Dr. Brent – Toxicologist at the Autism Omnibus hearing

25 May

Listening to Mr. Williams (lawyer for the parents) cross examine Dr. Brent the toxicologist (from May 19, Day 6) was difficult most because after 45 minutes of discussion of the toxicokinetics of ethyl-, vs. methyl, vs. inorganic-mercury all I could hear was “Blah, blah, don’t you agree that the Charleston monkey adult brain study showedgreaterinflammationoftheinorganic glutamaturgicneuron silvergrainsBurbacherinfant paper? Blah blah and further, isn’t it true thattheVahtergroup onlygave80milligramsperkilogramsperdayofmercuricchloride because the defensereferencemasterlist 436page8 indicatesthatSeychellesIslanders spoke at the IOM?”

Nevertheless, I forced myself to listen to portions of it again and again until I thought I understood what they were talking about exactly. There were several times, maybe 8 or 10 even where it seemed obvious to me that Dr. Brent had totally demolished the point that Mr. Williams was attempting to make and Mr. Williams continued on as if it was of no consequence. I kept getting this picture of King Arthur and the Black Knight from Monty Python and the Holy Grail after King Arthur has sliced off the Black Knight’s arm:

ARTHUR:
Now stand aside, worthy adversary.
BLACK KNIGHT:
‘Tis but a scratch.
ARTHUR:
A scratch? Your arm’s off!
BLACK KNIGHT:
No, it isn’t.
ARTHUR:
Well, what’s that, then?
BLACK KNIGHT:
I’ve had worse.

.

The following is more of my rough transcribing of the audio. I have no idea what that word is that sounds like “AT-trib-ated.” If you know I’d be happy to correct my spelling of it. I believe this first paper he’s referring to is one of the Charleston or Vahter adult monkey studies where they gave very large doses of methyl mercury to the monkeys every day, orally. Click here to hear this segment of the cross examination of Dr. Brent.

.

Mr. Williams: It’s says: “the microglia population is a responsive cell type. Once damage has been repaired following activation after injury microglia are known to return to a quiescent state. However, the number of attribated (sp?) microglia remained elevated … in the monkeys of the clearance group which were kept unexposed for 6 months following 12 months of methyl mercury exposure . This group had very low concentrations of methyl mercury, but retained elevated concentrations inorganic mercury at levels comparable to the 12 month exposure group and this suggests that inorganic mercury may be the proximate species of mercury responsible for microglial activation…” a situation similar to that proposed for the cortex study we already looked at. Now, do you agree that normally microglia have a protective role, they come in and clean up whatever’s there and then they return to their quiescent state?

Dr. Brent: To the extent that I understand microglia… which is limited, I would say, yes.

Williams: And if they stay activated then they can become toxic to neurons and astrocytes.

Dr. Brent: Once again, my, my understanding of microglia is more limited than other people who will be testifying later… my understanding is that microglial activations is not necessarily a bad thing and that … the effects here are not necessarily indicative of any neuropathology.

Once again, you know, we are talking about inorganic mercury effects at the concentrations they give here, and if the inorganic mercury is causing adverse effects at the concentrations, then it’s the seafood and the chicken that people are eating and not the vaccines because that’s where the far greater exposure comes from. And that doesn’t make any sense, because everyone is eating seafood and chicken, including children who are getting mercury via breast milk, and we don’t think of breast milk as a neurotoxin!

Williams: If we go down the column on the same page to about 4 sentences above… yeah about where you have it highlighted…
It says: “Further loss of astrocytes would be expected to have deleterious effects on the neuron population, for example through a excitotoxic mechanism. You were here when Dr Kinsbourne testified that that was his … understanding of the mechanism that could likely be at work here that you would have astrocytes no longer able to take up glutamate, so yyou’d have excess of glutamate and have neurons get over excited. Right?

