Interview: Ian Lipkin’s Million Dollar Appeal for Microbiome Study

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Simon McGrath recently secured an interview with the world famous Dr Ian Lipkin – a scientist who continues to believe that ME/CFS has a physical cause – to discover more about his plans for a major study of the gut microbiome and to find out why he's asking the patient community for its support…


Dr W. Ian Lipkin has demonstrated a clear commitment to ME/CFS research. First came his study looking at Borna virus in the 1990′s, and then the landmark study that ruled out XMRV as a cause, and most recently we have heard about the huge pathogen and immune study – a vast collaboration with many key clinicians and researchers, including Dr Dan Peterson and Professor Jose Montoya.

That research had already found clear signs of immune activation in patients and, when I spoke to him, Lipkin was clearly excited about the very latest results to emerge from the study - I wish I could reveal more, but a paper has just been submitted and details are embargoed until publication.

Lipkin believes that immune activation may be responsible for driving the symptoms associated with ME/CFS. And that the immune activation and could itself be triggered by bugs, not in the blood, but found in the vast ecosystem of bacteria, viruses and fungi, that constitute the gut microbiome.

However, he doesn’t have the funds to pursue this research and so he’s appealing to the patient community for the one million dollars he needs to get the work done. The payoff? A better understanding of the illness and the possibility of new treatments.

Dr Lipkin on ME/CFS

Lipkin made a splash in the world of ME/CFS when he led the XMRV study that both disproved its role in the illness and also managed to unite the patient community. At the press conference for that study he said his first brush with CFS was a large study in the 1990s that demonstrated no connection between the Borna virus (one of many viruses he’s discovered) and CFS. But he stressed that their findings in the same study of B-cell activation in CFS patients was a clear sign that this was not a psychosomatic disorder. The findings in his new study have only confirmed his views:

“There is no question in my mind that this is a physical disorder. The fact that we haven‘t been smart enough or invested enough in it to sort that, doesn’t mean that this is anything else.”

The smoking gun

The immune activation he’s found could explain fatigue – it’s almost a universal symptom of infections like flu, and is actually a consequence of immune activation rather than caused by pathogens themselves.

The same could be true of other ME/CFS symptoms including disturbed sleep and brain dysfunction which again are typical symptoms of immune activation.

Lipkin is eager to build on this work. He believes the immune activation is a smoking gun and now wants to track down who or what pulled the trigger.

“I am more keen than ever … to see if we can identify the trigger”
- all quotes are from Dr Lipkin

There are several credible places to look for the culprits triggering the activation. One is white blood cells: some viruses could be hiding out in cells and so wouldn’t have been found by the initial search in the blood plasma – and Lipkin already has a white blood cell study lined up.

However, his attention is particularly focused on the microbiome, the large ecosystem of bugs that live on our skin and within our ‘inner tube‘ that leads from mouth to bottom.

There are at least one trillion bugs in the gut microbiome – and there are more immune cells in the gut than anywhere else: it’s a great place to hunt for bugs that might be triggering immune activation.

Microbiome problems are increasingly being linked to serious illness. The most striking example is the superbug Clostridium Difficile (C. diff), which has become a major problem in hospitals. C. diff lives in most of our guts harmlessly at low levels, but it can take over (particularly if ‘good’ bacteria are killed off) – causing diarrhoea and even death. Happily, doctors have discovered that severe C. diff cases can be treated relatively easily by restoring the microbiome; unhappily, this involves a faecal transplant.

The potential to treat disease by restoring the microbiome is one reason this area of research is attracting so much attention. This recent article explains more about the microbiome, how it might link to ME/CFS and looks at other research being performed.

“If the answer were simple, it would be done by now”

Irritable Bowel Disease is another example – here inflammation is believed to result from changes in the microbiome. Lipkin’s team have just been studying women in sub-saharan Africa and found that certain bacteria in the vaginal microbiome increase the risk of HIV infection. Lipkin thinks the gut microbiome could be playing a similarly important role in ME/CFS:

“By analogy with animals and human situations, we see that different populations of fungi, bacteria and viruses in the colon can have an impact on the immune system and give rise to cytokine activation which could cause the symptom complexes we see in ME/CFS”

in other words:

changes in microbiome > immune activation > symptoms of ME/CFS

I asked Lipkin if this meant particular bugs causing inflammation and he said that is certainly possible. But, he added, another route to illness is that an overgrowth of ‘’bad’’ bacteria could form a film, preventing ‘’good’’ bacteria from interacting positively with the immune system (see this article for more) – an indirect way of causing immune dysfunction.

