Sunday, July 31, 2005

Somewhere Over the Rainbow - The Search for an Autism Cure

To a humble biologist, like myself, the idea of "a cure for autism" is as simplistic as "a cure for cancer." This isn't because I think that either autism or cancer are necessarily "incurable", it's just that both ideas demonstrate a serious lack of knowledge.

The "cure" part isn't the problem - it's the "a" part.

You see, like cancer, autism is not a single disorder. Genetic studies point to several disorders, with linkages on several different chromosomes. Even a casual reading of case histories and parental anecdotes shows an amazing range of severity, types of disabilities, progression, and accompanying signs and symptoms.

If I wrote up ten or twelve case histories of autism today and tried to conclude that they were all suffering from the same disorder, I would be laughed at. Yet there are people - the autism-mercury cabal foremost among them - that insist ("demand" would be more like it) that autism is a single disorder.

Think about cancer. If we were to lump all cancers together, we would have the same sort of mess that is currently seen in autism. There would be no consistent presentation, no consistent progression of the disease and there would certainly be no treatment that would work on all (or even most) "cancer".

Yet, in a startling parallel, there are people in the world who claim to have found a cause for all cancer and even a cure for all cancer. Like the people who have found the cause for all autism and its cure, they are all - at the very least - terribly mistaken.

So, before we all run off like headless chickens looking for an autism cure, perhaps we ought to spend at least a few minutes making sure we know what autism is. After all, except for the autism-mercury experts, nobody knows what causes autism.

That's right, we don't know what the pathology in autism is. We don't even know, for sure, what part of the brain is involved (we are pretty confident that it is a brain disorder, rather than, say, a liver problem). There are those who feel that it is probably a disorder of the amygdala, but nobody has found any consistent abnormalities in the amygdala of autistic people. In fact, no physical abnormality - genetic, biochemical, radiological or other - has been consistently found in all autistic people.

This, of course, is just more evidence that autism is not a single disorder. To extend the cancer analogy, that would be like trying to find a consistent biopsy in all cancer patients - doing, for example, a lung biopsy in everyone. It would come as no surprise to us that a lung biopsy would fail to show cancer in someone with basal cell carcinoma, just as a skin biopsy would be highly unlikely to reveal lung cancer. So why is it that otherwise intelligent people can't see the reason there is no consistent pathology in autism?

And since we aren't even sure if we're dealing with a single disorder (except that some of us, myself included, are very sure that we aren't), it would seem extremely foolish to start looking for causes and treatments. Going back to the cancer analogy, looking at UV exposure as a cause for all cancers would fail to show a relationship, since pancreatic, lung, liver and kidney cancer are not correlated wth UV exposure - and would miss the cancers that are UV-caused, like basal cell and melanoma because of the "background" of non-UV-related cancers.

Likewise, treatments that might help a sub-set of cancers would not show any benefit when tested against all cancers because of the large number of non-responding cancers included in the subject mix. So too, a treatment that might be effective for a certain sub-type of autism will have its benefits "drowned out" by all the other disorders that don't respond to it.

In the final analysis, it does little good - and probably a good deal of harm - to go chasing off after various hypothetical causes and cures of autism at this point. First, we need to find out what the abnormalities (that's right, plural) in autism are and then sort the patients into their proper diagnostic groups. Otherwise, we're going down the rabbit hole after the "cure for all autism", which - like chasing the pot of gold at the end of the rainbow - is very engaging but never profitable.


Friday, July 29, 2005

Dr. Hornig's Autistic Mice

The September 2004 issue of Molecular Psychiatry (may not have been available at your local news-stand) contained an article by Dr. M. Hornig et al titled, "Neurotoxic effects of postnatal thimerosal are mouse strain dependent". Athough the title doesn't give any hints (other than the mention of thimerosal), the article is all about autism. This struck me as strange, since I had a hard time imagining how you would tell if a mouse was autistic. But, I digress.

The Autism Diva has already addressed the topic of autistic mice and Dr. Hornig in some detail in her delightful post, "Rain Mouse?", so I'll try not to cover the same ground. Instead, I would like to address some of the technical aspects of the study.

In a nutshell, Dr. Hornig and her colleagues gave intramuscular (i.m.) injections of either thimerosal or a placebo to newborn mice. The mice were from three different strains - one that was susceptible to autoimmune disorders (SJL/J) and two that were not (C57BL6/J and BALB/cJ).

In order to simulate the immunization schedule given to human infants (see where they're going with this?), they gave the injections on the 7th, 9th, 11th and 15th days of life. For reference, human infants receive their immunizations at ages 2 months, 4 months, 6 months and 12 months (one year). However, mouse infancy is much more accelerated than human infancy, requiring the injections to be spaced closer together in order to happen during the same developmental stages.

A plan of overdosage:

The timing of the injections is the first flaw that I would like to address. While it is true that this dosing schedule allows the thimerosal to be administered in the same neurodevelopmental stage as in human infants, it overlooks a big fact of biology.

The plasma half-life (time that it takes for the plasma concentration to decrease 50%) of methylmercury in humans is variously reported as being between 40 and 56 days. There are no published studies of the half-life of thimerosal in humans, but animal studies make it likely that it will be longer. The half-life of methylmercury in mice is much shorter - 158 hours.

So, a dose of mercury given to a human will be half gone in about 50 days and, in a mouse, 6 1/2 days. Let's look at what this means in the context of this study:

If an infant is given a mercury dose at time zero (0) that produces a blood mercury level of 1.0 (arbitrary units), that blood level will be down to 0.44 after 60 days. A second dose at 60 days (see where I'm headed?) will bring the blood level to 1.44. In another 60 days, the level will be down to 0.63 and another dose will bring it up to 1.63. After waiting 180 days (about three half-lives), the blood level is down to 0.13 and a fourth dose will raise it to 1.13.

Now let's look at it from the perspective of the mice in this study. If they receive a dose at time zero that produces a blood level of 1.0 (arbitrary units), after two days, the blood level will only be down to 0.81. Another dose raises the blood level to 1.81 and, after another two days, it is down to only 1.46. Another dose raises the blood level to 2.46, which is down to 1.61 when the final dose raises it to 2.61.

