Autism Street

An e-mail conversation with the lead researcher.

Southwest College of Naturopathic Medicine Chelation Study

Following my last post regarding this chelation study, I sent several e-mails to the researchers and doctors involved. My e-mails ranged from a request for a copy of their experimental protocol, to a simple request for answers to nine questions. Although I received many read receipts, in general the e-mails were not responded to.

I then had the good fortune of one of the other parents in the online support group I participate in here in Phoenix, submitting the questions herself to “Jim” (as he is referred to by the local parents). He responded to her almost immediately. I then responded to his seemingly irrelevant and evasive answers, and he was kind enough to continue the conversation (with that one other parent now “in the loop” so to speak).

What follows is essentially a transcript of our e-mail conversation. I have changed the name of the other parent (she appears to want nothing to do with this any more and stopped returning my e-mails), and I make occasional comments in [brackets] which were not part of the original e-mails. I’ve also changed the e-mail addresses for everyone, including Jim (to prevent robot spam). Interestingly he never used one of his university e-mail addresses.

*****E-mail to Jim from the other parent*****

[From: OtherParent@wahoo.com]
[To: Jim.PhD@bsu.edu]
Date: Sun, 22 Jan 2006 8:50 PM
Subject: Some questions about the Chelation study

Some people have been asking me some ethics related questions about the ASU chelation study and I thought I better send the your way to get the answers right from the horses mouth so to speak:

[The study actually has nothing to do with ASU, it’s being conducted by the Southwest College of Naturopathic Medicine]

1.Assuming it is possible that mercury toxicity causes or contributes to autism, is it ethical to administer chelation as part of the process to determine whether or not a child has toxic levels of mercury that require additional chelation (or qualify them for phase two)? As part of FDA guidelines for clinical trials involving the “off-label” use of FDA-controlled medications, was this study reviewed by an IRB?

2. Is there a recognized, and accepted standard for measuring/determining actual mercury toxicity by the process of chelation being employed in phase one?

3. What are the mercury excretion levels required (and associated standard) for qualification for phase two?

4. Why isn’t the Glutathione controlled or double-blinded in phase two?

5. Is the application of cream containing Glutathione being controlled? Are the parents applying it? If the quantities of cream are controlled, is the length of time it remains on the skin being controlled? If parents are to ensure that the cream is applied and remains for specific length of time on a specific area, are they all following an identical procedure?

6. Are the urine samples being collected throughout the study being collected by an independent third-party, or by the parents?

7. Are all samples (blood and urine) being sent to at least two independent laboratories for validation of lab results?

8. Phase two criteria stipulate no changes in medications, diet, supplements, or behavioral intervention. Why isn’t behavioral intervention being curtailed altogether so as to remove it as a possibility in skewing the results? It is clearly the case that most children receive differing quantities, qualities, and modes
of behavioral intervention. Combined with the fact that autistic children all experience developmental progress to different degrees, at often unknown times, at different rates, and quite possibly as a result of behavioral intervention, why not remove it as a variable, and isolate the effect of the chelation therapy alone?

9. Does the provision for medical care exclude emergency treatment for an adverse reaction (however unlikely) if needed?

Appreciate your time on these questions Jim I know you are busy

Thnx

[Other Parent]

*****Jim’s response was to the other parent only, she was kind enough to forward it to me for comment*****

———- Forwarded message ———-
[From: Jim.PhD@bsu.edu]
[To: OtherParent@wahoo.com]
Date: Jan 22, 2006 11:02 PM
Subject: RE: Some questions about the Chelation study

1) Everyone is exposed to toxic metals every day. The average person in mygeneration lost 4-7 IQ points due to lead poisoning. DMSA removes the toxic metals, and only slightly affects zinc. The most reliable way to determine mercury loads is to use a chelation challenge.All human studies, including this one, were reviewed by an IRB whichincludes medical physicians.

I would turn the question around and say that it is unethical for the FDA to have exposed children to the exceptionally high level in vaccines, withoutever having conducted proper animal tests on the safety of thimerosal. DMSA has undergone extensive human testing. We are being far safer than the FDA was.

2) There are lab reference norms for normal daily excretion of toxicmetals. Also, from my previous two studies of DMSA, we know how much toxic metals are excreted by typical children given DMSA, and those studies found that children with autism excreted more on average.

3) 100% of the labs reference range.

4) The glutathione and the DMSA are double-blind, placebo-controlled in phase 2.

5) The lotion is applied in the same way by parents, according to instructions they receive from the study personnel.

6) Urine is collected by the parents, for convenience and the child’sprivacy

7) Blood and urine samples are sent to one lab, per standard practice.

It is unethical to stop a therapy that is likely to be beneficial, and itwould be unscientific. It is standard to continue all treatments without stopping any.

9) Emergency care or any other care is allowed - but it may cause them to be disqualified from the study.

*****I then responded to Jim and the other parent*****

[From: dad_of_cam@autismstreet.com]
[To: Jim.PhD@bsu.edu; OtherParent@wahoo.com]
Date: Jan 23, 2006 11:45 AM
Subject: RE: Some questions about the Chelation study

[Other Parent] and Jim,

Regarding the responses provided.

1) “Everyone is exposed to toxic metals every day”.

This is an irrelevant statement.

“The average person in my generation lost 4-7 IQ points due to lead poisoning”.

Again, this is totally irrelevant. You are not hypothesizing lead poisoning.

