I received an interesting series of e-mail exchanges from the mother of a seven-year-old boy with autism and officials from the Centers for Disease Control. The e-mails concerned her request for information from the CDC about testing for the presence of the XMRV retrovirus in children with autism. The mother also suffers from chronic fatigue syndrome/ME.
The e-mail exchange was prompted by the publication of an article by David Kirby in The Huffington Post in December of 2009 in which Dr. Thomas Insel, Director of the National Institute of Mental Health mentioned that his intramural group at the NIH had been looking into the presence of the XMRV retrovirus in children with autism since August of 2009. HERE
The series of e-mail exchanges which took place in November of 2010 are interesting for what is said, and what is not. Dr. Insel provided a note from Dr. Swedo in respone to the inquiry from this mother.
Dr. Mike Iadorola is now ready to run the XMRV assays on samples from our children with autism (approx 100), typical development (60) and developmental delay (30). We did send him a batch of approximately 100 samples last summer (from the three groups), almost immediately after the initial report of the positive results in autism. However, that assay proved to be quite unreliable, yielding positive results in individuals who were known to be negative by more extensive testing.
The mother was confused by the response so sent back the following inquiry.
I am puzzled by the statement "yielding positive results in individuals who were known to be negative by more extensive testing" - as the testing for XMRV in humans is still not standardized, how can one test be considered "more extensive" than another one? What tests were used to give the original positive results? Were the samples taken and handled in the same way for these tests that gave the negative results? How were those initial positive results explained away - contamination? Cross-reactivity?
I would appreciate if you could share with me what assays were used for negative/retest findings and who developed them?
In response Dr. Mike Iadorola sent back a reply noting that the assay used was called luciferas immunoprecepitation systems and suggested she look at the results from a recent publication in the journal Molecular Autism by Satterfield/Cooperative Diagnostics.
The mother had her own comments about the negative XMRV/autism study authored by Satterfield/Cooperative Diagnositics.
The study 1. used a synthetic clone, which had never been isolated in blood, to establish the clinical sensitivity of the PCR, 2. did not use culture to raise the titer of the virus, 3. the blood collected for the purposes of this study spent many days in the post in unrefrigerated containers. None of the methods used, including those used by the CDC lab, were able to detect XMRV in 20 confirmed clinical positive samples - those from which virus had been isolated and sequenced and reported by Lombardi et al and the attached Virulence publication.
The samples obtained prospectively by Satterfield/Cooperative Diagnostics from the moms were subsequently tested by the methods of Lombardi et al and XMRV was detected in >70 when multiple methods were used. This work was presented at the First International Workshop on XMRV in Bethesda, September 7-8, (2010) and has been submitted for publication. The fact that neither the methods used by Cooperative Diagnostics or by the CDC could detect XMRV in yet another set of confirmed positive patient samples again confirms that neither set of methodology can in fact detect XMRV in a clinical positive.
Furthermore the assay method used by Cooperative Diagnostics has since been withdrawn from commercial use because it was simply unable to locate wild type virus in anyone - their method never detected one positive sample in humans. A number of individuals who originally tested negative through Satterfield's commercial test have since been retested through VIPdX (the testing lab utilized by the Whittemore-Peterson Institute) commercial test, many with positive results.
After this e-mail it appears that no meaningful interchange has taken place.
I have e-mailed Drs. Insel, Swedo, and Iadorola to furher clarify their comments and the criticisms made, but have received no reply as of the writing of this article.
The questions raised by this mother of a child with autism and who has chronic fatigue syndrome/ME herself need to be answered. As I see it, these are the questions which remain:
1. What was the test initially used which found high numbers of children with autism testing positive for the XMRV virus? In Dr. Swedo's original note she wrote, At present, XMRV positivity appears to be much more common than the the small initial study suggested. Considering that the small initial study to which she is apparently referring found XMRV in 82% of the children with autism it would be interesting to know what the CDC's finding was for XMRV infectivity. (An earlier account had the number at 40%, so it's unclear which number is being referenced.)
2. What was the sensitivity of these "newly-developed assays" and were they able to detect XMRV in known positives, rather than simply a clone of a section of the virus? (There is considerable discussion that what's being found is a family of gamma retroviruses and a clone may miss infection by related viruses which differ slightly in their genetic make-up. HIV taken from various areas of a person with AIDS will show significant variability in their genetic make-up which is why most tests are for the presence of HIV antibodies.)
3. Why are the protocols established for blood storage, preparation of the sample, and tests to be utilized, as detailed by the initial study group of the Whittemore-Peterson Institute, the Cleveland Clinic, and the National Cancer Institute as detailed in their October 2009 article in the journal Science not being followed?
4. If this issue revolved around the simple discovery of a new retrovirus and its association with various human diseases it seems these would be simple questions to answer. The fact that basic scientific protocols are not being followed raises the possibility these difficulties are political, rather than scientific in nature.
The autism community and the chronic fatigue syndrome/ME community wait for answers to these questions.
For more information on the potential importance of XMRV to autism you can read my previous article HERE.
Kent Heckenlively is Contributing Editor to Age of Autism