Archive by Author

The Autism Vaccine Controversy and the Need for Responsible Science Journalism

7 Jan

The Huffington Post has a new section on science. One of the first articles discusses the “Autism Vaccine Controversy”. In The Autism Vaccine Controversy and the Need for Responsible Science Journalism, Seth Mnookin starts out:

Earlier this week, The Panic Virus, my book on the controversy over vaccines and autism, was released in paperback. While there haven’t been many scientific advances in this particular issue since the hardcover edition was published — the evidence supporting vaccines’ paramount place in public health efforts and the total lack of corroboration supporting a causal connection between vaccines and autism remain as strong today as they were a year ago — there have been new developments in the story. Their coverage highlights an enduring passion of mine: The need for reliable, responsible science journalism.

Yes, Seth Mnookin, author of The Panic Virus, is writing for the Huffington Post, a site which has contributed greatly to misinformation about vaccines and autism. The Huffington Post has been home to David Kirby (who was a major promoter of the mercury/autism concept) as well as welcoming input from Jenny McCarthy and Jim Carrey, to name but a few of the poor choices for writers the Post engaged.

On PLoS blogs, Mr. Mnookin announced this new gig with Has the Huffington Post embraced science & closed the door on anti-vaccine quackery? We can hope. I wouldn’t place any bets on it though.

No Evidence of Murine Leukemia Virus-Related Viruses in Live Attenuated Human Vaccines

6 Jan

There has been much discussion of XMRV, Xenotropic murine leukemia virus-related virus, here at Left Brain/Right Brain and elsewhere in the past few months. The reason for the discussion here is the (now shown to be false) idea that XMRV is implicated in autism causation. Two papers have addressed this question and found no evidence of a link. XMRV came to prominence as a possible candidate in causing chronic fatigue syndrome (CFS). Multiple papers have found no evidence of a link between XMRV and CFS (fan example is discussed here) and the original paper on the topic was withdrawn by editors of the journal Science after it became clear that those results were suspect.

The idea that autism and XMRV was promoted by David Kirby, whose efforts also strongly promoted the debunked autism-epidemic-caused-by-mercury idea. Mr. Kirby’s article at the Huffington Post was Is Autism Associated with A Viral Infection?. In this he quoted CFS/XMRV researcher Judy Mikovits:

And then Dr. Mikovits dropped a bombshell that is sure to spark controversy.

“On that note, if I might speculate a little bit,” she said, “This might even explain why vaccines would lead to autism in some children, because these viruses live and divide and grow in lymphocytes — the immune response cells, the B and the T cells. So when you give a vaccine, you send your B and T cells in your immune system into overdrive. That’s its job. Well, if you are harboring one virus, and you replicate it a whole bunch, you’ve now broken the balance between the immune response and the virus. So you have had the underlying virus, and then amplified it with that vaccine, and then set off the disease, such that your immune system could no longer control other infections, and created an immune deficiency.”

Mr. Kirby went on to write:

So there you have it – a possible explanation of regressive autism in a significant number of cases associated with immune system deregulation triggered by vaccination.

Of course, much more work is needed to nail down the exact significance of such an association. For example, is the virus implicated in the cause of autism, or do children harbor the virus as a result of autism?

Yes, Ms. Mikovits and David Kirby were proposing a possible link between autism, XMRV and (of course) vaccines.

That was October 2009. Fast forward to today, two years later and we see

A) Neither Ms. Mikovits nor anyone else has published the data supposedly linking XMRV and autism

B) Two studies have looked for evidence (and failed to find any) of a link between XMRV and autism,

Lack of infection with XMRV or other MLV-related viruses in blood, post-mortem brains and paternal gametes of autistic individuals.

PCR and serology find no association between xenotropic murine leukemia virus-related virus (XMRV) and autism.

C) Evidence has arisen that much of the data linking XMRV to CFS is faulty.

Studies on XMRV are still ongoing. If experience from the vaccine-autism-epidemic idea tell us anything, the idea that XMRV causes CFS and/or autism will die slowly and even more data are needed.

To that end, a recent study explored whether XMRV is a contaminant in live virus vaccines. (note that in other vaccines, the XMRV is likely as dead as the other constituents of the vaccine). You can tell the result from the title: No Evidence of Murine Leukemia Virus-Related Viruses in Live Attenuated Human Vaccines.

Background

The association of xenotropic murine leukemia virus (MLV)-related virus (XMRV) in prostate cancer and chronic fatigue syndrome reported in previous studies remains controversial as these results have been questioned by recent data. Nonetheless, concerns have been raised regarding contamination of human vaccines as a possible source of introduction of XMRV and MLV into human populations. To address this possibility, we tested eight live attenuated human vaccines using generic PCR for XMRV and MLV sequences. Viral metagenomics using deep sequencing was also done to identify the possibility of other adventitious agents.

Results

All eight live attenuated vaccines, including Japanese encephalitis virus (JEV) (SA-14-14-2), varicella (Varivax), measles, mumps, and rubella (MMR-II), measles (Attenuvax), rubella (Meruvax-II), rotavirus (Rotateq and Rotarix), and yellow fever virus were negative for XMRV and highly related MLV sequences. However, residual hamster DNA, but not RNA, containing novel endogenous gammaretrovirus sequences was detected in the JEV vaccine using PCR. Metagenomics analysis did not detect any adventitious viral sequences of public health concern. Intracisternal A particle sequences closest to those present in Syrian hamsters and not mice were also detected in the JEV SA-14-14-2 vaccine. Combined, these results are consistent with the production of the JEV vaccine in Syrian hamster cells.

