Deth

1.  Introduction

Richard Deth Ph.D., is a neuropharmacologist, professor of pharmacology at Northeastern University in Boston, Massachusetts.

2.  Activation of methionine synthase by insulin-like growth factor-1 and dopamine: a target for neurodevelopmental toxins and thimerosal

2.1  Abstract

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 methylationsensitive 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: Cu2þ promoted enzyme activity and methylation, while Cuþ, Pb2þ, Hg2þ and Al3þ were inhibitory. The ethylmercury-containing preservative thimerosal inhibited both IGF-1- and dopamine-stimulated methylation with an IC50 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. [1]

2.2  The Issues

The basic gist of the Deth paper is that various toxins, including thimerosal, affect methionine synthase activity (a process that helps in building proteins) and that this can adversely affect children. In short, the Deth paper alleges that thimerosal causes methionine synthase dysfunction (MSD).

2.3  The Talking Points

There are several talking points about what relevance this paper has to autism.

1. MSD and autism do not resemble each other. Symptoms of MSD are: Anemia, moderate to severe developmental delay, lethargy, anorexia, and homocystinuria (mental retardation, dislocation of the crystalline lens of the eye, sparse blond hair, and cardiovascular and skeletal deformities) [2]
2. There is no active transport mechanism into the central nervous system currently known for ethylmercury (thimerosal) whereas there is an known and active transport mechanism for methylmercury.
3. Because its half-life is much longer, methylmercury is more likely to accumulate than ethylmercury, causing higher levels of mercury in the blood.
4. Exposing cells in vitro to ethylmercury eliminates the most important difference between those two forms of mercury, and ignores the fact that ethylmercury is unlikely to enter the central nervous system at concentrations likely to be harmful.
5. The authors chose to use a cell line derived from a metastatic peripheral nervous system tumor to make predictions about developing healthy cells of the central nervous system. If the authors were interested in making claims about the developing central nervous system they should use cells derived from their.
6. The authors make statements in their introduction about developmental disorders such as fetal alcohol syndrome, Rhett's syndrome, or Fragile-X syndrome, they fail to consider the fact that all of these diseases have their origins in the developing embryo and fetus, not postnatally.
7. The authors' reference a study that evaluated the causal association between thimerosal and vaccines using the Vaccine Adverse Events Reporting System (VAERS). This system is a bad resource. This is discussed why on the VAERS entry page.

Blogger Bartholomew Cubbins also provided a critique which is viewable here.

What isn't common knowledge is that this paper was funded by Safe Minds - one of the big autism/thimerosal groups. It also came to light that Richard Deth is registered as a paid expert witness in the vaccine litigation omnibus proceedings. In an email exchange between Richard Deth and Kathleen Siedel, Professor Deth said:

"I thank you for alerting me to the fact that my name was included on that expert witness list. It was done so without my knowledge or permission. It might be related to a phone call from that law office that was logged to my office while I was away on vacation in February. I never returned the call."

To which Ms Siedel replied:

"It was quite an oversight for the attorneys to fail to confirm your willingness to serve in that role prior to naming you as a plaintiffs’ expert in the Petitioners’ Initial Disclosure of Experts, and filing that document with the Court of Federal Claims. However, their certainty is understandable, given your indication during our brief telephone conversation that the lawyer with whom you discussed the matter was “Andy” Waters, lead attorney in the thimerosal cases."

Professor Deth did not reply further.

For more on these issues see Strategic Disregard and An Exchange of Views.

For an article about professor Deth's promotion of a (now vetoed) Thimerosal ban in Hawaii see Pineapples, Politics, and Science.

3.  Also See

Thimerosal | Burbacher | Bernard | Hornig