“DMSA removes the toxic metals, and only slightly affects zinc”.

This is irrelevant to my question as well, and is already known.

“The most reliable way to determine mercury loads is to use a chelation challenge”.

Who determined this? Is there any supporting research (peer-reviewed and published, preferably in the field of toxicology). Is there an accepted assay with associated and published norms for this process?

“All human studies, including this one, were reviewed by an IRB which includes medical physicians”.

I would like to see the complete protocol as approved by the IRB. I don’t see how this was approved with regard to ethics, which have not been addressed in this response at all. Ethics should address the scientific merit prior to human experimentation: An IRB would want good evidence that (1) mercury causes or contributes to autism and (2) that autistics have elevated mercury levels. That scientific evidence just isn’t out there. The paper you likely refer to [Am J Clin Nutr 2004;80:1611–7] with regards to the glutathione doesn’t mention Mercury. An IRB would also want applicable experimental methodology: standard assays for measurement and published norms as supported by correlative studies.

“I would turn the question around and say that it is unethical for the FDA to have exposed children to the exceptionally high level in vaccines, without ever having conducted proper animal tests on the safety of thimerosal. DMSA has undergone extensive human testing. We are being far safer than the FDA was.”

Again, this is completely irrelevant to the question. Please answer the question!

2) “There are lab reference norms for normal daily excretion of toxic metals”.
I did not ask about reference norms for “normal daily excretion”. I’m asking about the assay and reference norms for the “challenge” method being employed in phase I. Please answer the actual question.

“Also, from my previous two studies of DMSA, we know how much toxic metals are excreted by typical children given DMSA, and those studies found that children with autism excreted more on average.”

It is already known that children given DMSA will excrete metals. Please explain by which accepted “challenge” measuring standard and assay are you able to say, “We know how much toxic metals are excreted by typical children given DMSA, and those studies found that children with autism excreted more on average”. Have those two studies been peer-reviewed and published? Please detail the assays involved, and the research that supports the measurement via the challenge method in Phase I.

3) 100% of the labs reference range.

100 % of the labs reference range for what? Please detail the assays involved, and the research that supports the measurement via the challenge method in Phase I.

4) The glutathione and the DMSA are double-blind, placebo-controlled in phase 2

The glutathione is not double-blind or controlled, every child who receives DMSA will receive glutathione along with it. Effects (assuming an accepted, and research-supported method of determining actual mercury toxicity) by the process of DMSA chelation with, or without glutathione will be impossible to know, since everyone who’s chelated gets it.

5) The lotion is applied in the same way by parents, according to instructions they receive from the study personnel.

Good, but it will likely be argued that results could be affected by parental inconsistency.

6) Urine is collected by the parents, for convenience and the child’s privacy

I’ll withdraw this question.
[I later learned I probably should not have, as contamination is fairly common]

7) Blood and urine samples are sent to one lab, per standard practice.

I would withdraw this question upon understanding: assays used, reference norms for the “challenge” method being employed and the research that supports the measurement of mercury toxicity via that challenge method and the associated norms , and that the labs are industry-standard as used by other major medical providers in the Phoenix and Tucson areas (which they probably and hopefully are).

“It is unethical to stop a therapy that is likely to be beneficial, and it would be unscientific”. “It is standard to continue all treatments without stopping any.”

I’ll agree with unethical. As to unscientific, I’ll rephrase the question.

It is clearly the case that most [autistic] children receive differing quantities, qualities, and modes of behavioral intervention. Also, autistic children all experience developmental progress to different degrees, at often unknown times, at different rates, and quite likely as a result of behavioral intervention. How do you intend to address the fact that it will be impossible to isolate any effects of the chelation component of combined ongoing treatments such as behavioral intervention?

How do you intend to prove (not assert) that a difference in the chelated group vs. a control group is due to the chelation and not behavioral intervention or developmental progress, or a lack thereof in the control group?

9) “Emergency care or any other care is allowed - but it may cause them to be disqualified from the study”.

You avoided the question, so I will rephrase it.

The study describes the medical care that will be provided as part of the study - which does not include medical care (ambulance, hospitalization, treatment by a specialist, etc.) in the event of an emergency (anaphylaxis or other adverse reaction, as examples). Will the study provide for (logistically and financially) such emergency medical care if required (however unlikely)? Yes or No?

*****Jim responded later that evening*****

[From: Jim.PhD@bsu.edu]
[To: dad_of_cam@autismstreet.com; OtherParent@wahoo.com]
Date: Jan 23, 2006 7:10 PM
Subject: RE Chelation Study

I suggest you first read the DAN! Consensus Report on Treating Mercury Toxicity, which is a consensus document of over 30 expert researchers and physicisans. It is on my website, www.eas.asu.edu/~autism and contains extensive references. That should answer most of your questions.

Then, if you have additional questions, I will answer them.

Sincerely,

Jim

*****I sent him the following response, a little irritated that he did not really answer any of the questions*****

[From: dad_of_cam@autismstreet.com]
[To: Jim.PhD@bsu.edu; OtherParent@wahoo.com]
Date: Jan 23, 2006 8:30 PM
Subject: Re: Chelation Study

Jim,

If you are declining to answer my specific questions, and declining the release of your complete experimental protocol (as approved by your IRB), that’s fine. I have sufficient information to communicate my concern to Ric Zaharia about the DES/DDD conduct in this matter, or area parents who ask me about your responses to the questions I posed. I would think they might have questions for you, and I would encourage you to communicate specific actual answers in the future.