The exact role that microorganisms in the gut play in health and in the development of disease is complex and still being determined. There are many plausible hypotheses, says Lipkin, and only research can show which (if any) are right.

If the microbiome is the cause, is it treatable?

If the microbiome is the cause (or a cause, or even a contributor) of ME/CFS, it might be relatively easy to treat, perhaps with probiotics, restriction diets, drugs, or even faecal transplants.

Cause or effect?
Of course, the first step in this process is demonstrating a strong link between the microbiome and ME/CFS. If one is found then the next step is to look for evidence it plays a causal role: i.e. do microbiome changes cause immune dysfunction, as opposed to being a consequence of or simply associated with immune dysfunction?

Lipkin says one option is to use an animal model: the idea would be to introduce the microbes suspected of triggering ME/CFS into the gut microbiome of animals, to see if this leads to similar symptoms and immune activation as seen in humans. Something that has been used to study Metabolic syndrome.

Personalised medicine
If there is evidence of a causal role, Lipkin says they would look to establish clinical trials of treatments that could include probiotics, antibiotics followed by prebiotics, restriction diets and possibly even faecal transplants. He believes that there would not be a single microbiome cause of the illness, but different types – potentially fungal, bacterial and viral problems causing three separate types of immune dysfunction.

Lipkin calls these different types ‘endophenotypes’ and it could lead to personalised medicine, where the particular treatment depends on the specific form of the illness. There will be endophenotypes beyond those in the gut, such as genetics endophenotypes, and it is highly unlikely that the microbiome would account for all forms of ME/CFS – but this approach could tackle a very substantial proportion of cases.

The study breakdown

Lipkin’s proposed study will look at all three trees of life: bacteria, fungi and viruses in the microbiome of 100 patients and 100 controls recruited for a previous NIH study. It will cost a cool million dollars:

1. Sample collection: $150,000
Collection of faecal (and blood) samples from patients, including checking the initial ME/CFS diagnosis remains valid and shipping chilled samples back to the labs at Columbia.

2. Faecal Microbiome sequencing and Analysis: $317,000
- Separate, purify and perform high-throughput sequencing of viruses, fungi and bacteria
- Complete sequencing of viruses; partial sequencing to identify bacteria (using 16S rRNA) and fungi (using ITS, the ‘fungal barcode’)
- Generate microbiome profile for each patient, one each for bacteria, fungi and viruses​

Comparison of patient and control microbiomes: bacteria, fungi and viruses that differ in prevalence between CFS subjects and controls will be considered candidates for contributing to either health or disease.

3. Development of highly-accurate real-time PCR assays to confirm findings and levels of microbes: $328,000
This will quantify how much there is of each bug of interest (the main high throughput sequencing approach gives an indication of quantity but is less accurate than real-time PCR).

It’s possible, that the most important thing isn’t the presence or absence of a microbe, but the amount of it – as with C.Difficile. These assays will also be used to check that key microbes haven’t been missed in any patient or controls who were negative for them in initial sequencing, as PCR assays are far more sensitive than high-throughput sequencing.

4. Cytokine analysis: $86,000
The study will again measure cytokines in blood and undertake data analysis to see if there is an association between cytokine profiles and immune profiles. It would then provide strong evidence of an important relationship between the microbiome and immune dysfunction – the hypothesis driving this study. Sophisticated analysis will be required on the vast amount of data generated by microbiome and cytokine profiling; happily, Lipkin’s Center for Infection and Immunity have a team of biostatisticians dedicated to such work.

5. Development of antibody tests for important bugs identified by the microbiome work: $249,000
It could be a few individual species or particular groups of microbes, but antibody tests will be developed by Lipkin’s lab to allow much easier testing to see if the same problems in this sample are found in the wider patient population.

As well as guiding treatments, the PCR assays and antibody tests developed here could both provide a diagnostic test for ME/CFS.