So, the human experiences a maximum blood level of 1.63 (arbitrary units) and the mouse - since it is being dosed at a smaller fraction of its half-life - sees a maximum blood level of 2.61. In short, the mouse gets to a blood level 60% higher than the human.

The case of the underweight child:

Now, this all assumes that the mouse and the infant are not growing - which is not true - and that the doses they are getting are equivalent on a microgram per kilogram body weight basis, which also is not true. The study dosed the mice on a per kilogram basis equivalent to what a human infant would have received had they received their vaccinations on schedule. However - and this is a curious thing - they used the 10th percentile (10% of children that age weigh less, 90% weigh more) body weights for children at ages 2, 4, 6 and 12 months.

I found myself wondering, "Why didn't they use the 50th percentile (50% weigh more than this weight, 50% weigh less - sort of an 'average weight')?" I have no answer - but I have an idea. By using the 10th percentile, they were able to give the baby mice an even bigger dose of mercury. Let's run the numbers, as they say on NPR:

Dosing is based on the child receiving 62.5 micrograms of thimerosal at 2,4 and 6 months and 50 micrograms at 12 months. Using the numbers for 10th percentile weights and 50th percentile weights, this works out to doses of:

2 months
10th - 4.4 kg - 14.2 ug/kg
50th - 5.3 kg - 11.8 ug/kg (17% less)

4 months
10th - 5.7 kg - 10.8 ug/kg
50th - 6.8 kg - 9.2 ug/kg (15% less)

6 months
10th - 6.8 kg - 9.2 ug/kg
50th - 7.9 kg - 7.9 ug/kg (14% less)

12 months
10th - 9.0 kg - 5.6 ug/kg
50th - 10.3 kg - 4.9 ug/kg (13% less)

So, by using the 10th percentile weights, the authors were able to give the mice about 15% more thimerosal. This goes nicely with the dosing schedule to significantly raise the dose the mice receive.

The show must go on!:

What Dr. Hornig didn't show in her article, but is showing to concerned parents of autistic children, is the video of her autistic mice. The study article adresses such prosaic behavioral changes as decreased spontaneous movement, decreased exploration and decreased streotypic behaviors, but the video (CAUTION: large file) she shows includes such titillating tidbits as one mouse grooming another to death and another mouse biting its own tail. These, she says, are evidence that these mice have become autistic....

Hold the phone! Grooming is a social activity mice engage in, and autistic people are supposed to be averse to social interactions! And although self-injurious behavior is seen in autism, there are other, better explanations that were overlooked.

In fact, I felt a strange hot flush come over me as I watched the video (maybe it was just a hot flash). I have seen exactly this type of behavior before - but not associated with mercury.

Many years ago, I was associated with a group studying treatments for chronic neuropathic pain. The model we used was a rat model in which we injured the sciatic nerve and let it heal. A number of the rats would develop what was assumed to be neuropathic pain - evidenced (so we thought) by biting and chewing on the affected hind limb. It was a grisly sight and, what was worse, it wasn't really neuropathic pain.

Another group discovered that anything that caused abnormal sensation would cause rats (and other animals) to bite and gnaw on the affected limb. What I saw in these mice was exactly what we saw in the partially denervated rats. And - oh, by the way - mercury causes parasthesias (numbness and tingling). Dr. Hornig has probably managed to make these mice so neurotoxic that they are experiencing parasthesias - a common sign of mercury poisoning.

And now, a word from our sponsors!:

These days, no discussion of mercury and autism is complete without a thorough exposition of who paid for the study and who might have a conflict of interest. So, you might ask, who paid for this study?

The UC Davis M.I.N.D. Institute
The Coalition for Safe Minds

To remind you, the Coalition for Safe Minds' mission statement is:

"Our mission is to end the health and personal devastations caused by the needless use of mercury in medicines. "

But I'm sure that didn't influence the outcome of the study.

Happy reading!


Wednesday, July 27, 2005

If you want to drive the Bus...

Postponing my showdown with Dr. Hornig's autistic mice yet again, I would like to address a phenomenon that is nearly ubiquitous in the "alternative" medicine world. I am speaking of the concept that anybody - regardless of their education, training or experience - is qualified to speak knowingly and render expert opinion on scientific and medical matters, as long as they have personal experience of the subject under discussion.

This is a phenomenon that defies common sense - the very same people who take offense at being told they lack the proper education to make scientific and medical assertions are often "professionals" of another stripe - MBA's (and here), lawyers, and stock brokers - who would be aghast at the suggestion that a neophyte off the street could do their job with equal skill. Imagine their outrage (or amusement) if I, a humble biologist, announced that I was as competent as they were to, say, formulate a business plan for a multinational corporation, set up a tax-sheltered annuity or render an opinion on federal law.

The sad fact of the matter is that it takes a certain amount of education to be a scientist, or even a doctor. There are facts to learn, techniques to practice, skills to acquire and mental habits to develop. You can't get these from watching "ER", "CSI Miami" or even the Discovery Channel.

This is not unique to science. Lawyers, MBA's, stock brokers, plumbers, electricians, truck drivers, firefighters, bicycle racers, and even the folks flipping hamburgers all have to spend a certain amount of time learning how to do their job. If your education, training and experience is solely in business, law or marketing, then you have no more expertise in science than you have in firefighting - and what's your plan if the stove catches on fire tonight, eh?

So, why is it that people who wouldn't think about redoing the plumbing in their bathroom suddenly feel that they have innate skills in science? Part of it has to do with our education system, which gives everyone a small taste of "science" in the primary and secondary grades but fails to instruct them in the real methods of science. The average person thinks that a scientist is just a huge repository of "facts", since that was what their "science" classes in high school were all about. That couldn't be farther from the truth.

A real scientist has to learn a prodigious amount of information, true enough, but the real emphasis is on learning how to think. It is much easier to teach a student the Periodic Table than it is to teach them how to formulate a testable hypothesis. And it is far easier to teach the Kreb's Cycle than it is to teach how to draw an accurate and supportable conclusion from experimental data. This is probably why most college graduates with "science" degrees don't end up doing any research - they end up selling or being technicians or technical advisors.

