We’ve had a lot of discussion on Dr. Wakefield and his retracted paper. But seeing the actual paper with big red letters saying “RETRACTED” was something I was waiting for. I thought others might like to see it as well.
So, here is the first page of Dr. Wakefield’s article as it appears now.
This paper has caused so much harm in the autism communities. Too bad it won’t go to rest quietly.
The Interagency Autism Coordinating Committee (IACC) has posted the revised “Strategic Plan“. This is the document which is supposed to guide US Government funded autism research.
The Strategic Plan is written from a parent’s perspective. It is divided into 7 questions to be answered. Below I list the parts I think are the “meat” of the Plan–the proposed projects with estimated budgets.
In a very quick skim through the budget, I get 7 projects on environmental causes or gene-environment causes, with budgets totaling nearly $200M. Keep that in mind when people say there is no “environmental” research in the Plan.
There are a lot of new projects. My quick sum gives about $64M in projects for question 6 “What Does the Future Hold, Particularly for Adults?” I This is, to me, the most important part of the Plan.
Question 1: When Should I Be Concerned?
Short-Term Objectives
1. Develop, with existing tools, at least one efficient diagnostic instrument (e.g., briefer, less time intensive) that is valid in diverse populations for use in large-scale studies by 2011. IACC Recommended Budget: $5,300,000 over 2 years.
2. Validate and improve the sensitivity and specificity of new or existing screening and diagnostic tools, including comparison of general developmental screening versus autism-specific screening tools, in both high risk and population-based samples through studies of the following community populations that are diverse in terms of age, socio-economic status, race, ethnicity, characteristics of ASD, and general level of functioning by 2012. IACC Recommended Budget: $5,400,000 over 3 years.
3. New objective
Conduct at least three studies to identify reasons for the health disparities in accessing early screening and diagnosis services by 2012. IACC Recommended Budget: $2,000,000 over 2 years.
4. New objective
Conduct at least two studies to understand the impact of early diagnosis on choice of intervention and outcomes by 2015. IACC Recommended Budget: $6,000,000 over 5 years.Long-Term Objectives
1. Identify behavioral and biological markers that separately, or in combination, accurately identify, before age 2, one or more subtypes of children at risk for developing ASD by 2014. IACC Recommended Budget: $33,300,000 over 5 years.
2. Develop at least five measures of behavioral and/or biological heterogeneity in children or adults with ASD, beyond variation in intellectual disability, that clearly relate to etiology and risk, treatment response and/or outcome by 2015. IACC Recommended Budget: $71,100,000 over 5 years.
3. Identify and develop measures to assess at least three “continuous dimensions” (i.e., social reciprocity, communication disorders, and repetitive/restrictive behaviors) of ASD symptoms and severity that can be used by practitioners and/or families to assess response to intervention for people with ASD across the lifespan by 2016. IACC Recommended Budget: $18,500,000 over 5 years.
Question 2: How Can I Understand What Is Happening?
Short-Term Objectives
1. Support at least four research projects to identify mechanisms of metabolic and/or immune system interactions with the central nervous system that may underlie the development of ASD during prenatal-postnatal life by 2010. IACC Recommended Budget: $9,800,000 over 4 years.
2. Launch three studies that specifically focus on the neurodevelopment of females with ASD, spanning basic to clinical research on sex differences by 2011. IACC Recommended Budget: $8,900,000 over 5 years.
3. Identify ways to increase awareness among the autism spectrum community of the potential value of brain and tissue donation to further basic research by 2011. IACC Recommended Budget: $1,400,000 over 2 years.
4. New objective
Launch three studies that target improved understanding of the underlying biological pathways of genetic conditions related to autism (e.g. Fragile X, Rett syndrome, tuberous sclerosis complex) and how these conditions inform risk assessment and individualized intervention by 2012. IACC Recommended Budget: $9,000,000 over 5 years.
5. New objective
Launch three studies that target the underlying biological mechanisms of co-occurring conditions with autism including seizures/epilepsy, sleep disorders and familial autoimmune disorders by 2012. IACC Recommended Budget: $9,000,000 over 5 years.
6. New objective
Launch two studies that focus on prospective characterization of children with reported regression, to investigate potential risk factors by 2012. IACC Recommended Budget: $4,500,000 over 5 years.
7. New objective
Support five studies that associate specific genotypes with functional or structural phenotypes, including behavioral and medical phenotypes (e.g., nonverbal individuals with ASD and those with cognitive impairments) by 2015. IACC Recommended Budget: $22,600,000 over 5 years.Long-Term Objectives
1. Complete a large-scale, multi-disciplinary, collaborative project that longitudinally and comprehensively examines how the biological, clinical, and developmental profiles of individuals, with a special emphasis on females, youths, and adults with ASD, change over time as compared to typically developing people by 2020. IACC Recommended Budget: $126,200,000 over 12 years.
2. New objective
Launch at least three studies which evaluate the applicability of ASD phenotype and/or biological signature findings for performing diagnosis, risk assessment, or clinical intervention by 2015. IACC Recommended Budget: $7,200,000 over 5 years.
Question 3: What Caused This To Happen And Can This Be Prevented?
Short-Term Objectives
1. Coordinate and implement the inclusion of approximately 20,000 subjects for genome-wide association studies, as well as a sample of 1,200 for sequencing studies to examine more than 50 candidate genes by 2011. Studies should investigate factors contributing to phenotypic variation across individuals that share an identified genetic variant and stratify subjects according to behavioral, cognitive, and clinical features. IACC Recommended Budget: $43,700,000 over 4 years.
