Thursday, August 24, 2006

SOMETHING WICKED, INDEED

Dan Olmsted continues his “Age of Autism” series with “Something Wicked ⎯ 2.” In the latest installment, he traces the history of hypotheses linking chemical exposure to the development of autism. All of it leaves me wondering why was the notion of environmental involvement not taken seriously for so long after it was first suspected. Why did we have to wait for autism to become so pervasive before we took a hard look at the obvious?

12 Comments:

Blogger Do'C said...

"Five were chemists and three worked in related fields. The exposed parents represent 21 percent of the autistic group. This compared to 2.7 percent of the retardation controls and 10 percent of the normal controls. The data, subjected to statistical analysis, demonstrated a chemical connection."

"The results of this study point in the direction of chemical exposure as an etiological factor in the birth of autistic children."


Wade, what do you think of the possiblity that Chemists and related fields represent the genetic influence expressed as career choice/apptitude rather than some chemical exposure? You know, the scientist/engineer types likely possibly having ASD traits themselves? You claim to be open-minded. What's your take on that possiblity?

BTW, I couldn't find a 1981 citation for T Felicetti on pubmed for the actual study.

8/25/06, 12:57 AM  
Blogger Wade Rankin said...

Do'C,

I'm not overly surprised about not finding the article on pubmed; I've encountered similar problems before. I'm probably not the right person to comment on such things.

As for your question regarding a "genetic influence," I certainly don't discount the fact that the same genetic permutations that make some individuals more prone to environmental insult that triggers symptoms of autism may also be responsible for "gifts" that attract individuals to certain career paths. The respective extent to which those genetic differences play a role in the triggering of autism, vis-a-vis environmental insults, are still the subject of ongoing research.

But that's Mr. Olmsted's point, isn't it? The real question is why has it taken so long to give the issue the attention it merits.

8/25/06, 2:10 PM  
Anonymous Anonymous said...

I and my daughter were prone to autism, both having two snips on the MTHFR gene...which gives us an impaired glutathione pathway to begin with.

I am not autistic, nor am I on the "spectrum." I did not receive nearly as much toxic mercury exposure as my daughter did at a developmental age.

Had I been born the late 90's...and assuming I wasn't Amish... I would be autistic today.

Autism is NOT purely genetic, but is primarily environmental. Only someone who denies we have an epidemic could possibly disagree with that.

Erik Nanstiel

8/25/06, 5:20 PM  
Blogger Do'C said...

"Had I been born the late 90's...and assuming I wasn't Amish... I would be autistic today."

Erik,

Surely you are aware there is autism among the Amish. It's apparently the result of genetics in this population. From the TGEN press release:
Link

"According to Dr. Erik Puffenberger, laboratory director at the CSC, "We were able to unequivocally map the disease gene to chromosome 7 and identify a pathogenic sequence variant in the gene CNTNAP2, which codes for the CASPR2 protein. Although these patients were from an isolated population, we anticipate that CASPR2 mutations will be found in children from other populations with mental retardation, seizures, and autism."

You can probably still get the full text without going to NEJM.
Link

I'm assuming you are correlating the late 90's with mercury in vaccines - if I'm incorrect, let me know. Along those lines, what is your take on the CDDS data? Graph

Other than that, I'll assume that your assertion that you would be autistic is belief, and not a claimed ability to see alternate realities.

"Autism is NOT purely genetic, but is primarily environmental. Only someone who denies we have an epidemic could possibly disagree with that."

Strawman Erik. I don't claim that it is PURELY genetic. Even identical twins don't have the same fingerprints.

8/25/06, 10:28 PM  
Blogger María Luján said...

Hi
I will try to give a personal analysis about what has been said by Erik and DoC. I hope that neither of you are going to take this personal, because it is not my intention, as never is to make personal critics . NEVER. I will focus in the position/ideas as a paradigm more than in the person and I hope you are not unconfortable with this analysis.
I am a Bachelor in Chemistry, PhD in Chemistry and my job is in Chemistry Research. Therefore probably because of my brain peculiarities related to my genetics I have some predisposition (I like maths and chemistry enormously) that probably also my son receive as part of his heritage. BTW, during my pregnancies I avoided any kind of contact with chemicals, and also postnatally. I consider that at individual level, BOTH (genetics /environment )can be important (or one above the other) but we can not generalize.
Erik said
I am not autistic, nor am I on the "spectrum." I did not receive nearly as much toxic mercury exposure as my daughter did at a developmental age.

Had I been born the late 90's...and assuming I wasn't Amish... I would be autistic today.


