The article that won't die: Sally Beck's "Scientists fear MMR link to autism," published in the Daily Mail on May 28, 2006.
That's right, 2006.
It gets worse. Two of the complainants in the Omnibus Autism Proceeding, the Cedillos and Hazelhursts, relied upon the unpublished Walker et al. research. Both the Special Masters in the hearings, and the presiding judge in the following Hazelhurst appeal, dismissed the evidentiary value of the Walker et al. study (exerpts from the hearings and the appeal are below). In other words, the Walker data have been examined and found unconvincing, because it was scientifically suspect.
The Walker study (never published) in no way validates Wakefield's fraud. The MMR vaccine still does not cause autism.
Link to the Daily Mail article. http://www.dailymail.co.uk/news/article-388051/Scientists-fear-MMR-link-autism.html
Thanks to the Daily Mail's perverse habit of not date-stamping articles and scrubbing comments, plus having a date-stamp above the header, a casual reader may not realize that the article is 4 and a half years old.
As always, click to embiggen. Below: what appears at the Daily Mail's website, captured 1/26/11
Nonetheless, The Mail, through Beck, overstated the case. I suspect that Wake Forest University, and possibly the lead author, Walker, was embarrassed, and put out a press release dated June 1, 2006 press release from Wake Forest University Baptist Medical Center Wake Forest Researcher Warns Against Making Connection Between Presence of Measles Virus and Autism. (The complete text of the press release is below.)
Other coverage in late May and early June, 2006
- Commentary from Kristina Chew on May 28, 2006 The rush to report on MMR/regressive autism study
- June 1, 2006 press release from Wake Forest University Baptist Medical Center Wake Forest Researcher Warns Against Making Connection Between Presence of Measles Virus and Autism
- Commentary from Kristina Chew on June 2 2006 Dr. Stephen Walker: MMR and Autism: no link
- Commentary from Kristina Chew of June 3 2006 Dr. Stephen Walker: MMR and Autism: no link 2
- Commentary from Ben Goldacre MD on June 6 2006 MMR is back
Text from the IMFAR 2006 Program Booklet and Abstracts (PDF),p. 100-101 downloaded from http://www.autism-insar.org/index.php?option=com_content&task=view&id=19&Itemid=82 on January 24, 2010 and transcribed from PDF into text:
Persistent Ileal Measles Virus In A Large Cohort Of Regressive Autistic Children With Ileocolitis And Lymphonodular Hyperplasia: Revisitation Of An Earlier Study
Steve Walker, Karin Hepner, Jeffrey Segal, Arthur Krigsman, Wake Forest University School of Medicine
Background: Autistic enterocolitis, consisting of a nonspecific ileocolitis coupled with ileocolonic lymphonodular hyperplasia (LNH), was first introduced as a new, potentially virus-induced disease entity eight years ago in a group of ASD children with developmental regression.
Objectives: The primary objective of this study was to examine ileal biopsy tissue in a large cohort of pediatric patients who carry a diagnosis of regressive autism and whose chronic gastrointestinal symptoms warranted diagnostic endoscopic evaluation, for evidence of measles virus RNA.
Methods: Patients who had been diagnosed with autism and who were referred to a pediatric gastroenterologist for evaluation of chronic GI symptoms were eligible to participate in this IRB approved study. For each patient, medical histories, vaccination records, histopathology reports, and ileocolonoscopic biopsy tissue were available for evaluation. Terminal ileum (TI) biopsy tissue was assayed by RT-PCR for the presence of measles virus RNA and PCR-positive samples were sequenced.
Results: Medical and clinical data have been collected for >275 patients who fit the study inclusion criteria. PCR analysis on TI biopsy tissue from an initial 82 patients showed that 70 (85%) were positive for the F gene amplicon. Fourteen have been verified by DNA sequence and an additional 56 amplicons are being sequenced now. Work is ongoing to assay the remaining specimens (~200) and to identify and assay relevant control tissue samples. Conclusions: Preliminary results from this large cohort of pediatric autistic patients with chronic GI symptoms confirm earlier findings of measles virus RNA in the terminal ileum and support an association between measles virus and ileocolitis /LNH. Sponsors: ARI; NAA; individual donations
Compete text of the Wake Forest Press released dated June 1 2006. Downloaded from http://www.wfubmc.edu/News-Releases/2006/Wake_Forest_Researcher_Warns_Against_Making_Connection_Between_Presence_of_Measles_Virus_and_Autism.htm on January 22, 2011.
