Lipkin bad news folks

[currer]

I think we have no choice but to accept the Lipkin study. I always wanted this subject properly investigated, but to continue on with this would require a conspiracy theory of such vast proportions - I just cannot contemplate it.

You have to remember that Dr Mikovits initially found XMRV/MLVs quite readily in her samples. We are reasoning in such a way that we are pursuing ever tinier amounts of positives in blood to maintain a faith in this hypothesis.

Because of the importance of the implications of finding XMRV it was necessary to continue to look - and to pursue this - but atm I cannot take this idea further.

A couple of things trouble me. There was no discussion of the fact that XMRV is a genuinely new lab-created recombinant which has been transmitting itself within laboratories. There was no admission that this happens inadvertently and will occur again.

If MRVs are to be used as gene vectors we still need to ensure there are no MRVs of any kind in the population prior to their release. That 6% positive in controls by serology cannot simply be dismissed.

I would like to see a proper study of Dr Snyderman's blood results. Just ignoring his improvement is unacceptable.
I think we should know why he has improved.

I suppose there could still be an association of MRVs of some kind with disease - O'Keefe has found some evidence of this in prostate cancer.

The good thing is - an idea once thought - cannot be un-thunk!
So once an idea is out it cannot be put back into the bottle. This is good or bad depending on your perspective.

 

[Bob]

Even if the "cohorts" weren't perfect and not all the patients had CFS/ME then I would speculate that there would be more positives in the population, other than the ones they found and were discounted.

I think the point, that asleep was making, was that we don't know how many individual positive samples, by PCR, there were, because the information isn't given in the paper. I haven't read the paper in detail, so I can't comment on this.

 

[xrayspex]

Barb-This is a bit of a tangent, but what would you say are the main differences between evidenced based medicine and science based? I thought EBT people claim the point is their practice is based on science. I do have qualms about ebt though, its all the rage now, insurance-wise too but I am skeptical because it seems to limit things too much and so how will new ideas get generated......seems like a quandry.

 

[jace]

Why was Lipkin so quick to dismiss tissue sampling and autopsies, as shown in the press conference? Surely, the Macaque study showed us that the MRV quickly cleared from blood (within two weeks of infection, as I recall) and takes up residence in lymph tissue... Any MRV, not just XMRV, might behave in that way, for all we know.

Lipkin studies pMLV's not pMRVs.

ETA When Mikovits was at the WPI, these slides were part of a talk on the way forward. A long way from what happened in the Lipkin Study...

 

[Bob]

Just to add some more info, for balance...

Why was Lipkin so quick to dismiss tissue sampling and autopsies, as shown in the press conference?

Lipkin said in the press conference that the reason for this was that his study was an attempt to replicate the original studies. Mikovits and Alter found XMRV/PMRV in blood, not tissue.

He also explained that testing tissues would have added vast complexity to the project, such that they would only just be getting ready to take samples. He wasn't saying that's not a reason to not do it, but he didn't think it was necessary considering Mikovits' and Alter's results with blood.

Jace, those slides are interesting, and demonstrate part of the reason that I now think that XMRV was probably a contaminant. You include a slide that says they intended to determine if the HGRV isolates had been integrated into human DNA. The results of this research have been remarkably quiet (well, non-existant, actually) and I wonder if any negative results have been withheld from us, because they are inconvenient? They have had years now to get the isolates sequenced with NGS, and we haven't heard a peep about the results. I suspect that the results were not favourable to the HGRV hypothesis, and it might be why the WPI has moved on from HGRV research. This is purely speculation, because there just isn't any information available, and I'd like to know why not. Also there have been various aspects of contamination that has been admitted by various parties, but has been kept fairly quiet, and I wonder if we've even heard about all of it.

I do agree, though, that there are still a lot of questions, raised by all the research, that have not been answered.


BTW, Lipkin says he is going to carry out NGS in his pathogen study, including looking for retroviruses.

