Archive | Ian Lipkin RSS feed for this section

Criminal Charges Dropped Against Chronic Fatigue Syndrome Researcher Judy Mikovits

15 Jun XMRV

Science Insider has been reporting on the research and, well, drama surrounding the idea that XMRV (Xenotropic murine leukemia virus-related virus) and its proposed link to chronic fatigue syndrome.

XMRV has also been proposed as being linked to autism.

This research came out of the Whitemore Peterson Institute (WPI) and former WPI research Judy Mikovits.

There has been a lot of controversy over the research (for example, Science retracting one paper) as well as Ms. Mikovits. Judy Mikovits was let go from WPI and later charged with having materials removed from the institute. Charges around that have been dropped , but a civil case is still active.

Last November, the district attorney in Washoe County, Nevada, filed a criminal complaint against Mikovits that charged the virologist with illegally taking computer data and related property from her former employer, the Whittemore Peterson Institute for Neuro-Immune Disease (WPI) in Reno, Nevada. In a separate civil court that month, WPI filed suit against Mikovits over her alleged possession of similar material, which included the laboratory notebooks she compiled while doing the CFS research.

On 11 June, the district attorney’s office for Washoe County filed a petition to dismiss the criminal charges against Mikovits without prejudice (which means they can file a related complaint in the future), a clerk to the Justice Court of Reno told ScienceInsider.

Ms. Mikovits joined the team of Ian Lipkin who is part of the multi-site team investigating the proposed XMRV/CFS link:

Mikovits told ScienceInsider that the only work she has been able to find has been collaborating on a large study funded by the National Institutes of Health that should be the final word on the otherwise dismissed theory that CFS is linked to a mouse retrovirus, XMRV, or its relatives. “Everyone who wanted to work with me was deterred by the threat of litigation,” Mikovits wrote in an e-mail.

The results of the large study, led by Ian Lipkin of Columbia University, are expected to be revealed in the next few weeks.

The proposed XMRV/autism link was made public before any scientific results were made available. However, two papers have been published since that news broke pointing away from an XMRV/autism link

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

and

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

The Wakefield Rehabilitation? Not really.

18 Oct

Reading about Andrew Wakefield gets old and tiring. I’m sure that isn’t news to readers here. Writing about Andew Wakefield gets very tiring. Who wants to keep reminding him/her self about a man who has caused so much harm to both the autism communities and public health in general? Who wants to read about dishonesty and unethical behavior?

I can only imagine that Brian Deer must want to put his award on a shelf and move on.

Which all begs the question: why do I think people reading Left Brain/Right Brain might want to read about him again? Because in this case it isn’t about Mr. Wakefield. Rather it is about his supporters. People who put aside the proved charges of dishonesty and unethical behavior. People such as Kent Heckenlively of the Age of Autism blog who are looking for The Wakefield Rehabilitation. It’s about how and why authors cite previous literature, and not reading too much into citations.

Beyond the hopes of those supporting Andrew Wakefield, there is some good research here and a bit of information about how and why people cite certain papers in the scientific literature.

First, how is Mr. Wakefield being “rehabilitated”? Answer: his papers were recently cited in a recent study. Seriously, something that small. That’s how hard people have to look for validation for Mr. Wakefield. A few citations and he’s on the road to rehabilitation.

The new paper isn’t by just any team, though. The study, recently out in PLoS One is Impaired Carbohydrate Digestion and Transport and Mucosal Dysbiosis in the Intestines of Children with Autism and Gastrointestinal Disturbances. The study is a follow-on to the PLoS One paper by Hornig et al., Lack of association between measles virus vaccine and autism with enteropathy: a case-control study.