Dr. Brent: Once again your getting a little out of the mercury area, so my answer here is going to be quite limited, what I took away from Dr. Kinsbourne’s testimony was that he was hypothesizing it was excitotoxic mechanism, related to astrocyte effects. But here for example it says, “further loss of astrocytes,” in this study there wasn’t even that much loss of astroycytes! And certainly, uhm, well we talked about the exposure scenario, so I won’t bring that up again …

Williams: And although, you want to talk about the methyl mercury dose here, you recall that the authors of the infant monkey study made a point of saying that the levels of inorganic mercury in these adult monkeys was only 5 times higher on average than the levels they found in those infant monkey brains, right?

Dr. Brent: That’s right, and that’s very good evidence therefore, that the inorganic mercury is not acting as a neurotoxin, or else we are being poisoned every day, and we are having autism being formed every day, from breastmilk, from seafood, from chicken.

Williams: (Clears throat.)

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I don’t know if it’s immediately obvious to those who haven’t followed the discussion closely, but basically, Mr. Williams had pointed out that inorganic mercury is the “proximate” cause of damage to brain cells. Which is to say that, it doesn’t matter if the original source of the mercury was methyl-, ethyl- or inorganic mercury, because the mercury doesn’t hang around in the brain as either methyl- or ethyl-mercury. Those forms get changed into inorganic mercury, and it’s the inorganic mercury that hangs around. Inorganic mercury (referred to sometimes in the hearing as “Hg-plus-plus,” Hg++) is the same stuff whether or not it started out as methyl-, ethyl-, thimerosol, breast milk, or chicken. And the exposure to breast milk and chicken for the infant and toddler set is much higher than their exposure to thimerosal from vaccines, now or ever. Dr. Brent had said earlier in the cross examination that over the course of 6 months and infant gets “about 250 micrograms of methyl mercury.”

macaque monkey

Besides that the PSC keeps bringing up these studies where macaques were given significantly higher doses, even massively higher doses, of mercury, either thimerosal or methyl-mercury, than babies ever got. The monkeys in the Vahter study were given 50 mcg per kilogram per day of methyl mercury, which Dr. Brent explained is the equivalent in a 70 kg person getting 3,500 mcg a day of methyl mercury. The average diet for that 70 kg person would expose him or her to 11,000 mcg a year. A year! So essentially, the monkeys got a level of mercury in 3 days what they’d get in a year if they had been eating a typical American diet. But some of the monkeys were fed like this for a year. That’s the “12 month exposure group” referred in what I transcribed (above).

And even though they had had that large continual dose of mercury for a year and many of their brain cells were pretty much impregnated with mercury, the monkeys were normal behaviorally. Even if you wouldn’t expect them to become autistic because they were exposed as adults, surely they’d show some outward sign of brain damage if that much mercury were extremely dangerous to brain function.

It was also interesting to me that Burbacher had used 3 or 4 times the amount of thimerosal to dose his infant monkeys as humans got. Had Burbacher used the equivalent amount of thimerosal in the human vaccine schedule the outcome would likely have been that the levels of mercury in the monkey’s brains would have been so low that it wouldn’t have been detectable. (Clears throat.)

There was also some fun discussion about how there’s no increased autism in the Faroe and Seychelle’s islands in spite of the fact that infants have high levels of mercury in their brains (from maternal diet). Mr. Williams stated that “fish is very good for brains” as if that was a point for his side.

Dr. Brent was the first of the respondents expert witnesses to testify in this portion of the Omnibus hearing. He also had testified in the Cedillo hearing. Some of the points about Kinsbourne’s hypothesis regarding astroglial activation, glutamate excess, and cell death were dismantled by Dr. Johnson, and by other experts who testified in the past weak. Dr. Deth’s hypothesis about autism being the result of oxidative stress was pretty much smithereened by two or three of the petitioners experts. I’m still catching up with listening to all of their testimony, but of extensive portions I’ve listened to so far, well, I think it’s looking really bad for dead parrot hypothesis.

