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Expert opinions on vaccines and mitochondrial disorders

7 Nov

ResearchBlogging.orgThe Hannah Poling case has raised many questions about vaccines and metabolic disorders (of which mitochondrial disorders is a subset). Which is a way of saying, yes, the paper we are about to discuss covers more than just mitochondria. But, would you have read this if you saw the title of the paper:


Attitudes regarding vaccination among practitioners of clinical biochemical genetics

But, don’t let that stop you. The paper takes a look at questions asked by many since the Hannah Poling case went public:

The issue of vaccination in patients with diagnosed—or undiagnosed—metabolic disease has been an important question for those of us who care for patients with inborn errors of metabolism, but has come to the fore recently as an item of general interest.

While it is acknowledged that there is a lack of hard data on many questions, the paper’s authors polled experts in the field with a series of questions about vaccines. For experts, they chose members of the Society for Inherited Metabolic Disorders (for which there were 379 email addresses: that gives us an idea of how specialized this field is). They received 111 responses. But, it is worth noting that they requested one response from each group, not individual, so they consider this to be a fairly complete response.

So, what do these experts think about vaccines and their patients with metabolic disease (mitochondrial or otherwise)?

When asked, to respond to the position: ‘‘I view the risk of vaccination in known metabolic disease patients to generally be outweighed by the risk of the infectious diseases being vaccinated against”

63.2% strongly agreed
31.1% agreed
0.9% disagreed
and 0.9% strongly disagreed.

Asked about the opinion that the risk of vaccination in metabolic disease was ‘‘greater than the risk of the infectious diseases being vaccinated against”

52.9% strongly disagreed
40% disagreed
3.5% agreed
and none strongly agreed

One idea that has been floating around the autism blogosphere and discussion groups is that metabolic specialists prefer an alternate vaccine schedule. Well, only 21.3% said that they recommend the routine vaccination schedule, it is true. But, 73.1% use the routine schedule plus the annual influenza vaccination. 5.6% recommended a modified schedule. If you’ve been adding this up in your head, you already know that none indicated no vaccination.

Since this is such a key question, let’s repeat: over 90% use the recommended schedule or the recommended schedule plus the flu vaccine.

Similar trends were noted for live-virus vaccines:

45.7% recommending restriction of the practice for none of their metabolic disease patients
44.8% for a few
6.7% for most
2.9% for all of their patients

A big question that comes up often is “how many Hannah Polings are there?”, which in this community is a fairly narrow question of “how many people have had adverse reactions to vaccines resulting in autism or autistic-features”. The paper asks the more broad question, how many groups have seen a patient suffer “long-term deterioration or adverse outcome attributable to a vaccination:

78.3% ‘‘never”
8.5% ‘‘once”
12.3% ‘‘seldom”seen this in a patient

Again, this is not to say that autism or autistic features were seen, or that mitochondrial disease was the metabolic disorder linked in the deterioration. The group is more broad than that.

Now, the flip side of that coin: how many groups have seen long term deterioration from a vaccine preventable disease:

48.5% replied they had ‘‘never” seen this
12.1% ‘‘once”
33% ‘‘seldom”
3% ‘‘routinely”
3.0% ‘‘frequently seen this in a patient

Asked if whether ‘‘the benefits of the current vaccination schedule outweigh the risks to patients with undiagnosed metabolic disease in the general population,”

64.8% strongly agreed
27.8% agreed
4.6% disagreed or strongly disagreed

An open ended question was posed as to whether there were ‘‘reasonable health policy changes you would make regarding undiagnosed metabolic disease patients”. 43 groups responded, 29 said no, 4 said “no” or “not sure” and 1 suggested adding additional influenza and/or pneumococcal vaccine. A few stressed evaluation by IEM specialist in any case with deterioration after vaccination.

There is some more. All good stuff. But, I am at risk of basically copying the entire paper here if I add it.

If there is one thing to take away from this, it’s the concluding paragraph:

In summary, it is clear that the general opinion held by practitioners in the field of Clinical Biochemical Genetics favors the full schedule of vaccination for their patients. The overwhelming majority also feel that the benefits of the current schedule outweigh the risks to individuals with undiagnosed metabolic disease. Most have never observed any significant adverse event which was attributed to a vaccine reaction. Some respondents have seen the association once or seldom in their careers, but none felt it to be frequent. The fact that there were few encountered events of long-term deterioration due to a disease for which vaccination is available probably simply reflects the low incidence of those diseases, due to the effectiveness of vaccination practices. A panoply of questions remain, however, and there is a great need for more data.

B BARSHOP, M SUMMAR (2008). Attitudes regarding vaccination among practitioners of clinical biochemical genetics Molecular Genetics and Metabolism, 95 (1-2), 1-2 DOI: 10.1016/j.ymgme.2008.08.001

Sometimes the HuffPo gets it almost right

25 Oct

Regular readers will know of my concern regarding the HuffingtonPost and its clear antivax agenda. Kim Stagliano, David Kirby and (I think) Barbara Loe Fischer post there and whilst I don’t believe David has an antivax belief, I do think he is unfortunately promoting unfounded statements that feed antivax talking points (eg the claim HHS conceded vaccines caused Hannah Polings autism).

However, I was really pleased to see a post today in my Google Alerts from HuffPo that got it 95% right. Before I say why I have to clarify once again my position as a UK citizen and therefore my belief that I really shouldn’t take a position on the upcoming US elections. However, thats becoming increasingly difficult to do as I read such monumentally stupid things from McCain as:

[Sarah Palin knows]…more about autism then anyone I know…

Which I take to mean that the only person he knows with a connection to autism is Sarah Palin. Also his confused and pretty desperate looking pandering to the antivax crowd is downright annoying. But anyway.

The HuffPo post I’m referring to is Obama and autism by Elaine Hall. She describes:

Neal is my resident expert on autism. Now 14 years old, Neal was adopted from a Russian Orphanage at 23 months, and diagnosed with severe autism at age 3 . Neal is non verbal (or as we prefer to refer to him “a man of few words”) so when he speaks his truth through typing – WE LISTEN.

Me like.

Last January at one of his sessions with Darlene she asked, “”So, Neal, what have you been thinking about lately?”

“The Elections,” he typed on his Alpha Smart keyboard.

“What about the elections?” asked Darlene.

“I’m for Obama, he typed.”

“Obama? Why?”

“Obama is for Autism, ” he finished.