Why is that important? “Lack of association…” is the paper which definitively put an end to the Wakefield MMR hypothesis. The team tried, with meticulous attention to detail, to replicate the most important factors of various Wakefield MMR-autism papers. They studied children with autism and gastro-intestinal complaints. They restricted their study to children who had demonstrated clear need for endoscopy (one major difference from the Wakefield studies). They were very careful about correctly reporting the patient histories (another major difference). They tested intestinal biopsy samples for measles virus (similar to as study by the Wakefield team), but were very careful to avoid contamination (unlike the Wakefield studies). The recent study used multiple laboratories to test for measles virus (Wakefield used two: his own and the O’Leary laboratory). Unlike Mr. Wakefield, the recent study reported on results from all the laboratories (Mr. Wakefield neglected to mention the results from his own laboratory which were contradictory to his theory).

Hornig et al. wrote:

The work reported here eliminates the remaining support for the hypothesis that ASD with GI complaints is related to MMR exposure. We found no relationship between the timing of MMR and the onset of either GI complaints or autism. We also could not confirm previous work linking the presence of MV RNA in GI tract to ASD with GI complaints.

About as clear a conclusion as I’ve ever seen. “The work reported here eliminates the remaining support for the hypothesis that ASD with GI complaints is related to MMR exposure.”

So, what about the new paper and the citations? Well, members of the team that produced the Hornig et al. study did further research on the tissue samples taken. Brent L. Williams heads up the author list on the new study.

Here is the (highly technical) abstract from the new study by Williams et al.:

Gastrointestinal disturbances are commonly reported in children with autism, complicate clinical management, and may contribute to behavioral impairment. Reports of deficiencies in disaccharidase enzymatic activity and of beneficial responses to probiotic and dietary therapies led us to survey gene expression and the mucoepithelial microbiota in intestinal biopsies from children with autism and gastrointestinal disease and children with gastrointestinal disease alone. Ileal transcripts encoding disaccharidases and hexose transporters were deficient in children with autism, indicating impairment of the primary pathway for carbohydrate digestion and transport in enterocytes. Deficient expression of these enzymes and transporters was associated with expression of the intestinal transcription factor, CDX2. Metagenomic analysis of intestinal bacteria revealed compositional dysbiosis manifest as decreases in Bacteroidetes, increases in the ratio of Firmicutes to Bacteroidetes, and increases in Betaproteobacteria. Expression levels of disaccharidases and transporters were associated with the abundance of affected bacterial phylotypes. These results indicate a relationship between human intestinal gene expression and bacterial community structure and may provide insights into the pathophysiology of gastrointestinal disturbances in children with autism.

If this were really about the autistics and not about Andrew Wakefield, those claiming that there is something different about the GI disturbances in autistics should be extatic. Here is a top notch team pointing to a possible real difference. In the kids tested, the genes were expressing enzymes and transporters–i.e. the genes are performing differently–for autistic kids. Also, they are seeing differences in the bacteria in the autistic kids.

Not only that, but these kids benefited from dietary intervention, although it isn’t specific to the autistic kids: “Beneficial effects of dietary intervention on GI disturbances were reported for all AUT-GI and Control-GI subjects with FA.”

But, it apparently isn’t about the autistics or the research when it comes to the Age of Autism. It’s about rehabilitating Andrew Wakefield’s reputation. (With apologies in advance–the image that comes to mind is a team that has been performing CPR on his reputation for years now. It’s time to move on.)

The important piece of this study, according to Mr. Heckenlively, is that they cite some of Andrew Wakefield’s papers. In particular:

Wakefield AJ, Anthony A, Murch SH, Thomson M, Montgomery SM, et al. (2000) Enterocolitis in children with developmental disorders. Am J Gastroenterol 95: 2285–2295.

Wakefield AJ, Ashwood P, Limb K, Anthony A (2005) The significance of ileo-colonic lymphoid nodular hyperplasia in children with autistic spectrum disorder. Eur J Gastroenterol Hepatol 17: 827–836

Ashwood P, Anthony A, Torrente F, Wakefield AJ (2004) Spontaneous mucosal lymphocyte cytokine profiles in children with autism and gastrointestinal symptoms: mucosal immune activation and reduced counter regulatory interleukin-10. J Clin Immunol 24: 664–673.

