[Congressional Record Volume 153, Number 189 (Tuesday, December 11, 2007)]
[House]
[Pages H15279-H15282]
From the Congressional Record Online through the Government Publishing Office [www.gpo.gov]
BLOOD LEVELS OF MERCURY ARE RELATED TO DIAGNOSIS OF AUTISM
The SPEAKER pro tempore. Under a previous order of the House, the
gentleman from Indiana (Mr. Burton) is recognized for 5 minutes.
Mr. BURTON of Indiana. Madam Speaker, it's late at night here in the
Capitol, and most of my colleagues are in their offices or have gone
home. But I want to talk about an issue that's very, very important
that we've been talking about now for the last 8 years.
I was chairman of the Government Reform Committee for 6 years, and
during that time, my grandson became autistic; and we checked to find
out what was the cause, trying to find out, because my daughter and her
husband were just extremely upset about it, as we were as grandparents.
And we found that he had received nine shots in one day, seven of which
had a product called themarasol, a preservative, in it. And the
themarasol was 50 percent ethylmercury. And so I decided to have
hearings to try to find out if the ethylmercury in those vaccines had
anything to do with the autistic problem my grandson had. And we found,
by having many, many hearings over a 4-year period, we found that
scientists from all over the world and leading doctors and educators
here that work with autistic children, that the mercury in the vaccines
did contribute to the autistic epidemic that we had.
We used to have one in 10,000 children that were diagnosed as being
autistic. One in 10,000. Today the Centers for Disease Control will
tell you it's one out of 150. It's an absolute epidemic in this
country. And we have been fighting and fighting and fighting to make
sure that those families who have been damaged and those children who
have been damaged by autism get some kind of compensation. And that's
why, and I think in 1986 we passed what was called the Vaccine Injury
Compensation Fund, and it took some of the money from the
pharmaceutical companies when they sold their vaccine products to put
into this fund to take care of people who are damaged by vaccines. And
one of the reasons we did that was because of the issue of autism,
although at that time I didn't know much about it.
In any event, the Vaccine Injury Compensation Fund has about $3
billion in it, and the people who's children have been adversely
affected by mercury and have autism have not been able to get anything
out of that. They have to go through a process and see a special
master, and he has to judge whether or not the information that he has
and the information they have lead them to believe that the mercury in
the vaccines caused autism. And so far the special masters have not
been able to ascertain, according to them, that the mercury in the
vaccines does cause autism.
Well, last week, 2 years ago, let's see, 4 years ago there was a
report, 2004, that said that there was definitely no connection between
the mercury and the vaccinations and the children getting autism. Well,
this past November, just last month, two doctors, Dr. Catherine DeSoto
and Dr. Robert T. Hitlan, both very renowned doctors across this
country, they have Ph.D.s in medicine, they wrote an article in the
Journal of Child Neurology. And you can't discount this. What they're
saying is fact. I want to read to you the summary of what they said.
They said: ``The question of what is leading to the apparent increase
in autism is of great importance. Like the link between aspirin and
heart attack, even a small effect can have a major health implication.
If there is any link between autism and mercury, it is absolutely
crucial that the first reports of the question are not falsely stated
and that no link occurs.''
Now, get this: ``We have reanalyzed the data set forth originally
reported in 2004 and have found that the original P value was in error
and that a significant relation does exist between the blood levels of
mercury and diagnosis of an autism spectrum disorder. Moreover, the
hair sample analysis results offer some support for the idea that
persons with autism may be less efficient and more variable at
eliminating mercury from the blood.''
The fact of the matter is the mercury in the vaccines has autism.
It's not the only cause of autism. But now we have scientific evidence
by two leading doctors in the Journal of Child Neurology that says
without doubt, the mercury in the vaccines does cause autism, is a
major contributing factor.
Well, I've written, contacted Congressman Kucinich, who's chairman of
the subcommittee that deals with this in the Capitol, and I've also
contacted the special masters that decide these cases and have urged
them to re-evaluate all of these cases where people who have autistic
children have found that the mercury in the vaccines may have been a
major cause.
Now we know that it is a cause of autism, and those people who have
suffered, and those kids who have suffered need to be compensated out
of the Vaccine Injury Compensation Fund.
So I'd like to say to my colleagues, I hope you will join me in
making sure that the information I just read gets out to everybody.