That evening my husband and I Googled Obama and Autism. And there it was, pages and pages from people with autism. Supporting Obama.

Me like even more.

This tells me a number of things. First it tells me that Elaine Hall and her partner are smart enough to see their autistic son as the resident autism expert. What a refreshing attitude. Second it tells me that when their expert speaks – THEY LISTEN. Also a refreshing attitude. Thirdly it tells me that someone being non-verbal does not mean they cannot communicate. I can think of more than a few people who read this blog who need that lesson drummed into their heads. Fourthly, it tells me that autistic people by and large support Obama. This means (for whatever the opinion of a non-voting Brit is worth) that I’m for Obama too.

Now, I said at the start of this piece that HuffPo only got it 95% right. They would’ve got it 100% right if they’d let Neal do the typing. However, he is only 14 and maybe thats why he’s not contributing publicly just yet. For now, I’m more than happy to read Elaine Hall’s words. This is from the front page of her website The Miracle Project:

The Miracle Project is a theatre and film arts program for children with special needs and their typically developing siblings and peers. Our mission is to provide a loving, accepting nurturing environment which celebrates and honors the unique and often unrecognized talents of these young people by guiding them through creative workshops and artistic programs.

Thank you Elaine Hall and thank you Neal. I’ll be looking out for more from both of you.

Tags: ,

The next mito-autism case?

20 Oct

It’s been nearly a year since the first autism/mitochondria case was conceded. The question of mitochondrial dysfunction and autism has evolved significantly in the minds of the public and insiders in that time.

Shortly after the concession, Tom Powers, lead attorney for the petitions was asked

.”..whether this was a possible break in the case, he replied that the particular case dealt with a claimant who had a diagnosed mitochondrial disorder. As a result, it probably won’t have much of an effect on the other cases.”

It wasn’t really on the radar for the Petitioners.

But, that was in December of 2007. In February of 2008, the concession document was leaked, followed by TV, online and print news-stories on the topic. Coincidentally, mitochondria and autism has changed from not “much of an effect on the other cases” to some people claiming as much as 1/2 of the Autism Omnibus cases being associated with mitochondria.

We’ve seen one Omnibus test case removed from the Omnibus because, the parents claim, the child’s case needs to be argued as a mitochondrial dysfunction case. We’ve gone from diagnosing mitochondrial dysfunction involving a difficult task of many tests and specialist’s opinions, to the point where David Kirby, a blogger, claims to be identifying mitochondrial dysfunction based on parental reports. We now have self-taught “experts” ready to answer questions on discussion boards about mitochondrial disorders, one of the extreme specialties of medicine.

While this is all lamentable, we now have the first “test case” for the mitochondrial autism notion, post concession. A family is arguing mitochondrial disorder (or an oxygen depletion disorder).

The case has gone through the first steps in the Court of Federal Claims (the “vaccine court”). The case hasn’t concluded, but a decision has been published. To summarize:

First, note that the parents are representing themselves, it appears. The decision notes:

On August 29, 2008, petitioners filed a Reply to the Order, making two assertions: (1) [The child] suffered from a mitochondrial disorder and oxygen depletion disorder which a later vaccination significantly aggravated, leading to autistic like symptoms (somewhat similar to the Hannah Poling case that respondent agreed to compensate); and (2) the vaccinations which [the child] received caused him mercury poisoning from thimerosal or ethyl mercury (which is the subject matter of the second round of autism cases in the Omnibus Autism Proceeding, the first round of cases having to do with MMR and autism).

Tthey seem to be both arguing the mitochondrial disorder idea and the Omnibus thimerosal theory. In support, they gave no expert medical reports. Instead, they submitted a single paper (which presumably is supposed to cover both, very different assertions):

by D.S. Baskin, et al., entitled “Thimerosal Induces DNA Breaks, Caspase-3 Activation, Membrane Damage, and Cell Death in Cultured Human Neurons and Fibroblasts,” published in 74 Toxicological Sciences (2003), available on the internet.

That’s really thin evidence (as discussed at some length by the Special Master). Some sort of expert report should link the theory to the specific child. The parents state:

They have not filed a medical report in support of their assertion of significant aggravation of [the child’s] autistic like disorder, claiming that no doctor would risk criticism from the medical community by providing such a report.

Anyone want to volunteer some names of people who would risk the criticism?

But, seriously, diagnosing a mitochondrial disorder is not a simple task. This isn’t something a parent (or David Kirby) can do by looking for similar markers to another case. Heck, it isn’t as though all the biomarkers for the conceded case are universally accepted by mitochondrial experts.

With such little support for the case, the Special Master was forced to conclude:

Petitioners have still not proved their assertion of significant aggravation.

Basically, the decision ends with a statement that the family has not made its case, but they have a chance to come back with a status report as to what their intentions are.

They have already signaled a possible intention:

Petitioners express an interest in suing civilly.

This case is built on even thinner evidence than most internet-discussion-group claims. At least with those, there are challenge tests, porphyrin tests or some other questionable test, together with the opinion of the doctor who ordered the questionable tests to support an idea of “mercury poisoning” or some such diagnosis. But here, we seem to have: the child is autistic, therefore it is mercury and/or mitochondrial disorder aggravated by vaccines.

The Special Master gave the family information on how to contact a lawyer familiar with the vaccine court. I hope, for their sake, they did. I doubt it will have much of an effect on their case, but at least they would have some advice as they move forward to civil court–where the expenses will be charged to the family.

The Truth About Andrew Wakefield

14 Oct

Regular readers will know that an eminent UK scientist writes the occasional guest blog piece for LB/RB. Here is his piece in the wake of the the Lipkin/Hornig study and the amusing claim that it vindicates Wakefield. Enjoy – Kev.

A scientist who has followed the Wakefield saga from the start sets the record straight.

According to recent newspaper reports Andrew Wakefield is planning to publish his account of the MMR/autism controversy next year, under the title The Lesser Truth. He is currently facing charges of gross professional misconduct at the General Medical Council (the case is expected to conclude in April 2009). Meanwhile, Wakefield and his supporters continue to claim that his research is valid and continue to smear the investigative journalist Brian Deer who exposed the conflicts of interest and dubious ethics – as well as the junk science – behind the claims of a link between MMR and autism. But it was Wakefield who was obliged to back down in court from his libel allegations against Deer. Wakefield was unable to contradict Deer’s claim that he has been “unremittingly evasive and dishonest in an effort to cover up his wrong-doing”.