2. Within the highest priority categories of exposures for ASD, identify and standardize at least three measures for identifying markers of environmental exposure in biospecimens by 2011. IACC Recommended Budget: $3,500,000 over 3 years.
3. Initiate efforts to expand existing large case-control and other studies to enhance capabilities for targeted gene – environment research by 2011. IACC Recommended Budget: $27,800,000 over 5 years.
4. Enhance existing case-control studies to enroll racially and ethnically diverse populations affected by ASD by 2011. IACC Recommended Budget: $3,300,000 over 5 years.
5. New objective
Support at least two studies to determine if there are subpopulations that are more susceptible to environmental exposures (e.g., immune challenges related to infections, vaccinations, or underlying autoimmune problems) by 2012. IACC Recommended Budget: $8,000,000 over 2 years.
6. New objective
Initiate studies on at least 10 environmental factors identified in the recommendations from the 2007 IOM report “Autism and the Environment: Challenges and Opportunities for Research” as potential causes of ASD by 2012. Estimated cost $56,000,000 over 2 years.
Long-Term Objectives1. Conduct a multi-site study of the subsequent pregnancies of 1,000 women with a child with ASD to assess the impact of environmental factors in a period most relevant to the progression of ASD by 2014. IACC Recommended Budget: $11,100,000 over 5 years.
2. Identify genetic risk factors in at least 50% of people with ASD by 2014. IACC Recommended Budget: $33,900,000 over 6 years.
3. Determine the effect of at least five environmental factors on the risk for subtypes of ASD in the pre- and early postnatal period of development by 2015. IACC Recommended Budget: $25,100,000 over 7 years.
4. Support ancillary studies within one or more large-scale, population-based surveillance and epidemiological studies, including U.S. populations, to collect data on environmental factors during preconception, and during prenatal and early postnatal development, as well as genetic data, that could be pooled (as needed), to analyze targets for potential gene/environment interactions by 2015. IACC Recommended Budget: $44,400,000 over 5 years.
Question 4: Which Treatments and Interventions will Help?
Short-Term Objectives
1. Support at least three randomized controlled trials that address co-occurring medical conditions associated with ASD by 2010. IACC Recommended Budget: $13,400,000 over 3 years.
2. Standardize and validate at least 20 model systems (e.g. cellular and/or animal) that replicate features of ASD and will allow identification of specific molecular targets or neural circuits amenable to existing or new interventions by 2012. IACC Recommended Budget: $75,000,000 over 5 years.
3. Test safety and efficacy of at least five widely used interventions (e.g., nutrition, medications, assisted technologies, sensory integration, medical procedures) that have not been rigorously studied for use in ASD by 2012. IACC Recommended Budget: $27,800,000 over 5 years.
4. Complete two multi-site randomized controlled trials of comprehensive early intervention that address core symptoms, family functioning and community involvement by 2013. IACC Recommended Budget: $16,700,000 over 5 years.
5. New objective
Convene a workshop to advance the understanding of clinical subtypes and treatment personalization (i.e. what are the core symptoms to target for treatment studies) by 2011. IACC Recommended Budget: $50,000.
6. New objective
Launch five randomized controlled trials of interventions including biological signatures and other measures to predict response, and monitor quality of life and functional outcomes, in each of the following groups:* Five trials in infants and toddlers by 2013. IACC Recommended Budget: $30,000,000 over 5 years.
* Three randomized controlled trials of interventions for school-aged children and/or adolescents by 2013. IACC Recommended Budget: $18,000,000 over 5 years.
* Three trials for adults by 2014.IACC Recommended Budget: $18,000,000 over 5 years.Long-Term Objectives
1. Complete at least three randomized controlled trials on medications targeting core symptoms in people with ASD of all ages by 2014. IACC Recommended Budget: $22,200,000 over 5 years.
2. Develop interventions for siblings of people with ASD with the goal of reducing risk recurrence by at least 30% by 2014. IACC Recommended Budget: $6,700,000 over 5 years.
3. New objective
Conduct at least one study to evaluate the safety and effectiveness of medications commonly used in the treatment of co-occurring conditions or specific behavioral issues in people with ASD by 2015. IACC Recommended Budget: $10,000,000 over 5 years.
Question 5: Where Can I Turn for Services?
Short-Term Objectives
1. Support two studies that assess how variations and access to services affect family functioning in diverse populations, including underserved populations, by 2012. IACC Recommended Budget: $1,000,000 over 3 years.
2. New objective
Conduct one study to examine how self-directed community-based services and supports impact children, youth, and adults with ASD across the spectrum by 2014. IACC Recommended Budget: $6,000,000 over 3 years.
3. New objective
Implement and evaluate two models of policy and practice-level coordination among state and local agencies to provide integrated and comprehensive community-based supports and services that enhance access to services and supports, self-determination, economic self-sufficiency, and quality of life for people with ASD across the spectrum and their families, with at least one project aimed at the needs of transitioning youth by 2015. IACC Recommended Budget: $10,000,000 over 5 years.Long-Term Objectives
1. Test four methods to improve dissemination, implementation, and sustainability of evidence-based interventions, services, and supports in diverse community settings by 2013. IACC Recommended Budget: $7,000,000 over 5 years.
2. Test the efficacy and cost-effectiveness of at least four evidence-based services and supports for people with ASD across the spectrum and of all ages living in community settings by 2015. IACC Recommended Budget: $16,700,000 over 5 years.