As far as your suggestion to read the DAN! - I’ll pass. I’m not looking for a list of extensive and potentially irrelevant references, I was really more interested in the specific valid references relevant to your designed research. I’m quite sure my questions should have already been answered within your complete experimental protocol as approved by your IRB (or shown as not properly addressed), and that you should have had fairly easy access to answers for the questions I posed.

Please do me the courtesy of one more brief reply, declining to answer the specific questions, or answering them. I think this should prevent the need for me (or Ric Zaharia) to request anything else from you.

Sincerely,

Dad Of Cameron

P.S. Please do not ask for, or take advantage of any taxpayer money to facilitate your privately-funded research in any way (mailings or otherwise).

*****Jim responded still later that same evening*****

[From: Jim.PhD@bsu.edu]
[To: dad_of_cam@autismstreet.com; OtherParent@wahoo.com]
Date: Jan 23, 2006 10:15 PM
Subject: Re: Chelation Study

Attachment: [Bradstreet Paper]

Sir,

I have already tried twice

[Hmmm, I count once...]

to answer your questions. I will try again below, and I am willing to meet with you to discuss your concerns if you have further questions.

1) There are several ways to measure mercury levels. Blood, urine, and hair only reflect recent exposure. The advantage of a DMSA challenge combined with a prior baseline urine is that it tells you: a) if metals come out in the urine, then they were in the body b) DMSA is effective in removing them.Measuring urinary excretion is a standard practice in toxicology studies. It is also the recommended approach of the DAN! Consensus group. Finally, it was the method used in my previous published study (attached).If you want an extensive discussion of the substantial literature on the autism-mercury link, see the appendix of the DAN! report. It discusses the substantial evidence to suggest that many children with autism suffer from mercury
toxicity.

All IRB’s review the safety, ethics, and scientific merit of research, and our protocol was reviewed and approved on that basis. Much of the explanation is included in the appendix of the DAN! consensus report, which I again encourage you to read.It is not common practice to release protocols while a study is in progress, especially a double-blind study. You may submit a detailed bio and a reason for your request, and we will consider it.

2) The reference values for controls taking DMSA are reported in the Bradstreet paper. The lab we are using also reports the values for children not taking DMSA, which is useful for our baseline data.

3) The lab measures the amount of toxic and essential minerals in the urine using an ICP-Mass Spec. The reference range is based on their evaluations of the normal excretion level of typical children.

4) In phase one, everyone receives DMSA, and half receive glutathione. That allows us to ask the scientific question “does glutathione increase excretion of toxic metals when used in combination with DMSA.” In phase 2, half the participants receive real dmsa and real glutathione, and half receive placebo DMSA and placebo glutathione. That allows us to answer the scientific question “does DMSA plus glutathione lead to a reduction of body burden of toxic metals, and does it help children with autism.”

5) Answered.

6) Answered.

7) The testing lab is Doctor’s Data, which is a CLIA approved lab and has much more sensitive testing equipment than most local labs. It is the same lab as used in our previous studies, so that we can compare results. Finally, samples are sent “blinded” to the lab, so they do not know what is being tested.

[Doctor's Data? Hmmm, very interesting...]

All human trials involve some differences in participants. All autism studies involve children on different diets, in different schools, receiving different therapies, with different medications, etc. The accepted scientific norm is to keep all other treatment methods the same, and to introduce the treatment in a double-blind, placebo-controlled manner, and observe the effect of that treatment while holding all other treatments constant.

9) The provision of medical care is clearly discussed in our consent form, which is available on our website. Consultation with physicians is available in case of an emergency, and additional care might be provided at their discretion in the highly unlikely event of a problem. In our previous study of over 200 children, there were no adverse events.

In closing, let me say that this is a scientific study to evaluate a new treatment that is very promising, based on letters we have from over a half-dozen physicians treating over 3000 children with autism. Those letters indicate that this is one of the most promising interventions, with many (but not all) children showing great improvement. We are attempting to conduct a scientific study to evaluate their clinical observations. Since this treatment is widely used by tens of thousands of children with autism, we think it is important to study it scientifically.Again, feel free to contact me if you have further questions, or to set up a meeting to discuss your concerns.

Sincerely,

Jim

*****I responded back one more time that evening*****

[From: dad_of_cam@autismstreet.com]
[To: Jim.PhD@bsu.edu; OtherParent@wahoo.com]
Date: Jan 23, 2006 11:28 PM
Subject: Re: Chelation Study

Jim,

Thank you for your reply, and willingness to discuss this. It is appreciated. I will read your paper over the next couple of days - thank you for the copy. I see no point in wasting your time, or mine in meeting to discuss this, but I appreciate your offer. Your correspondence via e-mail is appropriate.

Sincerely,

Dad Of Cameron

*****I received an e-mail from Jim the next morning*****

[From: Jim.PhD@bsu.edu]
[To: dad_of_cam@autismstreet.com; OtherParent@wahoo.com]
Date: Jan 24, 2006 10:42 AM
Subject: Re: Chelation Study

Attachment: [Holmes Hair Study]

You may also be interested in the attached article by Holmes on mercury in baby hair.

Jim

*****I responded to this e-mail*****

[From: dad_of_cam@autismstreet.com]
[To: Jim.PhD@bsu.edu; OtherParent@wahoo.com]
Date: Jan 24, 2006 1:04 PM
Subject: Re: Chelation Study - Holmes hair study you sent.

