CHICKEN LITTLE THE BULLY, ELI STONE THE HERO
ANOTHER LOOK AT HOW IP AND WONG WENT WRONG

DAY EIGHTEEN AUTISM OMNIBUS PROCEEDING

Vincent_priceDay of the Doctors – Day Eighteen of the Autism Omnibus Proceeding – Snyder v. the Secretary of Health and Human Services

By Kent Heckenlively, Esq.

Do you remember how in those cheesy science fictions movies you watched as a kid there were always those scientists who caused the problem and those trying to fix it?

I bring up the science fiction comparison because I’ve spent a good deal of my life trying to understand what makes for a compelling story.  The various genres, from the western, the romance story, the crime saga, the war story, all remain vital because at some level they reflect reality.  Adversity reveals character as my screenwriting teacher used to say.

You start with some dramatic event, say the Nazis invade your country, and try to figure out who would take to the forests to become a partisan?  Who would become a collaborator?  And who would simply sit on the sidelines and let the war pass them by?

For most of us, our child’s autism pretty much tops the list of life’s dramatic events.  Some of us decided to fight.  And we’re pleased that people like Dr. Ronald Kennedy and Dr. Marcel Kinsbourne have decided to join us in the forest.

Direct Examination of Dr. Ronald C. Kennedy by Mr. Timothy Powers – Attorney for Family (Petitioners)

Dr. Kennedy is a Professor and Chair of the Department of Microbiology and Enterology at Texas Tech University, Health Sciences Center in Lubbock, Texas.  He filed a report in the Cedillo case and also testified.

He began his testimony by discussing how a virus infects a cell, how it replicates inside the cell, how the viral RNA is then turned into a protein, which in turn assembles itself into a new virus particle.  The measles virus belongs to a relatively unique group of viruses that contains its own RNA transcriptase, which is used to generate the messenger RNA, which in turn becomes a protein.

Measles virus replication occurs in a very orderly fashion from the left to the right side of the genome and these proteins can be detected by laboratory testing.

The first step in this process is that the H-protein attaches itself to a cellular receptor in order to gain entry to the cell.  The primary cell to the receptor for the measles virus to gain entry is known as CD46.  After attachment, replication takes place in the cytoplasm of the cell it infects.

The M-protein is then generated as it’s necessary for assembly and for the virus to be
released from the infectious cell.  Next is the F-protein which is responsible for fusion of
the virus envelope in the host cell membrane following attachment.  Finally, the
N-protein, or nuclear protein is created, which is vital for virus replication and also forms the first shell of the virus that protects the RNA.

The measles virus belongs to the Morbillivirus group and these viruses are generally very host-cell and host specific.  The diseases they produce are also usually somewhat similar.  For example, the canine distemper virus affects dogs, foxes, snakes, and wolves and is associated with neurological disturbances.  The same can be said of the phocine and dolphin morbillivirus which affects dolphins, seals, and porpoises.  The Rinderpest virus usually affects cattle, African buffaloes, and yaks, but is usually associated with gastro-intestinal problems.

Infection by the measles virus can often be easily diagnosed by certain clinical features, such as a fever, or a particular type of rash (Koplick’s spots) which is often found under the tongue.  However, the diagnosis of measles virus infection can also take place in a lab.

The two major methods of measles virus detection are serology and antibody infection, often referred to as ELISHA, for inflammation, inhibition, and neutralization.  There’s a third way to directly detect a virus through cell-culture and virus isolation, known as Reverse Transcriptase PCR or RT-PCR.

Scientists still don’t fully understand the mechanisms of viral persistence in an individual.  For example, the human papilloma virus is associated with cervical cancer in women.  However, not all women who have the virus will get cervical cancer.  In fact, some viruses can persist for 30 to 40 years in an individual before flaring up.  It’s understood that viruses can persist in a healthy immune system, but it persists more commonly in an immunodeficient or dysfunctional immune system.

