By Mary Holland, Esq.
Note: The experts testify before the Special Masters with Powerpoint presentations. It is difficult to comprehend their testimony without reference to their visual materials. Experts’ Powerpoint presentations will be available at the A-CHAMP website HERE.
Continued Cross examination of Dr. Aposhian
Ms. Renzi continued with questions about methyl vs. ethyl mercury exposures; can methyl mercury exposures lead to autism? Dr. Aposhian said these are important questions but that there are no certain answers. No one looked at autism rates in the Seychelles or Faroe Islands after the methyl mercury studies there, although Dr. Aposhian thought that Dr. Clarkson was now looking at this issue.
Dr. Aposhian apologized for a reference in his report suggesting that Dr. Clarkson and Dr. Magos’ papers should be read cautiously. He noted that he has great respect for them both and that he meant no offense. That said, he thinks all science should be read skeptically and with caution, including his own.
In response to a question, he indicated that he had not discussed any of his testimony for this hearing with other experts in this proceeding.
In response to questioning, he pointed out that he’d taken out most references to Pink disease in this testimony because data are lacking. But, he argued that it’s an example of how the medical establishment was unable to declare mercury powder the culprit, and the disease disappeared only because of government regulation taking the powder off the market. He also said that Pink disease seems to indicate that there are individuals with hyper susceptibility to mercury.
Ms. Renzi then asked whether urinary porphyrin data may be used to diagnose mercury toxicity. Dr. Aposhian said that he is not a physician or diagnostician, but that he knows doctors who use this method that is described in the medical literature. He said that urinary porphyrins probably are biomarkers for mercury toxicity, but that they cannot tell anything about mercury levels in the brain.
Can you describe the mercury efflux disorder more specifically? Do you know the level of mercury toxicity at which this disorder manifests? No. The hypothesis of a mercury efflux disorder only took form at the 2004 Institute of Medicine meetings.
Dr. Aposhian said that he believes that build up of mercury in the brain tissue is one of the causes of autism. He bases that view on studies by Holmes, Haley, Bradstreet and Adams, but he cautioned that it’s only one of the causes; autism is a broad spectrum. Ms. Renzi asked if Dr. Aposhian agreed with Dr. Deth and Dr. Mumper that a certain percentage of autistic children suffer mercury toxicity. Yes. Is mercury efflux disorder a lifelong disability? We don’t know. Is autism the only outcome of mercury efflux disorder? It took one hundred years to take mercury out of infant teething powders. While conservatism has been one of the American medical establishment’s strengths, it will take 50-100 years to draw certain conclusions about all aspects of mercury efflux disorder. Can you get mercury poisoning from diet? Yes. This is the Minamata story; there have been cases of mercury poisoning from eating fish near gold mines; you can get mercury toxicity from eating canned tunafish if you are hyper susceptible.
Is a mercury efflux disorder generally recognized in the medical community? I don’t know, but it is recognized by many who treat autism.
Dr. Aposhian noted that he’d been invited to certain think tanks on autism. He said that many people now see autism as treatable, but that in fact the likelihood of positive outcome is greater when the parents have more money to spend on treatment options; this is undemocratic.
Can you think of a mechanism by which mercury efflux disorder could cover only regressive autism? Dr. Aposhian discussed the teratogenic effect in certain narrow developmental windows, such as the birth defects from thalidomide, and he referred to Wilson’s disorder, the analogous copper efflux disorder.
When is the developmental window, how long does it last, how does it lead to autism? No one is studying this; NIH has been very reluctant to fund this kind of research. Although the estimate of the cost of treatment for an autistic child is $3 million per lifetime, money goes into the diseases of the elderly – cancer and heart disease. We wouldn’t have the body of autism research we have today but for parents pressuring NIH. I have been ashamed of NIH for not funding autism research.
During the window of vulnerability, is it vulnerability just to mercury? We don’t know, but usually susceptibility means vulnerability to many agents.
Ms. Renzi asked questions to point up problems in the Holmes hair study and problems with the Bradstreet chelation study. Can you show that chelation improves the neurological manifestations of autism? No. Where does the mercury come from that the chelating agent DMSA removes? Mostly from the kidneys, but also from other tissues. Ms. Renzi also asked questions on the Hornig mouse study, noting that it has been criticized.
Observing many problems with the studies that serve as the “pillars” of Dr. Aposhian’s views, Ms. Renzi asked, how many pillars do you need to establish a TCV – autism link? Is one pillar enough? Two? Dr. Aposhian said that it depends on the quality of the scientific papers.
Did you consult with the IOM in 2004 for the report on thimerosal and vaccines? Yes. Did the IOM cite to the Charleston papers on monkeys from the mid-1990’s? No. There were serious problems with that IOM study group – it was made up completely of epidemiology and vaccine people; there were no toxicologists, no immunologists and no biochemists. In all the IOM vaccine studies, there were no toxicologists to review vaccine safety issues and how thimerosal and ethyl mercury could affect a child’s brain.