These kids are going to live to be 50, 60, 70 years old, and unless
there's some help for them, they're going to be a real burden on the
taxpayers and on society. We have an obligation to make sure they're
taken care of.
I hope all of my colleagues will read this statement tonight and help
us to change the attitude of our health agencies and the special
masters dealing with this problem.
In November 2007, the well-respected scientific journal, the Journal
of Child Neurology, published an article authored by Drs. M. Catherine
DeSoto and Robert T. Hiltlan (PhDs), detailing their findings on the
relationship between mercury and autism spectrum disorders. The article
was entitled ``Blood Levels of Mercury are Related to Diagnosis of
Autism: A Reanalysis of an Important Data Set.''
To summarize the article, Drs. DeSoto and Hiltlan reanalyzed a data
set the subject of a 2004 study that found no relationship between
mercury and autism. By reexamining the data set, Drs. DeSoto and
Hiltlan determined that the conclusions of the 2004 study were wrong,
[[Page H15280]]
and that a relation does exist between the blood levels of mercury and
diagnosis of an autism spectrum disorder.
As Drs. DeSoto and Hiltlan noted in their article, there has been a
marked increase in the diagnosis of autism in this country over the
last 20 years. In fact we have gone from an autism rate of 1 in 10,000
to 1 in 150. So, answering the question of what is (and is not) a
possible contributing cause of autism is crucial, not only to the
millions of American families currently affected by autism but to
future generations.
We simply cannot dismiss or downplay scientific research, which has
the potential to unlock the mysteries surrounding what is causing our
Nation's autism crisis. We owe it to the thousands of families living
with autism to follow the science wherever it may lead.
That's why in late November, I wrote to the Chairman of the House
Subcommittee on Domestic Policy, Representative Dennis Kucinich; and
the Special Masters assigned to the Congressionally-created Office of
Vaccine Program within the U.S. Court of Federal Claims, alerting them
to the findings in Drs. DeSoto and Hiltlan's latest research.
Specifically, I asked the Special Masters to take Drs. DeSoto and
Hiltlan's latest findings into consideration as they carry out their
mandate of managing and adjudicating childhood vaccine claims. I asked
Chairman Kucinich to hold a hearing on the environmental risks of
mercury in childhood vaccines before the 110th Congress ends.
Given the high stakes involved, scientific reports discussing a
connection between blood mercury levels and autism deserve serious
consideration and review by the medical and scientific community.
During my tenure as Chairman of the House Committee on Government and
Reform, I spent 6 years researching and hearing testimony from the
autism advocacy and scientific communities about the autism epidemic
sweeping our country. Over and over again, questions of causation,
namely the use of thimerosal--the mercury-based vaccine preservative--
in childhood vaccines were raised.
Here's what I learned:
A number of credible national and international scientists testified
before the Committee that mercury in vaccines is a contributing factor
in developing neurological disorders, including, but not limited to,
modest declines in intelligent quotient, autism, and Alzheimer's
disease. And the body of evidence to support that conclusion gets
larger everyday.
Experience tells us that, as with any other epidemic, while there may
be underlying genetic susceptibilities, there usually is also some type
of environmental trigger as well--be it exposure to a virus, fungus,
heavy metal, or pollutant. There has never, to the best of my
knowledge, been a purely genetic epidemic.
Genetics alone cannot explain how we went from 1 in 10,000 children
with autism spectrum disorders 20 years ago to 1 in 150 today. The
increase happened far too quickly for a genetic shift.
As mercury is a known bio-accumulative neurotoxin, it is biologically
plausible that it is a contributing factor to our Nation's autism
epidemic.
Autism has no cure, and while it is a life-changing condition, it is
not a life-threatening disease. This means that the autistic children
of today will be the autistic adults and autistic seniors, 20, 30, 50,
even 70 years from now. Our Nation is ill prepared to deal with the
complex educational, financial, housing, and health care challenges
posed by a generation of autistic individuals.
My only grandson is autistic, so this is an issue that is very close
to my heart; and for the last several years I have fought hard to raise
awareness of this disease, and increase research into the causes of
autism, as well as new treatments for those suffering with autism.
As a Nation, I believe, we have a collective responsibility to do
everything we can to not only stop the further spread of this disease
but to help the millions of children, adults and families afflicted
with it.