The measles virus has been detected in the cerebral spinal fluid of living autistic children, and in the brain autopsies of children with autism who have died.  The Physician’s Desk Reference (PDR) notes that adverse events involving the MMR vaccine have included neurological disorders.

Dr. Kennedy is familiar with the Unigenetics Lab of Dr. John O’Leary and Dr. Laura Shields at Trinity College in Dublin, Ireland where measles virus RNA was diagnosed in the cerebral spinal fluid of Colten Snyder.  Dr. Kennedy believes that Dr. O’Leary and Dr. Shields are highly competent.  Dr. O’Leary continues to receive prestigious awards and honors for his work in molecular-based diagnostics, including the St. Luke’s Medical Chair and St. Luke’s Medal given by the Royal Academy of Medicine, as well as having an endowed chair in Pathology at Trinity University.  Dr. O’Leary continues to publish in peer-reviewed journals.

RT-PCR involves detection of measles virus RNA in biological fluids and is a standard practice.  A competent lab is more than equipped to deal with the problem of false positives.  The normal count for the detection of the measles virus RNA is 100 and a positive finding for infection is around 1,000.  The level of measles virus RNA found in the cerebral spinal fluid of Colten Snyder by the O’Leary lab was 37,000.  These high levels give Dr. Kennedy great level of confidence that the measles virus RNA is actually in the cerebral spinal fluid of Colten Snyder and replicating.  In addition, the F-protein was also detected in the cerebral spinal fluid, further supporting the finding of measles virus RNA.

Dr. Kennedy is familiar with the dispute between Dr. Oldstone and Dr. O’Leary about the presence of measles virus RNA in some samples which were supposed to be clear of the virus.  According to Dr. Kennedy, Dr. Oldstone was developing a transgenic mouse model that contained the CD46 human host receptor for the measles virus.  Some of the samples sent to the O’Leary lab were supposed to be free of the virus, but showed low copy numbers.

This raised the issue of whether the samples had been contaminated, and if so, where that contamination occurred.  Oldstone’s lab was actively working with the virus so that was a likely place to look for the source of contamination.  It was Dr. Kennedy’s understanding that the two sides had discussed the issue and come to a resolution.  Contamination is a common problem at labs, but a competent lab can easily resolve these issues.  It was important to note, thought Dr. Kennedy, that there was never an issue about high copy numbers of the virus, as were found with Colten Snyder.

According to Dr. Kennedy, Dr. O’Leary’s work has been replicated by others, most notably, Dr. Uhlmann.  Dr. Kennedy was also aware of Dr. O’Leary’s work being replicated by a Dr. Cotter, a molecular biologist and PCR expert at University College in London.  However, those reports are in the files of the U.K. litigation which are currently sealed under court order.

On the question of whether the attenuated measles virus in the vaccines can cause problems, Dr. Kennedy referred to a publication by Dr. Weibel and published in the well-respected journal “Pediatrics” in 1998 which described 48 individuals who had adverse events associated with neurological problems after receiving the MMR vaccine.

Cross-Examination of Dr. Kennedy by Ms. Alexis Babcock – Attorney for the Government (Respondent)

Ms. Babcock began her cross-examination by eliciting from Dr. Kennedy that his area of expertise is measles, but not specifically the MMR vaccine.  He is a researcher, not a medical doctor, and is not involved in the treatment of patients with the measles virus.

Dr. Kennedy admitted that the MMR shot is routinely given to children who are HIV-positive, but pointed out evidence that the children are delayed in clearing the virus.  He also admitted that a measles infection won’t necessarily depress the immune system. 

Dr. Kennedy believes the MMR shot can cause immune suppression and points to the well-known delayed type hypersensitivity on skin testing for allergens for children who have recently received an MMR shot.

Colten’s IgG test for the measles virus on March 3, 2000 showed a positive response for the measles virus antibody, demonstrating that his body was fighting off the virus.  Dr. Kennedy agreed that the only lab evidence of the measles virus persisting in Colten was the testing from the Unigenetics Lab.