Although there have been some excellent self-taught scientists in history, they are few and far between. And there haven't been too many of them since the middle of the last century. So, it seems pretty unlikely that someone is going to read a few semi-technical books and emerge able to compete head-to-head with an educated and experienced scientist when it comes to, say, critical evaluation of a scientific study. Yet there are numerous people who claim to be able to do this very thing.

I once witnessed an amazing exchange between a research physician and a parent of an autistic child. The parent had a degree in business and had been a fairly successful business person for many years. The physician had been researching autism for over thirty years. The discussion I overheard (and oversaw) was about - couldn't you just guess - whether or not autism was caused by mercury.

After the physician had explained the reasons why he felt that mercury didn't cause a majority of the cases of autism - along with the caveat that the research so far couldn't eliminate mercury as a minority cause, the parent said:
"Well, my assessment of the data is that mercury is the only cause of autism and that genetics has nothing to do with it."

The physician paused for a moment, clearly debating whether or not to reply, and finally said:

"You'll excuse me if I feel that you lack the qualifications to give that assertion much weight."

The parent then retorted, angrily:

"That's just typical physician arrogance - I'm just as qualified as you to decide what causes autism!"

I was stunned. Not because this parent "talked back" to a physician - I actually enjoyed that part - but I was stunned by the appalling ignorance of that statement. I was stunned that someone with no significant scientific education and a few years experience as a parent of an autistic child could honestly think that they were equal in qualifications to someone with an advanced degree inscience and thirty years of research in the field!

OK, this isn't "PC" - it's not "polite" to tell people that they don't know what they're talking about. But it's true! Just because someone has an autistic child does not make them an expert in the science of autism. Sure, they know a whole lot about raising an autistic child, but that does not give them any insight into the biochemistry or neurophysiology of autism.

In other words, if you want to drive the bus, you need to go to bus-driver school, first.


Tuesday, July 26, 2005

Men of Straw, Invisible Black Sheep and the Tale of Two Lemmas

In the rather short time that I have been writing this blog, I have become acutely aware of the deplorable state of reasoning skills among the supporters of "alternative" medicine. Today's lesson will be on Logic.

The Straw Man Fallacy:

Detailing the logical errors in most of their arguments would require a book, but there is one logical fallacy that the "alties" seems particularly fond of: the "straw man." For those who didn't take Professor Petersen's Logic class, the straw man fallacy is simply attacking an argument that your opponent didn't make. Usually, this is done by implying (or asserting) that your opponent has argued something easy to refute - usually something extreme and indefensible - and then attacking that argument instead of the one your opponent actually made.

As a hypothetic example, if your opponent said that there is no data supporting a causal connection between autism and mercury, you could attack them for saying that mercury is completely safe. You could ask them, "Do you think that mercury is a good thing to inject into children?"

This tactic does not refute your opponent's argument - it doesn't even address it - but it is a good way to switch the discussion from an argument you can't win (since you don't have any decent data) to one that you can win. It's not intellectually honest, but it works more often than not. Just watch any political campaign.

Some of the more popular straw man arguments that I've seen used in "alternative" medicine are:

[1] "People should be allowed to make medical decisions for themselves."

This straw man is usually used to dodge the issue of practitioners failing to be honest about the data supporting their treatments (usually none). By making it appear to be an issue of personal autonomy, rather than an issue of truth in advertising, the builders of this straw man hope to avoid the tough questions about a practitioner's obligation to be honest and open about what they are selling.

[2] "You're trying to take away our right to free speech!"

The First Amendment of the US Constitution, and similar constitutional guarantees in other countries, does not grant carte blanche rights to say anything one wants. Libel, slander, and mail fraud are all offenses that involve the improper use of speech. The right to freedom of speech and press is not a license to lie, deceive and defraud.

Argument from Ignorance:

Another favorite "altie" fallacy is usually expressed as, "You don't have any proof that it doesn't work (or cause cancer/autism/terminal moraine)."

This fallacy - the argument from ignorance - is used in much the same way as a straw man. It is much easier to argue that something isn't proven to never happen than to argue that it does. A classic story of this (told to me by the aforementioned Prof. Petersen) is the story of the two logicians:

On a train through Scotland, a senior logician and his junior colleague were observing the countryside. Upon sighting a huge flock of grazing sheep, the junior colleague casually remarked, "There's not a single black sheep in that whole flock."
The senior logician, roused from his doze, retorted, "You can't say that - you don't know if you can see the whole flock!" Chastened, the junior logician replied, "Well, all the sheep in view are white." The senior logician snorted into his mustache and said, "You can't say that, either!" "Well!" said the exasperated junior member, "What can I say?" With a smug look, the senior logician replied, "That all the sheep in view are white, on at least one side!"

So, the absence of visible black sheep does not eliminate the possibility of black sheep - no matter how many sheep are observed - because the presence of a single black sheep somewhere in the Universe (Past, Present or Future) firmly establishes the existence of black sheep.

However, in biology, it is not usually important to know if black sheep exist, as long as you know that they are exceedingly rare. For example, while it has not been possible to definitively prove that power lines do not cause brain cancer in children, it has been shown that the risk is between zero and a risk so small that it blends into zero (i.e. the uncertainty range includes zero).

Likewise, it may not be possible to prove that Dr. Alt's Sure-Fire Cancer Cure doesn't ever cure cancer, but it is possible to show that it happens less often than with other, more established treatments (or placebo, or the spontaneous remission rate of the cancer). So, even if it is true that someone (or even two or three someones) had their cancer "disappear" after taking Dr. Alt's treatment, it doesn't mean that it actually works.

False Dilemma:

One logical fallacy that shows itself time and again in "alternative" medicine is the false dilemma. This fallacy is basically a failure to consider (or present) all of the possible alternative choices. In "alternative" medicine, this fallacy is often somewhat hidden, as in the following:

"If we let the government regulate vitamins and supplements, then you won't be able to buy them anymore."