I consider that , because I only receive not more than 4 vaccines during my first 2 years, I was not exposed to the 22 vaccines my son received in the same period. Therefore, IF a predisposition is heritaged, evidently the “dose” of the insult- in accumulation- was much higher for my son than for me. Unfortunately, because I have not the overall information about what causes autism, I can not – and I prefer not- to make statements for sure because simply I do not know. However, I would say that there is a possibility than I would have more ASD traits (I have some) if I had been born in the late´s 90… but I have not the tools to demonstrate it for sure.

DoC said

Surely you are aware there is autism among the Amish. It's apparently the result of genetics in this population. From the TGEN press release:
"According to Dr. Erik Puffenberger, laboratory director at the CSC, "We were able to unequivocally map the disease gene to chromosome 7 and identify a pathogenic sequence variant in the gene CNTNAP2, which codes for the CASPR2 protein. Although these patients were from an isolated population, we anticipate that CASPR2 mutations will be found in children from other populations with mental retardation, seizures, and autism."

This kind of genetic particularity in Amish is akin to the Landau Kleffner in the general population. The fact that chromosome 7 is involved- a chromosome that has been linked to autism in many published scientific peer- reviewed papers it is extremely important for me.
My question
What would be the presentation in number and symptoms in Amish population if they were fully vaccinated, looking at the incidence of this particular genetic trait in this group??
Nobody knows
Therefore, this particular presentation of autism is not related to an answer if , in some cases, environmental insult has a role in the symptomatology. I consider that ASD can be mainly genetic in nature, mainly environmental in nature and the combination of both and the true root of ASD at individual level is very difficult to discriminate.
DoC said
I'm assuming you are correlating the late 90's with mercury in vaccines - if I'm incorrect, let me know. Along those lines, what is your take on the CDDS data?

DoC, nothing is to take on CDDS data because CDDS data can not be used to confirm or to deny an epidemics.
DoC said
Other than that, I'll assume that your assertion that you would be autistic is belief, and not a claimed ability to see alternate realities.

DoC, considering the presence of ASD traits or of certain polymorphisms, this is not alternative reality, is a probable – although not proven- path of alternative development, with a plausible root in altered biochemistry, based in partial evidence.

Erik said
Autism is NOT purely genetic, but is primarily environmental


Erik I have to disagree here for my son, but not for your daughter because I consider each child is different- and BTW we all do our best for them. For my son I think different, I think that autism in him is the combination of both and I can not say what is primarily involved. But I respect your position and your right to think so for your daughter because you know her better that everyone else and I supposed you have all the information to think this way.

Erik you said
Only someone who denies we have an epidemic could possibly disagree with that.

I respectfully consider that we can not talk of an epidemic FOR SURE with the scientific /educational data available. In the meanwhile not proofs are presented, you can believe what you consider appropiate, but I have to disagree in the presentation of the denying of an epidemics as wrong. For me it is not a question of right/wrong, there are proofs of nothing with the data available. Until genetic epidemiology and further biochemistry/epigenetics/proteomics/ physiology studies provide more clues, I consider that NOTHING can be said as for sure.

Hi Doc
Strawman Erik. I don't claim that it is PURELY genetic. Even identical twins don't have the same fingerprints

I consider that to present personal positions is not a strawman per se,it depends always on the intention and of the perception.

If you look around in the Hub or in blogs, generally the exchange of ideas are in this tone- and much much extremely much worse. Unfortunately. The situation is such that ALWAYS double intentions are suspected, the perception in advance is to have a confrontation- even unnoticed-and real learning is simply impossible.

Today, debate is impossible BUT only in selected places such as Wade´s Ian´s and very few more blogs. The generalized position is “I am right” “You are wrong”, and generalizing here, not in particular for Erik/DoC.

Again, I hope this is not going to consider personal, but as a reflexion. I agree/disagree partially with your both presentations and my concerns are related about how is presented as facts partial evidence that needs much more research to conclude FOR SURE something.

Finally, I consider the presentation of Mr Olmsted important and clever in terms of why - if there were some clues published so soon as 1981- the environmental connection has been so long dismissed and not studied.

María Luján

8/26/06, 4:20 PM  
Blogger Do'C said...

"DoC, nothing is to take on CDDS data because CDDS data can not be used to confirm or to deny an epidemics."

Agreed with respect to epidemics Maria, however, with regard specifically to the removal of the vast majority of Thimerosal from childhood vaccines, don't you think a Thimerosal induced etiology in general would noticeable if it were removed?

8/26/06, 5:16 PM  
Blogger María Luján said...