Lipkin’s record



Featured in the New York Times, described by Discovery magazine as the world’s foremost virus hunter, and consultant to a successful Hollywood movie, Dr W. Ian Lipkin has a higher profile than most researchers. But this profile is built on a stellar scientific reputation.

He’s discovered more viruses than anyone else. He’s part of the World Health Organization (WHO) diagnostic discovery and surveillance programme designed to catch pandemics as they arise. And the Chinese recruited him play a leading role in their fight against SARS.

Amongst other things he is John Snow Professor of Epidemiology and Director, Center for Infection and Immunity at Columbia University. Full biography.

He is passionate about communicating science to a wider audience but is insistent the science is right.

Lipkin only agreed to consult on Contagion, a movie about the terrifying potential of epidemics, because of director Steven Soderbergh’s desire to make a film that was true to the science – having turned down offers to advise on several movies with somewhat wilder plots.

When Lipkin was shown a near-final version of the film he threw up his hands at the scene near the climax where a scientist injects herself in the leg with the new vaccine, through her tights – a poor practice that could easily introduce an infection.

This might seem a small detail given everything else the film had right, but Lipkin was adamant it had to go: cue a $100,000 reshoot.

This near-obsession with getting things right is a Lipkin hallmark. The very first point he made to me about this study, before discussing any details, was the need for real, robust findings – because there have been too many false dawns in this field.

At the end of the interview he emphasised the need of crisp, rigorous data. Whatever the findings from this new study – positive or even negative, we should be able to rely on them.​


Scientist in a hurry for answers

Dr Lipkin is a scientist in a hurry for answers. That’s true both in his work trying to stop a new pandemic in its tracks, and in his work on ME/CFS.

He wants to follow up as many promising leads as possible, as soon as possible – rather than waiting for the results of a single study before planning a new one if the first draws a blank.

That’s why he set up a huge study looking for specific pathogens such as EBV, but also used deep sequencing alongside that to search for any other pathogen, known or unknown.

He’s looked in blood plasma for pathogens but is also about to look for them in white blood cells too.

He set the study up to look at immune markers including cytokines as well as for pathogens – and the significant findings of immune activation show the value of backing more than one horse.

On top of all this, Lipkin has invested in a gene expression study using samples from the same study, with results expected shortly that could throw up new leads in epigenetics and genomics.

Dr Lipkin has committed a huge amount of his 60-strong institution’s time to pursuing numerous studies, all aiming to uncover what’s really going on in ME/CFS

Too much, too soon?
However, it may be that the NIH is not in such a hurry as it has declined to fund the study at this time.

But then the NIH has only ever committed relatively small amounts of funding to ME/CFS – around $5 million a year, compared with around $115 annually for MS and $284m for Asthma.

Its funding record firmly suggests the NIH’s priorities lie elsewhere.

So, as Lipkin says, “we are stuck”. It’s possible that the NIH will fund this work in the future, and possible they won’t.

The question is, do we want to wait?

“We are already well behind where we should be”

Dr Lipkin has now appealed to patients to fund his latest study that aims to hunt in the gut microbiome for the ‘trigger’ of the immune activation his study found in ME/CFS. And he needs a cool million dollars to pay for the study outlined above.

Actually, the study comes to a bit over a million dollars (see above) - $1.13 million, to which another $140,000 of costs for maintaining the high-tech equipment used and general lab costs making $1.27 million in total. However, the initial target has been set at $1 million.

In his CDC telecast to patients last September, Lipkin explained the microbiome project was being held up by this lack of funds, and urged patients to contact their representatives in Congress.

He also appealed directly to patients who could afford to do so, to invest in research:

“it may not be appropriate to pass the hat, but that is exactly what I am doing”

How long will it take for the results? “Within a year”, said Lipkin

The man is in a hurry, and the study is all set up and ready to go – once funding is available.

“As long as I can do it, I will do it. I‘m eager to start, I‘m optimistic it will bear fruit, it‘s not just an academic exercise, it could lead to treatment”
When I mentioned to Dr Mady Hornig, the Principal Investigator on this study, that I was interviewing Dr Lipkin she added: “Terrific – we need the resources to get this done”.

Crowdsourcing: Together we can make it happen

I do think we are very lucky to have Dr Lipkin on our case and believe that we should back his new study, which will be performed at his Center for Infection and Immunity, Columbia University – the world’s largest and most advanced academic center in microbe discovery, identification and diagnosis.