Journal of Child Neurology
Blood Levels of Mercury Are Related to Diagnosis of Autism: A
Reanalysis of an Important Data Set
(By M. Catherine DeSoto, PhD, and Robert T. Hitlan, PhD)
The question of what is leading to the apparent increase in
autism is of great importance. Like the link between aspirin
and heart attack, even a small effect can have major health
implications. If there is any link between autism and
mercury, it is absolutely crucial that the first reports of
the question are not falsely stating that no link occurs. We
have reanalyzed the data set originally reported by Ip et al.
in 2004 and have found that the original p value was in error
and that a significant relation dose exist between the blood
levels of mercury and diagnosis of an autism spectrum
disorder. Moreover, the hair sample analysis results offer
some support for the idea that persons with autism may be
less efficient and more variable at eliminating mercury from
the blood.
Keywords: autism; mercury; environmental health;
neurotoxin; neurodevelopment; blood.
There is a marked increase in the diagnosis of autism. The
question of what is (and is not) related to this increase is
crucial to millions of persons affected by the disorder. This
article reanalyzes an original data set regarding the
relation between blood levels of mercury and diagnosis of an
autism spectrum disorder (ASD) by Ip et al. based on our
finding of discrepancies in the original article.\1\
A review of what is known about the neurotoxic effects of
mercury is beyond the scope of this paper,\2\ but the
observable symptoms of acute mercury poisoning have been
reported to match up with many of the problems observed in
autism.\4\ Furthermore, mercury poisoning has sometimes been
presumptively diagnosed as autism of unknown etiology until
the mercury poisoning has been uncovered.\4\ Because there
has been a several-fold increase in environmental mercury
exposure, the hypothesis that the rise in autism could be
related to an environmental increase in mercury levels is a
reasonable one to pursue. Autism may result from a
combination of genetic susceptibility (perhaps in the form of
reduced ability to remove mercury or other neurotoxins from
the system) and environmental exposure at key times in
development.5,7 This would mean a generalized
increase in mercury levels would be expected to co-occur with
a generalized increase in autism. but some people exposed to
relatively high mercury would not be affected if, for
example, their bodies were very efficient eliminators of such
toxins. Only if an exposed infant or fetus also had a genetic
susceptibility that makes one less able to remove mercury (or
other heavy metals) would normal levels of mercury exposure
lead to problems. Alternatively, it could be that genes that
help detoxify get switched on and start to express themselves
a little later than normal in those genetically predisposed
to autism; or perhaps. autism results from some combination
of these theories.
Nevertheless, if mercury does play any causal role in
facilitating a diagnosis of autism, there would likely be at
least some relation between high mercury measured in the
blood and symptoms of autism even if ability to metabolize
mediates the relationship between exposure and neural
toxicity. This is because even if exposure is identical,
those who remove mercury less effectively should still have
higher levels in the blood. Interestingly, results of hair
samples could be expected to be somewhat mixed. The level of
mercury in hair may be better understood as an indication of
how much mercury has been removed by the body as opposed to
the level in the body.\6\ If people are approximately equal
in their ability to remove circulating mercury from the
bloodstream, then these 2 indicators should match up closely,
but if a person's ability to excrete is low, their hair
samples might not be elevated even when their blood levels
are high.
Fido and Al-Saad found that mercury levels in hair samples
were higher in children diagnosed with autism.\8\ These
children were aged 4 to 7. In contrast, Kern et al. reported
that mercury hair levels were not significantly different,
but were lower at a marginally significant level.\9\ Kern et
al. used younger children, ages 1 to 6. Holmes et al.
performed the most direct test of the hypothesis that
autistic children may be deficient in terms of ability to
remove mercury from circulation.\6\ This study estimated
mercury exposure of the mothers via a mercury exposure survey
questionnaire. They then analyzed the first haircuts of the
autistic children and a group of controls (the first haircuts
would reflect mercury excretion in utero and very early
life). In the autistic group, severity of autism was
inversely related to hair mercury levels. This means that the
more severe autistic cases actually had less excretion of
mercury. Furthermore, among the normal children, hair levels
of mercury were correlated to the mother's mercury exposure
(as would of course be expected). But among the autistic
children, there was no linear relation between the mother's
mercury exposure and excretion of mercury in the hair. As the
authors state, this pattern of results is easily understood
if one considers ``detoxification capacity of a subset of
infants,'' \6\ such that the bodies of those diagnosed with
autism appeared to be less able to excrete and/or metabolize
the mercury they were exposed to.