3. New objective
Evaluate new and existing pre-service and in-service training to increaseskill levels in service providers, including direct support workers, parents and legal guardians, education staff, and public service workers to benefit the spectrum of people with ASD and promote interdisciplinary practice by 2015. IACC Recommended Budget: $8,000,000 over 5 years.
Question 6: What Does the Future Hold, Particularly for Adults?
Short-Term Objectives
1. New objective
Launch at least two studies to assess and characterize variation in the quality of life for adults on the ASD spectrum as it relates to characteristics of the service delivery system (e.g., safety, integrated employment, post-secondary educational opportunities, community inclusion, self-determination, relationships, and access to health services and community-based services) and determine best practices by 2012. IACC Recommended Budget: $5,000,000 over 3 years.
2. New objective
Evaluate at least one model, at the state and local level, in which existing programs to assist people with disabilities (e.g., Social Security Administration, Rehabilitation Services Administration) meet the needs of transitioning youth and adults with ASD by 2013. IACC Recommended Budget: $5,000,000 over 3 years.
3. New objective
Develop one method to identify adults across the ASD spectrum who may not be diagnosed, or are misdiagnosed, to support service linkage, better understand prevalence, track outcomes, with consideration of ethical issues (insurance, employment, stigma) by 2015. IACC Recommended Budget: $8,400,000 over 5 years.
4. New objective
Conduct at least one study to measure and improve the quality of life-long supports being delivered in community settings to adults across the spectrum with ASD through provision of specialized training for direct care staff, parents, and legal guardians, including assessment and development of ASD-specific training, if necessary, by 2015. IACC Recommended Budget: $7,500,000 over 5 years.
Long-Term Objectives
1. New objective
Develop at least two individualized community-based interventions that improve quality of life or health outcomes for the spectrum of adults with ASD by 2015. IACC Recommended Budget: $12,900,000 over 5 years.
2. New objective
Conduct one study that builds on carefully characterized cohorts of children and youth with ASD to determine how interventions, services, and supports delivered during childhood impact adult health and quality of life outcomes by 2015. IACC Recommended Budget: $5,000,000 over 5 years.
3. New objective
Conduct comparative effectiveness research that includes a cost-effectiveness component to examine community-based interventions, services and supports to improve health outcomes and quality of life for adults on the ASD spectrum over age 21 by 2018. IACC Recommended Budget: $6,000,000 over 5 years.
4. New objective
Conduct implementation research to test the results from comparative effectiveness research in real-world settings including a cost-effectiveness component to improve health outcomes and quality of life for adults on the ASD spectrum over age 21 by 2023. IACC Recommended Budget: $4,000,000 over 5 years.
Question 7: What other Infrastructure and Surveillance Needs Must be Met?
Short-Term and Long-Term Objectives
1. Conduct a needs assessment to determine how to merge or link administrative and/or surveillance databases that allow for tracking the involvement of people living with ASD in healthcare, education and social services by 2009 . IACC Recommended Budget: $520,000 over 1 year.
2. Conduct an annual “State of the States” assessment of existing state programs and supports for people and families living with ASD by 2009. IACC Recommended Budget: $300,000 each year.
3. Develop and have available to the research community means by which to merge or link databases that allow for tracking the involvement of people in ASD research by 2010. IACC Recommended Budget: $1,300,000 over 2 years.
4. Establish and maintain an international network of biobanks for the collection of brain, fibroblasts for pluripotent stem cells, and other tissue or biological material, by acquisition sites that use standardized protocols for phenotyping, collection, and regulated distribution of limited samples by 2011. This includes developing fibroblast repositories to produce pluripotent stem cells. Protocols should be put into place to expand the capacities of ongoing large-scale children’s studies to collect and store additional biomaterials, promoting detection of biological signatures. IACC Recommended Budget for establishing biobanks by 2011: $10,500,000 over 2 years. IACC Recommended Budget for maintaining biobanks: $22,200,000 over 5 years.
5. New objective
Begin development of a web-based toolbox to assist researchers in effectively and responsibly disseminating their finding to the community, including people with ASD, their families, and health practitioners by 2011. IACC Recommended Budget: $400,000 over 2 years.
6. New objective
Create funding mechanisms that encourage rapid replication studies of novel or critical findings by 2011.
7. New objective
Develop a web-based tool which provides population estimates of ASD prevalence for states based on the most recent prevalence range and average identified by the ADDM Network by 2012. IACC Budget Recommendations: $200,000 over 2 years.
8. New objective
Create mechanisms to specifically support the contribution of data from 90 percent of newly initiated projects to the National Database for Autism Research (NDAR) and link NDAR with other existing data resources by 2012. IACC Recommended Budget: $6,800,000 over 2 years.
9. New objective
Supplement existing ADDM Network sites to use population-based surveillance data to conduct at least 5 hypothesis-driven analyses evaluating factors that may contribute to changes in ASD prevalence by 2012. IACC Recommended Budget: $660,000 over 2 years.
10. New objective
Develop the personnel and technical infrastructure to assist states, territories, and other countries who request assistance describing and investigating potential changes in the prevalence of ASD and other developmental disabilities by 2013. IACC Recommended Budget: $1,650,000 over 3 years.
11. New objective
Encourage programs and funding mechanisms that expand the research workforce, enhance interdisciplinary research training, and recruit early career scientists into the ASD field by 2013. IACC Recommended Budget: $5,000,000 over 3 years.
12. New objective
Expand the number of ADDM sites in order to conduct ASD surveillance in younger and older age groups; conduct complementary direct screening to inform completeness of ongoing surveillance; and expand efforts to include autism subtypes by 2015. IACC Recommended Budget: $16,200,000 over 5 years.