In this case, the false dilemma presented is between the following two options:

[1] Unregulated advertisement and sale of vitamins and "supplements".

[2] Vitamins and supplements being banned from sale.

In reality, there are many other possible choices, such as:

[3] Vitamin and supplement retailers being required to provide sufficient data to support any claims they make in advertising or on the label.

[4] Limiting sales of vitamins and supplements to only those items whose safety has been established by legitimate studies.

[5] Requiring that vitamin and supplement makers (and sellers) make no health-related claims about their products.

[6] ... etc.

By using a false dilemma - an "either this or that" type of framework for the debate - the "alties" manage to make their preferred stand at least the lesser of two evils. However, they can do so only by picking an extreme option and making it appear to be the only other choice. If all the potential options are placed on the table, their preferred choice is the one that looks extreme.

Well, that's all for now. Class dismissed!


Thursday, July 21, 2005

An Embarassment of Riches

I can't believe it! I locked my door when I left for lunch and, when I returned, there were two articles on the floor of my office. Forensic evidence suggests that they had been inserted under the door. The Facilities Maintenance people have refused to put a tighter threshold on the doorway, so I guess I will have to adjust to this rich source of material (and amusement).

The first article was from a newspaper in Seattle, the Seattle Post Intelligencer and was titled, "The Abortion Debate that Wasn't". Despite the eye-catching title, the article really wasn't about abortion - except indirectly - it was about eugenics.

Eugenics is an old concept, dating back to at least the late 1800's. For those who aren't familiar with the concept, it is the idea that we can "improve the breed" (i.e. the human breed) by preventing "abnormal" people from reproducing. This has been tried in a number of places and in a number of ways, from "euthenasia" (an nice way of saying "murder") of the "unfit" to forced sterilization.

I don't want to debate the morality of eugenics - which could take decades and is rather beyond my area of expertise - but the reality of it. Although I may not be an expert in medical ethics, I can speak rather expertly about the genetic practicality of eugenics. Apart from the very real question of how to determine who is "unfit" to reproduce (refer that to the bioethicists), the bigger issue is that eugenics doesn't work.

The Seattle Post Intelligencer article focused on how aborting fetuses that have genetic defects is both unfair to the disabled (a good argument, but beyond my ken) and may cause our species to lose valuable genetic variations (my area of interest). This part of the argument, which was not well articulated, is a case of needless worrying.

Even in a simple autosomal recessive trait (see here for a good tutorial), eliminating all of the homozygous individuals (those who show the trait in question) will not necessarily eliminate the "abnormal" gene. Only by detecting all the people who carry the gene and preventing them from reproducing can you eliminate the gene. Even if detection of all the carriers is possible, it would be a much bigger problem to convince people of normal physique and intelligence that they can't have children.

If this seems a bit hard to believe, how about a large long-term (tens of thousands of years, at least) "study"? Does everyone know about Sickle Cell Disease (SSD)? This is an autosomal recessive disorder of the red blood cells that, until very recently, was rapidly fatal in homozygotes (i.e. they died well before they could have children). Despite this "natural" eugenics program, SSD is still with us.

SSD's persistence is due, in part, because the people carrying only one copy of the gene (heterozygotes) are somewhat less susceptible to malaria than people with zero copies of the gene. However, once the gene became established, it can only disappear if there is a strong selection pressure against not only homozygotes (two copies) but also heterozygotes (one copy). Without that selection pressure, the gene frequency will drift randomly. Over time, if malaria becomes a less significant health threat, the gene for SSD may decrease because of genetic drift, but this will take thousands of generations - if it happens at all.

So, people arguing for (or against) sterilization or murder of the disabled will have to do without the support of genetics. Eugenics doesn't work - either to eliminate genetic disorders or to eliminate "useful" genes.


Coming up... Dr. Hornig's Autistic Mice (the second article)

Wednesday, July 20, 2005

A Perfect Example of how NOT to do a Study - Part Two

Welcome back to the second part of our dissection of "Reduced levels of mercury in first baby haircuts of autistic children" (Holmes AS, Blaxill MF, Haley BE. Int J Toxicol. 2003 Jul-Aug;22(4):277-85)! This is the part where things may get a little messy, so be sure to have your gloves and goggles on before we start. I'll give you a minute to get ready.

The dissection of the Results section will require us to dissect a few parts of the Methods section, as the two are interconnected. I will try to make it clear when I switch areas.


Despite a "...first-order hypothesis of heavy metal toxicity in autism.", the hair mercury concentrations were as follows (parts per million [ppm] +/- standard deviation):

Autistic children: 0.47 ppm (+/- 0.28)
Controls: 3.63 ppm (+/- 3.56)

We will get to conclusions later, but I know what I thought when I read those numbers.

The numbers were different enough that, despite having standard deviations almost as large as the values, there was a very strong statistical significance (p<0.000004).From the Methods section, we know that they were using a two-tailed test and these standard deviations make a one-tailed test more appropriate (for a good introduction, see here), but let's just pass over that for now.

The authors further break down the autistic group into three sub-groups - "mild", "moderate" and "severe" - and show that the hair mercury levels are lowest in the "severe" group (0.21 ppm +/- 0.18), higher in the "moderate" group (0.46 ppm +/- 0.19) and highest in the "mild" group (0.71 ppm +/- 0.30).

A number of potential mercury "exposures" are listed, with data given only for injections of Rho D immunoglubulin, some of which contains thimerosal, a mercury-containing preservative. Of the rest of the "exposure data" collected, the authors only give the correlation between the number of maternal "amalgams" [amalgam dental restorations, also known as "fillings"] and hair mercury level. This is presented in a graph which is not particularly helpful. The other "exposure data" (vaccinations and fish intake) are not displayed.


The most important part of this section is the formula, derived by "multiple regression", that correlates three of the four exposure "variables" to hair mercury level - but only in the control group. You'll note that exposure to Rho D immunoglobulin, even though its association with the autistic subjects was highly significant and much discussed, is not part of the formula. The resulting equation is:

Hair mercury level = 5.60 + 0.04( amalgam volume ) + 1.15( fish consumption ) + 0.03( vaccinations )

Since the authors make extensive use of the results of this equation, it is worthwhile to take some time to examine it closely.