 

[currer]

You have to assume good faith on the part of the researchers.

One thing that distressed me on these forums was the assumption that individual researchers (Mikovits and Ruscetti) were committing "fraud" when their results seemed questionable. And similarly researchers who were against the XMRV hypothesis had a perfect right to that opinion - just disagreeing with research findings does not necessarily mean you can or should attribute improper motives to someone. Debate gets heated, but you must see it as debate, and not attack the integrity of individuals.

I cannot see that researchers of the calibre of Alter or Ruscetti would allow their work to be distorted.
(Dr Ruscetti particularly does not look as if he could be pushed around)
If they stand by the Lipkin trial results, we must accept it.

But there will be further research on pathogens, including retroviruses and human disease.

We do not know what will occur in future.

 

[currer]

In response to Bob, no-one seems to want to sequence samples from Dr Snyderman, and I am not happy about this.

http://www.x-rx.net/blog/2012/09/now-you-see-it-now-you-dont.html

"For medical-legal reasons, I had to have a personal one man drug trial. As an Oncologist I can say that my leukemia is garden-variety common every-day cancer and very representative of cancer in general. I agree that further study needs to be done, which is exactly my point. I am offering my sample and that of other physician-patients with cancer and CFS. I am sure that our material will be positive for retrovirus. I can’t imagine why scientists would not be interested in this offer.
Michael Snyderman, MD"

"What one finds depends on the quality of the sample one looks at. I am offering my blood and that of three other physician-patients with cancer and CFS. These are high quality samples. I am absolutely amazed that no scientist has offered to look at these.
Inaction speaks louder than words.
Michael Snyderman, MD"

 

[Mula]

Yes, Lipkin said, in the TWIV interview, that the interpretation was agreed before commencement of the study.
He said it was necessary to agree this beforehand, so the targets were not moving after the study commenced. (I think that his implication was that this was to avoid confusion and arguments at a later date.)



I was under the impression that she had influence over the selection criteria.
I thought that I had heard this stated in the past, but maybe my memory is false.
Maybe I have not seen or heard any evidence either way.



I think it's impossible to pick a perfect CFS/ME cohort.



In the TWIV interview, he described a comprehensive search for known and unknown pathogens, also looking at proteins and genes, using NGS/high throughput techniques, using faecal swabs, tears, saliva, blood. And there has been a suggestion that he is using spinal fluid as well.

He specifically said that if retroviruses are present, then he would 'hope' that they would show up.

But that all depends on whether people trust him or not.
I'm giving him the benefit of the doubt, because I've got no evidence to cause me not to trust him.
Plus, I would go insane if I harboured thoughts that there was a government conspiracy to hide a virus that caused my illness, that I had no power to change.

The laboratory scientists were told how the study would be interpreted. No other options were given and there was no negotiation, apart from the months it took the physicians to define the patients who had no abnormal laboratory findings. Dr Lipkin does say that CFS is not a single disorder, so the PCR detection data should be freely available to patients, unless there is a concern that they would not react well if 100% of the patients were found to be PCR positive in comparison to 0% of the controls, for example. Even a figure of 20% to 5% would be highly suggestive of a retroviral infection in a proportion of a CFS cohort. Which is what Dr Lipkin would expect to see in a constellation of disorders. The Lombardi study never had arbitrary instructions on interpretation for percentage of positives, so why have that imposed onto the data in this paper?

The use of NGS for known pathogens is proceeding with set primers. Those won't detect unknown retroviral sequences. This is not an issue of trust I am sure you will now agree.

 

[Bob]

The laboratory scientists were told how the study would be interpreted. No other options were given and there was no negotiation...

And what is your evidence for that, please?

...the PCR detection data should be freely available to patients...

I agree with that. Maximum transparency is obviously preferable in all medical research, and especially as it's a publicly funded study.

The use of NGS for known pathogens is proceeding with set primers. Those won't detect unknown retroviral sequences. This is not an issue of trust I am sure you will now agree.