13. New objective
Support 10 “Promising Practices” papers that describe innovative and successful services and supports being implemented in communities that benefit the full spectrum of people with ASD, which can be replicated in other communities by 2015. IACC Recommended Budget: $75,000 over 5 years.
OK, we might as well get this over with–here are the times the Plan mentions the “V” word:
Numerous epidemiological studies have found no relationship between ASD and vaccines containing the mercury based preservative, thimerosal (Immunization Safety Review Committee, 2004). These data, as well as subsequent research, indicate that the link between autism and vaccines is unsupported by the epidemiological research literature. However, the IOM report acknowledged that the existing population-based studies were limited in their ability to detect small susceptible subpopulations that could be more genetically vulnerable to environmental exposures.
and
Of note, the Committee receives many public comments that reflect concerns about vaccines as a potential environmental factor in autism. Some members of the public are convinced that the current data are sufficient to demonstrate that vaccines do not play a causal role in autism and argue against using limited autism research funds to do additional vaccine studies when many other scientific avenues remain to be explored. At the same time, those who believe that prior studies of the possible role of vaccines in ASD have been insufficient argue that investigation of a possible vaccine/ASD link should be a high priority for research (e.g., a large-scale study comparing vaccinated and unvaccinated groups). A third view urges shifting focus away from vaccines and onto much-needed attention toward the development of effective treatments, services and supports for those with ASD.
and
To address public concerns regarding a possible vaccine/ASD link, it will be important for the IACC to continue to coordinate with the National Vaccine Advisory Committee (NVAC), a Federal advisory committee chartered to advise and make recommendations regarding the National Vaccine Program.
under research opportunities:
Monitor the scientific literature regarding possible associations of vaccines and other environmental factors (e.g., ultrasound, pesticides, pollutants) with ASD to identify emerging opportunities for research and indicated studies.
There closest thing to an actual proposed project (i.e. something with an estimated budget) is this one:
# New objective
Support at least two studies to determine if there are subpopulations that are more susceptible to environmental exposures (e.g., immune challenges related to infections, vaccinations, or underlying autoimmune problems) by 2012. IACC Recommended Budget: $8,000,000 over 2 years.)
I should stop being shocked and amazed at how little groups like the Age of Autism blog think of their readership. Sorry to put it so bluntly, but it is pretty clear that they expect us all to just read what they have to say and never go to the original sources and think for ourselves.
Case in point, the GMC hearing on Dr. Andrew Wakefield. Dr. Wakefield was guilty of ethical violations in the treatment of his disabled patients. Not once, not twice but many many times. But you wouldn’t know that to read some of the reports on the blogs and even a couple in newspapers.
We have the NAA SafeMinds and TACA telling us all about how bad this ruling is. We have been told that there was “false testimony”.
OK, take a look at the actual charges. Just for a moment. Here are a few examples
1) Dr. Wakefield took money from the Legal Aid Board (LAB) for procedures paid by the NHS. He then diverted some of the LAB money to other projects.
2) Dr. Wakefield got ethical permission to do his study in December 1996, only on patients enrolled after that date. However, he had already started research on children. Here are two examples:
Child 2 had an MRI, colonoscopy and lumbar puncture in September of 1996.
Child 1 was also a research subject without ethical approval. Tests were performed which were not in the clinical interests of the child.
3) For people who promote the myth that “the only thing he did was start early”, note that Dr. Wakefield’s team did invasive tests that were not called for. For example:
Child 3 was also a research subject without ethical approval, having started before the approval. He underwent a lumbar puncture even though: “The Panel has taken into account the fact that there is no evidence in Child 3’s clinical notes to indicate that a lumbar puncture was required.”
Was this the result of some “false testimony? According to the GMC ruling, experts on both sides stated that the lumbar puncture was not clinically indicated.
Experts on both sides, Professor Rutter and Dr Thomas both considered that such a test was not clinically indicated.
Dr. Thomas is not accused by the defenders of Wakefield as “giving false testimony”.
The above are only a few of the examples of clear misconduct on the part of Dr. Wakefield.
How many times must a man be found guilty of not doing what was in his patients’ clinical interests before we are allowed to consider him as, well, someone who doesn’t always put his patient’s clinical interests first?
Kim Stagliano has taken to the Huffington Post with “The Censorship of Autism Treatment“. No mention of the actual charges. No mention of the fact that Andrew Wakefield was guilty. No mention of the fact that Andrew Wakefield’s research efforts for the past 12 years have centered on repairing his own damaged reputation, not on autism treatment.
Can you find a single mention of the word “ethics” in her post? How about any comment about the actual charges levied against Dr. Wakefield?
You know you are in trouble just with the title from this story: MMR doc’s just guilty of caring . At least that article makes one clear statement:
It [the GMC ruling] focused on the methods of research used, some of which were undoubtedly questionable, but which were performed in the name of finding solace for desperate parents convinced their children had changed for ever following their one-size-fits-all MMR injection.
Yes, you can be unethical if you are “finding solace for desperate parents”.
A blog post by the National Autism Association stated:
“Many parents of children with autism view the GMC investigation as little more than character assassination of a physician brave enough to investigate controversial issues”
Well, not this parent. Anyone who paints the GMC investigation as “character assassination” didn’t read the ruling. Seriously, trying to dismiss this fact-filled ruling as “character assassination” is just plain bizarre.
another post comments, discussing the work Dr. Wakefield’s team performed on his study subjects:
the procedures involved were routine
and
No children were harmed and no parent or guardian has complained about the care these three men provided.