Was there any discussion of neuroinflammation in the 2004 IOM study? No. This was a shock to me. The Zimmerman work will be classic. If he continues this work, he will probably win the Nobel prize.
Because Dr. Aposhian added information that was not included in the expert report submitted to the court several months in advance, the court gave the Respondent the opportunity to question Dr. Aposhian at a later time if it wishes to.
Direct Examination of Dr. Deth
Dr. Deth is a Professor of Pharmacology at Northeastern University; a member of many professional organizations and the author of about 70 peer-reviewed articles. He began autism-related research about five years ago after having discovered new signaling activity of the dopamine-4 receptors in 1998.
Mr. Williams reviewed with Dr. Deth his basic theory that inorganic mercury gets “trapped” in the brain. Inorganic mercury can bind to two groups of molecules -- sulfur or thiol groups, and even if one bond breaks, the mercury stays in place. Because of two thiols, mercury remains in the brain for an extraordinarily long time. Mercury disrupts sulfur metabolism in the brain and other tissues.
Thiols are the perfect bonding agents for mercury. The word “thiol” used to be called “mercaptan” because it binds to mercury. Thimerosal’s preservative function is similar to what Dr. Deth is describing – the preservative interferes with bacterial and fungal sulfur metabolism.
Dr. Deth reviewed certain vocabulary. An important part of sulfur metabolism is keeping a normal redox state in the cells. In the brain, astrocytes keep careful control of the amount of cysteine going to the neurons, and microglial cells monitor the redox state. When activated, they create a level of oxidative stress. Neuroinflammation is the state of oxidative stress in the brain with sulfur metabolism changes.
Methylation is the transfer of carbon atoms. There are 200 different methylation reactions. If something affects methylation, it will affect 200 different reactions, the most important of which is the methylation of DNA or genes. Methylation turns genes on and off; it is the epigenetic regulator of genes. When oxidative stress increases, methylation decreases. Sulfur metabolism is critical to life and oxygen control.
When Dr. Deth was studying cardiology, he found that the D4 dopamine receptor could carry out methylation and that problems with this receptor were THE genetic risk factor for ADHD. People with this problem had 3-5 times higher risk of ADHD. More than 100 peer-reviewed articles have identified this higher risk factor.
Dr. Deth reviewed the work of Dr. Jill James comparing the methylation cycles of autistic children vs. neurotypical controls. He then described his work on neuronal cells’ responses to thimerosal in vitro. Using the concentrations of thimerosal that are comparable to the levels in vaccines, they observed 2/3 reduction in cellular glutathione and more than a 90% reduction in cellular B-12. They also studied aluminum, another additive in vaccines, and found it was not as potent as thimerosal in changing methylation, but it was still very potent. He showed their most recent unpublished data using autistic autopsy brain tissue of the same kind used in the Vargas study. Their observations using PCR technology suggest a relationship between decreased RNA for methionin synthase and neuroinflammation.
In summary, Dr. James’ work shows that the autistic population is at risk of problems with methylation; genetic data are starting to identify genetic risk. Otherwise latent risk factors can become consequential risk factors.
Mr. Williams asked Dr. Deth to explain how chelation works if it does not pull mercury out of the brain. Dr. Deth explained that the whole body experiences oxidative stress; it’s a systemic problem, not restricted to the brain. Chelation of peripheral mercury can have useful effects. It can establish normal redox in the peripheral metabolism and can affect the brain. It can reduce the amount of inflammatory cytokines and availability of cysteine. There are benefits of correcting heavy metal toxicity even though mercury is not coming directly from the brain.
Can the levels of thimerosal used in the monkey studies cause autism in humans? Based on reading the literature and the results they had obtained, they saw the effects of thimerosal at every turn. Thimerosal has the molecular capacity to impair attention, sociability, awareness and neurological synchronization. Dr. Deth came to the “unavoidable conclusion” that thimerosal is a causative factor in autism.
Cross Examination of Dr. Deth
What do you consider to be the strongest evidence? Post-mortem brain tissue autopsies of autistic people and the work of Jill James measuring sulfur metabolism and genetic evidence of polymorphisms.
Mr. Matanoski asked Dr. Deth about his CV and a study proposal he submitted to the NIH. Dr. Deth explained that his proposal was rejected because the reviewer asserted that “thimerosal doesn’t cause autism” and that money shouldn’t be spent there. How does the NIH review grants? Government people and academics review proposals on an anonymous basis.
In response to questions, Dr. Deth reviewed some of his recent chapters and articles.