Here are some truths about Wakefield and his research that may not find their way into The Lesser Truth:

Wakefield was never a respected researcher. His first foray into the Lancet was a controversial paper in 1989 saying that Crohn’s disease was due to problems in the blood supply to the gut (vasculitis). But this was wrong. In the early 1990s he was funded by pharmaceutical companies for research along the same lines, mostly in animal models, and produced a series of low-impact, forgettable, papers.

Wakefield first courted notoriety in 1993 when he claimed to have identified measles virus in Crohn’s disease gut tissue. Coincidently, measles virus can cause vasculitis so it is easy to understand how, from 1989 onwards, Wakefield had to find measles in Crohn’s. We now know this result was not possible: there is no measles virus in Crohn’s disease and the antibodies Wakefield used were not specific for measles either. In Wakefield’s own lab, a good molecular biologist, Nicholas Chadwick, could not find measles in Crohn’s by sensitive molecular techniques. However, Wakefield said he could find measles, using crude techniques using flawed reagents. Suppressing data which ruins your hypothesis is scientific fraud.

In February 1996 Wakefield cooked up the idea that MMR was involved in autism with the solicitor Richard Barr and parent activist Rosemary Kessick. He wrote a research protocol to get into the children’s colons to look for measles virus and gut damage, and applied to the Legal Aid Board for £55K.

By October 1996, the Royal Free team had scoped enough children to provide Wakefield with tissue samples so that his technician could look for measles virus in the guts of autistic children by immunohistochemistry. This was clearly research, without clinical or ethical justification.

By spring/summer 1997 Wakefield had enough cases and enough creative data for his story. He believed that autistic children had gut inflammation and most importantly, he believed that he had discovered the cause – measles virus persisting in the gut from MMR. Wakefield first tried to get this study published in Nature but it was rejected.

Towards the end of 1997 he sent an abstract of this work to be presented at Digestive Diseases Week in the USA in May 1998. He also submitted two papers to the Lancet. The first was accepted and published as the now notorious February 1998 Lancet paper. The second, the study claiming to have identified measles virus in the gut by immunohistochemistry, was rejected. To see Wakefield’s pictures of measles virus in the guts of autistic children go here (slides 37 and 38). The second paper was never published and has now mysteriously disappeared, although Wakefield showed it all over North America for years.

In 2000, Wakefield published a larger series on “autistic enterocolitis”, the new disease he claimed to have identified (Wakefield et al 2000 Enterocolitis in children with developmental disorders. American Journal of Gastroenterology 95: 2285-95). Analysis of the data in this paper has revealed that it was a scam: autistic children do not have a chronic inflammatory bowel disease. Normal findings in children were called pathology, pathological results were re-examined and sexed up, and new abnormalities were manufactured, all to make it appear that these children had gut inflammation (MacDonald TT, Domizio P. Autistic enterocolitis; is it a histopathological entity? Histopathology. 2007 Feb;50(3):371-9).

As the litigation in the UK began to heat up around 2000, the defendants (the MMR manufacturers) started to ask simple questions, such as, where is the paper which shows measles in the gut of autistic children? This was part of the MMR/autism story that was rejected by Nature and the Lancet. Who knows why Wakefield never published it? Maybe he realised it was junk since at the same time his identification of measles virus in Crohn’s disease had unravelled. Maybe he knew that the experts for the defence had looked at the data and the methodology and shown it was junk.

Wakefield now hooked up with Dublin pathologist John O’Leary. O’Leary was supposedly an expert in an unsound and discarded methodology called in cell PCR, which he claimed allowed him to amplify measles genetic material in tissue samples, in this case, from the guts of children with autism, and identify its cellular location. He also set up PCR techniques to amplify measles from samples of gut. The O’Leary lab’s studies of Wakefield’s gut biopsy specimens were published in another notorious paper (Uhlmann et al. Potential viral pathogenic mechanism for new variant inflammatory bowel disease. J Clinical Path: Mol Pathol 2002;55: 84-90).

In his testimony to the Omnibus Autism proceedings in Washington in summer 2007, London-based molecular biologist Professor Stephen Bustin showed the utter incompetence of O’Leary and his lab. He revealed the fact that a result was called positive if the sample contained measles virus but no DNA (a biological impossibility). He also revealed that if they analysed the same autistic sample 6 times and got a positive once, the patient was deemed to be positive, even though they were also getting positive measles results out of samples of pure water.

It seems that O’Leary has belatedly seen the error of his ways: in the recently published Hornig study, his lab – in common with other labs in the USA – failed to find measles in samples from autistic children (Hornig et al 2008 Lack of association between measles virus vaccine and autism with enteropathy: a case-control study. PLOS One 3(9):e3140). The attempts by Wakefield and his acolytes to claim that the Hornig study vindicates the Uhlmann paper are preposterous. Distancing himself from Wakefield as fast as is possible for any man of 20 stone, O’Leary cleaned up his lab and did things properly.

A review of the career of Andrew Wakefield is a trawl through the underbelly of science. Wakefield did not do experiments to seek the truth – he did experiments to confirm his own beliefs. He produced junk science for over a decade and did immense damage to patients with Crohn’s disease, and autistic children and their parents. Hopefully the GMC will nail the charlatan, and show some sympathy for the Royal Free clinicians who thought Wakefield was honest. The Andy Wakefield show has now moved to the USA where he can get the attention he craves and he can play the role of the selfless seeker of truth whom the establishment had to silence. Being a victim is a good career move for him. It will help Thoughtful House sell junk therapies for autism to desperate parents and allow Andy to live in a really big house, where he can entertain his showbiz friends. He really wanted to be a famous scientist, but he was rubbish at that, so he had to become (in)famous by other means.

Jon Poling – no such thing as bad publicity

4 Oct

As broken by Kathleen and discussed further by Kristina, the Poling saga has taken another nasty twist and reveals the ‘respected’ Jon Poling as a scientist lacking even the most basic of scientific scruples.

In a series of three letters from Jon Poling, his co-authors Frye, Zimmerman and Shoffner and lastly Roger Brumback, the editor of the Journal that published their case study of Hannah Poling, Jon Poling is revealed as a man perfectly prepared to game the system.