Conclusions

We found no evidence of XMRV and MLV in eight live attenuated human vaccines further supporting the safety of these vaccines. Our findings suggest that vaccines are an unlikely source of XMRV and MLV exposure in humans and are consistent with the mounting evidence on the absence of these viruses in humans.

Yes, there is no evidence of XMRV in vaccines. This is rather anticlimactic given the evidence already in place that XMRV is not linked to autism, and the fact that the XMRV/CFS link is already tenuous at best.

The blogger erv has done the most thorough job following the XMRV study out there, including discussing the paper above. Others have taken up where David Kirby left off and promoted the idea that XMRV and autism are linked, and that vaccines are a possible part of that link. I would hope that those people would see the value in letting their readers know about this paper (and others, and the retractions).

BMJ instructs lawyers to “defend the claim vigorously” against Andrew Wakefield’s lawsuit

6 Jan

The British Medical Journal (BMJ) has issued a press release (below) about the lawsuit initiated by Andrew Wakefield claiming defamation arising from a series of articles published last year. The BMJ and Mr. Deer stand by their articles and statements and have instructed their attorneys to “defend the claim vigorously”.

Although not formally served with the legal papers, the BMJ is on notice that Andrew Wakefield has issued defamation proceedings, not in London as might be ordinarily expected as concerns a predominately English publication, but in Texas, USA, where he now lives. The proceedings primarily relate to an article written by Brian Deer and published a year ago on 5 January 2011, entitled Secrets of the MMR Scare: How the Case Against the MMR Vaccine was Fixed, and an accompanying editorial which related to Mr Wakefield’s now infamous Lancet Paper on MMR.

Of course, following the findings of the British General Medical Council’s Fitness to Practice Panel and Mr Wakefield’s history of pursuing unfounded litigation, any action brought against the BMJ and Mr Deer in London would have been immediately vulnerable to being struck out as an abuse of process.

Despite the findings of the GMC’s Fitness to Practice Panel and his co-authors having publicly retracted the causation interpretation put forward by the Lancet Paper, it would appear from the Claim filed at court that Mr Wakefield still stands by the accuracy of the Lancet paper and his conclusion therein, thereby compounding his previously found misconduct. While we await formal service, unsurprisingly the BMJ and Mr Deer standby the material published in the BMJ and their other statements and confirm that they have instructed lawyers to defend the claim vigorously.

NOTES TO EDITORS

1. The Lancet Paper was published on 23 February 1998 entitled “Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children”. Its claims of a temporal association between MMR vaccine and autism were retracted by the authors (excluding Mr Wakefield) on 6 March 2004, following the first findings from Brian Deer’s investigation for The Sunday Times. The paper was retracted in its entirety by the Lancet on 2 February 2010, with the Lancet noting that elements of the paper “have been proven to be false” during hearings of a General Medical Council fitness to practise panel.

2. Following a 217-day investigation by the GMC’s panel, on 24 May 2010, the panel found Mr Wakefield guilty of serious professional misconduct. It found that Mr Wakefield “had a clear and compelling duty to ensure that the factual information contained in the [Lancet] paper was true and accurate and he failed in this duty”. The Panel also found that Mr Wakefield was intentionally dishonest and misleading in describing the patient population, and that he had been dishonest when questioned about it later. Similarly, the panel stated that “the description of the referral process was irresponsible, misleading, and in breach of [Mr] Wakefield s duty as a senior author”. The Determination also set out how Mr Wakefield compounded his misconduct by failing to correct the content of the paper.

3. As a result of Mr Wakefield’s “persistent lack of insight” into his behaviour, the GMC determined that his name should be erased from the medical register.

4. Mr Wakefield adduced no evidence in mitigation and made no arguments or pleas in mitigation in front of the Fitness to Practice panel. He did not appeal its decision and has not attempted to replicate the Lancet paper’s findings in order to attempt to vindicate his position.

5. At various times in the past, Mr Wakefield has brought claims and made complaints against Mr Deer, The Sunday Times, Channel Four and Twenty Twenty Productions in respect of allegations of dishonesty relating to his Lancet paper. In no case has he been successful. Indeed, in each instance the case has been dropped by Mr Wakefield. In Wakefield v Channel Four Television Corporation, Twenty Twenty Productions Ltd and Brian Deer [2005] EWHC 2410 (QB) Mr Justice Eady refused to grant a stay sought by Mr Wakefield, stating that the case would turn on fundamentally serious issues going to the heart of the Claimant s honesty and professional integrity.

In refusing the stay, Eady J considered Mr Wakefield’s conduct in relation to the various proceedings he had brought. He noted that Mr Wakefield had written to a number of other organisations including: the Cambridge Evening News; Evan Harris (an MP who criticised Mr Wakefield on a radio programme); and the Department of Health (which provided a link on its website to the Channel Four Dispatches website).

Mr Wakefield informed these entities in correspondence that he had issued proceedings against The Sunday Times, Mr Deer and/ or Channel Four, indicating that proceedings were ongoing. He made no mention of the stays which he had obtained, or was seeking. Eady J considered this misleading, and concluded that Mr Wakefield wished to use the existence of the libel proceedings for public relations purposes, and to deter critics, while at the same time isolating himself from the downside of such litigation, in having to answer a substantial defence of justification. The Judge believed that there was a pattern of using the existence of libel proceedings, albeit stayed, as a tool for stifling further criticism or debate.

