Hosts: Vincent Racaniello and Alan Dove
On episode #89 of the podcast This Week in Virology, Vincent and Alan review recent findings on the association of the retrovirus XMRV with ME/CFS, reassortment of 2009 pandemic H1N1 influenza virus in swine, and where influenza viruses travel in the off-season.
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Links for this episode:
- Conflicting XMRV papers on hold
- Leak of PNAS paper
- CDC study on XMRV in CFS patients (Retrovirology) and Science update
- Where influenza viruses travel in the off season (EurekaAlert! and PLoS Pathogens)
- NPR article on Ebola siRNA treatment (thanks, Andreas!)
- Priming mechanism for reovirus entry (thanks, Agyeman-Badu!)
- Wired article on science PR (thanks, Dan!)
- Letters read on TWiV 89
Weekly Science Picks
Alan – Tree of Life graphic
Vincent – TEDx Oil Spill
Send your virology questions and comments (email or mp3 file) to twiv@microbe.tv or leave voicemail at Skype: twivpodcast. You can also post articles that you would like us to discuss at microbeworld.org and tag them with twiv.
Prof Racaniello, one of the co-author of the CDC XMRV study is Bill Reeves who was at the head of the CFS program until reassigned on Feb. 14 2010. He has caused an upset in October 2009 following the publishing of WPI in science saying that they would do a XMRV study but it was very likely they would not find it. It was with great dismay that we saw him as a co-author.
WPI issued a press release following the CDC publication in Retrovirology. http://www.wpinstitute.org/news/news_current.html and indeed WPI sent 20 positive samples to the CDC which were not mentioned on their study.
From another point of view, Dr Suzanne Vernon comments on the XMRV study of the CDC here : http://www.cfids.org/xmrv/070110study.asp
Patients have a big reason to discount and distrust the CDC. They have denied thousands of patients their health and health care. http://www.oslersweb.com/newsletter.htm
Thank you for understanding that the patients want the truth to come out and want treatment for a disease that has been burried so many times by the CDC.
Prof essor Racaniello, to understand why CFS patients have absolutely no faith in the CDC you creally need to read read the book “Osler's Web” by Hillary Johnston. You will see just why this is so, it is completely justified.
“A relentless, meticulous, and highly persuasive expose by a journalist who spent nine years investigating the medical research estasblishment's failure to take seriously chronic fatigue syndrome…A compelling, well-documented account, certain to be compared to Randy Shilt's And the Band Played On.”
–Kirkus Reviews
“Writing with quiet fury, (Johnson) builds a devastating picture of the U.S. government research establishment's decade-long strategy of avoidance and denial–groundbreaking, compelling.”
–Publishers Weekly
Thanks for an interesting discussion. For my part I'm sure CDC is objective. Objective enough to to, say, refrain from de-staining and melting down, for subjective reasons, a gel that would show that their research efforts have been making bold and exciting progress away from the truth for many years. But there's objective and then there's objective, which of course is the entire rationale for blinded or double-blind studies; out-and-out duplicity is not the one and only way that a little of the ol' objectivity can leak out of the process. Dr Dove points out the possible interestedness of WPI, and I think CDC may also have a degree of interestedness stemming from its history of strong statements about the etiology of CFS.
There is, of course, serious incoherence in XMRV findings — and so far the degree of incoherence is about the same for normal populations and for prostate cancer populations as it is for CFS. We do indeed need standardized assays and sample swapping. But it is striking that WPI, NCI, Cleveland Clinic, and now the very accomplished Dr Alter are in concord. Hopefully this whole thing will not drag on eternally like the MMTV question or something. HHS is not exactly clearing the air here by making it look like it could be putting its thumb on the scales. Even though it is highly unlikely, there is a sliver of a possibility that the entire research community could move (at least for some years) toward a false consensus, and for that reason HHS's recent “maneuver” cannot possibly be welcome to a patient like myself, however benignly intended it may in fact be.
At -51.17 minutes into this podcast, Dr. Racaniello pointed out that the CDC study had no positive controls in the form of a patient sample that is known to be XMRV positive. He suggested that it would be in WPI's best interest to share samples with other researchers.
According to the Whittemore Peterson Institute statement regarding the study, the CDC researchers WERE given XMRV positive samples, but did not use them to validate their assays.
“In September 2009, WPI sent the CDC twenty confirmed positive samples and the appropriate methodology to help them develop a clinically validated test. However, this team chose not to do this.”
http://www.wpinstitute.org/news/docs/XMRV-CDC%2…
This is a telling fact. Speaks volumes, to my ear.
And I think something's wrong with your URL; hopefully this one will work:
http://www.wpinstitute.org/news/docs/XMRV-CDC%2…
OK, clearly this blog's software is messing up the URL. Let me try it this way.
wpinstitute.org/news/docs/XMRV-CDC%20Statementrevisedawfinalawfinal.pdf
http://www.wpinstitute.org/news/docs/XMRV-CDC%2…
The CDC was also given the 'recipe' for finding XMRV by WPI, but did not follow it. They chose NOT to culture the samples.