9 Responses to “Dr. Brent – Toxicologist at the Autism Omnibus hearing”

  1. María Luján May 25, 2008 at 15:02 #

    . And the exposure to breast milk and chicken for the infant and toddler set is much higher than their exposure to thimerosal from vaccines, now or ever
    Sorry?
    Eur J Pediatr. 2007 Sep;166(9):935-41. Epub 2007 Jan 20.
    Hair mercury in breast-fed infants exposed to thimerosal-preserved vaccines.
    Marques RC, Dórea JG, Fonseca MF, Bastos WR, Malm O.
    Fundação Universidade Federal de Rondônia, Porto Velho, RO, Brazil.
    Because of uncertainties associated with a possible rise in neuro-developmental deficits among vaccinated children, thimerosal-preserved vaccines have not been used since 2004 in the USA (with the exception of thimerosal-containing influenza vaccines which are routinely recommended for administration to pregnant women and children), and the EU but are widely produced and used in other countries. We investigated the impact of thimerosal on the total Hg in hair of 82 breast-fed infants during the first 6 months of life. The infants received three doses of the hepatitis-B vaccine (at birth, 1 and 6 months) and three DTP (diphtheria, tetanus, and pertussis) doses at 2, 4 and 6 months, according to the immunization schedule recommended by the Ministry of Health of Brazil. The thimerosal in vaccines provided an ethylmercury (EtHg) exposure of 25 microgHg at birth, 30, 60 and 120 days, and 50 microgHg at 180 days. The exposure to vaccine-EtHg represents 80% of that expected from total breast milk-Hg in the first month but only 40% of the expected exposure integrated in the 6 months of breastfeeding. However, the Hg exposure corrected for body weight at the day of immunization was much higher from thimerosal- EtHg (5.7 to 11.3 microgHg/kg b.w.) than from breastfeeding (0.266 microgHg/kg b.w.). While mothers showed a relative decrease (-57%) in total hair-Hg during the 6 months lactation there was substantial increase in the infant’s hair-Hg (446%). We speculate that dose and parenteral mode of thimerosal-EtHg exposure modulated the relative increase in hair-Hg of breast-fed infants at 6 months of age.

    http://www.ncbi.nlm.nih.gov/pubmed/17237965?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DiscoveryPanel.Pubmed_Discovery_RA&linkpos=1&log$=relatedarticles&logdbfrom=pubmed

  2. María Luján May 25, 2008 at 15:06 #

    . And the exposure to breast milk and chicken for the infant and toddler set is much higher than their exposure to thimerosal from vaccines, now or ever
    Sorry?
    Eur J Pediatr. 2007 Sep;166(9):935-41. Epub 2007 Jan 20.
    Hair mercury in breast-fed infants exposed to thimerosal-preserved vaccines.
    Marques RC, Dórea JG, Fonseca MF, Bastos WR, Malm O.
    Fundação Universidade Federal de Rondônia, Porto Velho, RO, Brazil.
    Because of uncertainties associated with a possible rise in neuro-developmental deficits among vaccinated children, thimerosal-preserved vaccines have not been used since 2004 in the USA (with the exception of thimerosal-containing influenza vaccines which are routinely recommended for administration to pregnant women and children), and the EU but are widely produced and used in other countries. We investigated the impact of thimerosal on the total Hg in hair of 82 breast-fed infants during the first 6 months of life. The infants received three doses of the hepatitis-B vaccine (at birth, 1 and 6 months) and three DTP (diphtheria, tetanus, and pertussis) doses at 2, 4 and 6 months, according to the immunization schedule recommended by the Ministry of Health of Brazil. The thimerosal in vaccines provided an ethylmercury (EtHg) exposure of 25 microgHg at birth, 30, 60 and 120 days, and 50 microgHg at 180 days. The exposure to vaccine-EtHg represents 80% of that expected from total breast milk-Hg in the first month but only 40% of the expected exposure integrated in the 6 months of breastfeeding. However, the Hg exposure corrected for body weight at the day of immunization was much higher from thimerosal- EtHg (5.7 to 11.3 microgHg/kg b.w.) than from breastfeeding (0.266 microgHg/kg b.w.). While mothers showed a relative decrease (-57%) in total hair-Hg during the 6 months lactation there was substantial increase in the infant’s hair-Hg (446%). We speculate that dose and parenteral mode of thimerosal-EtHg exposure modulated the relative increase in hair-Hg of breast-fed infants at 6 months of age.