Mr. Matanoski asked how much money Dr. Deth’s research budget is. Dr. Deth said about $90,000 last year. Mr. Matanoski asked about the source of funds. Over the last five years, fund largely came from autism organizations: CAN, Safe Minds, NAA, ARI. Dr. Deth reviewed the amounts from different organizations. Doesn’t Safe Minds have an agenda to support studies that show that the mercury – autism hypothesis is true? Mr. Matanoski showed Safe Minds’ scientific mission statement on its website.
Mr. Matanoski asked questions about Dr. Deth’s recent book and about some of his recent presentations at conferences with citations to Drs. Geier. Mr. Matanoski asked why Dr. Deth had not cited to Drs. Geier in this report. Dr. Deth said that what he’s cited supports his remarks; he said that some of the work of the Geiers is very interesting and that they are very active. Do you think it doesn’t support what you’re saying? I wouldn’t necessarily draw that conclusion.
Would oxidative stress potentially implicate a wide range of diseases? It could. Did you discuss at a recent conference a possible link with obesity? Yes. Dr. Deth entertained the hypothesis that other conditions with epidemic outcomes might be related to shared causes.
What happened to the neurons in your 2004 study? Did they die after exposure to thimerosal? No; their shape changed, but the change was reversible; they didn’t die. This was a point of encouragement that recovery from neuroinflammation might be reversible. And it is consistent with the situation that some children improve significantly if not recover fully.
Do you think there’s an epidemic of autism that is tied directly to the use of thimerosal in vaccines? I do. Do you think there’s a rise in childhood obesity related to thimerosal? There’s been no parallel investigation. I raised this issue as a hypothesis. Thimerosal exposure might result in more than one consequence. Those with other polymorphisms might develop a different set of symptoms. If one hypothesis is true, one should look at others.
In 2003, you said it would be interesting to see if the incidence of autism decreased in 3-5 years. Was it your expectation that the autism rate would drop? I was hopeful that it would; I’m aware that the California data do not show a decrease.
What percentage of the population is susceptible to thimerosal toxicity? Perhaps 1 in 150.
Is autism the neurological manifestation of inorganic mercury in the brain? Yes. Will the same effect be the case with methyl mercury exposure? This is too general a question. Thimerosal exposure occurred in bolus doses. This is a very big difference for elimination. How much inorganic mercury would one need to result in autism? Concentrations at the sub-nanomolar level would likely cause graded levels of interference with sulfur chemistry. There will be a threshold concentration when cells can no longer compensate, but I don’t know what that concentration is in the intact brain. Can you extrapolate from anything what that threshold concentration might be? No. Do you have to have an efflux disorder for the effects you describe? It’s a titration issue. We don’t all have the same rate of how much we can clear a toxic substance in a day. Is your hypothesis independent of an efflux disorder? Both the efflux problem and redox problem are inextricably linked with glutathione. We were using autopsy cells, but they were human neuronal cells; 3,000 papers have been published using these cells. They are highly predictive for human and animal brain function.
What’s the strongest evidence for the role of impaired methylation and oxidative stress? The two papers of Jill James. Does oxidative stress elsewhere in the body affect neuroinflammation? Oxidative stress peripherally will affect neuroinflammation.
Mr. Matanoski asked questions to highlight that Dr. Deth modified slides for this report that he used in slightly different versions in past public talks; Mr. Matanoski noted that “neuroinflammation” was not on several past slides. Dr. Deth said that his hypothesis had not changed; oxidative stress and neuroinflammation are very closely related.
Redirect Examination of Dr. Deth
Mr. Williams returned to the question of funding from Safe Minds and why the NIH had turned down Dr. Deth’s research proposal. Mr. Williams read from the CBS News website which contained text from Dr. Bernadine Healy’s interview yesterday. As a former head of the NIH, Dr. Healy said that public health officials have been too quick to dismiss autism-vaccine links as irrational. She further said that public health officials had intentionally avoided doing research that might scare people away from vaccination. The link to the interview is HERE.
Do you think the NIH turned you down for these reasons? The reviewers took the government statement that “thimerosal does not cause autism” as a basis to say that it’s not appropriate to study thimerosal. Dr. Deth received the same reception from some foundations. He said he understands the issue of preserving public confidence, but the best way to do that is through validated studies. It’s been frustrating not to be able to pursue studies for lack of funding.
Recross Examination of Dr. Deth
Mr. Matanoski clarified that Dr. Deth’s NIH proposal was rejected by fellow academics, not be the government directly. Dr. Deth said that it could have been people in the private sector or academics and that he doesn’t know who the people were. But there has been very restricted funding, and parent-funded groups have had to take this on. “Cutting and pasting of a government position has no role in evaluating the scientific validity of a study.”
Mary Holland teaches at New York University Law School and may be contacted HERE. Thank you to A-CHAMP for providing this important service.