DR. JON POLING TO DR. STEVEN NOVELLA ON AGE OF AUTISM

By Dr. Jon Poling, father of Hannah Poling.

OPEN LETTER TO DR. STEVEN NOVELLA
IN RESPONSE TO "Has the Government Conceded Vaccines Cause Autism?"

Dr. Novella,

Thank you for generating interesting discussion regarding my little girl, Hannah Poling.  I would like to give you additional information in order to generate further productive discussions on this matter amongst the neurology community.  This information should assist you, Dr. DiMauro, and Dr. Trevethan, who have also commented publicly, to formulate better theories as to the significance of Hannah’s mitochondrial dysfunction in relation to her autism.

1. Mito Dysfunction or Mito Disease?  Chicken or Egg?

To begin with, I would like to point out that the spectrum of mitochondrial dysfunction is probably considered more broad and complex than the spectrum of neurobehavioral abnormalities seen with autism. Dysfunction of the mitochondria, specifically dysfunction of the oxidative phosphorylation pathway, most likely contributes, but may not be the cause of many diseases—including Parkinson’s disease, Friedreich’s Ataxia, Alzheimer disease, etc.  Thus, it is probably incorrect to refer to  mitochondrial dysfunctional and mitochondrial disease interchangeably. Indeed, the role of the dysfunctional mitochondrial are yet to be clarified in these diseases. Thus, I will refer to Hannah’s metabolic condition as a mitochondrial dysfunction, not a mitochondrial disease.

2.  Mito Genetic Finding?  Mito mtDNA ‘red herring’ ?

ADDITIONAL GENETIC TESTING NOT AVAILABLE IN THE J CHILD NEUROL CASE REPORT:  Dr. Shoffner performed genetic testing on both Hannah’s muscle and her mother’s leukocytes subsequent to our case report. Hannah (muscle mtDNA) and her mother (leukocyte mtDNA) were both found to be HOMOPLASMIC for the mtDNA T2387C transition mutation.
Our analysis of this genetic finding in the mtDNA was significantly different than those of other physicians that I’ve seen in scientific blogs or commentary.  I suspect it would have been fatal to both Hannah and her mother if this homoplasmic mutation was pathogenic since (as I am sure you are aware) the mutation is on the 16S ribosomal subunit which is highly conserved. Thus, this mutation probably represents a benign polymorphism rather than pathogenic mutation. It is unlikely, but possible, that the mutation is significant to Hannah, but in such a case, it must work in concert with other nuclear genes to cause her mitochondrial dysfunction.  To our knowledge, this point mutation has not been reported in cases similar to Hannah’s.

3.  Encephalitis? Metabolic Encephalopathy? Or “Regressive Encephalopathy with Features of Autism Spectrum Disorder”

The other interesting term you used was encephalitis rather than encephalopathy.  We are not sure that she had an “-itis” but we did clearly document a regressive encephalopathy based on not only our parental reporting, but also based on the pediatrician’s documents, affidavits from other family members, and the growth curve measurements (injury pattern).  Early on in the regression we did note back arching (opisthotonus), fever, and disrupted sleep. Although fever occurred a lumbar puncture was not performed.

An interesting developing story in autism research is the immune/inflammatory connection.  In her senior resident thesis, Dr. Anne Comi, a former JHU colleague, along with Dr. Andy Zimmerman, reported, the increased prevalence of autoimmune disease in families of autistic offspring. Interesting, Hannah also has a maternal family history of autoimmune disease. Dr. Carlos Pardo, another one of my former chief residents, along with Andy and Dr. Vargas, published a beautiful study in the Archives of Neurology, demonstrating neuroinflammation on autopsy of brain samples and inflammation cytokine markers in the CSF of individuals with Autism.  The interesting thing was that inflammation was demonstrated in autopsy specimens from adults as old as 44 years of age.  The conclusion was that further research would be required to determine if inflammation was a primary disorder in autism or; alternatively, if inflammation and microglial activation was secondary to neurodegeneration.  Dr. Sudhir Gupta at UC Irvine has a nice model of how the two pathways of neuroinflammation and mito dysfunction may not be mutually exclusive.  This remains to be seen; however, study of mitochondrial dysfunction and neuroinflammation hold the promise of treatment development.  The two avenues of research deserve funding at the highest levels.

4.  How many Hannah Polings are out there? 

The short answer is that nobody knows.  However, there is emerging data to suggest that she is not alone.

Dr. Shoffner will be presenting his experience with 37 patients with combined autism and mitochondrial dysfunction at the AAN meeting in Chicago this April. 65% of his referrals are positive for mitochondrial dysfunction.  Of course, his yield is subject to referral bias as a mito expert, so the prevalence of mitochondrial dysfunction in Autism is surely less than 65%.

The best estimate to date of the prevalence of mitochondrial dysfunction in autistic patients comes from Oliviera et al. in a population of 120, 5 of 69 (or 7.2%) showed mitochondrial dysfunction.  If this is generalized to the US estimate of 1 million patients with ASDs, then the number of kids like Hannah could be 72,000!  Isn’t this worth further study?