6. On 2O December 2011, the BMJ’s solicitors, Farrer & Co, wrote to Mr Wakefield’s Texan lawyers setting out the matters referred to above, as well as other points. No response has been received.

7. Mr Wakefield’s allegations, that the MMR vaccines causes or contributes to autism, were investigated in three test cases in the United States Court of Federal Claims, heard from July 2007 and with judgments handed down on 12 February 2009. Although listed as a witness, Mr Wakefield was not called to give evidence, and his allegations were rejected. The judgments were upheld on appeal. In the lead case, Cedillo v Secretary for Health and Human Services, Special Master George Hastings said in his judgment with regard to evidence in the case: “Therefore, it is a noteworthy point that not only has that autistic enterocolitis theory not been accepted into gastroenterology textbooks, but that theory, and [Mr] Wakefield s role in its development, have been strongly criticized as constituting defective or fraudulent science.”

Simons Foundation: Notable papers of 2011

5 Jan

The Simons Foundation has an article discussing their choices of Notable papers of 2011. Below are their choices and links to the Simons Foundation blog (SFARI) articles which discuss them. Also given are links to pubmed for the original research articles.

Study finds high rate of autism in South Korea
Pubmed

Family sequencing study boosts two-hit model of autism
Pubmed

Networks of genes altered in autism brains, study says
Pubmed

Studies find high rate of rare new mutations in autism
Pubmed
Pubmed
Pubmed

Protein networks link different forms of autism, study says
Pubmed

Experts critique statistics, conclusion of autism twin study
Pubmed

Large study finds ‘baby sibs’ at high risk of autism
Pubmed

Autism tests struggle to balance accuracy and speed
Pubmed

Tuberous sclerosis, fragile X may be molecular opposites
Pubmed

Neurons made from stem cells reveal cellular flaws in autism
Pubmed

Autism Speaks: Top Ten Autism Research Achievements of 2011

5 Jan

Autism Speaks has a list of Top Ten Autism Research Achievements of 2011. Here is their list (which they state is not in an order of importance) with links to their articles discussing them:

It’s More than Just Genes…
Population Screening Reveals Dramatically Higher Autism Rates…
Baby Siblings at Risk…
De Novo Genetic Changes Provide New Clues for Autism…
Different Forms of Autism Share Striking Brain Similarities…
Prenatal Vitamins Before and After Conception May Decrease Autism Risk…
Gene Knockout Mouse May Offer Leap Forward in Autism Animal Models…
Tweaking Electrical Activity in the Brain Impairs & Restores Mouse Social Behaviors…
More Evidence Linking Immune System to Some Forms of Autism…
Earlier Autism Screening Shows Promise…

NIMH’s Top 10 Research Advances of 2011

5 Jan

Below is a blog post, NIMH’s Top 10 Research Advances of 2011, from the blog of Tom Insel, director of the National Institute of Mental Health (NIMH) in the U.S..

Tom Insel is the chair of the Interagency Autism Coordinating Committee (IACC), which creates the Strategic Plan for autism research funded by the U.S. government.

It is very interesting to see how often autism research is noted in the list below.

Item 3: Ricardo Dolmetsch’s work using stem cells to study autism and Timothy syndrome. (discussed here on Left Brain/Right Brain)

Item 4: De Novo Genetic Variants and autism

Item 8: NDAR, the National Database for Autism Research

and

Item 10: Public Private Partnerships.

At NIMH and in our broad research community, this has been a year of exciting discoveries and scientific progress, as we strive to make a difference for those with mental illness. Here are 10 breakthroughs and events of 2011 that are changing the landscape of mental health research.
1. Complexity: Discovering New Sources of Genetic Variance.

The discovery of two new sources of genetic variation may have an enormous impact on mental health research.

Students in “Genetics 101” learn that messenger RNA precisely mirrors the DNA sequence from which it was transcribed. However, recent studies suggest a far more complex transmission of information. NIMH-funded researchers compared corresponding RNA and DNA sequences in 27 individuals, and found more than 10,000 sequence sites where the RNA and DNA of the same individual did not match (1). These RNA-DNA mismatches were found in multiple study participants and in different types of cells, including brain and skin cells.
Another study presents what may be the most extraordinary discovery of 2011: somatic ‘retrotransposition’ can alter brain tissue (2). Retrotransposons are mobile genetic elements that can copy and insert themselves within a genome causing mutations in dividing cells. Although these insertions rarely lead to harmful effects when they occur in germ line cells (sperm and egg), they are frequently harmful if they occur in somatic cells, such as neurons. While nearly all studies of the genetics of mental illness have focused on germ line DNA, this new discovery suggests that DNA variation occurring in the developing brain could contribute to mental illness, just as mutations in mature tissues contribute to cancer. These surprising findings suggest a whole new frontier for the biology of mental illness.