Hi DoC

I am going to present you a personal position, that I know that need -surely-further research to be considered proven but I consider that some clues are available to present as an explanation about why I do not think that thimerosal removal is going to have a very noticeable effect.
Considering the ASD children are different in biochemistry since birth because of individual genetics- there are some published clues about- I do think that one or several of the detox enzymes or cofactors systems can be inmature. Also the BBB, especially in children whose brain structure/physiology and cytokines/neurotrophic factors are different, making them vulnerable, especially the first years to environmental insult (there are recent published manuscripts about how BBB is more permeable than thougth before and how is affected by heavy metals). This different immune system also makes them vulnerable to antibiotics ( in terms of gut flora weakness) and vaccines ( especially to the combined insult because of a crowded schedule) and environmental insult ( what we breath, drink and we eat- the common childhood disease- viruses/bacterian (pharingitis) strep).
Therefore our susceptible child receives his first vaccine with thimerosal at the first day of birht ( if thimerosal is present in Hep B vaccine) and near 10-15 more in his/her first year (when included thimerosal) with all the composition of vaccines. Consider please also all the other potentially allergenic preservatives , the antibiotics used in childhood diseases and the chemicals that we must manage daily. Imagine that Hg /Al in combination with toxoids is too much ((after the first /second vaccine) therefore HM begun to accumulate. BUT the detox system is shut up for everything therefore HM from air is also bioaccumulated, and also Pb from air ( from leaded gasoline for example) and also Al beyond vaccines from foils in juices and Cd, As from flame retardants and plaguicides or water .PLUS the problems that viruses of MMR and toxoids can have done because of the permeable BBB and the lack of proper immune answer at the level of the gut and impact in liver due to detox (as is proposed to take place in malnourished children or children with some kind of immune problem, that the CDC recommends to not vaccinate).
The problem is that the immune system is shut down therefore it does not react and the child is more prone to infection (subclinical because of lack of answer or overloaded depending on individual) with herpes and streptococus and others, that make damage but unnoticed, only by the behavioral, developmental delays.

Now with this picture, that for me can change from child to child, with the introduction of new vaccines each year,
Why the avoidance of only ONE insult is going to show a decrease in the ASD numbers? In fact, I think that the numbers will be still increasing until a true analysis of the impact in the immune system of susceptible children of the stressors to a different immune system because of genetic susceptibility is going to be done.
Why only MMR/thimerosal is going to be problematic? For an immune system with a dysfunction, from pesticides to toxoids to gellatin can be problematic ALSO, depending on the individual, and there would be no discrimination from the source of the stressor being viral(a vaccine or a common childhood disease- a virus ) or HM ( Hg as thimerosal or Hg inhalated).

María Luján

8/26/06, 6:08 PM  
Blogger Do'C said...

Why the avoidance of only ONE insult is going to show a decrease in the ASD numbers?

You know Maria, I don't necessarily disagree. Obviously the science has a long way to go in terms of offering proof of anything. I think complex combination of etiologies and autisms is not only a possibility, but a likelihood. The possible combinations of genetics and environment may be near infinite. I also think environment described only as toxins is a simplistic view. In utero developmental enviroment can include so many other variables, even basic things like body temperature, blood pressure, and nutrition, just to name a few.

My view of the "vaccines cause autism" crowd has probably been prejudiced to some degree by following the work of Dr. Adams (ASU) who still states belief that most, if not all autism is caused by mercury (see recent autismpodcast interview), and that he apparently expected to see a change in the California numbers following removal of most of the Thimerosal in vaccines in the U.S. He also regularly cites the Bernard paper with a view that autism is a form of mercury poisoning. Mercury, mercury, and more mercury. Continued citation of the Holmes et al. baby haircut study and pursuit of chelation (without chelators that can cross the BBB) of research subjects older than a hypothesized temporary excretion impairment (see Adams et al. most recent hair study) seems misguided.

Obviously, just because Jim Adams appears to hold such a view, doesn't mean everyone else does.

I could be wrong, but as I understand it, the large litigation in the U.S. federal courts (Autism Omnibus Proceedings) is specific to Thimerosal and MMR.

If Adams (also a PhD chemist) is wrong, or his view simplistic, it would be nice to see him called on it by his peers.

Incidentally, leaded gasoline was phased out in the U.S. beginning in the 1970's, accounted for less than 1% of the gasoline supply in the early 1990's, and was banned entirely in 1996 for regular automobile use. It's still in use in a few applications.

Wade, apologies for straying off-topic.