He believes the finding of measles virus in the gut tissue of Colten Snyder was indeterminate because they appeared to hover at the level which it was possible to detect.  For this reason Dr. Kennedy does not believe the finding was negative, only indeterminate.

Questions from Special Master Denise Vowell for Dr. Kennedy

The first issue was a more complete explanation that Colten’s blood, gut, and cerebral spinal fluid tissue samples all arrived together at the Unigenetics lab.  This is important to understand because the differing result in the various tissues lowers the possibility of contamination.

Dr. Kennedy testified that the measles virus was high in the cerebral spinal fluid of Colten Snyder, low or indeterminate in the gut tissue, and negative in the blood.  A finding of anywhere from 10,000 to 100,000 is very high, suggesting active measles.  Colten’s reading from his cerebral spinal fluid was 37,000.

A comparison was made to how people with AIDS lack an immune system strong enough to clear the HIV virus and a comparison could be made that Colten also lacked an ineffective immune system as demonstrated by his inability to clear the measles virus.

Dr. Kennedy repeated his contention that problems with contamination in PCR samples could easily be remedied by a competent lab.

Dr. Kennedy was asked about his report submitted in the U.K. litigation and whether it ad been released.  Dr. Kennedy said he had no objection to its release and would do whatever the court requested in order to get that report released.

Redirect Examination of Dr. Kennedy by Mr. Timothy Powers – Attorney for Family (Petitioners)

Mr. Powers asked about whether an immunohistochemistry was performed by Unigenetics on Colten’s tissue samples.  Dr. Kennedy didn’t know, but based on the fact that Dr. Uhlmann did in his duplication of the Unigenetics work, it’s reasonable to conclude Unigenetics did perform immunohistochemistry on Colten’s samples.  The information which would clearly answer this question is in the U.K. litigation files, sealed by court order.

The factors which allow for measles virus persistence are still not well understood, but that uncertainty does not change Dr. Kennedy’s opinion that the virus persists in Colten Snyder.  It is clear that a persistent virus causes injury, even if we don’t fully understand what causes the virus to remain in the body.

Re-Cross Examination of Dr. Kennedy by Ms. Alexis Babcock – Attorney for Government (Respondents)

Ms. Babcock’s cross-examination focused a great deal on Dr. Oldstone.  Dr. Oldstone was not involved in the U.K. litigation and not much is known about Dr. Oldstone’s opinion on Unigenetics because he has not discussed those thoughts publicly.

Dr. Kennedy did not see the actual physical lay-out of the Unigenetics laboratory, but did see a visual lay-out.

On the question of how the measles virus might contribute to autism, Dr. Kennedy deferred to Dr. Kinsbourne’s testimony.

Direct Examination of Dr. Marcel Kinsbourne by Mr. Timothy Powers – Attorney for Family (Petitioners)

The testimony opened with a discussion about the U.K. litigation and how the attorneys might work together to get information from that case.

Dr. Kinsbourne is a Professor at The New School in New York City.

In answer to the earlier assertion by defense counsel that Dr. Wakefield’s work had been “debunked”, Dr. Kinsbourne felt the need to give a significant amount of time to his response.

While not necessarily because of Dr. Wakefield’s work, but in the nearly ten years since the publication of his original findings in The Lancet, there has been a change from regarding autism as a static deficit to part of an ongoing disease process happening every moment of a person’s life. 

There has also been a wholesale recognition to the idea that just because there may be a genetic link does not exclude the possibility of environmental influences.  The Institute of Medicine recently held a two-day conference on the way genes and the environment can interact to produce autism.  The Centers for Disease Control have some groups looking into this area, and UC Davis even has a medical program in this area.

Autism is also being recognized as a disease that affects not just the brain, but other organs as well, including the gastro-intestinal system.  Most everybody now concedes that there are multiple causes of autism in both individuals and populations.  The issue of autistic regression, even though it’s been recognized for some time, has not been subjected to investigation in its own right.

Dr. Kinsbourne believes that Colten Snyder was normal, then regressed.  He also believes the increase in autism rates is real, and not the result of changing diagnostics.