2. Transcriptome: Developing Brains Have Unique Molecular Signatures.

Messenger RNAs, or transcripts, are intermediate products that carry the message from DNA, the genetic blueprint, to create proteins, and ultimately, the many different cell types throughout the brain. Each gene can make several transcripts, which are expressed in patterns unique to each of us. To better understand how these patterns of gene expression influence the developing brain, NIMH supported the first map of how RNA expression changes across the life span through two parallel studies of postmortem brains, ranging in age from two weeks after conception to 80 years old (3, 4). The researchers found that nearly 90% of genes are expressed differently during prenatal development, infancy, and childhood. While each of these stages has a distinct transcriptional identity, the fetal brain looks like a different organ compared to the postnatal brain, with 60% of genes expressed differently and 83% of transcripts processed to make unique proteins. Many of the genetic variations associated with mental illness appear to have a specific effect on the form of the gene expressed uniquely during fetal life.
3. Induced Pluripotent Stem Cells: Disease in a Dish.

In 2011, induced pluripotent stem cells (iPSCs) enabled a new round of findings on anomalies in neurodevelopment underlying disorders of mental health. The technology permits scientists to take adult cells and reprogram them to have the capabilities of stem cells to divide and differentiate into specific cell types. Growing iPSCs from adults with diagnosed disorders permits direct observation in cell culture of how the development of neurons is altered in these disorders from the very earliest stages. Scientists studying cells from patients with Timothy syndrome, a condition in which children often show autism-like symptoms, and Fragile X syndrome, an inherited cause of intellectual disability, found the kinds of changes in developing neurons that would disrupt their ability to form normal neural networks and tissues (5, 6). Strikingly, observations of iPSCs derived from patients with schizophrenia showed changes in neurons at stages that would correspond to very early development, years before symptoms emerge (7, 8). These reprogrammed cells also offer a means of medications testing; in these studies, scientists were able to observe the effects of medications in cells from patients with Timothy syndrome and schizophrenia.
4. De Novo Genetic Variants.

This year scientists looking at families with only one case of autism found that up to eight percent of cases in these families were the result of de novo (unique to the person affected) copy-number variants—stretches of DNA that were either multiplied or truncated (9, 10). Analysis of the gene regions affected by these variants implicated a network of genes involved in the development of synapses and neuronal function (11). Another study, focusing specifically on sequences of DNA that code for protein, yielded other de novo genetic changes in one-case families (12). While providing information on genetic contributors to a significant fraction of sporadic autism cases, the work also reveals gene regions for future investigation and ultimately, information on functional changes underlying autism that will offer clues to therapy.
5. Epigenomics: How Experience Alters Behavior.

In any one individual, patterns of gene expression vary widely among cells, leading to a diversity of cell types and functions, even though the cells all have the same DNA sequence. Epigenetic processes—heritable changes in gene expression that are not related to DNA sequence—help explain this diversity. Research suggests that epigenetics may also be a sort of programming language through which experience can have lasting effects on behavior, not only in an individual over a lifetime, but across generations. This effect was demonstrated in a 2011 study of male mice exposed to social defeat—repeated bullying by another aggressive male (13). The bullied males developed behavior resembling depression, and in subtle ways, so did their offspring. This was true even though contact between mother and bullied father was brief and took place well before the birth of the young, suggesting that epigenetic mechanisms played a role. Understanding the nature of epigenetic changes opens possibilities for therapy; scientists also showed this year that they could reverse the silencing of a gene involved in a rare neurodevelopmental disorder, a proof of concept for interventions targeting epigenetic processes (14).
6. Grand Challenges in Global Mental Health.

Mental, neurological, and substance use (MNS) disorders account for 13% of the global burden of disease, more than cancer and cardiovascular disease (15). The Grand Challenges in Global Mental Health initiative, led and funded by NIMH, assembled the largest ever international Delphi panel—over 400 participants representing work conducted in 60 countries—to determine priorities for research relevant to MNS disorders (16). The initiative convened an international community of research funders, engaged them in the consensus-building process, and has already resulted in a $20 million (Canadian) commitment to fund research targeting one Challenge. To date, the Grand Challenges have served as a resource for organizations and governments as they select policy and mental health services priorities. Moreover, the Grand Challenges come at a time of increasing recognition of the economic costs of mental illness (17) and the importance of including mental health in global health care (18, 19).
7. Precision Medicine.

In most fields of medicine, focusing on clinical symptoms is no longer adequate for diagnosis. In line with the National Academy of Sciences’ call for the development of a new nosology based on multiple levels of analysis across medicine, NIMH continues to advance the Research Domain Criteria (RDoC) project. Aiming to define basic dimensions of functioning, from genes to neural circuits to behaviors, RDoC will cut across traditional disorder definitions and facilitate rapid progress in basic neurobiological and behavioral research. In psychiatry, as in other fields of medicine, such an integrated understanding of the foundations of mental disorders may lead the development of new or more personalized treatments.
8. NDAR.

For those familiar with the National Database for Autism Research (NDAR) and its mission to accelerate discovery in autism research, the naming of this resource as one of the top three HHS Secretary’s picks in the HHSinnovates program this fall was well-deserved recognition. As the largest database of its kind to date, NDAR provides approved users with simultaneous access to an unprecedented amount of autism research data, tools, and related resources, drawing on records directly submitted to NDAR as well as from four partner databases—the Autism Speaks’ Autism Genetic Resource Exchange (AGRE) and Autism Tissue Program, the Kennedy Krieger Institute’s Interactive Autism Network (IAN), and the NIH Pediatric MRI Data Repository. Approved NDAR users will have access to data from the 25,000 research participants represented in NDAR, as well as 2,500 AGRE families and more than 7,500 participants who reported their own information to IAN. In the two years since its launch, NDAR has managed to set a new standard for data sharing and collaborative research, not only for autism, but other fields as well.
9. New Culture of Discovery: Team Science.