In his letter, editor Roger Brumback says (he calls his letter ‘the Appalling Poling Saga’) he says:

In the United States Federal Register of May 21, 2003 (volume 68, number 98), on page 27829, there is an entry (“145. Terry and Jon Poling on behalf of Hannah Poling, Vienna, Virginia, Court of Federal Claims Number 02-1466V”) mentioning a filing under the National Vaccine Injury Compensation Program listing of petitions received. This occurred before the manuscript was submitted for consideration by JCN and clearly represents a conflict of interest. Yet the authors made a definitive statement to the Editor-in-Chief and to potential peer reviewers that there was no conflict of interest (Figure 1).

Let no one tell you any different. Jon Poling did not ‘forget’ to tell the publishing journal about the fact his daughter was part of the Autism Omnibus, he purposefully misled the Editor-in-Chief by stating conclusively there was no conflict of interest. Being a gentleman, Brumback avoids calling Poling an out-and-out liar. Brumback goes on to say:

Although, according to the leaked testimony (available to be viewed on numerous websites) [Brumback is referring to the testimony leaked to David Kirby – KL], it does not appear that the JCN article was used in the legal proceedings, media linkage of the published article to the legal outcome implies scientific support from JCN for this legal opinion. Of course it is possible to view this media exposure along the lines of the quip: “There is no such thing as bad publicity—just publicity”.

Quite.

Two things stand out for me – aside from this pathetic litany of dishonesty of course.

Firstly, Jon Poling is his letter says:

A third party subsequently leaked, without our knowledge or permission, my daughter’s
identity and the government’s concession report to the media.

Now lets have a look at this timeline. ‘The media’ Poling is referring to above is David Kirby who posted the details to the HuffPo on Feb 26.

Starting a bare 9 days later, the Polings are holding a press conference, being interviewed on Good Morning America, Larry King Live, Cable News Network, USA Today and The Atlanta Journal-Constitution.

Wow. I guess Brumback is right – there is no such thing as bad publicity because in little over a week, the totally non-media savvy Poling’s had managed to get themselves interviews on the leading media outlets in the USA. And they expect us to believe they did it ‘without our knowledge’ of the documents being leaked to quote Poling.

Something else really stands out from Poling’s letter. Its this:

2001. Because our daughter has diagnoses of autism, regressive encephalopathy, and mitochondrial dysfunction, her case was placed in the Omnibus Autism Proceedings.

Before HHS government physicians conceded that Hannah’s July 2000 vaccinations triggered her encephalopathy…..

Woah there…..what? Triggered her _what_ ? Encephalopathy? Thats funny because David Kirby and the anti-vaccine world has been swearing up and down the HHS conceded her vaccinations triggered her _autism_ .

This is a true bombshell. Jon Poling, Hannah’s father has just stated that HHS conceded vaccinations caused her encephalopathy as oppose to her autism. He’s quite clear and specific. In the first paragraph I quote he lists three separate things:

….autism, regressive encephalopathy, and mitochondrial dysfunction…

and in the second, he states which of these three HHS conceded was triggered by vaccinations. Encephalopathy. Not autism.

Next time anyone tells you HHS conceded Hannah Poling’s autism was caused by vaccines, point them here where they can read the words of her father.

Good Information being spread on Capital Hill

2 Oct

Last week, there was a briefing for U.S. legislators by Mr. David Kirby and Mr. Mark Blaxill. As you can imagine, the topic was vaccines and autism. As you can imagine, there were some inaccuracies and there was at least one outright misrepresentation.

I applauded an effort by Amy Pisani of Every Child By Two, who wrote the staffers ahead of the meeting. I was also appreciative of a letter by Voices For Vaccines.

Well, now I give a great big thank you to Congressman Waxman. Congressman Waxman is the chair of the Congressional Committee on Oversight and Reform. To put that in perspective, “Oversight and Reform” is the committee that Congressman Dan Burton used to investigate autism and vaccines. (a very good discussion of what went wrong there is in Autism’s False Prophets).

Congressman Waxman’s office sent out a “Dear Colleague” letter. It is a good, succinct discussion of autism and vaccines, and, as such, I think it worth posting. And forwarding to people who may have questions about this issue.

It’s also worth thanking Congressman Waxman for taking the time to work on autism issues.

Resources Regarding Vaccines and Autism

October 1, 2008

Dear Colleague,

Since 1998 some people have been raising concerns that there may be an
association between childhood immunizations and autism spectrum
disorder. I am writing to let you and your staff know that there are a
number of resources available to understand what the science says
about whether vaccines could contribute to autism.

Institute of Medicine report on vaccines and autism

In 1999 the Department of Health and Human Services contracted with
the Institute of Medicine (IOM) to review a number of different
vaccine safety issues and to make recommendations about future
research needs. IOM convened a committee of experts that was carefully
vetted for conflicts of interest. The committee issued nine reports,
all of which are available on line at: http://www.iom.edu/CMS/3793/4705.aspx.

In 2004, the committee issued its final report, which analyzed the
studies, published and unpublished, that looked at two theories:
whether the Measles-Mumps-Rubella (MMR) vaccine could cause autism;
and whether the mercury-containing vaccine preservative thimerosal
could cause autism. The committee concluded that the “evidence favors
rejection of a causal relationship between thimerosal-containing
vaccines and autism” and the committee also concluded that the
“evidence favors rejection of a causal relationship between MMR
vaccine and autism.” This report is available at:
http://www.iom.edu/CMS/3793/4705/20155.aspx.

Other resources on vaccines and vaccine safety

Since the IOM report was published there have been additional studies
that looked at a possible link between vaccines and autism. Below are
several other links to government or private organizations with
helpful information about the latest research into vaccines, vaccine
safety, and autism and vaccines:

The Centers for Disease Control and Prevention
http://www.cdc.gov/ncbddd/autism/vaccines.htm

National Network for Immunization Information
http://www.immunizationinfo.org

Institute for Vaccine Safety at Johns Hopkins University
http://www.vaccinesafety.edu

American Academy of Pediatrics
http://www.aap.org/healthtopics/Immunizations.cfm

Information regarding mitochondrial disorders and vaccines

Another concern that has received some attention is whether people
with mitochondrial disorders are more susceptible to vaccine injury.
This issue was in the media after it became public that in 2007, the
Vaccine Injury Compensation Program (VICP), the no-fault compensation
program for people who have been injured by immunizations, compensated
nine-year-old Hannah Poling for injuries she sustained from her
immunizations. Hannah Poling suffered from a mitochondrial disorder,
which is a genetic or acquired defect in the part of each cell that
helps produce energy. People with these disorders are susceptible to a
number of stressors, including fever, illness, dehydration and certain
kinds of medication. In Hannah Poling’s case, after her immunizations
she developed a fever, lethargy, irritability, and other symptoms of
encephalopathy. These symptoms worsened over a period of months to
includ! e muscle weakness and features of autism. Instead of taking
this case to the vaccine court, the VICP conceded the case and agreed
to compensate Hannah Poling.