You may also be interested in this analysis!
http://autismdiva.blogspot.com/2005/12/dr-amy-holmes-was-just-trying-to-help.html

Perhaps you could write a rebuttal. I’d be happy to submit it to the author of this blog for a response.

Dad Of Cameron

*****In between then, I had been doing some research about the Bradstreet Paper Jim had sent the night before, and I sent this response*****

[From: dad_of_cam@autismstreet.com]
[To: Jim.PhD@bsu.edu; OtherParent@wahoo.com]
Date: Jan 24, 2006 11:26 AM
Subject: Re: Chelation Study

Dear Dr. Jim, et. al.

I appreciate your attempts to educate me with your responses and literature, and your open-mindedness to this discussion is admirable. I thought I was specific enough in my request for substantiating research regarding your “challenge” methods of mercury measurement, in that the research be “peer-reviewed”.

I am disappointed in your attempt to answer the questions I have, by providing research that would largely be ignored by the mainstream medical and the scientific community. I am not looking for research that fits your theory - and published anywhere. I am looking for research where your theory is proven, subsequently “peer-reviewed”, and then published where an IRB should have required to see the evidence of scientific merit prior to experimentation with human subjects.

In reasearching PubMed at http://www.ncbi.nlm.nih.gov/ I am unable to find ANY articles by ANY of the doctors involved with your research directly related to autism and measuring mercury toxicity via your challenge method with DMSA. Am I missing something? I was also unable to find your article from 2003 there as well.

Obviously I am concerned that a ‘real’ “peer-reviewed” medical journal, as seen in the eyes of a mainstream physician, medical school, or university, would be required for this study to be ethical in terms of scientific merit prior to testing on human subjects. I still fail to see how this was approved by an IRB with regards to methodogy in light of the lack of correlative studies to your methodology in the mainstream medical “peer-reviewed” journals that should be easily found at http://www.ncbi.nlm.nih.gov/.

I’m going to make this as specific as I can: Can you provide any research, as published by a “peer-reviewed” journal that CAN be found on PubMed at http://www.ncbi.nlm.nih.gov/ to support: any of your assertions about measuring mercury toxicity in autistic children via your “challenge” methods (including assays/published norms, and correlative studies?

Yes (and provide references)
No
Or decline to answer.

Please don’t waste either of our time by suggesting reference to the DAN! consensus. (Review of the Rimland’s work at PubMed http://www.ncbi.nlm.nih.gov/ alone is pretty self-explanatory). Also please don’t waste our time where an IRB wouldn’t by suggesting:

http://www.doaj.org/
http://www.jpands.org/
http://www.aapsonline.org/

Sincerely,

Dad Of Cameron

*****Jim responded with*****

[From: Jim.PhD@bsu.edu]
[To: dad_of_cam@autismstreet.com; OtherParent@wahoo.com]
Date: Jan 24, 2006 1:39 PM
Subject: Chelation Study

Sir,

Our group is the first to use DMSA in a study of children with autism. If there were already published studies on that very specific case, then there wouldn’t be a need for another study.

There is substantial evidence in peer-reviewed journals to support our work and the use of DMSA challenges. For example,

The study by James et al clearly demonstrates that children with autism have low glutathione, and hence would have an impaired ability to excrete mercury and other toxins. This would result in a build up of toxic metals in the body. A DMSA challenge or a tissue biopsy would be the only way to test the level.

The study by Holmes et al clearly demonstrates severe abnormalities in metabolism of mercury by children with autism.

The DMSA study by Bradstreet et al clearly demonstrates that children with autism excrete more mercury than typical children, which strongly suggests that they have a higher mercury exposure.

The TTFD study by D. Lonsdale shows that another chelator, TTFD, was beneficial to children with autism.Neuro Endocrinol Lett. 2002 Aug;23(4):303-8. Related Articles, Links Treatment of autism spectrum children with thiaminetetrahydrofurfuryldisulfide: a pilot study. Lonsdale D, Shamberger RJ, Audhya T.Preventive Medicine Group, 24700 Center Ridge Road, Westlake, OH 44145, USA. dlonsdale@pol.net OBJECTIVES: In a Pilot Study, the clinical and biochemical effects of thiamine tetrahydrofurfuryl disulfide (TTFD) on autistic spectrum children were investigated. SUBJECTS AND METHODS: Ten children were studied. Diagnosis was confirmed through the use of form E2, a computer assessed symptom score. For practical reasons, TTFD was administered twice daily for two months in the form of rectal suppositories, each containing 50 mg of TTFD. Symptomatic responses were determined through the use of the computer assessed Autism Treatment Evaluation Checklist (ATEC) forms. The erythrocyte transketolase (TKA) and thiamine pyrophosphate effect (TPPE), were measured at outset and on completion of the study to document intracellular thiamine deficiency. Urines from patients were examined at outset, after 30 days and after 60 days of treatment and the concentrations of SH-reactive metals, total protein, sulfate, sulfite, thiosulfate and thiocyanate were determined. The concentrations of metals in hair were also determined. RESULTS: At the beginning of the study thiamine deficiency was observed in 3 out of the 10 patients. Out of 10 patients, 6 had initial urine samples containing arsenic in greater concentration than healthy controls. Traces of mercury were seen in urines from all of these autistic children. Following administration of TTFD an increase in cadmium was seen in 2 children and in lead in one child. Nickel was increased in the urine of one patient during treatment. Sulfur metabolites in urine did not differ from those measured in healthy children. CONCLUSIONS: Thiamine tetrahydrofurfuryl disulfide appears to have a beneficial clinical effect on some autistic children, since 8 of the 10 children improved clinically. We obtained evidence of an association of this increasingly occurring disease with presence of urinary SH-reactive metals, arsenic in particular.