In an age when events in one country can inspire and incite action in another, so too has global research become a more interconnected and collaborative community. Last year, we saw this with the 1000 Connectomes project, which collected resting state fMRI maps of the brain from over 1000 people around the world and made these results broadly accessible via the Neuroimaging Informatics Tools and Resources Clearinghouse (NITRC). This year, we saw this cultural shift toward team science when the Psychiatric Genomic Consortium reported on genetic variants associated with bipolar disorder and schizophrenia based on over 100,000 samples collected from 200 scientists in 65 institutions and 19 countries. Moreover, 2011 was the year when “standardization, integration, and data sharing” became a mantra for all science at NIMH, ensuring that results from individual labs could be leveraged by the global scientific community.
10. Public Private Partnerships.

As the pharmaceutical industry withdrew from psychiatric medication research and development this year, several new public-private efforts began to re-define the pathway for discovering new treatments. Arch2POCM, a public-private partnership comprising academic, industry, and regulatory scientists and clinicians, created a “precompetitive” initiative, free of intellectual property, for identifying new medications for schizophrenia and autism (20). One Mind for Research grew out of Patrick Kennedy’s moonshot for the mind, building an umbrella organization for neuroscience research related to all brain diseases. The Critical Path Institute led the way with common data elements for clinical research and new tools to promote data sharing. In addition, the Biomarkers Consortium brought industry, advocates, FDA, and NIH together to define biomarkers for neuropsychiatric diseases.
References

(1) Li M, Wang IX, Li Y, Bruzel A, Richards AL, Toung JM, Cheung VG. Widespread RNA and DNA sequence differences in the human transcriptome. Science. 2011 Jul 1;333(6038):53-8.

(2) Baillie JK, Barnett MW, Upton KR, Gerhardt DJ, Richmond TA, De Sapio F, Brennan PM, Rizzu P, Smith S, Fell M, Talbot RT, Gustincich S, Freeman TC, Mattick JS, Hume DA, Heutink P, Carninci P, Jeddeloh JA, Faulkner GJ. Somatic retrotransposition alters the genetic landscape of the human brain. Nature. 2011 Oct 30;479(7374):534-7.

(3) Colantuoni C, Lipska BK, Ye T, Hyde TM, Tao R, Leek JT, Colantuoni EA, Elkahloun AG, Herman MM, Weinberger DR, Kleinman JE. Temporal dynamics and genetic control of transcription in the human prefrontal cortex. Nature. 2011 Oct 26;478(7370):519-23.

(4) Kang HJ, Kawasawa1YI, Cheng F, Zhu Y, Xu X, Li M, Sousa1 AMM, Pletikos M, Meyer KA, Sedmak G, Guennel G, Shin Y, Johnson MB, Krsnik Z, Fertuzinhos MS, Umlauf S, Lisgo SN, Vortmeyer A, Weinberger DR, Mane S, Hyde TM, Huttner A, Reimers M, Kleinman JE, Šestan N. Spatio-temporal transcriptome of the human brain. Nature. 2011 Oct 26;478(7370):483-9.

(5) Pasca SP, Portmann T, Voineagu I, Yazawa M, Shcheglovitov O, Pasca AM, Cord B, Palmer TD, Chikahisa S, Seiji N, Bernstein JA, Hallmayer J, Geschwind DH, Dolmetsch RE. Using iPS cell-derived neurons to uncover cellular phenotypes associated with Timothy Syndrome. Nature Medicine. 2011 Nov 27;17(12):1657-62.

(6) Sheridan, SD, Theriault, KM, Reis, SA, Zhou, F, Madison, JM, Daheron, L, Loring, JF, Haggarty, SJ Epigenetic characterization of the FMR1 gene and aberrant neurodevelopment in human induced pluripotent stem cell models of fragile X syndrome. PLoS ONE 2011 Oct;6:e26203.

(7) Brennand, KJ, Simone, A, Jou, J, Gelboin-Burkhart, C, Tran, N, Sangar, S, Li, Y, Mu, Y, Chen, G, Yu, D, McCarthy, S, Sebat, J, Gage, FH. Modelling schizophrenia using human induced pluripotent stem cells. Nature. 2011 May 12;473(7346):221-5.

(8) Chiang, C-H, Su, Y, Wen, Z, Yoritomo, N, Ross, CA, Margolis, RL, Song, H, and Ming, G-I. Integration-free induced pluripotent stem cells derived from schizophrenia patients with a DISC1 mutation. Molecular Psychiatry 2011 Apr;16:358-360.

(9) Levy D, Ronemus M, Yamrom B, et al. Rare de novo and transmitted copy?number variation in autistic spectrum disorders. Neuron. 2011 Jun 9;70(5):886?97.

(10) Sanders SJ, Ercan?Sencicek AG, Hus V, et al. Multiple recurrent de novo CNVs, including duplications of the 7q11.23 Williams syndrome region, are strongly associated with autism. Neuron 2011 Jun 9;70(5):863?85.

(11 )Gilman SR, Iossifov I, Levy D, et al. Rare de novo variants associated with autism implicate a large functional network of genes involved in formation and function of synapses. Neuron. 2011 Jun 9;70(5):898?907.