This case raised concerns that there may be an association between
mitochondrial disorders and autism. Mitochondrial disorders are poorly
understood and there is much research that needs to be done. However,
according to the United Mitochondrial Disease Foundation: “There are
no scientific studies documenting that childhood vaccinations cause
mitochondrial diseases or worsen mitochondrial disease symptoms. In
the absence of scientific evidence, the UMDF cannot confirm any
association between mitochondrial diseases and vaccines.” This
statement is available at: http://www.umdf.org/site/c.dnJEKLNqFoG/b.3616911/apps/s/content.asp?ct=5087517.

Following this case, NIH, HHS, and CDC organized a workshop entitled
“Mitochondrial Encephalopathies: Potential Relationships to Autism.”
The workshop was held on June 29, 2008 in order to explore this
complicated topic and panelists included experts from around the
country. The proceedings from this workshop state that because
acquired infections and the associated inflammatory responses are a
known trigger for mitochondrial disease, “the workshop panelists
strongly encourage vaccinations in the hundreds of children they treat
for mitochondrial disease.” A summary of this workshop is available
at: http://www.ninds.nih.gov/news_and_events/proceedings/20090629_mitochondrial.htm

CDC has additional information on its website at:
http://www.cdc.gov/ncbddd/autism/mitochondrial.htm

I hope you find these links useful. If you are interested in other
resources, please do not hesitate to call Sarah Despres or Dr. Stephen
Cha on my staff at 5-5056.

Sincerely,

/s
HENRY A. WAXMAN
Member of Congress

Mitochondrial disease discussion in Indianapolis

29 Sep

You may recall that there was a panel discussion on Mitochondrial Disease and Autism following the United Mitochondrial Disease Foundation’s (UMDF) meeting in Indianapolis. This, of course, was prompted by the news reports of the Hannah Poling case.

If you are looking for the incredibly short answer, quote mine, here it is:

To reduce the risk presented by acquired infections, the workshop panelists strongly encourage vaccinations in the hundreds of children they treat for mitochondrial disease. Among thousands of patients they had collectively seen, very few had deteriorated following vaccination, and in those few cases, it is difficult to determine that other stressors besides the vaccine did not play a role in the neurologic deterioration.

The panel discussion was held June 29th, and the report from that has just been published.

The panel was organized by people from NIH, NINDS, HHS and CDC.

Thomas R. Insel, M.D.
Director, National Institute of Mental Health, National Institutes of Health

Walter Koroshetz, M.D.
Deputy Director, National Institute of Neurological Disorders and Stroke, National Institutes of Health

Daniel Salmon, Ph.D., M.P.H.
Vaccine Safety Specialist, U.S. Department of Health and Human Services

Ed Trevathan, M.D., M.P.H.
Director, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention

The panel included a lot of the names you would expect to hear from:

Kim M. Cecil, Ph.D.
Research Associate Professor, Cincinnati Children’s Hospital Medical Center

Bruce Cohen, M.D.
Department of Neurology, Cleveland Clinic Foundation

Stephen R. Dager, M.D.
Departments of Radiology, Psychiatry, and Bioengineering, University of Washington School of Medicine
Interim Director, University of Washington Autism Center,

Darryl DeVivo, M.D.
Sidney Carter Professor of Neurology and Pediatrics, Columbia University

Salvatore DiMauro, M.D.
Lucy G. Moses Professor of Neurology, Neurological Institute of New York, Columbia University Medical Center

Pauline Filipek, M.D.
Associate Professor of Pediatrics and Neurology, University of California, Irvine

James F. Gusella, Ph.D.
Director, Department of Genetics, Center for Human Genetic Research, Massachusetts General Hospital

Richard Haas, M.D.
Co-Director, Mitochondrial and Metabolic Disease Center, University of California, San Diego, School of Medicine

Robert K. Naviaux, M.D., Ph.D.
Co-Director, Mitochondrial and Metabolic Disease Center, University of California, San Diego, School of Medicine

Joseph Piven, M.D.
Director, Neurodevelopmental Disabilities Research Center, University of North Carolina, Chapel Hill

Roberto Tuchman, M.D.
Director, Autism Programs, Miami Children’s Hospital Dan Marino Center

Douglas Wallace, Ph.D.
Director, Center for Molecular and Mitochondrial Medicine and Genetics, University of California, Irvine

The proceedings are a summary, not a transcript of the actual event. It is a very good summary of what is known about mitochondria and mitochondrial disorders. It’s worth reading, and it is not very long. However, I’ll pull some summary information out here:

Mitochondrial genetics and biology

We all have two sets of DNA–the nuclear DNA (nDNA) that we are used to hearing about as the “blueprints” for inheritance and mitochondrial DNA (mtDNA) that are inside the mitochondria and help with the processes in the mitochondria.

Even though mitochondria are inherited from the mother, mitochondrial disease can involve both the nuclear and mitochondrial DNA, and, thus, mitochondrial diseases have multiple inheritance pathways.

You can have different mtDNA in a single cell or in different tissues–this is called heteroplasmy.

An overview of mitochondrial diseases

There are 200 mtDNA mutations and 2,000 nDNA mutations that can lead to mitochondrial disease. (The nDNA is much bigger than the mtDNA, so it isn’t surprising that more of the mutations are found on the nDNA).

The incidence of mitochondrial disease is between 1-5 in 10,000. But, the understanding is evolving.

Mitochondrial diseases present a very large spectrum. But, some generalizations can be made.

…they are typically progressive and multisystemic, most often affecting organs that have high energy demands such as the brain and nerves, skeletal and cardiac muscle, and the liver and kidneys.

There are a number of possible flags for mitochondrial disease, often when more than one area is affected at once. They noted, when the idea of autism and mitochondrial disease is discussed:

Of particular interest for this workshop, central nervous system manifestations of mitochondrial disease can include hypotonia, seizures, encephalopathy, ataxia, intellectual disabilities, global delay, and brain malformations. Sensory and peripheral nerves can also be affected, leading to deafness, blindness, or neuropathy.