From the Methods section, "amalgam volume" was calculated from the number of amalgam dental restorations (no data about actual size was collected) and was simply the square of the number of amalgam restorations. In this way, two small restorations on the sides of the teeth were calculated to release four times the amount of mercury that one large restoration on the chewing surface - a conclusion not supported by either common sense or experimental data.

The variable "fish consumption" is presumably an integer derived from the "none, little, moderate, heavy" scale and the variable "vaccinations" is presumably the number of vaccinations received prior to the haircut.

I must admit to a certain degree of confusion about the formula, since it would appear that the lowest hair mercury level would be 5.60 ppm, assuming that all exposures were zero. I could find no subsequent correction, so this is the only formula we have.

I note that the constant in the equation (5.60) is in parentheses in the article. Mr. Blaxill has (in various Internet postings) subsequently claimed to have done the actual writing of the article and since his education is in business, perhaps he was using the accounting practice of placing negative numbers in parentheses. This would allow for hair mercury levels below 5.60 ppm, but would mean that zero exposure would lead to a negative hair mercury level - a clearly nonsensical result. Either way, the formula is suspect - at best!


This is the smallest section, but it has the biggest bang! After leading the reader down the path of mercury toxicity and the consequences of poor mercury excretion (and without showing any studies or supporting data that autistic children excrete mercury poorly), the authors veer sharply away from what their data can support:

"Despite hair levels suggesting low exposure, these infants had measured exposures at least equal to a control population, suggesting that control infants were able to eliminate mercury more effectively." [my emphasis]

Earlier, I asked you to remember that the mercury exposures were calculated and not measured and I believe I have shown that the calculations are also fairly questionable. Now, in the conclusion, the authors seem to have forgotten that they never measured mercury exposure. How amazing! Even more amazingly, the reviewers and editors failed to catch this BIG mistake!

Even more amazing is that the authors, the reviewers and the editors failed to notice two other points:

[1] There are no data or citations provided to support the implied assertion that mercury is actively excreted in the hair.

[2] There are no data citations provided to supports the assertion that mercury elimination in the hair is a significant means of clearing mercury in humans - especially infant humans, who have little hair relative to their body weight.

The reason for [1] is that there are abundant data and studies showing that mercury enters the hair - in all studied species - passively from the blood, attracted by the sulfur-containing amino acids in hair. The only way to "impair excretion" is to cut off the blood supply to the hair - which causes it to fall out.

The reason for [2] is that humans, and especially human infants, have a very small mass of hair relative to their body weight - a much lower relative amount than many of the other species studied (e.g. rodents and primates). For this reason alone, excretion in the hair cannot be a major route of mercury excretion in humans.


The authors imply, in the introduction, that one of the reasons they began this study was that some autistic children had presented to Dr. Holmes' practice with low hair mercury levels. Finding that all 94 autistic subjects in this study had low hair mercury levels, they then proceded to a conclusion that was not supported by their data.

Given that the only thing they measured in this study was hair mercury level, the only thing that their data support is that autistic children have low hair mercury levels. Since mercury moves passively from the blood to the hair, the explanations for this finding are:

[1] These autistic children had low mercury exposure, despite what historical data collected a median of 5 1/2 years after the fact may suggest.

[2] The low hair mercury level is the result of a laboratory or specimen collection error that was sytematically applied to only the autistic subjects. There is not enough information in the paper to address how this might have happened, but it is my personal favorite.

[3] Something about autism changes the amino acid composition of hair in such a way that it has less affinity for mercury.

You will note that none of these hypotheses requires the reversal of decades of previous study results or the discovery of currently unknown biochemical pathways. They also don't support the hypothesis that mercury causes autism (and they don't refute it), which is probably why they were rejected by the authors of this silly study.

Class dismissed!


Tuesday, July 19, 2005

A Pefect Example of how NOT to do a Study - Part One

A week ago, I posted an article that touched on a truly appalling study of autism and mercury, "Reduced levels of mercury in first baby haircuts of autistic children" (Holmes AS, Blaxill MF, Haley BE. Int J Toxicol. 2003 Jul-Aug;22(4):277-85).

On careful reading, I have determined that this study is so bad it deserves a more careful analysis. So, in the interest of public education, I have decided to dissect it here in my blog. Those of you who are squeamish may want to check back in a few days. OK, gloves on, protective eyewear in we go!


The first thing to look at in any study is who did it. Although some people persist in the egalitarian notion that a study should stand on its merits regardless of who did it, I have found it helpful to examine the authors. All authors have - believe it or not - a bias or preconceived notion of how the study should turn out. A few of them (very few, fortunately) have a history of letting this bias interfere with their conclusions or - even worse - the data.

In this study the authors are as follows:

Amy Homes: A radiation oncologist who turned to biomedical therapies of autism (especially mercury chelation) after having a child with autism. She had a practice in Baton Rouge, Louisiana for the treatment of autism, but that has apparently closed.

Mark Blaxill: A Senior VP at The Boston Consulting Group with expertise in global corporate strategy, Mark has an A.B. from the Woodrow Wilson School of Public and International Affairs at Princeton and an M.B.A. from Harvard Business School. He has no formal training or education in any of the sciences, but has been talking as though he did. He is also on the Executive Board of SafeMinds, an organization that states:

"Our mission is to end the health and personal devastations caused by the needless use of mercury in medicines."

Fortunately, the study wasn't affected by this preconception (heavy sarcasm).

Boyd Haley: Professor and Chairman of the Department of Chemistry at the University of Kentucky at Lexington, he has an impressive list of publications, including three on the effects of mercury on tubulin. Unfortunately, he hasn't updated his web page to include this study. Nor has he mentioned on his University of Kentucky web page his research interests in autism. Strange.