Wake Forest Researcher Warns Against Making Connection Between Presence of Measles Virus and Autism 6/1/2006
WINSTON-SALEM, N.C. – An American scientist whose research replicates a connection published in England in 2002 between the measles virus and bowel disease in autistic children strongly warns against making the “leap” to suggesting that the measles vaccine might actually cause autism.
“That is not what our research is showing,” said Stephen J. Walker, Ph.D., an assistant professor of physiology and pharmacology at Wake Forest University Baptist Medical Center. Walker and colleagues have issued an abstract to be presented at this week’s International Meeting for Autism Research, indicating that a high percentage of autistic children that they have tested with chronic bowel disease show evidence of measles virus in their intestines.
Some observers have said that the presence of the measles virus indicates a strong possibility that the measles vaccine, a possible source of the virus, could have caused the children’s autism. That possible connection has caused a major controversy in the United Kingdom, where the connection was first made in 2002. The vaccine is first given as part of a triple vaccine called MMR – for measles, mumps and rubella – at ages 12-18 months. That is shortly before a particular type of autism (regressive) begins to appear in children afflicted with the condition, which has fueled the speculation about a connection.
Walker says the new research does not support the connection, and he notes that the results have not even been published in a peer-reviewed journal. “Even if we showed association (between measles virus and bowel disease) and we published it in a peer-reviewed journal, the conclusion will be simply that there is measles virus in the gut of a large number of children who have regressive autism and bowel disease. End of story.
“We haven’t done anything to demonstrate that the measles virus is causing autism or even causing bowel disease.”
Walker explains that exploring the causes of chronic bowel disease in autistic children is the major impetus for his research. “There are lots of viruses in the gut, and any one of them could be causing inflammation. If it truly is from a vaccine and this virus causes inflammation and a chronic bowel condition in some susceptible children, then that’s something that needs to be known.”
The main task at hand, Walker said, is to determine what is causing the bowel condition in the autistic children, a condition that has a direct influence on cognitive and behavioral issues associated with autism.
A high percentage of autistic children have chronic bowel disease, a discovery in the late 1990s that eventually led to the measles virus connection.
“If anybody has severe GI problems, it causes problems with focus, it causes problems with everything. You can’t do anything until you get that resolved. We’ve all experienced that.
“These kids experience it hour after hour every single day of their lives. Many of them are non-verbal so they can’t tell anybody what the problem is, and the behavior that they exhibit as a result of a severe stomach ache was once attributed to just being autistic and having weird behaviors – for example, leaning over the sharp edge of a coffee table for hours at a time. That seems weird, but what they’re doing is relieving pressure on their lower abdomen.”
Walker said that relieving the bowel discomfort has been shown to improve other conditions associated with autism, such as cognition and the ability to learn. “There’s case after case where kids improved cognitively, behaviorally and biomedically when you treat the bowel disease. There is a great improvement from better nutrition alone. You see improvements in their overall condition.”
Walker said he will continue to look for possible causes, the biological mechanism, and new treatments of the bowel condition. “That’s the goal for me: understanding the biology of what’s causing the disease and then gaining insight into the most effective way to treat it, so that clinicians will not have to go through a trial and error approach.”
# # #
Media Contacts: Mark Wright, firstname.lastname@example.org, Karen Richardson, email@example.com, or Shannon Koontz, firstname.lastname@example.org, at (336) 716-4587.
Wake Forest University Baptist Medical Center is an academic health system comprised of North Carolina Baptist Hospital and Wake Forest University Health Sciences, which operates the university’s School of Medicine. The system comprises 1,187 acute care, psychiatric, rehabilitation and long-term care beds and is consistently ranked as one of “America’s Best Hospitals” by U.S. News & World Report.