Another change pointed out by Dr. Kinsbourne in medical views about autism is the recognition that the brains of those with autism do not appear to have static deficits, but rather abnormalities in the way the neural network is functioning.  Changes in the excitation and inhibition ratios account for at least some of the autistic behaviors observed in many children.

While Dr. Wakefield’s specific proposition has not been firmly validated, Dr. Kinsbourne believes the approach taken by Dr. Wakefield is very much in tune with the way science has been going since he first presented his ideas.

Dr. Kinsbourne acknowledges that while measles virus in the brain of Colten Snyder does not present like the known brain measles virus maladies of Sub-Acute Sclerosing Pan-Encephalitis (SSPE) or Measles Induced Brain Encephalopathy (MIBE), there’s no reason to preclude that the measles virus might infect the brain in another way.  No less an authority than Dr. Paul Dykken, one of the world’s leading experts on SSPE and who is in charge of the SSPE World Registry has written that he finds it easy to believe that autistic might be suffering from a measles infection in the brain which is neither SSPE or MIBE.

The cluster of infections Colten experienced after his MMR shot provide some evidence of immune system suppression which may have allowed the attenuated measles virus to persist in his body.

The brains of children with autism show abnormalities of the organization of neurons in various parts, specifically a shortage of pyramidal cells in the cerebellum, but limited evidence of the loss or destruction of neurons.  It’s a reasonable hypothesis that viral inflammation and the effects of that inflammation may be affecting neurotransmitter function.  Inflammation has been found in both the brains of autistic children who have died, as well as inflammatory markers in the cerebral spinal fluid of living autistic children.

According to Dr. Kinsbourne, it appears as if the viral invader is harboring itself in the brain cells, while the immune system batters it with cytokines, which while being unable to go inside the cell, nonetheless, damages the area around the neurons.  The cells around the neurons are called astrocytes.  In response to a perceived infection, they release high amounts of glutamate, which is part of the excitatory system.  The brain of an autistic person is awash in glutamate, an excitatory neurotransmitter.  This probably explains why 30% of autistics have some level of seizure activity, and 70% have abnormal EEGs.

It’s been known since 1959 that when a person becomes over-activated, over-aroused, and anxious, their focus of attention becomes narrower.  It’s been suggested that the stimming and repetitive behavior of children with autism is an attempt to decrease this anxiety.

Cross-Examination of Dr. Kinsbourne by Mr. Vincent Matanoski – Attorney for the Government (Respondents)

Mr. Matanoski began by questioning Dr. Kinsbourne as to whether there are changes to an infant’s brain after birth.

Dr. Kinsbourne replied that as an infant’s brain develops the connections between the neurons become more mature, more myelinated, and can communicate over greater distances.  In the brain of many autistic children there appears to be a triggering event, but that triggering event is unknown.  These children stop speaking; appear to stop understanding, then plateau.

In reviewing the areas of his agreement with Dr. Bradstreet’s poster he found himself in agreement with the issues of brain inflammation, viral persistence, and oxidative stress.  In Colten Snyder’s case there was no evidence of immune problems before the MMR shot.

On the question of how the measles virus can cross the blood/brain barrier Dr. Kinsbourne says it isn’t known, but we know it does in both SSPE and MIPE.  In Dr. Kinsbourne’s opinion, the connection between inflammatory markers and the autistic brains seems pretty tight.  Even if the information about viral infection is thrown out, there’s still the question of what’s causing the inflammation.

In discussing the specifics of Colten Snyder, Dr. Kinsbourne said the first sign was the lethargy after the MMR shot.  There was the behavioral regression within 6-8 weeks, the gut inflammation, the biopsy of gut material consistent with viral inflammation, the viral material found in the cerebral spinal fluid, and the markers for inflammation.  In determining whether a child had regressive autism it’s important to find whether they’d hit important milestones and regressed within a few months

Mr. Matanoski asked what standards he would use in ordering a spinal tap for a child.  Dr. Kinsbourne replied that in order for a child to get a spinal tap there should be a scientifically legitimate reason for the test, informed consent, and minimal risks.