Patients of many years know about the Goverment Accountability Office's investigation of the CDC.
http://www.gao.gov/new.items/he00098.pdf (go down to the chapter titled “Accounting Issues at CDC)
The CDC took millions of dollars allocated for Chronic Fatigue Syndrome and spent it on other illnesses such as measles. Coupled with Hillary Johnson's allegations of government employees dismissing early claims of CFS epidemics and ridiculing patients at conferences, it's understandable why many of us are so angry.
As a patient I've long given up on government research. More research is spent on illnesses like ezcema and erectile dysfuction (which, to my knowledge, has never cost someone their education or livelihood). According to Hemispherx Biopharma, the company that's been trying to get Ampligen past the FDA, the SSA pays out over a billion and a half dollars a year on disability claims for CFS.
The latest study illustrates the CDC's confusion over the patient cohort. It's not surprising and unbelievably frustrating.
Dr. Racaniello,
In the Spring 2010 issue if the IACFSME newsletter (iacfsme.org), Dr. Mikovits described the procedures by which they were detecting XMRV. Not being a virologist, I am not in a position to evaluate the adequacy of her instructions. I'd be interested in your opinion:
http://www.iacfsme.org/BULLETINSPRING2010/Sprin…
(I'm crossing my fingers as I'm posting this URL – if it doesn't work I'll send it as an e-mail)
Dr. Racaniello, You discussed the ethics of leaking the Alter paper. It was the IPFA/PEI Workshop 2010 conference itself that posted the Alter pdf on their own web-site. It appears that the Dutch news site Ortho announced the news: http://www.mmdnewswire.com/xmrv-9040.html (albeit very enthusiastically).
On July 1, 2010, a group comprised of Drs. Robert Silverman (Cleveland clinic), E. Klein, G. Casey, J. DeRisi and D. Ganem and a separate group comprised of Drs. Judy Mikovits, S. Ruscetti and F. Ruscetti (the WPI and NCI) filed for separate patents for process to detect XMRV:
Silverman et sl. – http://www.faqs.org/patents/app/20100166797
Mikovits et al. – http://www.faqs.org/patents/app/20100167268
The applications appear to have been coordinated (same date).
If I am reading the patents correctly (and much of it is way beyond my understanding) it appears that fundamentally, the processes differ in where they are designed to detect XMRV:
Silverman – used to detect XMRV in tissue (eg. prostate tissue), blood or serum
Mikonits – blood, serum, plasma, spinal fluid
Again, any clarification you could provide would be most appreciated.
24:46 “I think people also need to calm down a little bit about this whole thing. It's not that anybody is trying to deceive or trying to angle things a particular way…”
Actually, the CDC has been trying deceive for the past 25 years.
Dr. William Reeves, coauthor of the Retrovirology paper, designer of the study, and supplier of the study population and specimens, has repeated the same mantra for over a decade: “there is no viral cause” for chronic fatigue syndrome he said, “there are no immune system abnormalities” in CFS patients, and there are no outbreaks. He said the outbreak at Lake Tahoe reported by Drs. Paul Cheney and Daniel Peterson (the latter of the Whittemore Peterson Institue) was “hysteria”. (Is the high rate of rare mantle cell lymphoma seen among Dr. Peterson's patients a result of hysteria?)
Dr. Reeves is partly responsible for misspending millions of dollars that were appropriated by Congress specifically for CFS research on other pet projects and then lying to Congress about how the money was spent.
All signs point to Dr. Reeves and the CDC deliberately engaging in a deception.
The problem is patients have been too calm, they have let the CDC get away with these travesties for far too long.
26:29 “The CDC study–there are no positive controls in the form of a patient sample that is known to be XMRV positive. I personally don't feel it is really useful to continue with these studies unless you include those positive controls. That means WPI is going to have to give out some samples.”
In September 2009, WPI sent the CDC twenty confirmed positive samples and the appropriate methodology to help them develop a clinically validated test (http://www.wpinstitute.org).
Mindy Kitei of CFSCentral.com reported, “the CDC tested 22 independently confirmed positive controls from different labs, but in the CDC’s experiment none of those confirmed 22 was positive.”
The CDC conveniently left this fact out of their paper.
Another deception.
Dr. Racaniello, As patients we look to you and other virologists ( and rely massively on the help of patients with science backgrounds) to look for holes in these studies. We did look with a critical eye at the WPI/NCI/CC work, since many of us have not been tested. It looks like they dug deeper and deeper and confirmed their findings several ways. They grew XMRV, found antibodies and are sequencing it. No one has reported a flaw in their studies to date.