Selected abstracts from the Cedillo decision
In the United States Court of Federal Claims OFFICE OF SPECIAL MASTERS No. 98-916V (Filed: February 12, 2009)
Finally, Dr. Hepner pointed to a study that is currently in progress, conducted by herself and several others, to which I will refer as the “Walker study.” She stated that the “preliminary data” from that study “present another step in support” of the proposition that the measles virus persists in the intestinal tissue of autistic children. (Ex. 63, p. 5; Tr. 634A-35A.)
c. The Walker study
Petitioners have also relied on a study that is currently in progress, conducted by Dr. Hepner and several others, often described as the “Walker study.” (See Ex. 59, Tab K; P. Trial Ex. 3.) Dr. Hepner stated that the “preliminary data” from that study “present another step in support” of the proposition that the measles virus persists in the intestinal tissue of some autistic children. (Ex. 63, p. 5; see also Tr. 634A-35A.) After consideration of the Walker study and the testimony about it in the record of this case, however, I conclude that the study does not provide any substantial support to the proposition that the measles virus persists in the bodies of Michelle Cedillo or any other autistic individuals.
Dr. Hepner reported that she and three other researchers--Steve Walker, Jeff Segal, and Dr. Arthur Krigsman, the latter being another of petitioners’ experts in this case--are engaged in a study similar to the Uhlmann study, in that their objective is to perform PCR testing for the detection of measles virus on intestinal biopsies of children with both developmental delay and gastrointestinal symptoms. (Ex. 63, p. 5; Tr. 634A-35A.) Dr. Hepner stated that the researchers generated “multiple primer sets” and “tested them for their specificity and sensitivity” in identifying the presence of measles virus. (Tr. 635A; Ex. 63, p. 5.) Dr. Hepner and Dr. Krigsman testified that the study, which began in 2003, is not yet complete, but that the group conducted some initial testing and presented “preliminary data” from the study at an autism-related conference in 2006, in the form of a “poster presentation” (literally, a poster board describing the study was set on an easel at the conference). (Ex. 63, p. 5; Tr. 474A-75, 634A.) Dr. Hepner reported that of 82 biopsy samples tested in the study’s initial testing, which all came from children with both “developmental delay” and “GI [gastrointestinal] symptoms,” 70 tested positive for measles virus. (Ex. 63, p. 5.) She further stated, without explanation, that her group was able “to confirm vaccine strain specificity” in some of the positive samples. (Tr. 635A.)
Petitioners, in their post-hearing briefs, have relied on the Walker study as supportive of their view that the Unigenetics measles virus testing should be considered reliable. (P1, pp. 141, 154-55, 242; P3, pp. 33-34.) After full consideration, however, I cannot agree. First, two of respondent’s experts, Dr. Ward and Dr. Bustin, each pointed to a number of flaws in the Walker study, based on the description in the poster presentation. (Tr. 1861-65; 1952A- 59A.)
Moreover, a second important reason to discount the Walker study is the testimony of Dr. Hepner herself. Dr. Hepner stated that the initial data from her study were only “very preliminary data.” (Tr. 659.) She acknowledged that it would be inappropriate to “draw any conclusions” from those preliminary results. (Tr. 682.) She acknowledged that her group at this time is still attempting “to test this assay, to optimize the assay” (Tr. 660A)--i.e., to develop the test to a point where they can then be confident that their test is yielding reliable results. Part of developing any such test is to use “negative controls”--i.e., to test samples that are known to be free of the target, to make sure that the test is not erroneously identifying the target in samples that do not contain it. However, Dr. Hepner explained that her group is still at the point of developing their negative controls. (Tr. 658, 681.)
In short, Dr. Hepner was forthright in acknowledging that, in terms of drawing any conclusions with regard to the issue of the validity of measles virus testing, the preliminary data available from her study simply are “not useful at this time.” (Tr. 659.) In sum, it is clear that the Walker study must be disregarded. First, both Dr. Ward and Dr. Bustin pointed out a number of reasons why one cannot draw any conclusions from, or place any reliance on, the preliminary data from the Walker study. And even petitioners’ expert Dr. Hepner, one of the study’s own authors, has acknowledged that the preliminary data from the study are “not useful at this time.” (Tr. 659.) Accordingly, I must agree with Dr. Hepner on this point. I conclude that the Walker study is not useful in deciding the issue of whether the Unigenetics measles virus detection testing was reliable.
b. The Walker study
Petitioners also, in their final post-hearing brief in this case, pointed to another item of evidence in the record. (P4, pp. 33-34.) They pointed to the ongoing Walker study, discussed above, and note that one of their experts who has worked on that study, Dr. Krigsman, stated that in the study’s initial testing, six specimens were determined to be positive “for vaccine-strain-specific RNA.” (Tr. 487A.) However, as I have already discussed above, the preliminary data from the Walker study, in the words of the petitioners’ own expert and co-author of that study, Dr. Hepner, is simply “not useful at this time.” (Tr. 659.) Thus, again in Dr. Hepner’s own words, it would not be appropriate for me to “draw any conclusions” from that data. (Tr. 682.)