8/27/06, 12:11 PM  
Blogger Wade Rankin said...

No problem, Do'C. I don't think this is too off-topic for the comments to wander into. You and I disagree about the impact of vaccines and their components (I happen to think that impact was immense), but I agree that it may be short-sighted to ignore other potential insults. And I think focusing on the broader environmental issue is exactly what Mr. Olmsted is doing.

8/27/06, 12:25 PM  
Blogger María Luján said...

Hi DoC
Thank you very much for your answer.
I understand that in the present situation, and under a personal analysis, the main problem we must face are the extremists positions.
Mercury has been the main concern because of potential of damage but I disagree with the overemphasis on it. However, I understand the emotional "charge" on it because I had to face a similar situation to many about my concerns on my son´s health and about vaccines and they were totally dismissed without considerations. I have tried to analyze the most completely and objectively possible the overall situation.
There are scientific, politic, legal, sociological, medical, familiar and individual issues related to the connection autism-vaccines ( as a whole) and autism- environment that are too much important and huge to deserve a very careful look. The nature of the human beings involved at each field is also of huge relevance in the path of the research/decissions/practice, for me. Ethics, medical and political decisions about vaccination are involved here.
PErsonal experiences in autism and what we have faced in our children affect our thinking, this is inevitable in some degree. However, I do consider that the leaders of biomed research could be more cautious in the generalization, as much as I consider that the detractors of all the biomed should be more aware about how science evolves in time. For example, as I told many times, Holmes et al paper is out of date, but perhaps the findings they reported- analyzed different- are showing something that today, with the knowledge we have, we can not explain fully. For example, organic mercury is seen in hair, not inorganic. Perhaps in the case of autism, and this is to further research, the problem is mainly the inorganic Hg and not the organic one. And in this sense the results of this manuscript- that I agree were not analyzed considering the data of general population properly- can be seen under this light. This manuscript- like all in the field- are steps in research ( excellent, good, and not so good) looking for a certain issue. There are many more recent research to discuss about mercury for example. What I agree , also,is in this manuscript can not be considered a proof and has been misused in this sense. But this is for me to have an equilibrated view: it is a step of research, it can be a point about new research to confirm but it can not be used as a proof and it is not proper to mention it as such.
About Bernard, I have the same sensation. I think that the comparison that has made to a NT person poisoned with Hg is not adequate, such as is the assignation of ALL symptoms to Hg. But this does not imply that ALL the Bernard et al paper is WRONG, it implies that perhaps some/many symptomatology was improperly assigned to Hg poisoning or an effect of the biochemical cascade that originates. Because of the combination of medical problems that I do think ASD children many times have How do we know what symptoms assign to what? How do we know if a symptom is not the result of a combinaiton of factors? The comparison that has made of Hg poisoning with ingested Hg or inhalated of NT people (adults or children ) is not proper for me, as it is the assignation for sure to Hg poisoning of all symptomatology, because how do we know for sure in ASD?? Again, a step in the research. I consider that Bernard et al did a hge work of recopilation and they presented the topic, to improve and to discuss and to clarify. For me this is the scientific approach to the issue.
About Dr Adams. I personally disagree with many of his conclussions. In some way I do think if a different atmosphere of true discussion and not attack per se is present research would be conducted in a more heterogeneous team , avoiding the extreme positions and analyzing the facts with different views. Looking at the present situation, it seems that the research is conducted in two parallel worlds, where there is so much distrust between them that a true discussion is not possible. Surely, this approach could be better done, but I can also say that the pharmacovigilance of vaccines and research/testing of safety could be MUCH MUCH MUCH better done that today. However, this does not change the need of rigourous/scientific analysis in the biomedical field.
About Pb, I mentioned because in my country there is still some leaded gasoline available and from air would be the most notorious. There are many sources. I know that in USA you have phased out long time ago. Even in these terms, probably we would have discrepancies in the amount of toxicants involved from country to country around the world.
Another links about lead sources
http://risk.lsd.ornl.gov/tox/profiles/lead.shtml
You can see in table 1 the levels of exposure
http://www.atsdr.cdc.gov/tfacts13.html
Here the sources beyond gasoline
http://www.lead.org.au/lasn/lasn006.html
http://www.leadinspector.com/reduce.html
Sincerely
María Luján

8/27/06, 1:31 PM  
Blogger Joseph said...

DoC is correct about the cofound in Olmstead's article. It is known, for example, that there's a higher prevalence of mathmatecians and accountants as parents of autistics.

I discuss the link to environmental pollution here. I even invited the author of a recent paper on it to discuss the post, and talked it over with her over email. The conversation is posted in the comments.