Lumbar punctures are hardly “routine”. Further, there is no reason to do them if not clinically indicated. Colonoscopies are not routine, especially in patients whose symptoms don’t warrant them. Say, as in Child 1.
One child suffered a perforated bowel (in 12 places!). His family won a lawsuit against the Royal Free hospital.
High Court papers alleged that the colonoscopy procedure performed on Jack in 1998 was ‘not clinically indicated or justified’. They also claimed the ‘principal reason’ for the surgery was to further research into links between autism and bowel conditions rather than Jack’s clinical needs.
How does that not count as not “harmed”? Is it because he wasn’t one of the original 12 from the study in The Lancet?
The behavior of the Wakefield supporters is totally predictable. They have no science. They have no first (or second) tier researchers. They rely heavily on Dr. Wakefield. Who else has the perceived stature of Dr. Wakefield for them? When Brian Deer broke the story that Dr. Wakefield may have “fixed” data in his study last year, there was an immediate reaction from the Wakefield supporters: give him faux awards! Make him the keynote speaker at their conventions!
For the past year the message has been “Dr. Wakefield has not been discredited”. They’ve lost that now.
We’ve been warned that they are bringing out their big guns. Yes, David Kirby will blog about this on the Huffington Post. With apologies to Mr. Kirby, but when he’s their “ace in the hole”, you know they don’t have much.
As I finished this, David Kirby came up with his post: “The Lancet Retraction Changes Nothing”. Joining in the style of the times, Mr. Kirby also ignores the actual GMC ruling. Nothing that actually defends Dr. Wakefield against the real charges.
Seriously, go read for yourself. It’s David Kirby with his usual talking points and straw men.
I hope David Kirby is wrong. I hope that things have changed. I hope that the future is a world where the loudest voices in the autism communities fight for a better life for autistics, rather than for a political goal of recognition for bad science, badly done.
I hope.
The subject of twins and autism concordance comes up on LeftBrainRightBrain periodically. I find the questions raised to be very interesting and I’ve said a number of times I hope people take a closer look at twins.
Enter Dr. Antonio Hardan of the Lucile Packard Children’s Hospital (LPCH) at Stanford University in California. Dr. Hardan is a Child Psychiatrist with much experience in exploring brain structure in autistics. Yesterday there was a press release (which I can’t find now) calling for subjects for a twin study. The announcement is on the LPCH website.
Stanford/Packard autism researchers seek twins for brain-imaging study
Autism researchers at the Stanford University School of Medicine are recruiting twins for an investigation of the role of genetics in shaping the autistic brain.
“We’re doing a twin study to try to sort the impact of genetics on brain abnormalities in autism from the impact of the environment,” said lead scientist Antonio Hardan, MD, who is a child psychiatrist at Lucile Packard Children’s Hospital and associate professor of psychiatry and behavioral sciences at Stanford. Hardan’s team will use magnetic resonance imaging to scan the brains of 120 pairs of twins, some with autism and some without, to look for gene-brain associations.
Previous research has indicated about 75 to 80 percent of autism is explained by genetics, Hardan said. This means that if one member of a pair of identical twins has autism, the other will usually be affected. Having a fraternal (non-identical) twin or other sibling with autism raises a child’s likelihood of an autism diagnosis, but not as much.
Still, no one knows the degree to which genetic factors explain distinct structural and chemical characteristics in the brains of autistic individuals, which may include differences in total brain size and in the corpus callosum and amygdala.
Hardan’s research team will compare the level of similarity in brain structures of identical twins, who share all their genes, with the brain similarities of fraternal twins, who share half of their genes. They will also compare pairs of twins with autism with typically developing (non-autistic) twins to gain insight into which developmental patterns are distinct to autism. They then hope to figure out whether and to what degree there is a correlation between genetic profiles and the brain metabolites and structures of people with autism.
The team is seeking same-sex twin pairs aged 3 to 14. Study subjects can be identical or non-identical twins. The scientists plan to scan 80 pairs in which one or both twins have autism, and 40 typically developing pairs in which neither twin has autism. The scanning method, MRI, is non-invasive and does not involve any radiation exposure. All subjects will also receive standard cognitive and IQ assessments, as well as a battery of diagnostic tests for autism.
Testing will take four to five hours over two consecutive days, and each twin who completes the testing will be compensated $100. Subjects will receive summaries of their cognitive testing results, and confirmation of whether they are identical or fraternal twins. The twins’ families will also be compensated for travel expenses to and from Stanford.
“The scientific value of the study is a major one,” Hardan concluded. “We don’t know how much is inherited in terms of specific brain abnormalities in autism, and we also need to learn more about how environmental factors play into the development of the autistic brain. This study will help us gain that understanding.”
Hardan’s collaborators on the study include Joachim Hallmayer, MD, associate professor of psychiatry and behavioral sciences, and Allan Reiss, MD, professor of psychiatry and behavioral sciences and of radiology. Reiss also directs the Center for Interdisciplinary Brain Sciences Research at Stanford and practices as a child psychiatrist at Packard Children’s.
To obtain more information or volunteer for the trial, contact the study coordinator, Sue Cleveland, at (650) 723-7809 or cleve@stanford.edu.
There is some interesting research already on twins. One study (I only have the abstract so far) just came out last year: Gyrification patterns in monozygotic twin pairs varying in discordance for autism.
Kates WR, Ikuta I, Burnette CP.