Whatever the current state of his pathogen research, he has stated that he is going to carry out a pretty comprehensive pathogen study, and he gave some of the details regarding NGS etc. Listen to the TWIV interview if you're interested.

It's seems impossible to find any information about his pathogen studies, so I've only got what he said in the TWIV interview as a source of info.

 

[ukxmrv]

I guess when it boils down to it Lipkin has done nothing to bring our understanding of ME closer and to help us with a cure.

That's not to say that he won't in the future though. It remains to be seen and I'm sure that PWME will examine everything closely as we have always done.

 

[barbc56]

Well this is how science works. I don't think anyone expected this study to find a cause of our illness. However we can rule out xmrv and the other virus, brain fart here, so that does add to our knowledge base.

It's frustrating I know but sometimes things like this can't be rushed. In a perfect world the economy would be strong enough so that more money could be spent on research and everyone would have insight of our plight. And world peace, always world peace.

Unfortunately, the reality is different than that perfect world.

This is a step forward, albeit a tiny one and it does add to our knowledge aboue me/cfs. But at least, IMHO, we are going forward even if it seems like, (and sometimes is),going three steps forward and two steps back.

I am not saying people should not question and examine. However our energy and resources would benefit from concentrating on other causes which could conceivable, though I don't think likely to include other viruses as a causative factor.

Take care.

Barb C.:>)

 

[barbc56]

Barb-This is a bit of a tangent, but what would you say are the main differences between evidenced based medicine and science based? I thought EBT people claim the point is their practice is based on science. I do have qualms about ebt though, its all the rage now, insurance-wise too but I am skeptical because it seems to limit things too much and so how will new ideas get generated......seems like a quandry.

It's confusing and not all scientist or the medical community go by the strict definitions so at first glance the two concepts might look the same.

Good science is the best and only way to determine which treatments and products are truly safe and effective. That idea is already formalized in a movement known as evidence-based medicine (EBM). EBM is a vital and positive influence on the practice of medicine, but it has limitations and problems in practice: it often overemphasizes the value of evidence from clinical trials alone,

Within the practice of medicine there is already a recognition of the need to raise the standards of evidence and the availability of the best evidence to the practitioner and the consumer – formalized in the movement known as evidence-based medicine (EBM). EBM is a vital and positive influence on the practice of medicine, but it has its limitations. Most relevant to this blog is the focus on clinical trial results to the exclusion of scientific plausibility. The focus on trial results (which, in the EBM lexicon, is what is meant by “evidence”) has its utility, but fails to properly deal with medical modalities that lie outside the scientific paradigm, or for which the scientific plausibility ranges from very little to nonexistent.

My bold.

http://www.sciencebasedmedicine.org/index.php/about-science-based-medicine/

The difference is that SBM includes the plausibility of a hypothesis based on how the body works, current knowledge, other studies, etc. This is called a priori.

An often cited example of evidence based medicine would be a study that compares death rates among parachuters: wearing parachutes vs. those not wearing parachutes.

A lot of alternative medicine studies rely on EBM vs. SBM. They only consider the studies to the exclusion of other factors.

These terms are sometimes used interchangably by those whose interpretation of evidence based medicine semantically means the same thing. The distinction between the two is a recent development.

If other's want to weigh in on this, please do, as I may have been too simplistic, left some important information out or misinterpreted some of the facts in the distinction of these two definitions. It's late, I'm putting off going to bed even though I am extremely tired.

The above also includes references that go into greater depth about SBM vs. EBM.

Sorry about getting side tracked.

Barb C.

 

[snowathlete]

I guess when it boils down to it Lipkin has done nothing to bring our understanding of ME closer and to help us with a cure.

He hasnt been at it long don't forget. He has only just become involved and his first task was to check someone else's work. Which in fairness he did do well as this work was the first that the original authors felt confident in enough to accept that they had made a mistake in their original work. None of the other dozen or so replication studies achieved that.