  3. Catherina May 25, 2008 at 15:55 #

    the word would be “activated” microglia – have not listened to the tape, but that is the only word that makes sense in that context. Microglial cells reside in the brain and upon immune stimulation, they become activated, change their shape and migrate to the sites of inflammation or injury, where they gobble up what ever needs to be phagocytosed and then return to a quiescent state.

  4. María Luján May 25, 2008 at 17:17 #

    Hi Catherina
    I have found several times the microglial activation reference. For example
    Brain Res. 2008 Apr 18. [Epub ahead of print] Links
    Microglial activation is not prevented by tacrolimus but dopamine neuron damage is reduced in a rat model of Parkinson’s disease progression.Wright AK, Miller C, Williams M, Arbuthnott G.
    University of Edinburgh, Division of Neuroscience, Veterinary Biological Sciences, Summerhall, Edinburgh, EH9 1QH, UK.

    A progressive model of Parkinson’s disease has been recently developed in the rat where a unilateral excitotoxic injection into the globus pallidus leads to a gradual loss of dopaminergic neurons in the ipsilateral substantia nigra over a period of at least 6 weeks. In this model microglial activation is observed in the ipsilateral substantia nigra 3 weeks after the lesion and could contribute to neuronal death at this time. The immunosuppressant drug tacrolimus (FK506) reduces dopamine cell death at 3 weeks following a globus pallidus lesion, but not thereafter. Tacrolimus-mediated neuroprotection could result from suppression of microglial activation but the microglial activation at three weeks post-lesion was not much reduced. Microglial activation was observed even in the apparent absence of neuronal death, prompting the suggestion that tacrolimus may prevent, or at least delay, the release of toxic cytokines from activated microglia. By 6 weeks after the GP lesion, even this mechanism fails to protect the dopamine cells from damage.
    Epilepsy Curr. 2008 May-Jun;8(3):75-7. Links
    Innate immunity and inflammation in temporal lobe epilepsy: new emphasis on the role of complement activation.Vezzani A.
    COMPLEMENT ACTIVATION IN EXPERIMENTAL AND HUMAN TEMPORAL LOBE EPILEPSY: Aronica E, Boer K, van Vliet EA, Redeker S, Baayen JC, Spliet WG, van Rijen PC, Troost D, da Silva FH, Wadman WJ, Gorter JA. Neurobiol Dis2007263:497-51117412602 We investigated the involvement of the complement cascade during epileptogenesis in a rat model of temporal lobe epilepsy (TLE), and in the chronic epileptic phase in both experimental as well as human TLE. Previous rat gene expression analysis using microarrays indicated prominent activation of the classical complement pathway which peaked at 1 week after SE in CA3 and entorhinal cortex. Increased expression of C1q, C3 and C4 was confirmed in CA3 tissue using quantitative PCR at 1 day, 1 week and 3-4 months after status epilepticus (SE). Upregulation of C1q and C3d protein expression was confirmed mainly to be present in microglia and in a few hippocampal neurons. In human TLE with hippocampal sclerosis, astroglial, microglial and neuronal (5/8 cases) expression of C1q, C3c and C3d was observed particularly within regions where neuronal cell loss occurs. The membrane attack protein complex (C5b-C9) was predominantly detected in activated microglial cells. The persistence of complement activation could contribute to a sustained inflammatory response and could destabilize neuronal networks involved.
    and
    Modulation of microglial/macrophage activation by macrophage inhibitory factor (TKP) or tuftsin (TKPR) attenuates the disease course of experimental autoimmune encephalomyelitis
    http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1937009

  5. Catherina May 25, 2008 at 18:01 #

    Maria,

    the articles have nothing to do with autism, though?