There have been extensive studies of the use of DMSA in humans and animals.

Measuring mercury excretion in the urine is standard practice, because that is how DMSA is excreted.

For example, see the following (there are many more articles you can search for): J Toxicol Clin Toxicol. 1992;30(4):505-28. Related Articles, Links Human studies with the chelating agents, DMPS and DMSA.
Aposhian HV, Maiorino RM, Rivera M, Bruce DC, Dart RC, Hurlbut KM, Levine DJ, Zheng W, Fernando Q, Carter D, et al. University Department of Molecular and Cellular Biology, University of Arizona, Tucson 85721. Meso-2,3-dimercaptosuccinic acid (DMSA) is bound to plasma albumin in humans and appears to be excreted in the urine as the DMSA-cysteine mixed disulfide. The pharmacokinetics of DMSA have been determined after its administration to humans po. For the blood, the tmax and t1/2 were 3.0 h + 0.45 SE and 3.2 h + 0.56 SE, respectively. The Cmax was 26.2 microM + 4.7 SE. To determine whether dental amalgams influence the human body burden of mercury, we gave volunteers the sodium salt of 2,3-dimercaptopropane-1-sulfonic acid (DMPS). The diameters of dental amalgams of the subjects were determined to obtain the amalgam score. Administration of 300 mg DMPS by mouth increased the mean urinary mercury excretion of subjects over a 9 h period. There was a positive correlation between the amount of mercury excreted and the amalgam score. DMPS might be useful for increasing the urinary excretion of mercury and thus increasing the significance and reliability of this measure of mercury exposure. DMSA analogs have been designed and synthesized in attempts to increase the uptake by cell membranes of the DMSA prototype chelating agents. The i.v. administration of the monomethyl ester of DMSA, the dimethyl ester of DMSA or the zinc chelate of dimethyl DMSA increases the biliary excretion of platinum and cadmium in rats.

Those are the major studies that support my work, published in peer-reviewed journals, most or all available on pubmed.

[Note: The James Paper is observational and doesn't prove anything, nor does it even mention mercury - it's also a small non-representative sample population.]

[Note: The Holmes Paper stands, but not for long - see:
http://autismdiva.blogspot.com/2005/12/dr-amy-holmes-was-just-trying-to-help.html.]

[Note: The Bradstreet Paper was not published in a 'real' peer-reviewed journal, and is not available on PubMed. The science needs to be proven, not just made up.]

[Note: The Lonsdale Paper is interesting, but makes no specific conclusions about mercury that I can see (from the abstract), additionally it is a very small sample population (10).]

Finally, if you want more information on the measurement of mercury excretion in urine after the use of DMSA, I suggest the following references from pubmed.

[He sent the following PubMed search results, which I have not had time to follow-up on yet]