Department of Psychiatry and Behavioral Sciences, State University of New York at Upstate Medical University, Syracuse, New York 13210, USA. katesw@upstate.edu
In order to disentangle genetic and environmental contributions to cortical anomalies in children with autism, we investigated cortical folding patterns in a cohort of 14 monozygotic (MZ) twin pairs who displayed a range of phenotypic discordance for autism, and 14 typically developing community controls. Cortical folding was assessed with the gyrification index, which was calculated on high resolution anatomic MR images. We found that the cortical folding patterns across most lobar regions of the cerebral cortex was highly discordant within MZ twin pairs. In addition, children with autism and their co-twins exhibited increased cortical folding in the right parietal lobe, relative to age- and gender-matched typical developing children. Increased folding in the right parietal lobe was associated with more symptoms of autism for co-twins. Finally, the robust association between cortical folding and IQ observed in typical children was not observed in either children with autism or their co-twins. These findings, which contribute to our understanding of the limits of genetic liability in autism, suggest that anomalies in the structural integrity of the cortex in this PDD may disrupt the association between cortical folding and intelligence that has been reported in typical individuals, and may account, in part, for the deficits in visual spatial attention and in social cognition that have been reported in children with autism.
I find this to be rather interesting. “We found that the cortical folding patterns across most lobar regions of the cerebral cortex was highly discordant within MZ twin pairs.” In other words, the physical brain structure is different within “identical” twin pairs. Recall the twin pairs in this study “displayed a range of phenotypic discordance for autism”. It is hard for me to simplify that without oversimplification, but the twins do not have the same autistic traits, and perhaps differing ASD diagnoses.
There is also an earlier study by Dr. Hardan and colleagues that seems relevant, even though it is not a twin study: Increased frontal cortical folding in autism: a preliminary MRI study.
Hardan AY, Jou RJ, Keshavan MS, Varma R, Minshew NJ.
Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA. hardanay@upmc.edu
The gyrification index (GI), the ratio of total to outer cortical contour, was applied to measure the cerebral folding patterns in autism. GI was examined on a frontal coronal slice obtained from MRI scans of 30 nonmentally retarded individuals with autism and 32 matched healthy controls. In the autistic group, left frontal GI was higher in children and adolescents but not in adults. Cortical folding was decreased bilaterally with age in the total autistic sample but not in controls. These preliminary findings suggest that the gyrification patterns in autism may be abnormal, which could be related to the various cortical anomalies observed in this disorder.
Below is an image from the Hardan study. The “gyrification ratio” is a measure of the inner contour to the outer contour.
Manually traced inner and outer cortical contours used for measuring the gyrification index.
The results of the Hardan study were “preliminary”, and there was a statistically significant difference observed in those measurements. What was observed was “Interestingly, there was a significant decrease in the frontal gyrification patterns with age in the autistic group (right side: r=?0.44, P=0.012; left side: r=?0.48, P=0.006), which was not seen in controls (right side: r=?0.12, P=0.51; left side: r=?0.065, P=0.72). ”
I find this interesting–the GI (consider it the “folding” in the brain) differs by age for the autistics but not for the controls.
Again, I find the proposed twin study to be interesting and potentially very valuable. I hope Dr. Hardan can find enough study subjects to complete the study. There probably are not a lot of parents of autistic twins who live near Stanford reading this blog, but who knows?
Following the judgment of the UK General Medical Council’s Fitness to Practise Panel on Jan 28, 2010, it has become clear that several elements of the 1998 paper by Wakefield et al1 are incorrect, contrary to the findings of an earlier investigation.2 In particular, the claims in the original paper that children were “consecutively referred” and that investigations were “approved” by the local ethics committee have been proven to be false. Therefore we fully retract this paper from the published record.
So Andrew Wakefield has been found proved guilty of the vast majority of the accusations against him and been found dishonest and acting irresponsibly with both the children under his ‘care’ and the not inconsiderable sums of public money he had occassion to recieve and ‘manage’.
None of this would have come as a surprise to anyone who had taken the time to carefully read Brian Deer’s thorough works on the subject. That it was a major shock to the John Stone’s and Martin Walker’s of this world tells you more about their capacity for self delusion than how shocking the findings regarding Wakefield were.
So whats next for Andrew Wakefield? Now that the official findings have been made public, the GMC must consider:
…whether those facts found proved or admitted, were insufficient to amount to a finding of serious professional misconduct. The Panel concluded that these findings, which include those of dishonesty and misleading conduct, would not be insufficient to support a finding of serious professional misconduct.
Yeah, pointless double speak aside (would not be insufficient??) the panel are basically saying that Andrew Wakefield’s behaviour could easily constitute serious professional misconduct.
So what can result from that? Brian Deer, writing in the Times Online provides a possible answer:
Lawyers have told me that any one of the more than 30 charges that were proved against Wakefield would typically lead to his being struck off. His days as a medical practitioner will soon be history…
And so what is the next step?
In the next session, commencing 7 April 2010, the Panel, under Rule 28, will hear evidence to be adduced and submissions from prosecution counsel then Dr Wakefield’s own counsel as to whether the facts as found proved do amount to
serious professional misconduct, and if so, what sanction, if any, should be imposed on his registration.
From April 7th then Andrew Wakefield will be fighting for the right to refer to himself and be referred to by others as ‘Doctor’. That will be a victory for anyone concerned with patient care in the UK.
Apart from people who have boosted Andrew Wakefield’s discredited and dishonest wild theories about MMR vaccine over the years (Lucy Johnston, Melanie Phillips, Fiona Phillips et al), one journalist will forever be associated with Wakefield: Brian Deer.