Selected abstracts from the Hazelhurst decision ftp://autism.uscfc.uscourts.gov/.../Campbell-Smith%20Hazlehurst%20Decision.pdf
OFFICE OF SPECIAL MASTERS
E-Filed: February 12, 2009
I. The Preliminary Findings of the Walker Study
Petitioners also rely on unpublished findings of measles virus in tested bowel tissues taken from autistic children as support for their claim regarding measles persistence. Petitioners’ expert Dr. Hepner expressed the opinion that the published 2002 Uhlmann findings are “reliable,” see Cedillo Tr. at 639, and her confidence in the reported positive findings of measles virus is bolstered by the preliminary findings of a study on which she is working. Dr. Hepner discussed her current work with a team of investigators in the laboratory of Dr. Stephen Walker at Wake Forest University in Winston-Salem, North Carolina. Dr. Hepner described the project as a study “to create a highly reproducible, highly sensitive, very specific . . . experimental design to detect [measles virus] RNA in the bowel biopsies of ASD patients.” Id. at 634A-635A. She stated that the preliminary findings of the study, which were presented as an abstract at the June 2006 International Meeting for Autism Research (IMFAR), confirm the presence of vaccine strain measles virus in some of the bowel biopsies that were tested. Id. at 635.
Dr. Hepner stated that while positive controls (specifically “an artificial laboratory construct” of wild-type measles virus) have been run in each experimental run in the study, no negative controls have been run to date because the investigators are still looking for suitable negative controls. Id. at 658, 663, 674-675. The experimental controls are patients who do not have ASDs but have gastrointestinal symptoms. Id. at 675. The experimental group includes ASD patients who have “[inflammatory bowel disease]-like symptoms, but not all of whom have received the MMR vaccine.” Id. at 676. She described the preliminary results of the experiments as “a technical achievement” because the investigators “believe that they have developed some assays to detect [measles virus] in this cohort of patients in biopsied tissue that is vaccine strain specific.” Id. at 682. But Dr. Hepner declined to “draw any conclusions about the biological significance” of the investigators’ findings. Id.
However, respondent’s expert Dr. Bustin expressed some concern about the preliminary PCR results reported in the Walker abstract presented at the IMFAR conference and discussed in Dr. Hepner’s testimony. Dr. Bustin’s chief concern after reviewing the slides from the poster presentation is that there is evidence from the location of the bands in the experimental gel that the obtained results are not specific for the intended target. See id. at 1955A-1958A. Because the experiment did not include a negative control, a proper determination of what the observed bands show cannot be made. See id. at 1958. In the absence of both positive and negative controls during a PCR run, Dr. Bustin stated that he “[could not] have any confidence” in the test results. Id. at 1959A.
The testimony during the Cedillo hearing of the parties’ experts, Dr. Hepner for petitioners and Dr. Bustin and Dr. Ward for respondent, made clear that standard laboratory practice requires that positive samples (that always contain the targeted material), negative samples (that never contain the targeted material), experimental samples (the subjects with an exposure of interest tested for the presence of the targeted material), and control samples (the subjects without the exposure of interest tested for the presence of the targeted material) are run during each experiment. See Cedillo Tr. at 620A, 621A, 627A, 677 (Dr. Hepner); id. at 1842 (Dr. Ward); id. at 1959A (Dr. Bustin). The use of the positive and negative controls provides information about the internal consistency of the experiments. Informed that test results without the use of these controls during PCR experiments may not be reliable, the undersigned cannot place much weight on the preliminary findings of Walker study (addressed by petitioners’ experts Drs. Corbier, Hepner, and Krigsman), specifically the alleged findings of vaccine-strain measles virus in some of the bowel biopsies that were tested.