Items 1 - 20 of 25 of 2 Next
1: Hibberd AR. Related Articles, LinksDimercaptosuccinic acid loading test for assessing mercury burden in healthy individuals.Ann Clin Biochem. 2004 Sep;41(Pt 5):422-3; author reply 423. No abstract available.PMID: 15333200 [PubMed - indexed for MEDLINE]2: Miller NJ, Howard MA. Related Articles, LinksDimercaptosuccinic acid loading test for assessing mercury burden in healthy individuals.Ann Clin Biochem. 2004 Sep;41(Pt 5):421-2; author reply 423. No abstract available.PMID: 15333199 [PubMed - indexed for MEDLINE]3: Archbold GP, McGuckin RM, Campbell NA. Related Articles, LinksDimercaptosuccinic acid loading test for assessing mercury burden in healthy individuals.Ann Clin Biochem. 2004 May;41(Pt 3):233-6.PMID: 15117439 [PubMed - indexed for MEDLINE]4: Stark AM, Barth H, Grabner JP, Mehdorn HM. Related Articles, LinksAccidental intrathecal mercury application.Eur Spine J. 2004 May;13(3):241-3. Epub 2003 Oct 28.PMID: 14586664 [PubMed - indexed for MEDLINE]5: Soo YO, Wong CH, Griffith JF, Chan TY. Related Articles, LinksSubcutaneous injection of metallic mercury.Hum Exp Toxicol. 2003 Jun;22(6):345-8.PMID: 12856958 [PubMed - indexed for MEDLINE]6: Tominack R, Weber J, Blume C, Madhok M, Murphy T, Thompson M, Scalzo A. Related Articles, LinksElemental mercury as an attractive nuisance: multiple exposures from a pilfered school supply with severe consequences.Pediatr Emerg Care. 2002 Apr;18(2):97-100. No abstract available.PMID: 11973502 [PubMed - indexed for MEDLINE]7: Ly BT, Williams SR, Clark RF. Related Articles, LinksMercuric oxide poisoning treated with whole-bowel irrigation and chelation therapy.Ann Emerg Med. 2002 Mar;39(3):312-5.PMID: 11867987 [PubMed - indexed for MEDLINE]8: McFee RB, Caraccio TR. Related Articles, LinksIntravenous mercury injection and ingestion: clinical manifestations and management.J Toxicol Clin Toxicol. 2001;39(7):733-8.PMID: 11778672 [PubMed - indexed for MEDLINE]9: Frumkin H, Manning CC, Williams PL, Sanders A, Taylor BB, Pierce M, Elon L, Hertzberg VS. Related Articles, LinksDiagnostic chelation challenge with DMSA: a biomarker of long-term mercury exposure?Environ Health Perspect. 2001 Feb;109(2):167-71.PMID: 11266328 [PubMed - indexed for MEDLINE]10: Forman J, Moline J, Cernichiari E, Sayegh S, Torres JC, Landrigan MM, Hudson J, Adel HN, Landrigan PJ. Related Articles, LinksA cluster of pediatric metallic mercury exposure cases treated with meso-2,3-dimercaptosuccinic acid (DMSA)Environ Health Perspect. 2000 Jun;108(6):575-7.PMID: 10856034 [PubMed - indexed for MEDLINE]11: Ozuah PO. Related Articles, LinksMercury poisoning.Curr Probl Pediatr. 2000 Mar;30(3):91-9. Review. No abstract available.PMID: 10742922 [PubMed - indexed for MEDLINE]12: Nierenberg DW, Nordgren RE, Chang MB, Siegler RW, Blayney MB, Hochberg F, Toribara TY, Cernichiari E, Clarkson T. Related Articles, LinksDelayed cerebellar disease and death after accidental exposure to dimethylmercury.N Engl J Med. 1998 Jun 4;338(23):1672-6. No abstract available.PMID: 9614258 [PubMed - indexed for MEDLINE]13: Grandjean P, Guldager B, Larsen IB, Jorgensen PJ, Holmstrup P. Related Articles, LinksPlacebo response in environmental disease. Chelation therapy of patients with symptoms attributed to amalgam fillings.J Occup Environ Med. 1997 Aug;39(8):707-14.PMID: 9273873 [PubMed - indexed for MEDLINE]14: Pfab R, Muckter H, Roider G, Zilker T. Related Articles, LinksClinical course of severe poisoning with thiomersal.J Toxicol Clin Toxicol. 1996;34(4):453-60.PMID: 8699562 [PubMed - indexed for MEDLINE]15: Aposhian HV, Maiorino RM, Gonzalez-Ramirez D, Zuniga-Charles M, Xu Z, Hurlbut KM, Junco-Munoz P, Dart RC, Aposhian MM. Related Articles, LinksMobilization of heavy metals by newer, therapeutically useful chelating agents.Toxicology. 1995 Mar 31;97(1-3):23-38. Review.PMID: 7716789 [PubMed - indexed for MEDLINE]16: Cloarec S, Deschenes G, Sagnier M, Rolland JC, Nivet H. Related Articles, Links[Arterial hypertension due to mercury poisoning: diagnostic value of captopril]Arch Pediatr. 1995 Jan;2(1):43-6. French.PMID: 7735425 [PubMed - indexed for MEDLINE]17: Louwerse ES, Buchet JP, Van Dijk MA, de Jong VJ, Lauwerys RR. Related Articles, LinksUrinary excretion of lead and mercury after oral administration of meso-2,3-dimercaptosuccinic acid in patients with motor neurone disease.Int Arch Occup Environ Health. 1995;67(2):135-8.PMID: 7672858 [PubMed - indexed for MEDLINE]18: Houeto P, Sandouk P, Baud FJ, Levillain P. Related Articles, LinksElemental mercury vapour toxicity: treatment and levels in plasma and urine.Hum Exp Toxicol. 1994 Dec;13(12):848-52.PMID: 7718304 [PubMed - indexed for MEDLINE]19: Zwiener RJ, Kurt TL, Ghali F, Day LC, Timmons CF. Related Articles, LinksPotentiation of acetaminophen hepatotoxicity in a child with mercury poisoning.J Pediatr Gastroenterol Nutr. 1994 Aug;19(2):242-5. No abstract available.PMID: 7815249 [PubMed - indexed for MEDLINE]20: Sandborgh Englund G, Dahlqvist R, Lindelof B, Soderman E, Jonzon B, Vesterberg O, Larsson KS. Related Articles, LinksDMSA administration to patients with alleged mercury poisoning from dental amalgams: a placebo-controlled study.J Dent Res. 1994 Mar;73(3):620-8.PMID: 8163732 [PubMed - indexed for MEDLINE]

I hope this answers your questions. Our theory is not proven, but that is the purpose of our study - to determine the validity of our hypothesis. We believe it is plausible and worthy of investigation since many parents are currently using this treatment.

Finally, it is interesting that your critique Dr. Rimlands work. He was the man who disproved the “Refrigerator Mother” theory that autism was due to mothers hating their children, which was the conventional wisdom at that time. Without him, many parents might still be going to psychotherapy to admit their “hatred” of their children.

Today the conventional wisdom is that autism is a combination of a genetic vulnerability and an environmental exposure - what other toxin is known to cause the symptoms of autism other than mercury?