Lipkin has only just started looking beyond the very specific search for one/two retrovirus(es). Hopefully, he will now find something but we have to give him time to do what he good at. In one to five years time he might be all our favourite person, or he might not. We will just have to wait and see, but he certainly sounds confident, so I am hopeful.

 

[Bob]

And let's not forget that this study wasn't only a Lipkin study.
Mikovits, Ruscetti, and Alter were all involved: All three signed up to it, and they have signed up to its conclusions.
Obviously, there are still questions unanswered, but these scientists know something about what they are doing.
And if they want to continue retroviral research, or CFS/ME research, then they can. (Hopefully Mikovits will find employment somewhere.)

 

[natasa778]

And let's not forget that this study wasn't only a Lipkin study.
Mikovits, Ruscetti, and Alter were all involved: All three signed up to it, and they have signed up to its conclusions.
Obviously, there are still questions unanswered, but these scientists know something about what they are doing.
And if they want to continue retroviral research, or CFS/ME research, then they can. (Hopefully Mikovits will find employment somewhere.)

Does anyone remember Ago of Autism article by Kent Heckenlively of few months ago about an eminent scientist who was being threatened with losing job and pension etc unless he publicly agrees with certain conclusions of a certain study that he didn't support. The article has since been taken off. I would LOVE to hear more.

 

[Bob]

Does anyone remember Ago of Autism article by Kent Heckenlively of few months ago about an eminent scientist who was being threatened with losing job and pension etc unless he publicly agrees with certain conclusions of a certain study that he didn't support. The article has since been taken off. I would LOVE to hear more.

Yes, I remember that, but I never worked out who it was referring to. Did anyone else?

 

[Bob]

Lipkin has always asserted that Mikovits was in charge of her own research design, and it seems that I was correct when I said that Mikovits designed her own methodology, including deciding how to determine if a sample was positive or not...


If I remember correctly, the 'International ME Association' was set up by members of one of the other forums.

This is posted on their facebook page...

> In response to patient questions about whether or not any "positives" were found by labs in the Multi-Center study, Dr. Ian Lipkin replied (quote):

> "The investigators reported results as positive or negative according to their own criteria. The only requirement was that once criteria were established results could not be changed through modifications in criteria. I know this is not the intention of those who continue to pose these questions; nonetheless, the impact of this continued challenge to work of the team is that some people in the scientific community who might contribute are becoming reluctant to work on CFS/ME. Additionally, it causes distress to Mikovits, Ruscetti, Alter and Lo who have already spoken their views and would like to invest their expertise and resources productively. The origin of XMRV as an artifact has been clearly established in CFS/ME and prostate cancer."

https://www.facebook.com/permalink.php?story_fbid=478847245480642&id=191236810908355

 

[Bob]

This response from Lipkin, above, suggests that some significant mis-information has been posted on this thread, by a couple of members who have failed to provide evidence for their assertions, re the criteria for determining positive samples.

 

[patient.journey]

http://trialx.com/curetalk/2011/11/...equencing-and-proteomics-to-hunt-cfs-viruses/

Dr. Ian Lipkin, Hunting Down Viruses using Deep Sequencing, as Seen in the NYTimes.
In the end, cutting edge technology may be the game-changer in chronic fatigue syndrome – a condition that strikes an estimated 1-4 million patients in the United States.
Viral involvement and immune system abnormalities have long been suspected as contributing or causing the disease. But for many reasons, including the multiple definitions used, delays in diagnosis and small sample size, study results have been mixed.
Now however, researchers have powerful state-of-the art tools at their disposal, and the Center for Infection and Immunity at Columbia University stands at the nexus.
“We have the best tools to do the work and the funding required to pursue it,” said center director Dr. Ian Lipkin, “and will bring the very best possible minds to the problem irrespective of institution. We will be taking a broad, open-minded approach to the problem.”
The CII, and other institutions, using venture philanthropist seed money provided by the Glenn Hutchins Foundation, will focus their efforts on three components:

• Identification of disease markers.
• Disease mechanisms.
• Finding the specific bacteria, fungi and or viruses – alone or in combination – responsible for causing or exacerbating the disease.