Mr. Heckenlively appears to have built a nice straw man argument in which every thing Mr. Wakefield has done is now discredited. Somehow citing a paper by Mr. Wakefield then becomes some sort of a statement that everything he did was actually right. Both sides of that argument are false. The authors should cite what is in the literature. By citing, say, the Ashwood (2004) paper, they aren’t saying that, say, the 1998 Wakefield Lancet paper is now “rehabilitated’.

Notice that the authors didn’t cite the 1998 Lancet paper. One big reason: it’s been retracted. Which begs the question, why are the authors citing Wakefield et al. (2000)? The paper in the American Journal of Gastroenterology has also been been retracted:

On 28 January 2010, the UK General Medical Council’s Fitness to Practice Panel raised concerns about a paper published in the Lancet by Dr Wakefi eld et al. (1). The main issues were that the patient sample collected was likely to be biased and that the statement in the paper, that the study had local ethics committee approval, was false. Th ere was also the possibility of a serious conflict of interest in the interpretation of the data. Th e Lancet has now retracted this paper (1). Th is paper in the American Journal of Gastroenterology (AJG) (2) also includes the 12 patients in the original Lancet article and therefore we retract this AJG paper from the public record.

One really shouldn’t cite things that have been retracted from the public record. So, is there some message that Williams et al. are trying to send us? Are they saying that Andrew Wakefield was correct all along? Hardly. That paper was retracted in May of 2011, the same time that Impaired Carbohydrate Digestion and Transport and Mucosal Dysbiosis in the Intestines of Children with Autism and Gastrointestinal Disturbances was submitted to PLoS One. The authors weren’t aware of the retraction. Says a lot about how closely they follow Andrew Wakefield, don’t it?

Apparently, the authors have contacted PLoS about the citation, and it will be corrected to notify readers of the retraction. That is the right thing to do. It isn’t a statement about Mr. Wakefield’s research, other than this paper was retracted.

Authors can’t control the message bloggers may try to create from their research (heck, one of the authors, Ian Lipkin, consulted on the recent movie “Contagion”, a main character is a blogger whose message is unscientific and irresponsible). From what I’ve heard, the authors are still very clear on the message of their first PLoS paper: “The work reported here eliminates the remaining support for the hypothesis that ASD with GI complaints is related to MMR exposure. “

I think the point was made pretty clearly. Mr. Heckenlively in his excitement read way too much into this new paper. Not surprisingly, he just goes on and on making more mistakes. Consider this paragraph:

Isn’t Dr. Wakefield supposed to be some super-villain, leading all of us gullible parents to believe that vaccines aren’t quite as safe as sugar water? Didn’t he make up fake diseases? So, after being stripped of his license to practice medicine in the U. K., it turns out there really is something called autistic entercolitis and ileo-colonic lymphoid nodular hyperplasia in children with autism. At least Dr. W. Ian Lipkin seems to think so.

Wow. All this is extrapolated from a single sentence in the introduction of the paper: “Macroscopic and histological observations in ASD include findings of ileo-colonic lymphoid nodular hyperplasia, enterocolitis, gastritis, and esophagitis [2], [3], [4], [5], [6], [7].”

What does that sentence mean? Simple interpretation: others have reported these findings. Not “we confirm that these findings are real”. Given that reference [3] (a retracted Wakefield paper) may be removed or noted to be retracted, the only support for “enterocolitis” will be gone from the paper.

Mr. Heckenlively wrote “Although this study used a relatively small sample of gut biopsies from children with autism (Hey, isn’t that what Wakefield got in trouble for? Or is my memory failing me?),”

Mr. Heckenlively, your memory is failing you. The findings of the General Medical Council are easily found online.