  6. María Luján May 25, 2008 at 18:11 #

    Microglial activation is used also in studies related to ASD;
    J Pharmacol Exp Ther. 2007 Jul;322(1):16-22. Epub 2007 Mar 30.
    Neuroinflammation and behavioral abnormalities after neonatal terbutaline treatment in rats: implications for autism.Zerrate MC, Pletnikov M, Connors SL, Vargas DL, Seidler FJ, Zimmerman AW, Slotkin TA, Pardo CA.
    Department of Neurology, Pathology 627, 600 N. Wolfe St., Baltimore, MD 21287, USA.

    Autism is a neurodevelopmental disorder presenting before 3 years of age with deficits in communication and social skills and repetitive behaviors. In addition to genetic influences, recent studies suggest that prenatal drug or chemical exposures are risk factors for autism. Terbutaline, a beta2-adrenoceptor agonist used to arrest preterm labor, has been associated with increased concordance for autism in dizygotic twins. We studied the effects of terbutaline on microglial activation in different brain regions and behavioral outcomes in developing rats. Newborn rats were given terbutaline (10 mg/kg) daily on postnatal days (PN) 2 to 5 or PN 11 to 14 and examined 24 h after the last dose and at PN 30. Immunohistochemical studies showed that administration of terbutaline on PN 2 to 5 produced a robust increase in microglial activation on PN 30 in the cerebral cortex, as well as in cerebellar and cerebrocortical white matter. None of these effects occurred in animals given terbutaline on PN 11 to 14. In behavioral tests, animals treated with terbutaline on PN 2 to 5 showed consistent patterns of hyper-reactivity to novelty and aversive stimuli when assessed in a novel open field, as well as in the acoustic startle response test. Our findings indicate that beta2-adrenoceptor overstimulation during an early critical period results in microglial activation associated with innate neuroinflammatory pathways and behavioral abnormalities, similar to those described in autism. This study provides a useful animal model for understanding the neuropathological processes underlying autism spectrum disorders.

  7. Catherina May 25, 2008 at 18:30 #

    Maria,

    and what are your thoughts re: this paper?

  8. Ms. Clark May 25, 2008 at 20:48 #

    Hi,

    The word that Williams said, to my ear, is nothing like “activation.” Perhaps the document he was reading from was very blurred or something and he misread the word, but it sounded like “atterbation” or “attribation”. I haven’t found a similar word in any online dictionaries yet. I guess the thing to do is to get the paper he was reading from.

    I don’t know why you are sorry Maria. The point is that the amount of mercury a child gets from vaccines is less, and even far less, as the child gets older, than he accumulates from food, breast milk or baby food.

    And lets not forget, that the baby is not not in any sense born “mercury free.” There is in fact some evidence that all babies born with a good portion of the mercury that had been in their mother’s bodies before mom got pregnant.

    Humans, all humans, all of them, every one of them, can deal with normal amounts of mercury or they wouldn’t survive very long. The amount of mercury in thimerosal is minor and in a form that clears the body quickly. There is no reason for anyone to cite papers that will cause people to fear mercury in vaccines. All it does is raise needless fears.

    If a baby goes unprotected from particular vaccine preventable disease and that baby gets sick her or she will be subject to uncontrolled, perhaps fatal levels of known toxins, including known neurotoxins.

    So why fear the known level of thimerosal in a vaccine that is NOT harmful to even the smallest baby, and just blow off as inconsequential the known levels of toxins that might kill or permanently damage that same baby (the toxins coming from infectious diseases that will become more and more common as people read fear inducing propaganda from antivaxers and their friends)?

    Seriously. Antivaccinism kills babies. Frightening people off of vaccines kills babies. Before attacking or inanely criticizing vaccines, even tangentially, lets all picture a baby dead from a vaccine preventable disease. I think that would be helpful.

  9. isles May 26, 2008 at 05:25 #

    Thanks for doing the tedious work of listening to the recordings. The answers to so many questions are being laid right out for us, but it takes your translation to make them accessible.

    Ain’t looking too good for the petitioners, I don’t think.

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