Diagnosing mitochondrial disease

If you’ve already read about diagnosis of mitochondrial disease, you know it is a very complicated process.

The workshop panelists explained that diagnosis is often a lengthy process beginning with a general clinical evaluation followed by metabolic screening and imaging and finally by genetic tests and more invasive biochemical and histological analyses.

Metabolic screening, MRI, genetic testing and enzyme function through biopsy are all noted as tests, but no single test or even set of tests are definitive.

Known triggers of mitochondrial disease

If there is one section that the online autism communities are likely to zero in on, it’s this.

Mitochondrial diseases can go undetected for many years, and many cases display an episodic course with relatively stable periods punctuated by abrupt degeneration that may coincide with an infection or other stress to mitochondrial function.

If you’ve been thinking about this a lot, you’ve probably asked yourself how the mitochondria react during a fever. Fevers are an increase in temperature, which, naturally, takes an increased energy output.

Of possible importance, mitochondria are the major generators of body heat and are therefore extremely active during fever. It is not known whether fever or other aspects of the inflammatory or immune response to a virus or bacteria trigger deterioration after infection

The phrase that probably will be the one take-away for most people in the autism community who have been following the mitochondrial issue:

To reduce the risk presented by acquired infections, the workshop panelists strongly encourage vaccinations in the hundreds of children they treat for mitochondrial disease. Among thousands of patients they had collectively seen, very few had deteriorated following vaccination, and in those few cases, it is difficult to determine that other stressors besides the vaccine did not play a role in the neurologic deterioration.

From what I’ve heard, they were very, very strong in their recommendation for vaccination to protect against infectious disease in this very vulnerable population.

Other triggers include dehyration, reduced caloric intake or, in some cases, exercise.

Environmental causes of mitochondrial impairment: AZT, valproate, statins, chemicals like MPTP and the pesticide rotenone, fungal toxins, and even cigarette smoke and alcohol.

Mitochondrial diseases and autism: clinical parallels and evidence for a relationship

Both Autism and Mitochondrial Disease are broad spectrums. The subtypes for autism are less well defined, making it hard to make good comparison. It is difficult to pull only a couple phrases out of this section, but I will pick two:

Workshop panelists who treat children with mitochondrial disease noted that some of these children have autistic features, and some children eventually found to have mitochondrial disease are initially diagnosed with an ASD. In addition, siblings of children with maternally inherited mitochondrial disorders sometimes present with autism. Presumably, they have inherited the same mitochondrial mutation from their mother, but the mutation may be difficult to find. Workshop panelists who mainly see individuals with a primary diagnosis of autism found parallels with clinical observations in mitochondrial disease such as developmental regression, seizures, and gastrointestinal complications

and,

Additional parallels between ASDs and mitochondrial disease noted by the workshop panelists were in family histories and patterns of inheritance. These included possible maternal inheritance in some ASDs, a similar higher prevalence in males for both ASDs and some mitochondrial diseases, and a high frequency of psychiatric conditions such as depression, delusions and attention deficit disorder in families with mitochondrial disease, including in relatives who seem otherwise unaffected.

Advancing research on the relationship between mitochondrial disease and autism: needs, priorities and emerging tools

This section notes two types of studies which they suggest should be done: a targeted and an unbiased approach.

By targeted they mean a study that

…would involve a thorough investigation of a relatively small ASD population selected for characteristics that indicate a greater likelihood of mitochondrial involvement. Such a strategy might involve more in-depth or invasive testing, including, for example, muscle biopsy and brain imaging with MR spectroscopy.

On the other hand, the unbiased approach:

… would instead survey a larger, more diverse population and could inform questions about the extent to which mitochondrial disease contributes to ASDs more broadly.

From my perspective, both sound like good avenues for research–neither better or more important than the other.

If you are following this subject, I would again urge you to read the entire summary. It isn’t very long. It is unfortunate that people (myself included) will pull bits and pieces out.

Vaccines on the Hill

25 Sep

With a hat-tip to Kim Stagliano at the Age of Autism blog. They got ahold of an email sent by Amy Pisani of Every Child by Two to legislators who were sending staffers to a briefing by Mark Blaxill and David Kirby on vaccines and autism.

Mr. Kirby promised to talk about, amongst other topics, Hannah Poling. That’s not what I would call a good briefing. A good briefing would be if the legislators asked HHS to talk to them about what the concession meant. Somehow, I think the two briefings would be significantly different. Then again, I suspect a briefing by the doctors who are studying that potential cause of developmental regression via mitochondrial dysfunction would also have a very different story to tell than Mr. Kirby. I strongly suspect that.

But, I digress, as I often do. You see, Every Child by Two thought that the legislators who were sending staff to the Kirby/Blaxill briefing should be informed that the information provided by that team was, well, not accepted by the mainstream.

The letter, respecfully written, respectfully submitted is quoted below. One reader of this blog asked Ms. Pisani for permission to reproduce it here. I am using the text from the AoA blog.

Why reproduce it here? Because many in the greater autism community agree with Ms. Pisani. This blogger certainly does. I hope that legislators know that many members of the autism community side with Every Child by Two on this subject.

So, after much delay, here is something written much better than the ramblings I’ve put together:

Today you have been invited to attend a briefing to provide “updates on the recent autism-vaccines debate”. While I recognize that most of you will likely be dealing with other priorities and will not attend the Maloney briefing, I write to you this morning because I feel it is critical to clarify that there is no debate among the scientific community regarding vaccines and autism. Instead, the debate rages on in the media due to the efforts of those who wish to sidetrack critical research away from finding the true cause(s) of autism and treating children and their families struggling with this condition.

‘Last week Dr. Paul Offit’s new book “Autism’s False Prophets, Bad Science, Risky Medicine, and the Search for a Cure” was published by Columbia University Press. This book is a must read for all those concerned with children dealing with autism. The Philadelphia Inquirer writes that “Offit’s account, written in layman’s terms and with the literary skill of good storytellers, provides important insight into the fatal flaws of the key arguments of vaccine alarmists, including such well-known names as Robert F. Kennedy Jr., Sen. Joseph Lieberman (I., Conn.), and Sen. John Kerry (D., Mass.).” And the Wall Street Journal writes “Ever since psychiatrist Leo Kanner identified a neurological condition he called autism in 1943, parents whose children have been diagnosed with the most severe form of the illness — usually in the toddler stage, before age 3 — have found themselves desperately searching for some way not to lose their children to autism’s closed-off world. Unfortunately, such parents have often found misguided doctors, ill-informed psychologists and outright charlatans eager to proffer help.”