As the rise in autism is relatively recent, it is not
surprising that research into the etiology has not kept pace.
Indeed, there are few published articles that consider blood
levels of children with mercury that utilize a control group;
a psycInfo search using the words ``autism,'' ``mercury,''
and ``blood'' yields only one hit.\1\ Given the high stakes
involved, it is crucial that early reports of the connection
between blood mercury levels and autism not be misstated.
Even a small effect size would be of great theoretical and
practical consequence.
In 2004, Ip et al. reported that no relationship existed
between mercury blood levels and diagnosis of autistic
spectrum disorder among a group of children with an average
age of approximately 7 years. While attempting to estimate
the effect size based on the Ip et al. statistics, we
realized that the numbers reported by Ip et at could not be
correct. The means and standard deviations reported in the
2004 article yielded an easily
[[Page H15281]]
significant t value (autism mean = 19.53 nmol/L, SD = 5.6, n
= 82; control mean = 17.68 nmol/L, SD = 2.48, n = 55 gives a
t = 2.283, two-tailed P = .024 or one-tailed P = .012). Ip et
al. wrote that the P value was ``(P) = .15,''
1(p432) and that their data indicate ``there is no
causal relationship between mercury and as an environmental
neurotoxin and autism.'' \1\ After the error was brought to
the attention of the authors, a new analysis was conducted by
the original authors and they found the original t test to be
in error and the P value to be a mistake (refer to Erratum,
p. 1324). Based on their corrected analysis, the authors
report the revised P value for their t test to actually be P
= .056. We disagree on several grounds that these data
indicate no significant effect exists, and report on a
completely new reanalysis of the original data set.
Methods
Outliers were removed prior to statistical analysis. An
outlier is defined as a score that is ``substantially greater
or less than the values obtained from any other
individual.''\10\ Outliers have an unduly large influence on
the outcome of a statistical test. What actually qualifies as
an outlier differs depending on the research question and the
statistician analyzing the results; however, values greater
than 3 standard deviations either above or below the mean
generally qualify as extreme cases.\11\ Within the Ip et al.
data, there were 2 such values that were not removed prior to
our reanalysis. These 2 values were more than 3 standard
deviations above the mean, and both of these values were far
from any other score. (Other scores were within 3 points of
the next individual; these 2 scores were each 15 or more
points away from any other score in the distribution.) To
avoid the appearance that these 2 outliers were removed to
influence the statistical outcome as opposed to objective
criteria for cleaning a data set, it should be noted that the
biggest outlier of the 2 was an unusually high blood mercury
level of 98, which was in the autistic group. To be clear--if
anything, removal of the outliers resulted in a more
conservative test as it actually decreased the mean
difference between the 2 groups.
Results
Logistic regression was performed using blood mercury level
as the predictor and the autistic/control group as the
criterion. Results of this reanalysis indicate that blood
mercury level can be used to predict autism diagnosis. Data
included: r = .20, r\2\ = .04, F(1, 133) = 5.76, P = .017.
This finding indicates that there is a statistically
significant relationship between mercury levels in the blood
and diagnosis of an autism spectrum disorder.
There was no difference in the mean hair levels where
t(l35) = .24 and one-tailed P = .40; this is essentially the
same result reported in the original article. However, given
that hair levels would normally be expected to be highly
correlated to blood levels, it might be surprising that blood
levels could predict an autism spectrum diagnosis, but that
hair mercury levels could not. Indeed, hair and mercury
levels for the full sample were correlated (r = .86, P <
.001) indicating that about 75% of the variance in hair
levels was accounted for by the mercury level in the blood.
To us, the question turned to what the other 25% of the
variance might be due, and whether the assumptions of the t
test were violated. Although not the central focus of this
report, these results could certainly help to inform future
researchers of the nature of the relation between autism and
mercury, and we include this information for completeness.