The research will be two-pronged and coordinated by Dr. Mady Hornig, an associate professor of epidemiology at the Mailman School of Public Health and director of Translational Research at the CII.
Multiple deep sequencing platforms will be used for pathogen discovery.
“One of the challenges in a chronic disorder like ME/CFS is that we may be dealing with a situation where the trigger, which we have good reason to believe is an infectious trigger, may precede the onset of symptoms or recognition of the chronicity of the pattern by quite a long period,” said Dr. Hornig. “The agent could have a hit and run; its levels reduce over time, or induce a biologic situation even in the absence of continued high levels of infectious agent.”
Unlike microarray chips that have a finite number of known pathogens for testing, deep sequencing allows researchers to find not only an unlimited number of varying strains of known pathogens, but novel pathogens as well. Testing will most likely be done at a sequencing center pooling the resources of several large centers as the equipment is very expensive and personnel have to be specially trained, according to Dr. Hornig.
Researchers will be looking for patterns that are consistent across geographic areas, time and clinical status, said Dr. Lipkin.
“We show quite clearly a wide range of infectious agents can trigger similar pathways in immune system that result in similar outcomes so it may well be that there are many pathogens who have capacity to cause chronic fatigue syndrome by either inducing autoimmunity or some sort of impact on the immune function which results in activation,” said Lipkin, who plans to examine other hypotheses as well depending on the results of initial tests.
Defining biomarkers through the use of proteomics will also be carried out at the Yale Keck Biotechnology Resource Laboratory as well as at Columbia University.
In terms of disease in general, biomarkers, that is proteins that carry out body functions, have been analyzed for diagnostic purposes for more than a century. Recent advances in protein analysis have expanded the opportunities. Proteomics, which is the study of proteins in a specific time frame, is currently the best bet for creating new approaches to diagnosing and treating human disease, and designing new drugs to treat disease.
“The effort in ME/CFS is to try to find some biomarkers that will be likely to identify a set of pathways that are likely to involved. That will be an enormous gain for the field and of course the patient,” said Dr. Hornig. Biomarkers in ME/CFS can be used to create diagnostic laboratory tests as well as to determine therapy response and prognosis.
The key to maximizing the outcomes of these tests is the criteria of the patients selected, according to Dr. Lipkin. He said this will give the greatest possibility of finding objective measures for monitoring and measuring the disease. University of Miami researcher and physician Dr. Nancy Klimas, who has been involved in several clinical definitions of ME/CFS, is in charge of the cohort recruitment to draw 200 patients from five sites located throughout the U.S.
“What we want to do is start with patients who have been characterized extensively using standardized criteria established by a group of widely respected clinical researchers,” said Dr. Lipkin.
Both Dr. Lipkin, who is a board certified neurologist, and Dr. Hornig, who is a board certified psychiatrist, stress that while they believe ME/CFS is a neuropsychiatric disorder because of the problems with concentration, memory and autonomic nervous system involvement, they do not consider it psychosomatic.
“It’s very difficult in my mind to make this a psychological disorder,” said Dr. Hornig,“We do patients a disservice if we focus solely on secondary phenomena of being disabled or being unable to carry on life to your capacity – that shouldn’t ever be viewed as being the primary problem.”

 

[snowathlete]

Hopefully there isnt too much damage caused by the challenged Lipkins talks about above. With the negative press our illness gets, the last thing we want is more reasons for scientists to stay clear of looking at the condition.

Omar88, thanks for posting that article. I read the same article last night but couldnt find it again today. I think this article is really one of the best i've read. I sent it to family and friends because it gives a really good explaination, briefly, about what the study is aiming to achieve. There is a real possibility that the results of this work could be game changing for us in my opinion.