See Bernard’s article (also peer-reviewed on pubmed)

1: Blaxill MF, Redwood L, Bernard S. Related Articles, Links Thimerosal and autism? A plausible hypothesis that should not be dismissed. Med Hypotheses. 2004;62(5):788-94.PMID: 15082108 [PubMed - indexed for MEDLINE]2: Bernard S, Enayati A, Roger H, Binstock T, Redwood L. Related Articles, LinksThe role of mercury in the pathogenesis of autism. Mol Psychiatry. 2002;7 Suppl 2:S42-3. Review. No abstract available.PMID: 12142947 [PubMed - indexed for MEDLINE]3: Bernard S, Enayati A, Redwood L, Roger H, Binstock T. Related Articles, LinksAutism: a novel form of mercury poisoning.

Clearly there are many scientific articles in the peer-reviewed literature suggesting a link between autism and mercury - isn’t it time we carried out a treatment study to see if it helps treat an “incurable” lifelong disorder?

If only a fraction of children were helped, wouldn’t it be worth it?

And if we find out that it does not help, isn’t that useful knowledge?

Sincerely,

Jim

*****I responded to the last e-mail I received from Jim in 3 parts - Part One*****

[From: dad_of_cam@autismstreet.com]
[To: Jim.PhD@bsu.edu; OtherParent@wahoo.com]
Date: Jan 24, 2006 2:29 PM
Subject: Re: Chelation Study

Dr. Jim, et.al.

This is perfect! I can clearly demonstrate to Ric at DES/DDD that it would be virtually impossible for a typical parent to make a completely informed decision about a study like this - they’d almost have to take your word for it, and the DES/DDD should not be facilitating it with taxpayer money. It’s going to take me some time to adequately research your response, but I intend to. I ultimately hope to see the results of your study in a ‘real’ peer-reviewed journal on PubMed, for the benefit of all our children - second to actually helping autistic children, that is your intention isn’t it (a ‘real’ peer-reviewed journal on PubMed)?

I’m not necessarily hopeful, because I don’t see ANY for Bradstreet so far (other than a 30-year old “pH mediated inhibition of the cell to cell spread of herpes simplex virus infection”), but I’ll remain open minded on this. If this study is not published in a ‘real’ peer-reviewed journal and available on PubMed, will you eat your hat, and personally apologize to participants?

You said, “The study by Holmes et al clearly demonstrates severe abnormalities in metabolism of mercury by children with autism”. I’ll look forward to your rebuttal of the analysis I sent you - when your study is done of course.

Best regards,

Dad Of Cameron

*****I responded to the last e-mail I received from Jim in 3 parts - Part Two*****

[From: dad_of_cam@autismstreet.com]
[To: Jim.PhD@bsu.edu; OtherParent@wahoo.com]
Date: Jan 24, 2006 5:10 PM
Subject: Re: Your mostly PubMed cited research

Dear Dr. Jim,

I will not waste your time by going into any detail beyond the first 4 “major studies” that you offered as support for your work. We can respectfully agree to disagree, and that’s fine. I will read the other couple later on.

“Our group is the first to use DMSA in a study of children with autism. If there were already published studies on that very specific case, then there wouldn’t be a need for another study.”

Lack of published studies does not constitute need. Scientific merit based on: 1) Proof that mercury toxicity causes autism and 2) proof that autistic children have higher concentrations of mercury would constitute the need for a study using DMSA to remove said mercury. For example a study about how to remove rocks from your back yard would not be warranted merely by a lack of existing studies, unless 1) Some of those rocks were known to be cause a specific illness, and 2) Your backyard actually contained those dangerous rocks.

“There is substantial evidence in peer-reviewed journals to support our work and the use of DMSA challenges. For example,”

“The study by James et al clearly demonstrates that children with autism have low glutathione, and hence would have an impaired ability to excrete mercury and other toxins. This would result in a build up of toxic metals in the body. A DMSA challenge or a tissue biopsy would be the only way to test the level.”

I just re-read that study. It is comprised of a very small group of (20) kids, all regressive autistics, which comprise only about 20-25% percent of all autistics. Her paper recommends further study but it does not prove anything! See the discussion section. Also, it does not even mention mercury.

“The study by Holmes et al clearly demonstrates severe abnormalities in metabolism of mercury by children with autism.”

This study stands for now, but is very likely to be discredited in the future. I understand they used Doctor’s Data Labs too. Analysis of this research is at
http://autismdiva.blogspot.com/2005/12/dr-amy-holmes-was-just-trying-to-help.html

“The DMSA study by Bradstreet et al clearly demonstrates that children with autism excrete more mercury than typical children, which strongly suggests that they have a higher mercury exposure.”

This study was not published in a “peer-reviewed” journal and available on PubMed. I’m not going to speculate on a reason, I’ll stick to the established “good science” of PubMed, and encourage other Parents to do the same. If this study has scientific merit, it should be published in a “peer-reviewed” journal on PubMed, so everyone can benefit from the knowledge it can offer. Since your current study will likely cite it, I also think it difficult to survive real scientific peer-review and subsequent publication on PubMed. I don’t see how an IRB would use this to determine the scientific merit, and ethics of using this methodology in your current research, but that was their decision to make.

“The TTFD study by D. Lonsdale shows that another chelator, TTFD, was beneficial to children with autism.Neuro Endocrinol Lett. 2002 Aug;23(4):303-8. Related Articles, Links”

I read the abstract you sent. There is no mention of a change in mercury levels in this study whatsoever. It only refers to trace amounts existing prior to receiving TTFD. Furthermore this study is of 10 children (8 who clinically improved). Is there anything a little more compelling in the whole study?