Exploratory Analysis. If one hypothesizes that persons with
autism are less able to excrete mercury, especially when
their blood levels get in the higher range, one might expect
that the correlation between blood and hair levels would
break down at the higher blood levels among the autism
spectrum group (a type of heteroscedasticity).\5\ Another way
of looking at it, the relationship between blood level and
hair excretion may be different for persons with autism than
those without autism. Levine's test of equality of variance
indicated the variance in hair mercury was not evenly
distributed between the autism and control groups (F = 5.98,
P = .017). We calculated the correlation for persons whose
circulating levels of mercury were in the top quartile
separately for the autism and control groups. The correlation
between blood and hair levels of mercury was r = .91 for the
control group (accounting for 84% of the variance). For the
autistic group, the correlation was r = .73, meaning only
about 55% of the variance in the hair mercury levels was
attributable to the blood mercury level differences.
To check the hypothesis that hair excretion was overall
lower than would otherwise be predicted based on a certain
blood level in the autistic group, a best fit regression line
was calculated (y = 10.3, x = -2.48) indicting that for each
unit increase in hair level, blood level increased by 10.3
units. Attest on the residuals showed that autistic
participants were significantly more likely to have lower
hair mercury levels than would be predicted as a function of
their blood levels, t(133) = -2.92, P < .005; see Figure 1).
It should also be noted that the presence of unequal
variances or nonrandom residuals (in this case, autistic
persons are both more likely to have greater variability at
high levels of circulating mercury and a lower hair value for
a given blood level) are both violations of important
assumptions of the t test; a t test of hair mercury is
therefore probably not a valid means to predict autism
diagnosis as a function of mercury exposure. We performed an
analysis of covariance (ANCOVA) with autism diagnosis as the
independent variable and hair mercury level as the dependent
predictor using blood levels as a covariate. Results indicate
that hair level may be related to diagnosis of autism, not as
a predictor in terms of absolute value, but such that for
equivalent circulating levels of mercury in the body, those
with ASD excreted less than normal such that F(1,134) = 3.9
and P = .05. To sum, the relationship between blood levels of
mercury and mercury excreted in the hair is reduced for those
with autism compared with nonautistic persons; furthermore,
the difference between autistic and nonautistic persons is
most pronounced at high levels of mercury.
Discussion
In statistics, obtaining a probability value of P < .05
indicates that the obtained test statistic (based on one's
sample) is extremely unlikely (less then 5% chance) to have
been obtained by chance alone. By convention, this value is
usually set at .05 (as a balance of type 1 and type 2
errors); however, this value is, in fact, arbitrary and
statistical probability tables for hypothesis testing always
include a range of probability values--not only probability
at the .05 level. Given that this is the first direct test of
this hypothesis and considering the potential importance of
finding a relation between mercury blood levels and autism,
it is just as important to avoid a false negative as a false
positive. As the original authors have now currently
calculated, the obtained difference suggests that there is
probably a real difference (specifically that the chance that
a real effect exists is about 94%, or, conversely, that the
chance null effect is true is less than 6%, which misses the
conventional .05--or 5%--mark of statistical significance).
Given the close value to conventional significance, most
researchers would not call this a firm rejection of the
hypothesis, but might say it was marginally significant. Most
researchers facing a P value of .056 would not want to
categorically state that results ``indicate that there is no
casual relation between mercury level . . . and autism.'' \1\
It concerns us that the original authors would want to let
this conclusion stand in light of the new P value (which
differs markedly from the .15 previously reported in 2004).
Another issue to consider is the question of a one-tailed
or a two-tailed hypothesis test. Usually, researchers use a
two-tailed test, which tests if there is a ``difference''
between 2 groups. However, when the literature leads a
researcher to propose a specific direction of the difference,
a one-tailed test is called for, ``Often a researcher begins
an experiment with a specific prediction about the treatment
effect. For example, a special training program is expected
to increase student performance, or alcohol consumption is
expected to slow reaction times . . . The result is a
directional test, or what is commonly called a one-tailed
test.'' \10\
Whether to use a one-tailed test or a two-tailed test can
be decided based on considering what would happen if the
results ended up in the opposite direction of what one
suspects. In this case, it would mean that the blood mercury
levels were lower in the autistic group. Would this support
the original hypothesis? (No!) However, if this were to
happen, that is, if the autistic group were significantly
lower in their blood mercury levels than the normal group,
the researchers would find themselves in the incongruous
position of having to accept their hypothesis that autism is
related to elevated levels of mercury in the blood! The key
point here is that their hypothesis was directional, and a
one-tailed test should have been used. In this case, the just
missed significance of their new analysis using a two-tailed
t-test (P = .056) would have reached a conventional level of
statistical significance (with P <.03).