In 1999 I was pregnant with my first son just as the questions first arose regarding the MMR vaccine and subsequently the thimerosal in vaccines. After attending Congressman Burton’s hearings (quite pregnant I might add) I too became alarmed. Fortunately, as the Executive Director of Every Child By Two I had at my disposal the scientific research and advice of the world’s leading experts on vaccines and I was able to confidently vaccinate my son without fear of side effects. As of today, eleven studies now show that the MMR vaccine doesn’t cause autism, six have shown that thimerosal doesn’t cause autism, and three have shown thimerosal doesn’t cause neurological problems.

I urge you to read a few of the reviews of Dr. Offit’s book which are listed below and contact us if you wish to have a copy sent to you.

I also ask that you please visit our new website www.vaccinateyourbaby.org – this site was unveiled in August with our new spokeswoman Actress Amanda Peet specifically for parents who have questions about vaccine safety.

at the risk of making this an extremely long blog post, let me do what the Age of Autism did not do: list some of the reviews of the book.

A definitive analysis of a dangerous and unnecessary controversy that has put the lives of children at risk. Paul A. Offit shows how bad science can take hold of the public consciousness and lead to personal decisions that endanger the health of small children. Every parent who has doubts about the wisdom of vaccinating their kids should read this book. — Peter C. Doherty, Ph.D., St. Jude’s Children’s Research Hospital and Nobel Laureate in Medicine for fundamental contributions in Immunology

As a parent it is my job to protect my children. Hearing all the rumors about vaccine side effects made me question the right thing to do. This book makes it clear that vaccines save lives, and that they clearly do not cause autism. — Amy Pisani, mother

In his latest book Paul A. Offit unfolds the story of autism, infectious diseases, and immunization that has captivated our attention for the last decade. His lively account explores the intersection of science, special interests, and personal courage. It is provocative reading for anyone whose life has been touched by the challenge of autism spectrum disorders. — Susan K. Klein, MD, Ph.D., Case Western Reserve Hospital, and Rainbow Babies and Children’s Hospital, Case Medical Center

No one has been more vocal-or courageous-than Paul A. Offit in exposing the false and dangerous claims of the growing antivaccine movement. Offit’s latest book lays waste to the supposed link between autism and vaccination while showing how easily Americans have been bamboozled into compromising the health of their own children. Autism’s False Prophets is a must read for parents seeking to fully understand the risks and rewards of vaccination in our modern world. — David Oshinsky, winner of the Pulitzer Prize in History for Polio: An American Story

All good reviews. But, dang, a Nobel Laureate in Medicine. Not just medicine but immunology? Plus a Pulitzer prize winner? Begs the question of why the Age of Autism didn’t include them.

I am so glad that they offered Dr. Offit’s book to the legislators. I hope that the legislators, or their healthcare legislative assistants take them up on the offer. It’s a well written book, and fairly concise. It really explains how we (the autism communities) got here (into a big mess where vaccines are such a high profile subject–at least in the media) even though we shouldn’t be (because the science has been done repeatedly and shown no link).

Word back on the briefing is that about 75 people attended–a mix of staffers, parents, possibly even a member of the press. One representative was noted. Mr. Kirby gave the short version of his talk (the full version is quite long–take a look at his power point presentations sometime!). But, we can all rest assured that Mr. Kirby is there to save the vaccine program (I do hope that autism-one puts this briefing on their website. I need to hear that claim by Mr. Kirby with my own ears). Mr Blaxill took on the “sickest generation ever” theme, common to the vaccine rejectionists (a claim that has been addressed ably by epiwonk).

But, again, I digress. Let me bring you back to what I see as the one message I think you should take home from this post (repeated from above):

Why reproduce it [Ms. Pisani’s letter] here? Because many in the greater autism community agree with Ms. Pisani. This blogger certainly does. I hope that legislators know that many members of the autism community side with Every Child by Two on this subject.

The exoneration of John O'Leary

5 Sep

Since the publication of the latest MMR study to refute any connection to autism, the principal believers in the idea that vaccines _simply must_ have some connection to autism have been floundering to spin some positives from the study. They have decided to concentrate on getting this study to exonerate Unigenetics (the lab of Professor John O’Leary). A little backstory is necessary here.

The idea that MMR leads to autism was first perpetuated by Andrew Wakefield. The idea goes that the MMR is injected, the measles component travels to the gut where it persists and causes severe gastric issues. It travels on to the brain and causes autism. Hence, it is – in the Wakefield scenario – the measles virus component of the MMR that causes autism.

In order to test this hypothesis, Wakefield tested for the presence of measles virus in the gut of autistic kids and lo and behold found loads. The way he found them was to send his biopsy samples off to the lab of John O’Leary, Unigenetics, in Dublin. Unigenetics ran the tests on the Wakefield samples and reported they had found measles RNA in significant percentages in Wakefield’s samples. They tested the samples using a technique called PCR.

So, later on, as study after study failed to replicate Wakefield’s – except, tellingly, for studies that went through Unigentics – investigators became suspicious of the results being generated at Unigenetics. As part of the UK litigation into MMR Professor Stephen Bustin – quite possibly _the_ world expert in PCR – went in and spent over 150 hours examining the methods used at Unigenetics to get their results. What he found was a bombshell.

Two things clearly arose from Bustin’s investigation. The first was a clear error of methodology. They forgot to perform an ‘RT Step’. What this was and what it meant is cleared up nicely here by commenter Brian:

The RT stands for “Reverse Transcriptase”, an enzyme that makes a DNA copy of an RNA molecule.

Measles virus exists as an RNA molecule. The polymerase chain reaction (PCR) assay amplifies DNA. Thus to detect an RNA molecule in a PCR assay, the RNA must first be copied (by the reverse transcriptase enzyme) into DNA, which can then be amplified.

Bustin showed that the O’Leary lab reported positive results even when they could not possibly have detected an RNA molecule because they had left out the step to copy that RNA into DNA. Thus the positive results reported for such assays were undoubtedly false positives.

Its worth noting here that Bustin found this methodological error by following Unigenetics lab manual if I recall correctly.