(12) O’Roak BJ, Deriziotis P, Lee C, et al. Exome sequencing in sporadic autism spectrum disorders identified severe de novo mutations. Nat Genet. 2011 Jun;43(6):585?9.

(13) Dietz, D.M., LaPlant, Q., Watts, E.L., Hodes, G.E., Russo, S.J., Feng, J., Oosting, R.S., Vialou, V., and Nestler, E.J. Paternal transmission of stress-induced pathologies. Biological Psychiatry 2011 Sep 1;70:408-414.

(14) Huang, H.-S., Allen, J., Mabb, A., King, I., Miriyala, J., Taylor-Blake, B., Sciaky, N., Dutton, J. Jr., Lee, H.M., Chen, X., Jin, J. Bridges, A., Zylka, M., Roth, B., Philpot, B. Topoisomerase inhibitors unsilence the dormant allele of Ube3a in neurons. Nature. Published online ahead of print December 21, 2011, doi: 10.1038/nature10726.

(15) World Health Organization. The Global Burden of Disease: 2004 Update (WHO, 2008).

(16) Collins PY, Patel V, Joestl SS, March D, Insel TR, Daar AS et al. Grand challenges in global mental health. Nature. 2011 Jul 6;475(7354):27-30.

(17) Bloom DE, Cafiero ET, Jané-Llopis E, Abrahams-Gessel S, Bloom LR, Fathima S, Feigl AB, Gaziano T, Mowafi M, Pandya A, Prettner K, Rosenberg L, Seligman B, Stein A, Weinstein C. The Global Economic Burden of Non-communicable Diseases. Geneva, Switzerland: World Economic Forum, 2011

(18) Eaton J, McCay L, Semrau M, Chatterjee S, Baingana F, Araya R, Ntulo C, Thornicroft G, Saxena S. Scale up of services for mental health in low-income and middle-income countries. Lancet. 2011 Oct 29;378(9802):1592-603.

(19) Raviola G, Becker AE, Farmer P. A global scope for global health–including mental health. Lancet. 2011 Nov 5;378(9803):1613-5.

(20) Norman T, Edwards A, Bountra C, Friend S. The Precompetitive Space: Time to Move the Yardsticks. Science Translational Medicine. 2011 March: 3(76): 76cm10.

Andrew Wakefield takes to the courts again

5 Jan

Andrew Wakefield, one of the doctors who was stricken from the register by the U.K.’s General Medical Council, has filed a complaint in Texas claiming that Brian Deer (Journalist) and Fiona Godlee (Editor of the British Medical Journal). The complaint alleges that the articles, editorials and statements made later about those include “false and defamatory allegations” about Mr. Wakefield.

From the complaint filed:

This defamation lawsuit arises, in part, out of the publication on or about January 5, 2011 and thereafter, in the British Medical Journal, of an article authored for the BMJ by Brian Deer, titled Secrets of the MMR Scare (Exhibit A) and accompanying editorials by the BMJ’s editor, Fiona Godlee (Exhibit B 1-2). Defendants’ article and editorials, distributed to subscribers in Texas and which fonn the basis of Plaintiffs claims, contained unfair, incorrect, inaccurate and unjust criticisms of findings previously reported by Dr. Wakefield and 12 other co-authors. More significantly, Defendants accused Dr. Wakefield of fraud and of fraudulently and intentionally manipulating and falsifying data and diagnoses in connection with a clinical paper he co-authored called Ileal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children, originally published in the medical journal The Lancet in 1998 (the “Lance,t Paper”). Defendants’ false and defamatory allegations have been widely disseminated by Defendants through the BMJ and other sources since their original publication.

Mr. Wakefield sued Mr. Deer in the past, but dropped that suit.

Mr. Wakefield’s legal team consists of William M. Parrish, J.D. Ellwanger, John D. Saba Jr of DiNovo Price Ellwanger & Hardy LLP, a firm which primarily focused on intellectual property and commercial litigation.

Mr. Wakefield does not specify an amount for damages:

Dr. Wakefield hereby prays for a trial by jury as to all disputed issues of fact, and upon findings appropriate, further prays for judgment from this Court against the Defendants for: nominal damages, actual and compensatory damages, special damages, including injury to reputation and character, injury to feelings, humiliation, loss of earning capacity, exemplary damages pursuant to TEX. CIv. PRAC. & REM. CODE §41.001, et. seq., declaratory relief, costs and expenses, prejudgment and post-judgment interest as allowed by law, and for such other and further relief to which he may be justly entitled.

Should this go to court, Mr. Wakefield, In arguing a “injury to reputation and character, injury to feelings, humiliation, loss of earning capacity, will have to quantify the state of his reputation and character, feelings, humiliation and loss of earning capacity at the time. This will have to take into account the fact that he had already been struck off the medical register in the UK after being found to have committed “serious professional misconduct” and had lost his job at Thoughtful House. Were the donors to the “Strategic Autism Initiative” less likely to contribute after the BMJ articles?

Honestly, I thought the Andrew Wakefield saga was over and I was glad of it.

Michele Bachman drops out of race for U.S. President

4 Jan

Yesterday was the first contest in the primary race for president here in the U.S: the Iowa Caucuses Michele Bachmann placed 6th in her bid for the republican party nomination with 5% of the vote. Today she announced that she is pulling out of the race.