Dr. Haley is also a part owner (47.6% of the shares) in ALT, Inc., a company which - in one of its two for-profit divisions,
"...provides oral toxicity testing products and services and develops tests to aid in the diagnosis of neurological diseases."

In addition to providing this desperately needed service they also provide information about the dangers of mercury in dental amalgam and the thimerosal preservative in vaccines. Dr. Haley seems quite convinced that autism is caused by mercury.


The basic idea of the study was to collect hair samples taken at the first haircut ("first baby haircut", in the study) and saved by parents for a group of autistic children and a group of non-autistic controls. These samples were then analyzed for mercury at a commercial laboratory that specializes in "toxicity" analysis.

There are a lot of problems with the methods in this study, but I will only hit the "high points", since some of the errors may seem tedious and nit-picking to non-scientists. Besides, an exhaustive listing of the errors would take me longer than it probably took them to write the article.

[1] Sample age - The median age at haircut was 17 - 18 months in both the autistic and control groups. The median year of birth was 1994 for both groups. The study was received for publication in October 2002. Although the authors fail to mention when the study was carried out, even assuming that it was done in 2001, the hair samples had been in storage under unknown conditions for a median of five and a half years.

[2] Calculation of "Maternal Exposures" - The mothers of the study subjects were interviewed for possible exposures to mercury from:

[a] Amalgam fillings
[b] RhoD (anti-Rh antibody) injections (given when the mother is Rh negative)
[c] Childhood vaccinations (presumably given to the children in the study)
[d] Fish consumption ("none", "little", "moderate" or "heavy") during pregnancy

To begin with, this information is provided - largely from memory - about events that occurred a median of seven (7) years and as long as sixteen (16) years previously.

Based on this rather questionable information, the authors then applied a formula - which they derived from the data - to calculate (remember this - it will come up later) the amount of mercury that the chilren were exposed to in the womb (in utero, for you purists).

Note - the authors did not measure the mercury intake of the mothers, they calculated it.

In addition, they used the data they collected in order to come up with the formula they used to calculate the mercury exposure - which they then used to explain the data they came up with. The same data they used to calculate the mercury exposure. See the circularity? Like a puppy chasing its tail. This is not good science - it is something my high school biology teacher would have marked me off for.

Tomorrow: Results and the startling Conclusion!

'Til then,


Friday, July 15, 2005

Breaking News!

Last night on WCNC (Channel 6 in Charlotte, North Carolina), the (in)famous Rahid Buttar, D.O. showed that, given enough rope, he would hang himself. For those who would like to see a video clip of a man hanging himself with his own tongue, click here.

I tell you, debunking this autism-mercury nonsense is easier than shooting fish in a barrel...with a cannon! It's more like shooting fish taped to the end of the gun barrel. You can't miss! If you give these clowns enough videotape, eventually they will show just how crazy (meant in a non-clinical sense) they truly are.

Please don't miss the opportunity to hear Rashid Buttar say the following:

[1] In answer to questions of whether he has tested to see if his transdermal DMPS (TD-DMPS) drops are, in fact, absorbed through the skin -
“No, we haven't done that. Why would I waste my time proving something that I already know is working innately?”

[2] In response to accusations that he is selling "snake oil" -

“If this is snake oil and what they're doing is medicine, then I choose to practice snake oil. And I have no embarrassment with it,”

[3] In response to accusations that his treatment is a sham -

“If this was a sham then I'll tell you what. This is the best sham that has ever been put on. I think you'd have to agree with that,"

I can't add anything to that.


Thursday, July 14, 2005

Dumpster Diving (Republished)

[For reasons beyond my ken, the original of this post was lost in the "blogosphere". Here it is again]

As I have mentioned before, the more I look into the various autism-related “alternative” hypotheses and therapies, the more amazed I become. And not amazed in a good way. “Appalled” might be a better choice of words – occasionally “disturbed” and “disgusted” are appropriate choices, as well.

While browsing through the literature on autism and thimerosal, I ran across a number of articles by the father-son team of Mark and David Geier. The elder Geier is a geneticist; the younger will soon graduate or has recently graduated from medical school. Together, they have written over ten papers on autism, vaccines and thimerosal.

The source of Geier & Geier’s “data” for much of this flock of publications is the Vaccine Adverse Event Reporting System (VAERS) database. And thereby hangs a tale…

You see, the VAERS database is not a good source of material for any epidemiological study, a fact acknowledged by the very people who maintain it. The purpose of the VAERS database is to act as a repository for any complications following a vaccination. These complications may be due to the vaccines or may be coincidental, but the VAERS team wants to hear about them all. After all, their purpose is to watch for any unexpected consequences of vaccinations.

Anyone can make a report to the VEARS database – not just doctors – and it will be accepted. In fact, there is no requirement for documenting that a vaccine was given or a complication experienced. This makes the VAERS database very sensitive, but not particularly accurate. This is not a secret - the VAERS website spells it out clearly.

To further complicate matters, many of the autism advocacy groups have, starting as early as 1996, decided to contaminate the VAERS database. By urging people to enter their autistic children – and the autistic of their friends and relatives – into the VAERS database as vaccine-related injuries, they have made the database even more useless as an accurate tool of epidemiology though spurious and duplicate reports. But, they’ve made it a much better tool for political maneuvering.

Enter the Geiers, pere et fils.

By tapping into this vast reservoir of contaminated data, the Geiers have made themselves heroes of the autism-mercury movement. Given the concerted effort of over eight years to contaminate the VAERS database with reports of thimerosal-containing vaccines causing autism, it should come as no surprise that the Geiers have found that it supports the autism-thimerosal connection. This is no more of a surprise than catching trout in a lake that has been stocked with trout.

Now, the Geiers are intelligent people and they can read the VAERS disclaimers. They are also very aware of the ongoing effort to “stock” the VAERS database with vaccine-caused autism. Having thus eliminated ignorance and stupidity, there appears to be only one conclusion left.

I have occasionally been accused of cynicism. In fact, I have been accused of being one of the most cynical people on the planet. But the degree of cynicism that is required to publish “scientific” articles with data you know (or should know) to be false is far beyond my meager abilities. The Geiers appear to have joined the inner core of the autism-mercury cabal that is willing to do whatever it takes to “win”.

