a reason. Children react to drugs differently than adults, and are a much harder group to work with for both practical and ethical reasons.
As a result, in order to know how drugs will work in children (its not reasonable to think these drugs *won't* wind up being given to kids, even if its not indicated), we have to provide incentives. Its a system preferable to 'Huh...well that's unexpected' after a drug has been put on the market.
Eric,
That is all well and good if the drug is needed for kids in the first place. Here, it really isn't, because we have statins.
In addition, my other point was that ezetimibe has not been shown to work in adults. That can only be shown through trials with clinical endpoints (heart attacks, strokes, death, etc.). Merck/Schering-Plough were slow to start such a trial and it won't be completed until 2012. ENHANCE did not show any effect of ezetimibe on atherosclerosis, which makes it less likely that it will be shown to have clinical benefits.
In kids with heterozygous FH it is not necessary to reach very low LDL targets.
Would you want YOUR child to take ezetimibe?
D. C. Sessions wrote: Actually, formaldehyde is not used as a preservative in vaccines
You are, of course, 100% correct. As soon as you pointed out my error I had one of those head-smacking "why the hell did you write that" moments.
The chemical I was looking for is phenol; used as a preservative in some older vaccines.
It wins when this sort of idiocy is halted, just like it wins when university budgets aren't taken up with research attempting to find a chemical process to turn lead into gold.
The study was halted because they thought DMSA could cause brain damage? DMSA doesn't cross the blood-brain barrier, thus can do no harm to the brain.
The fact that there is no known effective method for removing mercury that has entered the brain, is the main reason that the theory that mercury can cause autism has been so hard to debunk.
The researcher at the NIMH who was in charge of this study is Susan Swedo. She's known for a questionable syndrome she discovered, it's up in the air as to whether it is real or not, it's called PANDAS... it's basically supposed to be tics/Tourette syndrome following a strep infection in children.
Anyway, she's also got her name on a study that is just as bad as this chelation study, perhaps worse, and as far as I know this one hasn't been canceled. It's a study that starts by asking autistic kids if they are willing to have a lumbar puncture (twice) in the off chance that it might make them normal. If the kid agrees to it then they'll do a lumbar puncture and measure some kind of purported indicator of brain inflammation. Then dose the kid with an antibiotic and then take another CSF sample.
The odds of this doing ONE good thing for a child is nill. But they are willing to torture little autistic kids to please some freaking quack and the parents he has conned.
Susan Swedo's name needs to be spread far and wide as a person who would put the most vulnerable of all populations at risk for her career.
Chelation therapy works by infusing the patient with anions found to chelate certain types of metal ions. There is desferroximine for iron; dimercaprol for arsenic, mercury, and lead; penicillamine for copper; and EDTA for calcium, mercury, and lead. The problems are that no chelation agent is specific for a single metal ion. They only work in cases of massive overdose.
Trying to use EDTA to remove trace amounts of mercury would result in death from hypocalcemia before there was any significant mercury removal.
Dimercaprol (also known as BAL or British Anti-Lewisite) therapy is unpleasant becaise it requires intramuscular injections. It causes fever in most children, hypertension in many patients and tachycardia in some patients, paresthesias in many patients, hemolysis in patients with G6PD deficiency, etc. It requires continuous monitoring of fluids, electrolytes, renal function, hemolysis, and bone enzymes.
Newer chelators exist, but they have similar problems. Chelators should only be used in life-threatening situations. The reviewers were correct to turn down this absurd and dangerous study.
http://clinicaltrials.gov/ct2/show/NCT00409747?term=autism&rank=8
This is the one where Susan Swedo or friends will ask children as young as 3 if they are willing to undergo two lumbar punctures in the off chance that they will turn into nice normal children as opposed to staying little autistic disappointments.
Joseph,
I wish that the multiple controlled studies that showed secretin was no better than placebo in the treatment of autism had countered the "alternative" medicine testimonials about it. If you have time, check out the latest rant from Stephen Edelson at ARI - he's convinced - as are many "alternative" autism "therapists" - that secretin actually works for autism, but that the studies (the largest of which focused on the groups most likely to benefit) looked at the "wrong" children and used the "wrong" secretin (the fools - they should have kept using porcine secretin!).
Serious woo is reality-proof.
Prometheus
really, i don't see any scientific basis for the study in the first place.
even if the argument that mercury causes autism had a shred of evidence to back it up, what the hell is chelation therapy going to do? it would have to be the mercury in the brain causing the problem- we can't blame mercury in the kidneys for issues in the cns, after all. and as such, we would have to get the mercury out of the brain. but we can't, because mercury doesn't come out of the brain with chelation therapy. it's not like fat soluble drugs, where eventually equilibrium pushes it out of the fat and back into the bloodstream. mercury hides out in the brain and stays there.
so the problem is based entirely on conjecture, the solution proposed isn't even a valid solution to the problem proposed, and logic is defied yet again. i'm glad that idea was sacked.
No, the main reason the theory has been so hard to debunk is because the people who believe it are willing to completely ignore any and all evidence. There is absolutely nothing having to do with the biology, medicine, or science of it involved.
"he people who believe it are willing to completely ignore any and all evidence"
I think this is because their belief is based on a deep-rooted fear of needles. I wonder if there is an instinct at work, evolved to protect humans from scorpions, hornets, etc.
We are dealing with a rationalisation of a strong emotional reaction.
bottom line guys ... my son started speaking in sentences 3 days after starting chelation ... that is scientific enough for me. Brain damage? Not in our case since it improved cognition, speach and interactive play. If we wait around for the NIH to do something our kids will be in their 80's and non-verbal.
mlb, the plural of anecdote is not data. Also, what kind of parent experiments on their own kid?
mlb:
I know a child who started talking in sentences 3 days after first seeing Sesame Street. That is scientific enough for you.
So what do you suppose went wrong with JB Handley's son? Did he not start chelation early enough or maybe he didn't have access to the best treatments DAN! doctors had to offer? If your story is a success story, his must be a failure.