Dr. Shoffner furthermore advocates, along with us, that vaccination is important even for kids with mitochondrial dysfunction.  I would argue that you should not give nine at one time and that none of them should contain Thimerosal (mercury). 

5.  Thimerosal—On or Off the Table?

I don’t want to dwell on mercury, as this theory is not why HHS conceded Hannah’s case (imo).  Dr. DiContanzo just wrote an interesting blog about how his opinion of mercury in vaccines has changed (http://drugs.about.com/b/2008/03/08/mercury-in-vaccines-and-autism-the-burden-of-proof-may-shift.htm).
 
My opinion is that mercury is a potent neurotoxin. Therefore, don’t inject it into kids!  Interestingly, basic research studies have shown that Thimerosal toxicity occurs through mitochondrial pathways.  Officials point to the large epidemiology studies as proof that there is no link between thimerosal and autism.  However, these studies are not powered to disprove the null hypothesis when considering that the mitochondrial autistic population may be just a small percent of the case totals.  Remember that while the CDC sponsored Verstraten study is hyped as a negative study, it DID find a statistically significant increase in childhood tics in those exposed to higher doses of thimerosal. 

6.  Hannah was destined to regress? Or was she?

Some experts have already stated that ‘mitochondrial disease’ is degenerative so the vaccine reaction was just the start of an inevitable decline.  This was neither the opinion of Dr. Richard Kelley at KKI nor Dr. John Shoffner.  In fact, the markers that led us down the mitochondrial trail (inc AST but not ALT, low serum bicarbonate, and slight increased CK, increase in the alanine to lysine ratio on PAA) are no longer present.  Furthermore, in our pilot study (unpublished but mentioned in the J child neurol paper), Dr. Frye (the statistician for our study and also a child neurologist) found a non-significant trend that AST decreased toward normal with increasing age.  With further studies we hoped to examine the hypothesis that this abnormality may be representative of a developing/immature biochemical pathway present in some children.

7.  Triple Hit Hypothesis—#1Underlying genetic susceptibility #2Insult must occur during specific developmental period #3 A certain vaccination or combination thereof is the environmental trigger  (?vaccine component like thimerosal ?direct immune stim/fever reaction ?live virus reaction?)

The implication is that Hannah’s type of autism requires a genetic susceptibility and properly timed insult to manifest disease.  We have not subjected Hannah to another muscle biopsy or re-examined ox phos functional assays that were published in the paper.  I can inform your readers though that the serum biochemical markers have resolved, growth resumed and continues along a normal trajectory, and there have been no other episodes of regression since 2000.  We are however left with autism and later in 2006, epilepsy.
It is recommended that studies be initiated immediately to screen siblings of cases to identify biochemical markers so as to identify potential screening tests.

I agree with the mainstream that my daughter’s case has raised many intelligent discussions and questions.  I’m very proud of her for starting this discussion.  Our hope is that further research into this case and others like it, we will be also to find screening tests to prevent what happened to my daughter from happening to anybody else.

(Dr. Poling acknowledges the editorial comments and insightful suggestions of Dr. Richard E. Frye.  He also would like to declare his conflicts of interest.  First of all, he is the father of Hannah Poling.  Dr. Poling has also accepted consultancy or speakers honoraria from Pfizer, Eisai, Ortho-McNeil, Biogen, Teva, Immunex (now Amgen), and Allergan.)
PS While I thought it useful to clarify some of the neurological issues raised by the government's concession of my daughter's case, please understand that I will not be able to respond to individual comments posted.  Thank-you. Jon

Comments

[Joan Petty]

It is a known fact that Congress omitted Product Liability for Prescription drugs, in 1962 when they amended the FDA to include FDCA ACT as Public Law. All vaccines are prescription drugs. There is no remedy for a defective prescription drug that kills or injuries any innocent consumer. Our Congressmen and Representatives have knowledge and they deleted from the Product Liability Fairness Act Prescription drugs everytime it came up for Healthcare Reform. including vaccines. There is NO LAW, No State Law or NO Federal Law. Congress preempted it from the FDCA ACT and you as a consumer and your children are at risk while Drug manufacturing companies are protected by a shield of protection called immunity. Congress can keep the cost of Medicare and Medicade and Social Security and any healthcare reform price up in cost by allowing the drug companies to continually and intentionally injuring and killing off the population all in the name of Good Healthcare. Who is immune? YOU or Merck? Show me the Law! There is NONE.