Since any scientist who even takes a cursory (and unbiased) look at the Geier & Geier studies will immediately know they are garbage, who are they writing them for? Obviously not doctors or scientists. How about…politicians?

Yes, it’s really that cynical – publishing articles using garbage data in order to have “scholarly” citations for testimony to Congress. It’s all part of the political plan of the autism-mercury cabal – have autism declared, by an Act of Congress, to be caused by mercury. It isn’t science, but it might just work.

If we let it.


Wednesday, July 13, 2005

Mercury Nostalgia

Remember the "Good Old Days", when the only people who suffered from mercury-induced insanity were those who had been exposed to a significant amount of it? Today, through the medium of the Internet, we have thousands of virtual mercury-poisoning "victims", not to mention those additional thousands who have lost their minds from worrying about mercury poisoning. I refer, of course, to people like:

Raymond Gallup
Andrew Cutler
Sallie Bernard
Boyd Haley
David Kirby
And many, many (many) more...

When I first started blogging on the autism-mercury non-connection, I had no idea how deep and how wide the madness extended. It was like stepping through a black hole into an autism-mercury "alternate universe" (without the inconvenience of being ripped to shreds by tidal forces or compressed in the singularity).

In this alternate universe, post hoc, ergo propter hoc ("After this, therefore because of this") is the "Gold Standard" for causality and anyone can be an expert on anything they want, just by saying they are. For example, an MBA can be a "scientist" (see also here and here) despite a complete lack of education or experience in any scientific field. In the autism-mercury alternate universe, the burden of proof is not on those who make a claim, but on those who dispute that claim. In many ways, this universe is as upside-down and topsy-turvy as Wonderland - and that seems fitting, somehow.

How else can you explain the slavish devotion among the autism-mercury cabal for such thoroughly discredited "scientists" as Mark Geier, Hugh Fudenberg, and Andrew Wakefield (see here as well)? In their universe, these people are legitimate scientists - in our universe (where different physical laws hold sway), they are laughable, incompetent, inept or unethical. Perhaps all four. How else can you explain how a work of fiction ("Evidence of Harm") written by a journalist can be held up by autism-mercury proponents as a work of scientific significance, if not "revealed truth"?

The alternate universe hypothesis also explains why the autism-mercury cabal insists that a single poorly-designed, questionably run study that supports their "side" is more than equal to five or six well-designed, well run studies that refute their position. No less an expert on the autism-mercury alternate universe than Sallie Bernard has been reported to believe that:

"She doesn't think the evidence proves thimerosal causes autism. But she does think the evidence points in that direction."

Apparently, in the autism-mercury alternate universe, one points 180 degrees away from the target. In this universe, a recent review of published studies showed that the better the study design, the less likely it was to support an autism-thimerosal (and therefore autism-mercury) connection. However, in the autism-mercury alternate universe, even simple math - like counting - has different rules.

Fortunately for those of us who live in this universe, mercury doesn't appear to cause autism here. At least, the data doesn't point that way.


Monday, July 11, 2005

When Scientists go Bad...

Today's post will be a double-header!

Part One: Placebo vs Placebo - Placebo Wins!

The first part is the result of my colleagues finding out that I'm blogging about autism - now they feel obligated to dump every autism-related piece of quackery that they receive on my not-too-tidy desk. The most recent contribution was a pamphlet from Biomed Comm, Inc. which is titled An Educational Primer on Autism Spectrum & Cell Signaling.

In this pamphlet, the virtues of Dr. Barbara Brewitt, MDiv., PhD., "scientist, visionary, minister and socially responsible activist" and her "Cell Signal Enhancer Medicines" are extolled. These "medicines" are: " integration of: advanced molecular biology, biophysics of cell-to-cell communication, and 250 years of safe and effective homeopathic medicine" (my bold).

Ah, well! It would appear that in all of Dr. Brewitt's study and research into "advanced molecular biology" and the "biophysics of cell-to-cell communication", she overlooked Avogadro's number. If she had picked up this bit of knowledge (it dates from 1811), she would have known that the odds against a vial of homeopathic solution containing any of the substance are greater than the odds of winning the Powerball Lottery. And, since most of the people doing research in "advanced molecular biology" and the "biophysics of cell-to-cell communication" (including your humble scribe) know that cells need some sort of signal to experience cell-to-cell signaling - which is not supplied by a homeopathic dilution - it is pretty clear that Dr. Brewitt is - at best - mistaken.

However, the folks at Biomed Comm (Inc.) are not without supporting information - they have testimonials! To be fair, they also have vague graphs from undescribed - and unpublished - studies, but they have a lot more testimonials! Here is one of my favorites:

From a naturopath in Michigan:

"I had one child who was completely nonverbal, and six months later he was not only talking, he was reciting the alphabet"

Strange as this may seem, the exact same thing happened to my niece (without any homeopathic cell-signaling) - when she was eleven months old, she was nonverbal and six months later, she was talking! Wait...that's just normal development.

So, the bottom line appears to be that if you do nothing, even autistic children will show some developmental progression (after all, it's developmental delay, not developmental stasis). I say this since homeopathic "remedies" are placebos to well beyond the level of detectability by the best of modern analytical methods.

Part Two: Autism Researchers Show Mercury Protects Against Autism!

I've got to start locking my office door - while I was at lunch, someone dropped a copy of a hilariously bad study on my desk. It was Reduced levels of mercury in first baby haircuts of autistic children (Holmes AS, Blaxill MF, Haley BE. Int J Toxicol. 2003 Jul-Aug;22(4):277-85).

In this study, the authors measure the mercury content of hair saved by parents from the first haircut of their children; 94 with autism and 45 age- and sex-matched controls. Leaving aside the many methodological (and logical) errors in this study, it is their stubborn refusal to accept the obvious conclusion that makes it so laughable.

