Monday, December 17, 2007

Dr. Miles Airs Today

Our package about Dr. Judith Miles airs today on KOMU. I'm really excited for you all to see it. Dr. Miles works at the Thompson Center which we featured earlier in the series here in Columbia. We thought that it was important to feature Dr. Miles in the series because she presents a side of the causation argument we've yet to feature. Also, it was a story on Dr. Miles' RhoGAM study that started this whole series. You can look at that study which found no link between thimerosal and autism on KOMU's website.

Go to the website to check out the story on Dr. Miles and take a look at our extra web features including a slideshow and a behind the scenes video.

You will also see Dr. Miles featured in the investigation portion of the series which will air next week.


Anonymous said...

Finally. Some real science. What took so long?

EFFIIIMD said...

The Miles and Takahashi paper is science that fails to completely address its intended question and leaps to the conclusion that is has answered the question of a causal relationship between thimerosal and autism. Their intent is stated in the AMJMedGen paper on page 1398 as "To address the question of whether thimerosal exposure causes autism, we investigated thimerosal exposure during pregnancies which resulted the birth of a child subsequently diagnosed with autism."

Not a bad idea if the only dose of thimerosal delivered was in utero and associated with rhogam. Did they exclude any mothers who had thimerosal in flushots during pregnancy or other vaccines in the affect subjects subsequent to the in utero rhogam dose in early childhood? This being overlooked is a fairly concerning, and a blanket statement that there is no causal relationship between thimerosal and autism really needs a prospective controlled study, ideally in a higher risk patient population such as those families with history of auto-immune or neuropsychiatric issues such as Alzheimers, depression, schizophrenia and other relatives with autism.

Really, the promising science is that we may find the at-risk kids on a functional basis (urinary prophyrins testing) and eventually prevent the unintended rare (relative term, is 1 in 1000 rare enough?) bad outcomes associated with intensive mass vaccination protocols. Screening parents for detoxification kinetics may be an idea that will come around soon too. If these vulnerable populations are better defined, we will see the association much more clearly and protect the vulnerable 0.5% of the population. The average pediatrician will understand the importance once this finer scrutiny teases out biochemical risk stratifiers. Certainly, even leaving a full 1-2% unvaccinated is an acceptable percentage left uncovered oterwise protected by herd immunity. Restoring the public's confidence in vaccines is badly needed; a mature admission that there is a vulnerable population that we need to screen for and exclude from vaccination protocols is due. Evidence based medicine would dictate that checking titers after initial vaccination in any series should be in order, and recalibrating titer decay rates in children via this approach would also due much advance the understanding of vaccine science. Since neurologic injury is a concern, another great way to assess the effects of vaccines having an idosyncratic reaction causing neurologic insult would be in the use of MRI immediately after a suspected vaccine reaction (I read MRIs for much less justifiable reasons). Yeah actually, that should be a requirement of VAERS reporting; MRI documentation of normal findings or abnormal findings. Evolving promising sequences such as diffusion tensor imaging and standard diffusion weighted imaging should start becoming standard of care that any kid who suddenly regresses within a week of vaccination gets an MRI of the brain. Pictures say a thousand words, one could hypothesize the images might reflect a Posterior Reversible Encephalopathy Syndrome type pattern in some that have a particularly damaging reaction and those would be the ones to pull out of the CDC protocol. A good pediatrician could then tailor a more gentle and age appropriate schedule. Of course having that day 1 dose of Hepatitis B gives you little baseline for knowing any subtle reaction maybe brewing. Obviously all the tools of medicine, the most powerful of which is MRI imaging which can actually give us amazing details of structure, function, pathology and even spectroscopic chemical analyses are not being used well to investigate the situation. A retrospective scrutinizing of the potential connection with some significant confounding issues seems weak evidence for exonerating thimerosal.

One point of note in the Miles paper is the correct observation that methylation of DNA is influenced by various environmental factors but indicate mercury is not known to affect DNA methylation. Seems to be understudied, see abstract below attached below; flaws and all, there has been a little work on this issue published before Dr. Miles' paper, further work is need to investigate the connection between thimerosal and DNA methylation, seems that more research into the in vivo effects of toxins like mercury and aluminum on methionine synthase needs to proceed not sure how to get 1 nanomolar responses tracked in vivo which seems to be required for a vaild study according to some subsequent commentary on this piece, maybe F-18 PET analogs could get that in vivo evidence going, in the meantime it would appear that since this study isn't enough to concern the experts we can put the thimerosal back into the vaccines for a thoughtful well-controlled studies to be performed in prospective fashion for safety.

This is great, UM School of Journalism really needs to be applauded for showing both sides of this story. Moving science forward is not easy and often takes outside players and an atmosphere of inquiry not encumbered by financial conflicts or fear of asking questions we couldn't answer in the past but may be able to now.

Edward F. Fogarty, MD
Chairman of Radiology
University of North Dakota School of Medicine

Mol Psychiatry. 2004 Jul; 9 (7):644
Activation of methionine synthase by insulin-like growth factor-1 and dopamine: a target for neurodevelopmental toxins and thimerosal.
Waly M, Olteanu H, Banerjee R, Choi SW, Mason JB, Parker BS, Sukumar S, Shim S, Sharma A, Benzecry JM, Power-Charnitsky VA, Deth RC.
Department of Pharmaceutical Sciences, Northeastern University, Boston, MA 02115, USA.
Methylation events play a critical role in the ability of growth factors to promote normal development. Neurodevelopmental toxins, such as ethanol and heavy metals, interrupt growth factor signaling, raising the possibility that they might exert adverse effects on methylation. We found that insulin-like growth factor-1 (IGF-1)- and dopamine-stimulated methionine synthase (MS) activity and folate-dependent methylation of phospholipids in SH-SY5Y human neuroblastoma cells, via a PI3-kinase- and MAP-kinase-dependent mechanism. The stimulation of this pathway increased DNA methylation, while its inhibition increased methylation-sensitive gene expression. Ethanol potently interfered with IGF-1 activation of MS and blocked its effect on DNA methylation, whereas it did not inhibit the effects of dopamine. Metal ions potently affected IGF-1 and dopamine-stimulated MS activity, as well as folate-dependent phospholipid methylation: Cu(2+) promoted enzyme activity and methylation, while Cu(+), Pb(2+), Hg(2+) and Al(3+) were inhibitory. The ethylmercury-containing preservative thimerosal inhibited both IGF-1- and dopamine-stimulated methylation with an IC(50) of 1 nM and eliminated MS activity. Our findings outline a novel growth factor signaling pathway that regulates MS activity and thereby modulates methylation reactions, including DNA methylation. The potent inhibition of this pathway by ethanol, lead, mercury, aluminum and thimerosal suggests that it may be an important target of neurodevelopmental toxins.