Here is Bustin himself:

If you detect a target that is _apparently_ measles virus in the absence of an RT step by definition it can’t be measles virus because it has to be DNA [measles virus does not exist as a DNA molecule]. It’s a very simple concept. At least it is to me. It’s not to everyone else.

So what were they reporting as measles virus? Lab contamination. That was the second error.

OK, so now back to today and the new MMR paper and the drive to make it exonerate O’Leary.

The new study used three labs to perform its detection. All three performed excellently. One of the labs was (you guessed it) John O’Learys in Dublin.

So, two new press releases have hit since then. I’ll quote from them both.

This is from Thoughtful House (Andrew Wakefield’s Texan fiefdom):

This new study confirmed that results from the laboratory of Professor John O’Leary….were correct, and identical to the results obtained by the laboratories of the Centers for Disease Control and Prevention (CDC) and Dr. Ian Lipkin of Columbia University.

In that this new study affirms the reliability of Professor O’Leary’s laboratory and therefore of his previous findings, a major impact upon the current hearings in vaccine court is likely, wherein the government’s defense relies largely on the claim that Professor O’Leary’s finding of measles in the intestinal biopsy of Michelle Cedillo (a child with severe autism and epilepsy) was unreliable. The historical reliability of the measles assay used in Professor O’Leary’s laboratory is now confirmed.

And SafeMinds:

One of the three labs involved in the Hornig study was led by John O’Leary who conducted the testing for the Wakefield study. The three Hornig study labs validated each other,
confirming the rigorousness of Dr. O’Leary’s work. Dr. O’Leary conducted the testing for one of the autism test cases now in the Federal Court for Vaccine Claims. The child, who regressed into autism
and bowel disease after receiving the MMR, tested positive for measles virus.

So, you can see that this is the spin – exonerating Unigenetics work that Stephen Bustin had demolished.

They take a rather simplistic viewpoint of things – that because the lab performed well now, it did then. I think that’s rather a large assumption.

I also think that they have forgotten the timeline of events surrounding the Cedillo case.

Michelle Cedillo’s positive measles virus finding was in 2002:

From the cross examination of Arthur Krigsman:

Q: OKay, now in support of your opinion that Michelle has persistent measles virus in the lymphoid tissue of her bowel, you cite to the positive finding in *2002* by the Unigenetics in Dublin, Ireland of measles RNA in the tissue sample tested in Michelle, correct?

A: By the published report, of their findings.

Q: But from Unigenetics, specific to Michelle?

A: Right.

(Page 531, line 9 – 18)

Stephen Bustin did not enter the lab until January 2004.

From the Direct examination of Stephen Bustin:

Q:…..Now, you were granted physical access to the Unigenetics laboratory?

A: I was, yes.

Q: When?

A: In January 2004 and then again in May 2004.

(Page 1964, line 12 – 16)

In other words, Michelle Cedillo’s test results were generated by Unigenetics, _before_ Stephen Bustin (or anyone else) had discovered the catastrophic errors that made it impossible they were detecting measles.

The question becomes – if you were John O’Leary and someone had made it perfectly clear that you had done bad work two years earlier would you then carry on missing out the RT step? Or would you not? By the time 2008 rolled around, would you hope that your lab staff could do their jobs properly? Or wouldn’t you really care?

The idea that this new MMR study somehow exonerates the work of Unigenetics prior to 2004 is a joke. Unfortunately, Michelle Cedillo’s testing was done prior to 2004. Two years prior, back to a time when Unigenetics weren’t so good at lab work.

Before the MMR science, the press conference

4 Sep

As I’ve already posted not once but twice, yet one more study has been published showing yet one more time that the MMR doesn’t cause autism.

Prior to the lifting of the embargo on the study itself, there was a press conference featuring some of the study authors (Lipkin and Hornig were both in attendance) and several journalists as well as ‘freelance writer’ David Kirby.

Most of the questions concentrated on what this study showed, however someone there wanted to try and use this new study to (somewhat bizarrely) exonerate the O’Leary lab’s role in the poor science done by Wakefield and in the lab’s role in the Cedillo hearing (where it was trounced for poor science).

The whole press conference is here.

As an example, here is David’s first question.

http://webjay.org/flash/dark_player

Now thats more a set of questions than _a_ question, the initial question regarding Hannah Poling is both inaccurate and pointless. Inaccurate as, regardless of what David claims, no statement has been published by anyone that states Hannah Poling’s autism was caused by a vaccine. Pointless as this science has absolutely no bearing on her case. It has never been claimed she had measles virus in her gut.

David’s second point regarding O’Leary is fascinating. Because one of the labs used in this new paper was O’Leary’s and because the lab performed well, David seems to be claiming that that exonerates the O’Leary lab from past errors. I’m not sure how that can be true. As Stephen Bustin clearly showed during the Cedillo hearing, the errors of the O’Leary lab were twofold. The first was one of methodology. They forgot to do an RT step. Now I don’t know what that means but it was clear that it was a fairly serious (and basic) error. What it caused was the O’Leary lab to falsely identify contaminants as measles RNA. The second error was failing to pick this contamination up. So its not just a case of contamination, its a case of poor procedure.

I’m going to hazard a guess here and suggest that since the time of Bustin’s initial investigation (some years ago now) the O’Leary lab have figured out how to do an RT Step.

David’s second question followed:

http://webjay.org/flash/dark_player

So, we’re back to the very small sub-population argument. I really want to know – if the leading supporter of the vaccine hypotheses is now angling towards this ‘sub-sub’ group, what impact does that have on the autism epidemic idea? I mean, how can you have an autism epidemic generated by a very small sub-sub group?

Anyway, the answer to David’s question from the assembled scientists was ‘uh, who knows? That’s not what our study was about’. Or words to that effect.

David’s third (and fourth) questions followed. Please listen carefully to the answers which I’ve left on. You might also want to note the (somewhat amusing) deep sigh from the guy answering David as David keeps trying to make him say that MMR isn’t totally 100% safe.

http://webjay.org/flash/dark_player

And then by the time of David’s attempted fifth question, the answering team were obviously getting a bit fed up.

http://webjay.org/flash/dark_player

So that (to me) is a pretty fascinating insight into the denial that exists even at the very highest levels of the autism/vaccine hypotheses.

Just as a postscript, David asked them (totally randomly it seemed) if the best study would be one of vaccinated vs unvaccinated kids. Here is the reply. A reply grounded in real science.

http://webjay.org/flash/dark_player

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