Despite the obvious expectations of the authors (one is on the Executive Board of SafeMinds, yet another is a well-known anti-mercury advocate), the study found that the autistic children had lower hair mercury levels than the neurotypical controls. Rather than concluding that mercury protects against autism (which the data supports but is nonsensical) or at least is not associated with autism, the authors take a sharp turn off the road of reason and propose that the autistic children had impaired mercury excretion.

They came to this conclusion without providing any data or other studies supporting this wild idea. In fact, studies done as long ago as the 1960's have shown that hair - including human hair - is a passive recipient of mercury from the blood. In other words, hair mercury levels follow the blood mercury levels - there is no excretion.

If this is the sort of "research" that the autism-mercury cabal is leaning on, it is less than the proverbial slender reed - it is the shadow of a slender reed. No wonder they are working the political angle - they haven't got a leg (or a reed) to stand on!


Saturday, July 09, 2005

The Cart before the Horse: Chelation for Autism

I don't intend to let autism become my idee fixe, but it is such a fertile field for psuedoscience and fuzzy-headed thinking that I have decided to frolic in it for a while. It is, as the military folks like to say, a "target-rich environment." So, let the games begin!

Chelation is all the rage in autism circles these days. I recently received a flier for a local autism conference that listed no less than six speakers who would - so the flier promised - extoll the virtues of chelation and describe the wonders it had performed on previously hopeless cases of autism. As a collector of patent medicine bottles and literature, I found the language in this flier to be eerily familiar.

There were many unsupported assertions that autism was caused by mercury (in the form of thimerosal in vaccines) and there were several glowing testimonials from parents who had seen their children improve or "recover" after chelation. This was all very impressive - on a superficial level - but the same sort of things were said of Lydia Pinkham's Vegetable Compound in the late 1880's. This "remedy" claimed to help all manner of "female complaints" and was also accompanied by testimonials and unsupported assertions.

The purveyors of chelation (and their apologists) claim that chelation will help "cure" autistic children (don't take my word for it - read it here and here). What seems to have gotten lost in the testimonials and assertions is that nobody has yet shown that autism is caused by mercury poisoning! Let me say that again: nobody - nobody! - has shown that autism is caused by mercury!

What the promoters of the autism-mercury connection have managed to show is that mercury is bad for your brain and other parts of your body, a fact that physicians have known for over a hundred years. What they haven't shown is any evidence that mercury - a pretty indiscriminant poison - can cause the collection of signs and symptoms we call "autism".

You see, mercury poisoning is accompanied by motor problems - problems with movement - such as tremor and incoordination. Autism is not. Most autistic people have no tremor and pretty normal coordination.

It appears that the autism-mercury junta has put the cart before the horse. They want us to treat autistic children with chelating drugs - to remove the mercury - before they've managed to demonstrate that mercury causes autism. That's like taking chemotherapy before you check to see if the lump is actually cancer.

Now, the autism-mercury faithful will point to the autism "epidemic" and scream that it all started after the big increase in mercury-containing (in the form of thimerosal) vaccines. Mind you, both the US and England had big increases in autism prevalence starting in the mid 1980's, about the time that the US began recommending more vaccines - many with thimerosal - for children.

However, England only had one thimerosal-containing vaccine during that time, so their children didn't have an increased exposure. Somehow, that didn't prevent the tremendous rise in autism seen in the United Kingdom.

So, we have large and pretty much identical increases in autism in two countries - one in which children's mercury exposure went up and one in which it didn't. And this is supposed to convince us that mercury causes autism? I'm just not convinced.


Friday, July 08, 2005

Legislating Science: can we make Pi = 3?

The autism-mercury "connection" stirs unquietly in its grave. It has been shot, stabbed, hacked to bits and incinerated by scientific data and yet still it rises from its grave to seek out new victims and drink their blood ... or drain their wallets. Faced with a new onslaught of scientific data - published in the past month - the Renfields of this New Age Dracula have fanned out to make the world safe for the coming of their Dread Lord.

Responding to an recent article in Pediatrics, Lenny Schafer, Editor of the Schafer Autism Report, had the following to say on the Evidence of Harm list:

"Not much there except propaganda, which of course is the point. We always knew the DOE [sic - I think he means the USDE; the DOE is the Department of Energy] numbers were not the cleanest. I have routinely warned my readers about this. Still Laidler's conclusion is that"there may still be an autism epidemic in the United States" as quoted in the article makes this hit piece weak. In my opinion, our counter-propaganda is to characterize business like this as the work of autism holocaust deniers with an anti-child, pro-pharma agenda.

A question to raise to the public is why is the government dragging its feet with finding out the numbers and the causes and instead does this steady stream of alibis-for-mercury research. "

Note the following points:

[1] The article is dismissed as "propaganda" and a "hit piece" even though Lenny has apparently not read the actual study. The quoted piece is from a Reuters' article and is not found in the Pediatrics paper.

[2] Lenny goes on to advocate a "counter-propaganda" strategy of asseting that researchers whose scientific findings oppose their political agenda are "...autism holocaust deniers with an anti-child, pro-pharma agenda" - kind of a stretch when you note that the author of the Pediatrics paper has an autistic child and is a graduate student. Apparently, the truth is the last thing that Lenny wants to hear.

The message here is that the autism-mercury cabal is committed to winning - even if they are wrong! They have clearly abandoned any pretense of scientific inquiry and are striving for a political solution. They want to have the public - and the public's representatives, the Legislature - declare their flimsy hypothesis (mercury causes autism) to be true, despite the overwhelming weight of evidence against it.

The danger here is that we will have a pseudofact enshrined as "revealed truth" - "revealed" by the legislature. The immediate result of this would be a tactical victory for Lenny Schafer, Mark Blaxill, David Kirby and others of their ilk - the long-term result would be a strategic defeat for people with autism. If the legislature declares that autism is caused by thimerosal, public research funding into autism will dry up - after all, after Congress has found the cause there would be no reason to spend tax dollars looking any further.

But the real tragedy in this scenario would be for society itself. Once the presedent is set, there would be nothing to prevent other deraged pressure groups from having their lunatic hypotheses declared "scientific truth" by an act of Congress. After that, it is but a short slide to the Abyss and a New Dark Age.