Although the statistics can be tedious, the bottom line is
that only by an apparent error in the original data analysis
was the original lack of effect found. The authors' revised
calculation (t test) still has problems (two-tailed test for
a directional hypothesis, not removing clear outliers). And
finally, the willingness to characterize a t test with a .056
level of statistical significance as no effect is
questionable, especially in this particular case.
Of utmost importance (which outweighs the discomfort of
writing about an error made by colleagues whom we know are
generally competent researchers) is that potential
researchers who are trying to understand what is and is not
behind the rise in autism are not misled by even the
slightest misinformation. It is imperative that researchers,
medical professionals, and the public at large have the full
set of information. To put it in perspective, the connection
between taking aspirin and prevention of heart attack has an
effect size equal to .038 which represents an effect size
approximately equal to what we find between circulating
levels and ASD diagnosis in this age group.\12\ Just as
important is the fact that for those physicians in the
aspirin group who did have a heart attack, the heart attack
was less likely to be fatal. The effect size for this latter
effect was .08 and did not represent a significant difference
from the placebo group by traditional dichotomous
significance testing.\13\ Yet, this does not mean no effect
exists or that the effect is not of practical importance. We
would encourage all researchers to not only report whether a
[[Page H15282]]
test of mercury and autism reaches significance with the
sample size used, but to report the exact statistic and also
effect sizes to help future researchers resolve all the
factors involved in the etiology of autism.
References
1. Ip P, Wong V, Ho M, Lee J, Wong W. Mercury exposure in
children with autistic spectrum disorder. J Child Neuro.
2004; 19:431-434.
2. National Academy of Sciences. Toxicological Effects of
Methylmercury. Washington, DC: National Academy Press; 2000.
3. Bernard S, Enayati A, Redwood L, et al. Autism: a novel
form of mercury poisoning. Med Hypoth. 2001;56:462-471.
4. Chrysochoou C, Rutishauser C, Rauher-Luthy C, et al. An
11-month-old boy with psychomotor-regression and auto-
aggressive behavior. Eur J Pediatr. 2003; 162:559-56.
5. Adams JB, Romdalvic J, Sadagopa VH, Legator MS. Mercury,
lead, and zinc in baby teeth of children with autism versus
controls. J Toxicol Eviron Health. 2007;70:1046-1051.
6. Holmes AS, Blaxill MF, Haley BE. Reduced levels of
mercury in first haby haircuts of autistic children. Int J
Toxico. 2003; 22:277-285.
7. Walker SJ, Segal J, Aschner M. Cultured lymphocytes from
autistic children and nonautistic siblings up-regulate heat
shock protein RNA in response to thimerosal challenge.
Neurotoxicol. 2006; 27:685-692.
8. Fido A, Al-Saad S. Toxic race elements in the hair of
children with autism. Autism. 2005;9:290-298.
9. Kern JK, Grannerman BD, Triverdi MH, Adams J.
Sulfhydryl-reative metals in autism. J Toxicol Environ
Health. 2007;70:715-721.
10. Gravetter FJ, Wallnau LB. Essentials of Statistics for
the Behavioral Sciences. 4th ed. Pacific Grove, CA:
Wadsworth; 2005.
11. Tabachnik B, Fidell LS. Using Multivariate Statistics.
New York: Prentice Hall; 2006.
12. Steering Committee of the Physicians' Health Study
Research Group. Preliminary report: findings from the aspirin
component of the ongoing physicians' health study. N Engl J
Med. 1988;318:262-264.
13. Rosnow RL, Rosenthal R. Statistical procedures and the
justification of knowledge in psychological science. AM
Psychol. 1989;44:1276-1284.
{time} 1945
The SPEAKER pro tempore. Under a previous order of the House, the
gentlewoman from California (Ms. Pelosi) is recognized for 5 minutes.
(Ms. PELOSI addressed the House. Her remarks will appear hereafter in
the Extensions of Remarks.)
____________________