Ms. Bachmann came into the discussion here on Left Brain/Right Brain after her claim that the HPV vaccine causes mental retardation. Even though she had no real evidence to back up her claims, she stood by them. Her comments received even more publicity when a bioethicist put up a $10,000 prize should she produce the evidence she claimed she had. After all this she did finally try to distance herself from that mistake three months later. As one might imagine, she became a favorite of groups who promote the idea that vaccines caused an autism epidemic.

While I doubt her vaccine comment was the prime reason she failed in her bid, it is being cited as one of her major mistakes. On Politico, it even rises to being #3 on top 10 misstatements of the GOP primary.

On an encouraging side note. In some discussions in the press, Ms. Bachmann is noted as having received criticism from the “autism community”. From Politico:

Leaving aside the fact that the terminology has long been outdated to describe people with developmental disabilities, Bachmann’s claim immediately drew fire from vaccination advocates, medical groups and the autism community.

With luck we can leave behind the legacy of the “autism community” being the promoters of bad information about vaccines.

Oxidative Stress and Down Syndrome: A Route toward Alzheimer-Like Dementia

30 Dec

A recent paper on Down Syndrome and dementia shows some similarities to some recent trends in autism research. Beyond that, it points out the type of knowledge that is missing about autistic adults. The type of research which begs the question of why there is relatively little effort ongoing into autistic adults.

Oxidative Stress and Down Syndrome: A Route toward Alzheimer-Like Dementia (abstract at the bottom of this article) is a review paper which seeks to explore if there is evidence for oxidative stress and mitochondrial dysfunction in the development of Alzheimer-like dementia.

Based on the abstract this doesn’t appear to be a very impressive paper. But it reminds one of the fact that in Down Syndrome there are health issues which result in reduced life expectancy. One of these health issues is Alzheimer’s disease:

People with Down syndrome, also called trisomy 21, develop a syndrome of dementia that has the same characteristics of Alzheimer’s disease that occurs in individuals without Down syndrome. The only difference is that Alzheimer’s disease occurs much earlier in people with Down syndrome; patients with Down syndrome begin to have symptoms in their late 40s or early 50s.

Most (and maybe all) people with Down syndrome develop the brain changes associated with Alzheimer’s disease. However, Alzheimer’s disease is not more common in individuals with intellectual disabilities from causes other than Down syndrome. An estimated 10%-25% of patients with Down syndrome have Alzheimer’s disease at age 40-49 years, 20%-50% have Alzheimer’s disease at age 50-59 years, and 60%-75% have Alzheimer’s disease when older than 60 years of age. Alzheimer’s disease decreases survival in people with Down syndrome who are older than 45 years of age.

Much effort and discussion goes into the question of medical concerns in autistic children (for example, gastro-intestinal complaints). Are there any medical concerns which are more common in autistic adults than in the general population? There are two ways to find out. (1) Identify and study autistic adults now. (2) Wait 50 years or so for this generation of children to age. It would seem clear that (2) would be the less desirable choice.

Here is the abstract for the paper, Oxidative Stress and Down Syndrome: A Route toward Alzheimer-Like Dementia:

Oxidative Stress and Down Syndrome: A Route toward Alzheimer-Like Dementia.

Perluigi M, Butterfield DA.
Source

Department of Biochemical Sciences, Faculty of Pharmacy and Medicine, Sapienza University of Rome 00185 Rome, Italy.

Abstract

Down syndrome (DS) is one of the most frequent genetic abnormalities characterized by multiple pathological phenotypes. Indeed, currently life expectancy and quality of life for DS patients have improved, although with increasing age pathological dysfunctions are exacerbated and intellectual disability may lead to the development of Alzheimer’s type dementia (AD). The neuropathology of DS is complex and includes the development of AD by middle age, altered free radical metabolism, and impaired mitochondrial function, both of which contribute to neuronal degeneration. Understanding the molecular basis that drives the development of AD is an intense field of research. Our laboratories are interested in understanding the role of oxidative stress as link between DS and AD. This review examines the current literature that showed oxidative damage in DS by identifying putative molecular pathways that play a central role in the neurodegenerative processes. In addition, considering the role of mitochondrial dysfunction in neurodegenerative phenomena, results demonstrating the involvement of impaired mitochondria in DS pathology could contribute a direct link between normal aging and development of AD-like dementia in DS patients.

Los Angeles Times: Discovering Autism

23 Dec

The Los Angeles Times produced a series of articles called “Discovering Autism”. The series is in four parts and represents was researched for years. The articles are:

Autism boom: an epidemic of disease or of discovery?
Autism rates have increased twentyfold in a generation, stirring parents’ deepest fears and prompting a search for answers. But what if the upsurge is not what it appears to be?

Warrior parents fare best in securing autism services
Public spending on children with autism in California varies greatly by race and class. A major reason: Not all families have the means to battle for coveted assistance.

Families cling to hope of autism ‘recovery’
An autism treatment called applied behavior analysis, or ABA, has wide support and has grown into a profitable business. It has its limits, though, and there are gaps in the science.

Autism hidden in plain sight
As more children are diagnosed with autism, researchers are trying to find unrecognized cases of the disorder in adults. The search for the missing millions is just beginning.

The first article brought a great deal of criticism, from many quarters. As you can imagine challenging the way the “autism epidemic” is viewed is not welcomed by those promoting vaccines as a primary cause of autism. This article also brought out at least one commenter who asserted that the rise in autism diagnoses is driven by people seeking social security payments (SSI), which goes to show that readers tend to bring their own preconceptions to what they read.