Petitioners’ claim that the measles virus can persist in the gut of certain vaccinated children and cause inflammation is based on reported findings of persistent measles virus in the biopsied gut tissue taken from autistic children who have received the MMR vaccine and developed gastrointestinal symptoms. Petitioners’ reliance, however, on the published reports of positive test results, the unpublished positive findings of the preliminary Walker study, and the positive lab results obtained by Unigenetics lab from biopsied gut tissue taken from children involved in the OAP litigation is unavailing. Strong evidence, including highly credible expert testimony, indicates there were numerous irregularities in the testing procedures. Those irregularities compromised the integrity of the conducted tests and have rendered the test results unreliable. Underscoring the unreliability of the test results is the inability of other laboratories (that is, accredited laboratories not affiliated with either Dr. Wakefield, his colleagues, or the Unigenetics lab) to replicate the reported findings in gastrointestinal tissues or blood cells.
Petitioners’ theory is based on the characteristics of the wild-type measles virus rather than on the characteristics of the attenuated vaccine-strain measles virus. Petitioners’ theory is further based on unreliable reports of positive measles findings. The bases for petitioners’ theory that the measles component of the MMR vaccine can lead to the development of autism are unsound. Petitioners have failed to offer reliable support for the proposition that the MMR vaccine can cause autism and have failed to meet their burden of proof under the first prong of the Althen standard.
Selected abstracts from the Hazelhust appeal, http://www.leagle.com/xmlResult.aspx?xmldoc=in%20fco%2020100513188.xml&docbase=cslwar3-2007-curr
downloaded January 24 2011
The Hazlehursts also argue that the special master disregarded critical evidence regarding the reliability of the Walker group's test results, in violation of the Vaccine Act's requirement to consider "all . . . relevant medical and scientific evidence." 42 U.S.C. § 300aa-13(b)(1). They assert that the special master ignored evidence— including testimony from Dr. Hepner and exhibits from the Walker group's 2006 IMFAR poster presentation—showing that the Walker group used genetic sequencing to verify its test results. If the special master had given that evidence proper consideration, the Hazlehursts argue, she would have found that the Walker study reliably detected persistent vaccine-strain measles virus in the bowels of autistic children. The Hazlehursts therefore assert that the special master's decision to accord little weight to the Walker group's test results was arbitrary and capricious. We disagree.
As an initial matter, even if the special master had made no explicit reference to the evidence that the Walker group used genetic sequencing, we would presume that she considered that evidence. See Medtronic, Inc. v. Daig Corp., 789 F.2d 903, 906 (Fed. Cir. 1986) ("We presume that a fact finder reviews all the evidence presented unless he explicitly expresses otherwise."). In this case, however, it is not necessary to rely on that presumption, as the special master's opinion specifically refers to that evidence. Discussing Dr. Krigsman's testimony, the special master explained:
Dr. Krigsman stated that the preliminary findings of that [Walker group] study show that based on the obtained PCR results, measles virus is present in the biopsied gastrointestinal tissue taken from patients with autism and bowel disease and examined by Dr. Krigsman. Dr. Krigsman acknowledged, however, as did Dr. Hepner, that not all of the samples had been sequenced for vaccine strain measles.
Hazlehurst, 2009 WL 332306, at *139 (citations to exhibits and testimony omitted). Thus, the special master clearly understood the testimony that some, though not all, of the Walker group's samples were sequenced to confirm vaccine-strain specificity. Moreover, the exhibits that the special master cited in her opinion included the June 2006 IMFAR abstract and IMFAR poster presentation—the very documents that the Hazlehursts contend were "ignored." We thus cannot conclude that the special master failed to consider the evidence in question, in violation of 42 U.S.C. § 300aa-13(b)(1).