Let me remind you of some of that document:

The Panel concluded that Dr Wakefield’s shortcomings and the aggravating factors in this case including in broad terms the wide-ranging transgressions relating to every aspect of his research; his disregard for the clinical interests of vulnerable patients; his failure to heed the warnings he received in relation to the potential conflicts of interest associated with his Legal Aid Board funding; his failure to disclose the patent; his dishonesty and the compounding of that dishonesty in relation to the drafting of the Lancet paper; and his subsequent representations about it, all played out against a background of research involving such major public health implications, could not be addressed by any conditions on his registration. In addition, the Panel considered that his actions relating to the taking of blood at the party exemplifies a fundamental failure in the ethical standards expected of a medical practitioner. It concluded that conditional registration would not mark the seriousness of such fundamental failings in his duty as a doctor

and

The Panel made findings of transgressions in many aspects of Dr Wakefield’s research. It made findings of dishonesty in regard to his writing of a scientific paper that had major implications for public health, and with regard to his subsequent representations to a scientific body and to colleagues. He was dishonest in respect of the LAB funds secured for research as well as being misleading. Furthermore he was in breach of his duty to manage finances as well as to account for funds that he did not need to the donor of those funds. In causing blood samples to be taken from children at a birthday party, he callously disregarded the pain and distress young children might suffer and behaved in a way which brought the profession into disrepute.

Mr. Heckelively also poses the question: “Didn’t he [Andrew Wakefield] make up fake diseases?”

That would be “autistic enterocolitis”, a term Andrew Wakefield coined and a condition which still, 13 years later, doesn’t have support. Autistic enterocolitis is not just any and all GI disturbances in autistics. Enterocolitis is “…an inflammation of the colon and small intestine”. Note the “and”, there. Even more important, the PLoSOne paper is not about inflammation at all.

Mr. Heckenlively finishes with the rather hopeful, wishful thinking statement: “But if a big shot scientist like Dr. W. Ian Lipkin is quoting Dr. Andrew Wakefield as a reliable source, maybe the rest of the world will soon be doing the same thing.”

Again, wow. Here we have Ian Lipkin, one of the team that just put an end to the Wakefield-MMR hypothesis. Again, let’s remind ourselves, Ian Lipkin is part of the team which wrote: “The work reported here eliminates the remaining support for the hypothesis that ASD with GI complaints is related to MMR exposure.” There is such a major disconnect between that statement (which, yes, Dr. Lipkin stands by) and what Mr. Heckenlively wrote that I am just left in amazement.

This isn’t a story about rehabilitation. This is a story about diversion. Diversion of attention away from important subjects in autism. These include the medical treatment of major health problems. How does one treat something like bowel problems in individuals with communication and/or sensory difficulties? That’s a big question that gets lost in this whole “Andrew Wakefield” discussion. Research like this new paper is important in that respect: is there something specific to kids with autism, regression and GI disease? Leave aside any discussion about GI being linked to the regression, how do you treat it? I, for one, am glad to see something come out of this research project than just the “MMR doesn’t cause autism and GI disease” conclusion. Instead of trying to read the tea leaves of this paper and try to recoup the damage Andrew Wakefield did to his reputation, why don’t we just read the paper in the context of what this might tell us about the health problems of autistics?

NIH funded research includes search for possible vaccine-autism link

11 Jun

Much time is spent discussing whether a study of autism and vaccination status could or should be undertaken. Generation Rescue has been trying to get funding for such a study, but their proposal is weak and vague. The question arises, why doesn’t any group with real strong credentials consider this project?

Would you be surprised to find out that it is already ongoing? And that the principle researcher is someone with mainstream credibility?

It turns out that potential environmental causation of autism, including vaccines, are a part of a study which (if all went according to schedule) just finished the data collection phase. The NIH funded project, GENE-ENVIRONMENT INTERACTIONS IN AN AUTISM BIRTH COHORT, was headed by Prof. Ian Lipkin of Columbia University. The project started in 2003 and was prospectively monitoring a cohort of children diagnosed with ASD’s and another cohort of controls.