It appears from the rhesus macaques study of XMRV and related viruses like FeLV that XMRV grows in other organs and blood has some resistance, so is at very low levels in the blood. (Since we are interested in getting tested we think about this.)
Didn't WPI amplify or culture samples before they did PCR while it appears the negative studies did not? Why aren't virologists using reverse transcriptase PCR as a first choice for archived blood? WPI also used several samples over time from some donors due to the low levels in the blood. Is a sensitivity of 10 copies per ug enough? Would there be any virus budding?
When I read the CDC study as a lay person it seems like they are twisting like a pretzel to avoid using positive human controls that were available from WPI, and we've heard about the blood studies group sharing positive samples for months. It's just the tests are lagging.
Please pick apart these studies. XMRV is out there. It's no use telling people to calm down. We personally have to deal with issues of transmission, mortality and experimental treatments every day.
The only comments in Science about WPI were from the European negative studies which were done with old blood samples, and as in the CDC study used samples provided by psychologists (Wesseley and Reeves) who use their own general fatigue definitions (see the CDC' website) and public funds to try to connect this vague group to a psychological causes such as sexual abuse. And they have all the CFS research money.
We thought we'd be more firmly in the hands of retrovirologists for this one.
We want people to look hard at this and be as creative as the WPI team. Everything we read about MuLV and gammaretroviruses matches up with our illness, or cancer. Did Eric Delwart take any stool samples from CFS patients and look at every pathogen?
I think in the www world the scientific community is going to have to release more information. We need data for public policy and fundraising on what studies are happening. Grant recipients have synopses listed from applications. There was no information from the CDC or NIH. This investigative reporting was the first information on any federal studies. The publishing lag time can be long. How long would you wait to find out there were no follow up studies on an infectious retrovirus? I don't think the CDC is planning any.
http://www.youtube.com/watch?v=PnWtTcCFlJY&feat…
XMRV studies into CFS put on hold
See comment from a US government scientist:
“I am a US scientist in a government agency who is trying to verify XMRV in our blood supplies.
AABB, Red cross, NIH, FDA, CDC, HHS and other government agencies are not working together on this but are in-fighting mainly due to the politics of this very controvertial matter. the CDC negative results are out in retrovirology to dispprove XMRV because of its history of doing so and destroying Dr. Defreitas's career when she found the retrovirus 20years ago. the CDC is trying to intimidate the NIH/FDA from publishing their positive results. this is all i can tell you for now. “
In your podcast, you questioned why CFS patients distrust the CDC. The following short news video from ABC does much to explain: http://vimeo.com/13048135
It is ironic that William Reeves, who is featured in this video, is one of the authors of this new CDC paper disputing the CFS-XMRV connection.
My new XMRV video is fun to watch and will answer several questions you've raised. Since the Lombardi/Mikovits paper came out in Oct. 2009, the WPI have created new tests that they've just filed a patent for and with this new testing they say they found XMRV in >95% of the samples which is a big jump from the 67% they had found to be positive from just PCR in Oct.
The WPI have stated that not only is there a strong correlation between XMRV and ME/CFS, they believe they have found the cause.
XMRV YouTube Video: http://www.youtube.com/watch?v=3XOor24YYmw
I find it at 26.25 minutes into the podcast. Yes, I find it hard to believe that the CDC didn't use the positive controls sent to them from WPI. Or maybe they just didn't release the results, for whatever reason. They must have tested it, though. (WPI said they could document their sending of specimens and method for another company that didn't include their controls. I am confident they can also document the positive specimens and method sent to the CDC.)
I hope at a bare minimum, that they calibrated their testing with a clone positive, at least.
Still, zero out of 100 samples, healthy or not, doesn't fit. Japan's blood supply shows 2% or so Xmrv, and WPI's healthy controls show 3.75%. With unhealthy samples included, the numbers should go up. Anytime I see zero in any lab measurement, I check if the lab apparatus is working properly with the positive controls.
Suzanne Vernon, former CFS researcher at CDC, says the CDC didn't use virus isolation test tubes as specified, but used their own assortment. That could explain why Koch and the other labs didn't find any Xmrv in their testing, too.
Also, as Vince says, improper case definition could have been involved. Still, I would have thought something should have registered a positive. I wonder if Goff has done some more rigorous population studies.
At any rate, CDC could have resolved questions by showing their results with the positive controls from WPI.
Dr. Racaniello,
Thank you for this excellent podcast and for your willingness to study the link between XMRV and ME/CFS.
As Daisymay suggested, reading *Osler’s Web*, by Hillary Johnson, is the best way to understand the history and politics of the CDC’s mismanagement of ME/CFS.
An alternative to wading through that thick tome is reading Ms. Johnson’s speech “The Why†at http://oslersweb.com/blog.htm?post=604271. Delivered in London last year, it provides a succinct and powerful account of the CDC’s misdeeds regarding our disease.