Dr. Kinsbourne currently teaches two classes a week, Introduction to Neuroscience, at The New School in New York.

Special Master Questions from Denise Vowell for Dr. Kinsbourne

Special Master Vowell questioned Dr. Kinsbourne about Dr. Paul Dykken, the expert on SSPE and the one in charge of the World Registry of SSPE. 

Dr. Kinsbourne testified that Dr. Dykken is a senior reputable individual in his field.  In coming to his opinion that autism might involve a measles infection, Dr. Kinsbourne said Dr. Dykken did his own review of the evidence assembled by Dr. Wakefield and came to his own conclusion.

The Special Master then asked Dr. Kinsbourne what issues in brain anatomy he associated with autism.  Dr. Kinsbourne replied that he saw three; the loss of Purkinje cells, mini-columnar development, and the limbic system.  The Purkinje cells are those cells which are most vulnerable to glutamate toxicity.  The question of mini-columnar development is difficult because we can’t tell whether the cells died, or were never there in the first place.  As far as the brain maturation question it’s an issue of myelination,
which can be affected by inflammation.

Last, Special Master Vowell asked Dr. Kinsbourne what the signs of brain inflammation would be in Colten Snyder if the measles virus findings were taken away.  Dr. Kinsbourne replied that the only remaining information would be the finding of anti-bodies to myelin basic protein.

Re-Direct Examination of Dr. Kinsbourne by Mr. Timothy Powers – Attorney for Family (Petitioners)

Powers began by asking Dr. Kinsbourne to walk through the medical history of Colten Snyder.

It was Dr. Kinsbourne’s recollection in reviewing Colten’s medical files that within 13 days of getting his MMR vaccination he was fussy, crying, and not sleeping.

It was also his recollection that within 31 days of Colten getting his shot he was admitted to the hospital for dehydration and the attending ER doctor noted a cognitive change based on the parents’ observation.  Over the Memorial Day weekend Colten was not making eye-contact and was lethargic.  All of these medical observations are consistent with Dr. Kinsbourne’s theory of measles infection.

Dr. Kinsbourne believes in the future there may be new technologies which make it easier to detect the measles virus.

Re-cross Examination of Dr. Kinsboure by Mr. Vincent Matanoski – Attorney for Government (Respondents)

Dr. Kinsbourne is unaware of any new tests on the horizon which might make it easier to detect the measles virus.

The article by Dr. Dykken regarding the possibility of a measles infection similar in nature to SSPE causing autism was an editorial in a medical journal. 

Since his editorial Dr. Dykken has made no further comments on this question.

Final Thoughts on this Day of Testimony

At its best, science explains the world around us.

Dr. Kennedy did an excellent job explaining how viruses get inside a cell and take control of it for their own purposes.  He was also clear in discussing what Colten’s high measles readings meant and why he trusted the work of Dr. O’Leary’s lab.  It’s difficult to imagine how his testimony could have been any more illuminating.

Dr. Kinsbourne was equally as good in discussing how the field of autism research has changed since Dr. Wakefield first published his findings in The Lancet.  Something has gone wrong in the brain, but the traces can be found throughout the body.  The markers of inflammation in the brain are clear.

One of the world’s leading authorities, Dr. Dykken, has little trouble imagining autism as the result of a measles infection in the brain.  The testimony about the excitatory/inhibitory system of the brain being off-kilter provides a clear way to understand much about autism.

If this was a science fiction movie, Dr. Kennedy and Dr. Kinsbourne would be the scientists trying to solve the problem.  In reality they’re no different.

Kent Heckenlively is Legal Editor for Age of Autism.

Comments

Richard

Ken,I greatly appreciate and look forward to your omnibus articles.You have a way a summarizing the trial that is makes it so the average Joe can get a handle on what is actually happening at these hearings.
Thankyou.

Richard

Theresa

Ken, as always, thank you for the excellent summary, and for giving us all hope that the heroes in your story will one day prevail.

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