In any event, an examination of the cited exhibits and testimony reveals inconsistent and preliminary data that provides only minimal support for the petitioners' claim that the Walker group confirmed the presence of vaccine-strain measles virus, as opposed to wild-type measles virus. While the abstract states that "PCR analysis on. . . tissue from an initial 82 patients showed that 70 (85%) were positive" for measles virus, the poster presentation states that "PCR analysis on . . . tissue from an initial 86 patients showed that 57 (66%) were positive" for measles virus. With respect to sequencing, the abstract observes that "[f]ourteen [samples] have been verified by DNA sequence," but it does not state whether the sequencing was vaccine-strain specific. The poster presentation, on the other hand, states: "Thirty five [samples] have currently been verified by DNA sequence. Six of the thirty five MV [measles virus] positive [samples] bear sequence that is specific to vaccine strain MV." That information, which suggests that only a small number of samples were successfully sequenced for vaccine-strain measles virus, is confirmed by Dr. Krigsman's testimony: "All we could say at the time of this poster is that, as far as vaccine-strain-specific sequencing positivity, a total of six specimens  were positive . . . . So genetic material that was specific for vaccine-strain measles virus was positive in six."[ 3 ] Given that the Walker group's data reflects only a small amount of vaccine-strain-specific sequencing, it was not inappropriate for the special master to include only a brief discussion of the Walker group's sequencing efforts in her opinion.
The special master's decision to accord little weight to the Walker group's data was largely based on the study's other shortcomings and was thus well within her discretion in weighing the evidence. Most significantly, the special master found that the Walker group's research was unpublished, preliminary, and incomplete. Hazlehurst, 2009 WL 332306, at *124-25, *139, *150. Embodied only in a poster presentation, the Walker study was not subject to peer review and therefore has not been subjected to scrutiny from the greater scientific community. See id. at *16, quoting Daubert v. Merrell Dow Pharms., Inc., 509 U.S. 579, 594 (1993) ("The fact of publication (or lack thereof) in a peer reviewed journal thus will be a relevant, though not dispositive, consideration in assessing the scientific validity of a particular technique or methodology."). In fact, Dr. Krigsman and Dr. Hepner repeatedly described the Walker group's data as "partial" and "preliminary." As the special master observed, Dr. Hepner testified that she "certainly wouldn't draw any conclusions about the biological significance" of the Walker group's test results at that early stage. In particular, Dr. Hepner noted the lack of a "proper control source" of tissue samples from children without autism spectrum disorders. She explained that the Walker group's current data does "not give us any information yet about this cohort of patients relative to a different cohort of patients."
The special master also expressed misgivings about the Walker group's use of controls in its study. The special master noted that "while positive controls (specifically `an artificial laboratory construct' of wild-type measles virus) have been run in each experimental run in the study, no negative controls have been run to date because the investigators are still looking for suitable negative controls." Hazlehurst, 2009 WL 332306, at *125. In their reply brief, the Hazlehursts dispute the special master's statement that "no negative controls have been run." They argue that negative "technical" controls were run with every sample to check for contamination and to assure the reliability of the PCR testing, even though the Walker group lacked certain "experimental" controls, namely, control samples of tissue from children who tested negative for autism.
The record is unclear as to precisely what negative controls were run. Although Dr. Hepner testified that "no-template negative controls" were run "as a control for contamination," she also stated that the Walker group was still "in the process of procuring samples that would be appropriate negative controls." She further noted that "the negative control at this point generally has been a no-template control because we don't have access to the right material." The confusion is compounded by Dr. Bustin's testimony that he could not rule out the possibility of contamination—suggested by several indicators of unidentified genetic material in the Walker group's poster presentation—because "there's no negative control there."
What is clear from the record is that, at the time of the omnibus autism hearings, certain key controls used by the Walker group were incomplete and in flux. Most critical is the undisputed lack of a sufficient control group of non-autistic children with which to compare the positive findings in autistic children. If the Walker group were to find persistent measles virus at comparable rates in both autistic and non-autistic children, for example, such a finding would significantly undermine the petitioners' theory that persistent measles virus contributes to the causation of autism spectrum disorders. Moreover, Dr. Hepner's testimony suggests that the Walker group was also seeking a different type of positive control to rule out the possibility of cross-contamination. That evidence further underscores the preliminary and unconfirmed nature of the Walker group's results.
Like the Court of Federal Claims, we do not believe that the Walker group's small amount of vaccine-strain-specific genetic sequencing "carries enough weight to overcome the special master's conclusion that the Walker group's results were preliminary, unpublished, and not entitled to substantial weight." Hazlehurst, 88 Fed. Cl. at 488. We therefore find no error in the special master's determination that she could not "place much weight on the preliminary findings of Walker study . . . specifically the alleged findings of vaccine-strain measles virus in some of the bowel biopsies that were tested." Hazlehurst, 2009 WL 332306, at *125. III