Interest in the online discussion of the series dropped off dramatically after day one.

Autism boom: an epidemic of disease or of discovery? looked at the rise in autism diagnoses observed in many places. Writer Alan Zarembo points out quite rightly that autism rates vary dramatically by school district in California, as well as state to state.

Such variability of autism rates across geography speak strongly against the idea of a single cause, such as vaccines. Autism Diva wrote about the strong variation by regional center district within California years ago (her piece is not up, but this article from LBRB discusses her article)

The variation by school district and by race/ethnicity was a major factor in helping me see that the vaccine-epidemic of autism did not make sense, back when I first started to read up on autism.

The LA Times quotes Prof. Peter Bearman of Columbia University, who studied the California Department of Developmental Services data closely and showed, amongst other things, that a large autism “cluster” existed in Southern California. The Times notes that similar clusters were found by U.C. Davis Professor Irva Hertz-Picciotto. (I was present when Autism Diva discussed the regional center graph with Prof. Hertz-Picciotto, by the way).

Prof. Bearman also showed that social forces were at work–awareness, if you will–which has aided the increase in autism diagnoses.

In other words, autism is not contagious, but the diagnosis is.

“`Is it real or not?’ is a meaningless question,” Bearman said of the surge in cases. “The sociological processes are as real as the biological processes.”

A diagnostician (neurologist) is quoted in the Times:

Dr. Nancy Niparko, a child neurologist in Beverly Hills, said that whether she identifies a child as autistic can come down to whether she believes it will do any good.

“If it’s going to improve the possibility of getting services that will be helpful, I will give the label,” she said.

“I don’t work for labels. Labels work for me.”

In Warrior parents fare best in securing autism services makes the point that it takes work, hard work, to get the services that a child may need. An autism diagnosis is not a ticket to services, it is a first step. Parents who fight harder and longer tend to get higher levels of services for their children.

The Times points out that within a single district (albeit one of the largest in the U.S., Los Angeles Unified), the fraction of students with 1:1 aides varies by geography and race/ethnicity:

District officials acknowledge that advocacy efforts make a big difference in who gets services, but see things differently than parents on the value of 1:1 aides:

L.A. Unified officials offered a similar explanation for the disparity. As parents successfully lobbied for outside aides, the idea spread, and in certain schools it became standard practice to offer them.

“Parents learned from each other,” said Nancy Franklin, a top special education administrator. “It became a cottage industry in LAUSD.”

The district is trying to break the pattern by persuading parents that its own staff can meet children’s needs in many cases.

“We’re paying lots of money for services that are of questionable value,” said Eileen Skone-Rees, who oversees the district’s contracts with companies that supply one-on-one aides.

In Families cling to hope of autism ‘recovery’, the Times focuses on ABA. Biomedical approaches are not really discussed.

The article talks about ABA from the early work of Ivar Lovaas to the present day, where it is common in some school districts and regional centers. The high costs and the level of research support are discussed along with examples of children who are success stories and those who are not.

In Autism hidden in plain sight, the Times looks at how autism is often missed in adults.

The Times presents an intriguing look at the past in medical records from a child diagnosed by Leo Kanner (whose work coined the term “autism”).

The times provided a number of slide show vignettes of people they interviewed.

I can’t link to them directly, but I’ve watched a few and enjoyed them. Jeane Duquet, autistic adult diagnosed at age 39 (right side, middle). Jesse Castillo, age 11 (bottom right corner)

The author of the series, as well as Catherine Lord were interviewed by NPR:

http://www.npr.org/v2/?i=144022386&m=144022377&t=audiowidth=”400″ height=”446″ />

I would certainly have done some things differently had I written the series. I would have chosen different wording, for example. Yes, the pieces brought out some less than pleasant perspectives. I’ve read a few complaints about the series, from not supporting vaccine causation or biomedical approaches to presenting autism as a costly burden. Ironically, these complaints come from the same people who repeatedly say that “autism costs society $3.5 million per individual”. A big piece of that $3.5M is ABA and if we as a community (or part of the community) are to defend the need for ABA, we have to accept that there is a cost. I believe, and I commented, that the choice of language at times put a negative slant where one was not needed. However, the series put some very good information out, including: 1) the “epidemic” has a large portion which is driven by social factors, with a much smaller part that may be a real change in the number of autistics, 2) services are not handed out on a silver platter. Parents and autistics have to fight for what supports the law says they should get, 3) 1:1 therapies such as ABA may be effective, but they are expensive and the research behind them is still incomplete and 4) adult autistics are out there in greater numbers than is currently reported.

The biggest complaint about the series is that it portrays parents as seeking diagnoses for their kids for some sort of financial gain. Dr. Jay Gordon (a major promoter of the vaccine-epidemic idea) has noted this where Mr. Zarembo has been interviewed (http://www.scpr.org/programs/patt-morrison/2011/12/22/21866/autism-diagnoses-spike-an-epidemic-in-the-making). Mr. Zarembo makes it clear in the interview that this is not his point. That the autism diagnosis “opens the door” and that parents are doing what they should for their children–including fighting hard to obtain appropriate services once the door is opened.

For those complaining that the LA Times series didn’t cover the vaccine-epidemic idea or biomedical approaches to autism: I’d recommend you be thankful. Quite frankly an evidence driven newspaper series on these issues will not go the way you want.

← Older Entries
Newer Entries →