[Lisa Tampa]

I have an 11 year old son with Tourettes Syndrome. I have often wondered about the connection of vaccines, environmental toxins and Tourettes syndrome in addition to the information out there about Autism and Vaccines. Not only has the rate of Autism increased but the rate of Tourettes Syndrome among children is increasing in astronomical proportions. My son's friend who lives a few houses from us was also diagnosed with Tourette's syndrome recently and I have to say I notice many other children, boys in particular, in his school with Tic symptoms as well that I think are not being diagnosed. I truly believe Tic disorder numbers are higher than the 1 in 200-250 children that is being reported on currently. I wonder how long it will take for the Government to admit to and try to correct what has gone wrong with our environment. Will it take 8 out of every 10 children displaying neurological and other anomalies before they admit something has gone very wrong? I fear within the next few generations we just may come to those types of ratios the way things are increasing now.

[CAROLYN]

my heart goes out to you with a child with autism-I losted my Mother And Aunt with c. o. p.d. they pass away in my home my moter-in-law and father-in-law also pass away in my home it has been hard to see them pass but then I THINK OF YOU AND I PRAY TO GOD TO PLESE HELP YALL I JUST WANT YOU TO NO THEIR ARE STILL ONES THAT CARE AND WE PRAY FOR YOU AND YOURS

[JOAN M. PETTY]

WHY DID MERCK & CO. INC. DISTROY ALL THEIR 3 IN 1 VACCINE THAT THE HAD STORED AFTER THE FDA ORDERED A RECALL. DR. POLING DID YOU EVER GET A COPY OF THE WARNING LETTER TELLING MERCK THE MANUFATURERE OF THE VACCINE TO RECALL THE VACCINES.?? WHY DID MERCK DUMP ALL THE VACCINES IF THE 3 & 1 WAS NOT DANGEROUS? OUR RESEARCH DISCOVERED THAT MERCURY IN THE VACCINE DOES CAUSE EVERY 5TH CHILD TREATED WITH THE VACCINE IS THE ONE WHO GETS THE LARGEST DOSE OF MERCURY. CHECK THIS RECORD OUT. MERCK HAS FRAUDED MANY REPORTS TO FAST TRACK DRUGS. THIS IS A PROVEN FACT AND EVIDENCE. my phone is 863-465-1200.

[Kelli Ann Davis]

Terri,

You Rock! The designated "welcome wagon" greeter for AoA. Love it!

Please e-mail me again. My computer didn't save your e-mail from last time.

This time, I'll put you in my address book -- I promise.

You, girlfriend, are someone I can definitely relate to!

Best,

Kelli

[Terri Lewis]

Question Vaccines,

Welcome! (I don't believe I've seen you here before?) Welcome one and all to an enlightened community that's taking action daily, and making news daily.

My motto: We no longer need to debate the ignorant.

As David Kirby put it so beautifully on Larry King Live on April 2, 2008: "THE DEBATE IS OVER."

Thus--we now join together for change. I still can't believe how many parents are right here, right now, and bringing about the changes we have so long needed.

Welcome! And forgive me if you've been here longer than I have. . .I'm just so excited to see so many knowledgeable, powerful, active people now gathered in one place.

Terri L.

[Question Vaccines]

I guess this Dr Novella is not aware that babies are actually given their first dose of a neurotoxin while in utero, via the flu vaccine given to their mother, laced with mercury. And that assault continues as the relatively new recommendations ensure that infant will get a couple more doses by the age of 6 months, and most likely, will also be laced with mercury. Clinical trials are looking at vaccinating them even younger.

My own son received his 3rd dose of DPTH and 1st dose of Hep B at the age of 7.5 months, and deteriorated from that day forward. Stopped eating, wasted away before my eyes, and all I got from the medical profession was denial. Just sickening what is being done to our children.

[Patricia]

I have a 9-year old with Tourette's Syndrome/ADHD and an anxiety disorder. She was given the Hep B at birth and 5 shots at one time with mercury. Autism is always in the media but what about the explosion of kids with tic disorders? There are at least 5 kids with tic disorders in the lower grades at my daughter's private school of 300 children...and those are only the ones I am aware of! The Verstraten study PROVED mercury causes an increase of tics in kids exposed to it! This is called a "rare" disorder? Tics are embarrassing, life changing and at times, debilitating, just like autism. It touches not only my poor daughter but our entire family due to her difficult behavior and learning disabilities. Let's add the Tourette's kids to the list of autistic kids that are harmed and make the list even longer.

[Icing on the cake]

"It is likely (although this needs further research) that children excrete ethyl mercury more quickly than adults, and the safety buffer that was in place was more than sufficient to accommodate the increased vaccine schedule."

This particular one deserves the Nobel Prize. Maybe we ought to send it to David Letterman and ask him to do a Top 10 List on vaccine safety ridiculous answers. I can "see" it, just give it a year or two. At the most.

[Kelli Ann Davis]

“It is likely (although this needs further research) that children excrete ethyl mercury more quickly than adults, and the safety buffer that was in place was more than sufficient to accommodate the increased vaccine schedule.”

You’re right Kim, what a crock – or as Mark would so eloquently say, “That’s bullsh**!”

And what exactly is the “increased” level that the safety buffer is designed to handle, doc?

You gotta “magic” number for us? “Nothing up my sleeves, presto – here’s one.”

Now THAT’S what I call hard science.