The project is discussed below:

Reports of increasing prevalence of autism spectrum disorders (ASDs), a set of highly genetic conditions, are intensifying interest in the role of environmental exposures, including infectious, immune, and toxic factors. Retrospective studies exploring associations between environmental factors and ASDs are compromised by selection bias, small sample sizes, possibly invalid diagnosis, and absence of biologic measures. This prospective study will employ an unselected birth cohort of 75,500 in which cases are ascertained through screening of the entire population, diagnoses established using uniform procedures, extensive histories and clinical data obtained, and biologic samples collected serially throughout pregnancy and early childhood. The application of high throughput laboratory assays to derive maximal information from developmentally-influenced, finite, and nonrenewable biologic samples, and inclusion of early screening and diagnostic assessments, will permit an unprecedented, rich view of the longitudinal trajectory and nascent signs and symptoms of ASDs, facilitate discovery of biomarkers, and afford unique insights into the role of gene:environment interactions in ASD pathogenesis. Specific aims are to: (1) establish the autism Birth Cohort (ABC) through ascertainment of cases of autism spectrum disorder (ASD, N=150-233) and selection of controls (N-1000) from the Norway Mothers and Child (MoBa) cohort; (2) examine biologic pathways that may predispose to ASD, through evaluation of immune, endocrine, and neuroregulatory factors in mothers during early gestation or at birth and in children, at birth or 30 months postnatal; (3) identify environmental factors that may be directly or indirectly associated with ASD, including pre- or postnatal infection, vaccination, very low birth weight or other obstetric risk factors in which infections are implicated, dietary and/or environmental exposure to methylmercury; (4) describe the natural history of clinical, anthropometric, and neurobehavioral features of ASD; and (5) explore genotypic influences that may be directly or indirectly associated with ASD by testing associations of ASD and/or its endophenotypes with family history of autoimmune disease or selected candidate genes, and investigating conditional gene-environment effects using antecedent factors found to influence ASD risk.

Emphasis added.

Prof. Lipkin was a member of the team which looked at children with gastrointestinal disorders, Lack of Association between Measles Virus Vaccine and Autism with Enteropathy: A Case-Control Study. Amongst other findings, they found that (a) regression was not correlated with MMR vaccination and (b) persistent measles infections are not present in the guts of autistic kids more than in non-autistic kids. Basically it was the study that most closely replicated some of Mr. Wakefield’s team’s efforts and showed that Mr. Wakefield’s results were not reproducible.

Another study, THE CHARGE STUDY: CHILDHOOD AUTISM RISKS FROM GENETICS AND THE ENVIRONMENT, includes “vaccines” in the project terms. This study has been funded to the tune of about US$5,000,000 and is headed by Prof. Irva Hertz-Picciotto, who has stated that vaccines should be considered for research into autism causes.

If you are wondering if mercury is being investigated, AUTISM IN A FISH EATING POPULATION continues study on methyl mercury exposures in the Seychelles. Also, the University of Washington has a study ongoing, NEUROIMMUNOTOXICOLOGY OF MERCURY. Johns Hopkins has a study now going on 4 years, GENETIC SUSCEPTIBILITY TO MERCURY-INDUCED IMMUNE DYSFUNCTION IN AUTISM & ASD. Also, the University of Texas has a study, EPIDEMIOLOGICAL RESEARCH ON AUTISM IN JAMAICA, which also is monitoring heavy metal exposures.

I have two questions. First, why do groups like Generation Rescue, SafeMinds, the National Autism Association and TACA claim that vaccine-autism and mercury-autism research isn’t being done? They are represented on government committees. Second, what do they hope to learn from doing their own study that isn’t going to be done better and sooner by other groups?

Before the MMR science, the press conference

4 Sep

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

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

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

The whole press conference is here.

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

http://webjay.org/flash/dark_player

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

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

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

David’s second question followed:

http://webjay.org/flash/dark_player

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

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

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

http://webjay.org/flash/dark_player

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

http://webjay.org/flash/dark_player

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

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

http://webjay.org/flash/dark_player

Follow

Get every new post delivered to your Inbox.

Join 954 other followers