As to the autism "epidemic" refer to this post of mine and this post by Mike Stanton.

Erik says that if he had been born in the 1990s, he'd be autistic. If he's not autistic now, chances are he would not be autistic regardless of when he was born. Well, you never know. But Erik is assuming that his odds would be higher because the prevalence of autism in adults is supposedly low. When screened, the prevalence of autism in adults is not low at all, however. I think it's at least 1%.

8/27/06, 3:51 PM  
Blogger María Luján said...

Hi Joseph
Thank you for the links.
I have read your link. However, the focus is always ONLY on mercury and I think that , again, only epi data were discussed. I consider the environmental pollution topic much more wide in impact, importance and variation, since pesticides to organic chemicals.
I have also read your post and from Mike´s. However, I still think the way I do: until genetic epidemics is going to be done no true answers- or at least more close to the truth- will be given. All the epi data published since epi was done in ASD has a lot of confounding variables, many of them nor mentioned neither considered, IMHO.
Although I have presented these ideas elsewhere, I consider important to point out the following:
I am thinking in
1- How medicine has been more and more medicalized last 20 years in the treatment of for example ADHD and drugs to control behaviors and how diagnostic criteria have changed last 30 years.
2-How parental attitude in general has changed. Doctors are not more to follow blindly, especially with the amount of things we do not know today about ASD.
3- Internet access to a lot of information- with the adequacy in the source of and the availability- has given a lot of background to ask informed questions to do medical decissions working in a team with doctors
4-There are a lot of concerns about how the discussion about vaccines can affect the vaccination programs around the world. Also, the idea has been so much discredited- whatever the cause- that it seems that it does not matter if it is truth or not some kind of participation in autism presentation at least in a subgroup of autistic children, simply it seems that it is an embarrasement to get involved in that kind of research. However, there are several researchers involved in pharmacovigilance of vaccines and the study of HOW to do pharmacovigilance of vaccines.
5-Educational programs and policies in terms of disabled children attention has changed a lot, especially by parents pressure and disability rights movements and the need of . Policies about educational support have changed during years. How these kind of changes are analyzed when educational data are used?
In epidemiology studies, for example, I have seen one point (MMR) or another (Thimerosal) studied. But the following confounding variables have not been addressed:
1-Changes in vaccinations schedules and introductions of new vaccines. There are no mentions about how the introductions of new vaccines in the analyzed period can be affecting data (studies of USA and UK epidemiology) .If an study has been done about data for 10 years, how many changes in vaccinations schedules have taken place? Even more, how many children at 3-4 years have received these vaccines when introduced and not in the first 2 years of life and how was this analyzed?If a supposed effect is being studied and the immune system would be the potential target, how do you know that further vaccines are not an insult ALSO? Where are the tools to discriminate specifically THIS variable?
2-Changes in regulation policies for emissions of Heavy metals, pesticides contents, of industries that can be near certain cities whose data are used. Quality of the water and changes in regulations about. True amount of HM in air, food and water in different zones. How is it known the effect of this if the supposed effect of injected thimerosal is studied?
3-Analysis of hidden sources of HM or the impact of childhood diseases. Combination effect of schedule, not of only ONE vaccine.
4-Why if the vaccines are analyzed the potential role of viruses or bacterian infections- beyond vaccines, the normal diseases of childhood- are not analyzed? Why the use of antibiotics is not analyzed-especially when children with autism are anecdotally reported to have up to 10 times more antibiotics treatments during the first year than NT children? Why the amount of antibiotics rounds in the first 2 years of life are not analyzed as a component?
5-Why the overall management of pediatrics in terms of schedule, approach to diseases and treatments ( with the use of corticoids, antibiotics and so on) are not analyzed ALSO?

Please note that I am not considering FOR SURE that a role is present for ALL children and as a causal per se; without a genetic component. What I say is that no epidemiology study considers the search of the answers to the questions I presented above as confounding variables in the analysis.
The data involve or can involve all this and more. How can a trend/correlation - if present-be obtained with only ONE if there can be so many as dozens of collaborations in the true data and only 1/2 are being analyzed without the analysis of the importance of all the others?
Only when the true picture to be present about CAUSES and overall presentation of Autism the analysis is going to be done complete, but with the information we have today for me all the variables I presented are discarded in advance without the knowledge of their potential role.

I read as much as possible all the ideas related, but I have not to say more than I said before , related to your post or Mike´s, about these specific topics.

Wade, sorry by going off topic.

María Luján

8/27/06, 5:00 PM  

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