Dad Of Cameron

*****I responded to the last e-mail I received from Jim in 3 parts - Part Three*****

[From: dad_of_cam@autismstreet.com]
[To: Jim.PhD@bsu.edu; OtherParent@wahoo.com]
Date: Jan 25, 2006 1:27 PM
Subject: Re: 2nd half of your last e-mail

Dear Dr. Jim,

I wanted to respond to the second half of your last e-mail, because you raised some very interesting philosophical questions at the end that I think all parents should consider.

Again, I want to sincerely thank you for all your time and discussion on this matter. Although I think it’s quite clear that I disagree with your version of “the science” behind your research, I respect your right to your opinion, and your ability to communicate it. I hope to have an opportunity to hear you speak at some future autism research gathering, as I think you are probably what I (and many) would consider an excellent presenter (I will always question the facts and do research afterwards of course).

In light of all my questioning of your version of “the science” behind your research, I sincerely hope you prove me wrong (in a real peer-reviewed journal of course). From the second half of your last e-mail…

“There have been extensive studies of the use of DMSA in humans and animals. Measuring mercury excretion in the urine is standard practice, because that is how DMSA is excreted.”

Measuring mercury in the urine, based on the challenge method you employ is NOT standard practice. It has not been scientifically proven and subsequently truly peer-reviewed with respect to the ethics, or scientific validity.

“Human studies with the chelating agents, DMPS and DMSA.” Aposhian HV, Maiorino RM, Rivera M, Bruce DC, Dart RC, Hurlbut KM, Levine DJ, Zheng W, Fernando Q, Carter D, et al.”

I don’t think you would suggest DMPS for children. DMSA has obvious value – this is already known.

“Those are the major studies that support my work, published in peer-reviewed journals, most or all available on pubmed.”

Does DMSA have value for treating autistic children? – The “hypothesis” of your research? Maybe, because it is known to remove metals, but prior to human experimentation it would be ethical to know that 1) mercury actually causes autism and 2) autistic kids actually have higher levels of mercury. The four “major” pieces of research you cite in the beginning of your last e-mail do not represent scientific proof that would support this. It would also be important to have scientifically proven (through the process of real peer-review) the methodolgy - beforehand.

“Finally, if you want more information on the measurement of mercury excretion in urine after the use of DMSA, I suggest the following references from pubmed.”

I don’t have any argument with the effectiveness of DMSA as a chelator.

Real peer-review and publication of your 2003 research would eliminate my concern with the methodology portion of your research.

“I hope this answers your questions. Our theory is not proven, but that is the purpose of our study - to determine the validity of our hypothesis.

All my questions have been answered, thank you.

“We believe it is plausible and worthy of investigation since many parents are currently using this treatment.”

This is utter scientific nonsense. I don’t think you would submit that to an IRB?

“Finally, it is interesting that your critique Dr. Rimlands work. He was the man who disproved the ‘Refrigerator Mother’ theory that autism was due to mothers hating their children, which was the conventional wisdom at that time. Without him, many parents might still be going to psychotherapy to admit their “hatred” of their children.”

This was not intended as a critique of Rimland, I apologize for the poor wording on my part. I was simply attempting to communicate that I don’t see the DAN! Consensus report as relevant reading. There is plenty of scientific evidence (as published in peer-reviewed medical literature) out there about Rimland’s work over the years. There is no doubt that many of his contributions are very important in this field. My point is that you don’t need to read the DAN! consensus report in order to understand the scientific literature.

“Today the conventional wisdom is that autism is a combination of a genetic vulnerability and an environmental exposure - what other toxin is known to cause the symptoms of autism other than mercury?”

“See Bernard’s article (also peer-reviewed on pubmed) Autism: a novel form of mercury poisoning.”

[An article from Medical Hypotheses? Is he joking? Bernard's assertion was thoroughly refuted in Pediatrics]

Medical diagnosticians would not assert that mercury causes the “symptoms of autism”, rather that mercury toxicity and autism have [shared] co-morbidities. Speech disorders are probably the only medically arguable characteristic to the separate diagnoses. [Shared] co-morbidities can make mercury poisoning present clinically similar to autism, but they are not essential to autism. [Some] co-morbidities do not definitively indicate an autism diagnosis, because they are not present in all autistics.

[I reworded and restated an argument originally made by Kevin Leitch]

This line of reasoning is like claiming that if someone has a high fever, a bacterial infection caused it. It could in fact, be a viral infection (in which case antibiotics are likely useless, and could be dangerous in the long run).

“Clearly there are many scientific articles in the peer-reviewed literature suggesting a link between autism and mercury - isn’t it time we carried out a treatment study to see if it helps treat an “incurable” lifelong disorder?”

Suggesting, and scientifically establishing are two very different things. It is time for treatment studies, no argument there.

Investigational treatments must be legal, ethical, have scientific merit (by providing valid and useful data as determined by the scientific community through the process of ‘real’ peer-review and publication), and safe.

“If only a fraction of children were helped, wouldn’t it be worth it?”

It would be worth it, if they were actually helped and the science proves it, as determined by the scientific community through the process of real peer-review.

It would not be worth it if they were led to ‘believe’ they were helped, and they were led to ‘believe’ that science proves it, if in fact it did not, or the real scientific community was never given an opportunity to review it.

“And if we find out that it does not help, isn’t that useful knowledge?”

Yes it would be useful, but ethically, that end may not justify these means.

[They'd also need to prove it, not assert it]

Thank you for all your work on this Dr. Jim,

Dad Of Cameron