Brian Deer is no shill for the pharmaceutical industry. Back in the 90s he tackled the harms of Septrin (a widely prescribed antibiotic), and later went on to tackle Merck over Vioxx. Brian has pursued Wakefield in the same way as he carried out his investigations of “big pharma”. Not that this has protected him from allegations about his motivations, his detractors being unable to accept that a journalist might investigate the Wakefield hoax without help from “big pharma” or a conspiring UK government. Melanie Phillips alleged he was part of a witch hunt, although she was incorrect. Last year, the increasing lunatic fringe of the UK’s anti-vaccine movement alleged Brian’s sexuality was the reason for his investigative reporting:
By all accounts a gay man and therefore unlikely ever to have to face the multiple vaccine risk agonised over by parents from around the world in relation to their children, Brian Deer has made it his business to portray the parents of these autistic vaccine damaged children as deluded mendacious chancers.
We now know that the man with callous disregard for children’s welfare was the man they have supported; Andrew Wakefield. He had a financial conflict of interest. He treated children unethically. He exposed children to “high-risk” procedures without ethical approval and against their best clinical interests [Here’s an example of what can happen].
Brian was also subjected to a libel action brought against him by Wakefield, the current toy of the rich (Wakefield leads a comfortable life in Texas now, working at a quack treatment centre for £170,000 a year). In an article at the Sunday Times today, Deer talks of the benefits of exposing Wakefield.
Wakefield will probably never admit to his errors. But exposing his methods has been worthwhile, according to medical sources.
“People can’t understand whether a scientific study is valid or invalid,” said a senior doctor who had watched vaccination rates slump, even in the face of endless research on MMR safety. “But they can understand ‘right’ and ‘wrong’, and they can understand ‘honest’ and ‘dishonest’.”
Lawyers have told me that any one of the more than 30 charges that were proved against Wakefield would typically lead to his being struck off. His days as a medical practitioner will soon be history. A further hearing will determine whether “serious professional misconduct” was committed.
Yet more troubling for Wakefield’s future are his prospects for research, or at least of getting it published.
“Any journal to which a researcher shown to be dishonest submitted a paper would reject it,” said Richard Smith, former editor of the British Medical Journal, this weekend. “They would say, ‘This man can’t be trusted’. His career as a researcher is effectively over.”
On the latter point, I’m not so sure. His days as a real researcher are over, but he and his friends already have a plan to tackle that obstacle.
I had a strong feeling that an article by Brian Deer would appear in today’s Sunday Times. Brian Deer has followed the story of Dr. Andrew Wakefield closer than anyone, uncovering much of what has now brought the doctor one step away from being struck off the register in the U.K.. So, I was not surprised when I found ‘Callous, unethical and dishonest’: Dr Andrew Wakefield on the Sunday Times’ website.
The article describes the events as the GMC decision was read out. Brian Deer was there, Andrew Wakefield was not.
Dr. Wakefield was found guilty on multiple counts, but the most important from my perspective:
Other proven charges included nine of mistreating developmentally challenged children: causing invasive “high-risk” research to be carried out without ethical approval and against their best clinical interests.
Mr. Deer points out that this ls likely the end of Dr. Wakefield’s career as a researcher. Well, yes and no. I think his career as a mainstream researcher was over years ago. But, as a contributor (and editor) to the world of third-tier research, he appears to be moving ahead.
Based on previous public statements by Mr. Deer, I am hopeful that more articles delving into the details of the research Dr. Wakefield performed at the Royal Free Hospital are forthcoming.
The double standards applied by the autism alternative medicine community never cease to amaze me. Typically they do a game of “six degrees of separation” with any one they disagree with. Do you have ties to anyone who has worked on vaccines? Do you have ties to anyone who knows anyone who might have worked with a governmental agency? Well, if so, anything you say is ignored as biased.
Funny that no one took a good look at the Journal that the recent “confirmation” of Dr. Wakefield’s research was published in. The alt-med community doesn’t question research they like.
Confused? Here’s the back story. A recent article was published Clinical presentation and Histologic Findings at Ileocolonoscopy in Children with Autistic spectrum Disorder and Chronic Gastrointestinal symptoms in a journal called “Autism Insights”. The paper came out the day before the decision from the GMC on Dr. Wakefield. The paper was touted as “Wakefield’s Science Proven Valid Again In New Study That Replicates Findings” in a blog post (guess where?)
Have you ever heard of “Autism Insights“? Neither had I. Don’t feel bad. Unless you read one of the two other articles published in that “journal”, you couldn’t have heard of it.
Yes, two other articles. One is an editorial.
This new article brings the total published in “Autism Insights” to 3.
The first:
Trends in Developmental, Behavioral and Somatic Factors by Diagnostic Sub-group in Pervasive Developmental Disorders: A Follow-up Analysis
Authors: Paul Whiteley, Lynda Todd, Kalliopi Dodou and Paul Shattock
Then an editorial:
Autism Etiology: Genes and the Environment
Authors: A.J. Russo
and now
Clinical Presentation and Histologic Findings at Ileocolonoscopy in Children with Autistic Spectrum Disorder and Chronic Gastrointestinal Symptoms
Authors: Arthur Krigsman, Marvin Boris, Alan Goldblatt and Carol Stott
Yep, that’s it. The entire production of “Autism Insights” is two papers and one editorial.
So far, every paper has had an author on the journal’s editorial board.
Take a look at the Editorial Board. This paper, timed to come out exactly when Dr. Wakefield needed good press has no fewer than four people from Dr. Wakefield’s own clinic, ThoughtfulHouse.