For example, Ms. Johnson makes a convincing case that the CDC purposely chose a benign-sounding name–â€chronic fatigue syndrome‖to downplay the gravity of the disease and mask its likely infectious etiology.
You will learn about the atmosphere of contempt toward PWCs at CDC that led a staffer to write a fake letter mocking people with the sickness. Pinned to a bulletin board at CDC in the 1980s, it began, “Dear Sirs: I am SICK…It took me 6 days to dictate this letter to my secretary…†and ends, “I have had [the above diseases] for over 40 years now, and I am only 29 years old.â€
(The full letter may be read at http://oslersweb.com/files/dear_sirs_I_am_sick0…)
Then, of course, is the matter of the CDC’s diversion of millions earmarked for CFS research to other diseases, culminating in a 1998 Congressional investigation, as Robin pointed out.
Next, you’ll find out how Bill Reeves, as head of the ME/CFS research program at CDC, strove to re-define the disease as psychosomatic. Most notably, in 2005 he authored the empirical definition (“Reeves Criteriaâ€), which significantly broadened the “CFS†label and diagnosed more than ten times as many people with “CFS†as its predecessor, the Fukuda Criteria. (See work by Reyes et al, 2003, and Reeves et al, 2007.)
Leonard Jason PhD of Depaul University–probably the world’s foremost expert on CFS case definitional criteria–discusses the problems with the empirical definition at http://www.iacfsme.org/IssueswithCDCEmpiricalCa….
After reading his remarks, you’ll conclude that any research based on the empirical definition is virtually meaningless.
Upon completing the above tour, Dr. Racaniello, consider the CDC’s recent suppression of the positive XMRV paper by Alter et al, as reported by Ms. Johnson and Mindy Kitei, and you’ll grasp why people with ME/CFS view the CDC as we do.
quote todays UK Independent newspaper,
“However, scientists who have seen the FDA study have told The Independent that it is seriously flawed and should not be published in its present form because it cannot support its assertion of a link between chronic fatigue syndrome and XMRV.”
http://www.independent.co.uk/news/science/study…
This article is typical British journalistic sensationalism. All unsupported statement – No critique of the CDC study – cohorts, blood storage etc.
The title of the article is just as sensational in the opposite direction:
“Study that 'solves' chronic fatigue syndrome blocked”
vs.
“However, scientists who have seen the FDA study have told The Independent that it is seriously flawed and should not be published in its present form because it cannot support its assertion of a link between chronic fatigue syndrome and XMRV.”
Neither statement is worth the time it took to read it.
Concerning whether viruses are alive or not .. could it be thought that humans are a virus, and that they've taken over human bodies so they can replicate? What are humans, if they are not their human body. I look forward to future podcasts.
Please check out,
http://www.youtube.com/watch?v=YOIIyH3oECQ
My bad here. I was under the impression WPI ran an LNCaP culture before PCRing. Looks like the methods between labs are similar, so differing results could very well be explained by case definition, and maybe a bit of other things. Time will tell.
I'm thankful for all the groups that ran the PCRs. At the same time, I hope some will look further at biological amplification by LNCaP culture. Mikovits said in her ProHealth Webinar that LNCaP was key to their discovery of XMRV in CFS, and Goff said it causes vigorous replication of XMRV.
The other term for CFS is Myalgic Encephalomyelitis (ME) which is a low-grade brain inflammation. I hope we never make too many inflammatory remarks, but some of it comes from the pain in our brains. And some of it comes from mistreatment from some organizations.
Thanks for Twiv and the knowledge and wisdom that you impart.
Compliments, Dr. Racaniello, you've found acclaim on WSJ today. It appears a WSJ reporter was listening to you speak about XMRV and writes:
“And that wait may not be a short one, say experts participating in a webinar today sponsored by the advocacy group CFIDS Association of America. Vincent Racaniello, a professor of microbiology and immunology at Columbia University, said that there’s a lot of work yet to be done in patients in order to answer the key questions surrounding the issue, and the full dimensions of the XMRV story will take time to understand.
“We can learn a lot from history,†he said on the webinar, noting that it took 15 years from the time clusters of AIDS patients were identified to the development of effective therapies. Racaniello doesn’t study XMRV in the lab, but he blogs about the controversy.
In a follow-up chat with the Health Blog, Racaniello said that so far, all the published studies have been done in relatively small numbers of patients — 50 or 100 people.
What’s needed to really get answers, he says, is a 500- or 1,000-person, federally funded study conducted at more than one research site. Ideally participants would be existing CFS patients who’d be available to be interviewed for detailed medical and case histories, and who could give fresh blood samples. And centers would use uniform definitions of CFS and lab methods, he said.”
Here's the link:
http://blogs.wsj.com/health/2010/07/15/potentia…