Bryan Jepson, MD
Director of Medical Services, Medical Center at Thoughtful House Center for Children, Austin, TX, USAArthur Krigsman, MD
Director of Gastrointestinal Services, Pediatric Gastroenterology, Thoughtful House Cener for Children, Austin, TX, USACarol Mary Stott, PhD
Senior Research Associate, Research Department, Thoughtful House, Austin, TX, USAAndrew Wakefield, MBBS, FRCS, FRCPath
Research Director, THoughtful House Centre for Children, Austin, TX, USA
There are prominent DAN doctors, Richard Deth, and others from the alt-med community on the editorial board as well.
Come on guys. Is this really the standard of science that is acceptable to support Dr. Wakefield?
As an aside, a year or so back I emailed some friends with a speculation that the alt-med community would create their own journal. As far as predictions go, this wasn’t really a longshot. Still, it is interesting to see the prediction come true.
As to the paper itself? I’ll only say a few brief words as it really isn’t worth the time.
1) I recall in the Omnibus hearings that many of the GI “findings” claimed by the petitioners were found to be misinterpretations by the experts who reviewed them
2) No one has ever said that autistic kids are somehow immune from GI complaints, including inflammation.
3) There are multiple details where, even if correct, this research is very dissimilar from that of Dr. Wakefield’s original Lancet paper and later work.
It is too bad that these researchers chose to make clinical findings into what amounts to a political statement of support for Dr. Wakefield. If there is any valuable information gained from these children, I don’t see how this paper respects their contribution.
edit to add: I forgot to acknowledge that this post came from a tip from Prometheus at the Photon in the Darkness blog.
One question that has been actively discussed here on LeftBrainRightBrain is whether Dr. Wakefield’s patent covered the use of his “transfer factor” as a preventive vaccine against measles. This is important because it would indicate an undisclosed conflict of interest.
One of the charges the General Medical Council investigated had to do with a proposed company to work on the “transfer factor” that Dr. Wakefield was a co-inventor on (i.e. Dr. Wakefield was one of the inventors on the patent). A proposal was submitted to the Royal Free Hospital (Dr. Wakefield’s employer) about the possible company. The proposal was drafted by “Mr 10”, the father of child 10 in the Lancet study.
That Lancet paper was published on February 28th, 1998. The proposal was submitted to the Royal Free on March 4th, 1998.
The “transfer factor” is discussed in charge #40. Subsection f of charge 40 discusses the company. I quote the GMC charge sheet as it stood last week, before the decisions were handed down.
f. A proposal, dated 4 March 1998 and drafted by Mr 10, was submitted to the Royal Free Hospital School of Medicine in relation to the proposed company,
Admitted and found provedi. seeking funding for a clinical trial of Transfer Factor in the treatment of Inflammatory Bowel Disease, and Pervasive Developmental Disorder, and for research into using Transfer Factor as an alternative measles specific vaccine,
Admitted and found proved with the exception of the words ‘an alternative’
So, you can see that a company proposal was submitted (admitted and found proved). Further, in sub-subsection “i” of subsection “f” (complicated, isn’t it?), you see that there was a charge that the “Transfer Factor” could be used as “an alternative measles vaccine”. Dr. Wakefield admitted to this with the exception of the words ‘an alternative’. This is consistent with his public statements (e.g. on Dateline) that the vaccine was a treatment only.
Here is how that section reads today, in the GMC ruling. Note the final paragraph which was added for the ruling.
f. A proposal, dated 4 March 1998 and drafted by Mr 10, was submitted to the Royal Free Hospital School of Medicine in relation to the proposed company,
Admitted and found proved
i. seeking funding for a clinical trial of Transfer Factor in the treatment of Inflammatory Bowel Disease, and Pervasive Developmental Disorder, and for research into using Transfer Factor as an alternative measles specific vaccine,
Admitted and found proved with the exception of the words‘an alternative’
Found proved in respect of the words “an alternative” on the basis of the proposal referred to above in 40.f. where it states, “The company will also investigate the potential of Transfer Factors as vaccine alternatives.”
Yes, the GMC ruled that the company proposal showed that the intent was to “…for research into using Transfer Factor as an alternative measles specific vaccine”.
In other words, the GMC appears to accept that, in addition to the use of the transfer factor as a “theraputic agent”, there was an intent to investigate the potential for the transfer factor as “vaccine alternatives”. I hope the full document is made public so we can see this sentence in full context.
As recent as last year, on Dateline, Dr. Wakefield steadfastly denied that his patent and plans had anything to do with a measles vaccine. Below is that clip.
Here is Brian Deer discussing the patent activities with Matt Lauer:
I wonder if Mr. Lauer’s reporting would differ, now that the existence of the company proposal is made public. It appears clear from this proposal demonstrate that Dr. Wakefield and his colleagues (Mr. 10 and whoever else was going to be in the company) had the intent to investigate the “transfer factor” as a vaccine alternative. This proposal was submitted a few days after the Lancet article was published, and after the news conference. I don’t see that excusing not informing the public of the potential commercial interests.
The GMC ruling states:
At or around the same time as the events set out at paragraphs
40.a.and 40.b., you were involved in a proposal to set up a company called Immunospecifics Biotechnologies Ltd to specialise in the production, formulation and sale of Transfer Factor,
(amended) Admitted and found proved with the exception of ‘40.a.’
Note that paragraph 40b describes events of February 2, well before the publication of the Lancet Article and the press conference. I.e. the intent to form a company dates from before the study became public.
I am left wondering how “The company will also investigate the potential of Transfer Factors as vaccine alternatives” can be interpreted differently than how the GMC has read it.
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