“Why don‘t we crowdsource this, we are all losing valuable time in our lives?”
Vanessa Li, Phoenix Rising member and fundraiser

ME/CFS patient, Vanessa Li, responded to Lipkin’’s call last year, by contacting his office and suggesting crowdsourcing in a similar way to MEandYou, which through the efforts of Dr Maria Gjerpe had raised an astonishing $0.5 million towards the Norwegian Rituximab trial in 90 days.

Lipkin was a physician in San Francisco at the start of the AIDS epidemic and commented how, when the government was reluctant to pay, much of the important early work was funded by private donors so he’s very open to this possibility. He continued to seek funds for his work from institutions, but as that hasn’t worked he is now asking patients if they can make the study happen - and has given this interview to launch the million dollar appeal.

Donate to the the ME/CFS microbiome study
I have just donated and hope many other patients will do too. Just click on the button below and follow the instructions. The option is to donate to CFS research, but in the next page you can add ‘special instructions’ such as ‘for the microbiome study’.

We need only for every US patient to donate $1. Or one in ten patients to donate $10.


If people want to do more to help – and this is a big target – they can help to promote this crowdsourcing initiative at this new group, or email Vanessa Li. I will give her the last word:

The CDC says there are more than one million ME/CFS patients today in the US alone. There is no reason why, if every patient were made aware of Dr. Lipkin’s appeal and donated $1, that we should fail to raise the $1 million. An esteemed researcher doing high-caliber work is taking a serious interest in finding out the cause of our desperately under-researched illness. Now is the time to act!​

Simon McGrath tweets on ME/CFS research:


Phoenix Rising is a registered 501 c.(3) non profit. We support ME/CFS and NEID patients through rigorous reporting, reliable information, effective advocacy and the provision of online services which empower patients and help them to cope with their isolation.

There are many ways you can help Phoenix Rising to continue its work. If you feel able to offer your time and talent, we could really use some more authors, proof-readers, fundraisers, technicians etc. and we’d love to expand our Board of Directors. So, if you think you can help then please contact Mark through the Forum.

And don’t forget: you can always support our efforts at no cost to yourself as you shop online! To find out more, visit Phoenix Rising’s Donate page by clicking the button below.


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Comments

@Wally Maybe we can try to put some pressure on the NIH to cough up some funding by shaming them for the lack of funding in the past, present, and the CDC misappropriation incident.

$1 mil is nothing relative to our collective disability.
NIH isn't about to cough anything up after they spit on us. I hope I am wrong, but I doubt it for the time being. They have shown at least me that they have no shame.
 
We are working on it. The pressure will most likely need to come from Congress and of course a more unified voice from the ME/CFS community. :woot: More to follow on this plan very soon . . . :nerd: Lots of :hug: working on this as we speak. ;)
Thank You Wally! :):thumbsup:
 
Yes, we did ask this, partly prompted by your questions on another thread and the breakdown was given in the article. I do hope you were persuaded to donate by what CII told you.
I would argue the high tech equipment maintenance costs (about $30k, I think) are actually a direct cost of the study, leaving "admin" which includes providing the building, heating and lab benches, general service costs amounting to around 9%. That struck me as fair enough.

Feel free to publish the detail here (assuming it's the same one page breakdown I had) - I checked with Columbia and they were ok for it to go public (but my article was long enough without includig any more budget detail!).
Thank you, Simon (from Wally)




I phoned Columbia this afternoon. The weather there is getting awful!! AS I said earlier, I donated. Thank You, Simon.
 
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@Simon , thou art too humble... obviously the two people I owe the greatest thanks to are yourself and @Firestormm , about whom I can say the same thing--without either of you this also would not have happened! Shouts out also go to @Sasha , @Legendrew, @Mark and any other member of the Content Team I might've missed.

Thought I would take this opportunity to report that Columbia has informed me that, from 10/2013-2/2014, they have received 14 gifts for ME/CFS research totaling $2,935 :balloons::balloons::thumbsup: Unfortunately I do not know how much of that total went to the microbiome study, and I strongly suspect that not all donations given after Simon's article came out have been processed (seeing that I only sent Columbia this enquiry yesterday evening). If you would like me to find out please tag me in a reply and I will ask how much of that total went to the microbiome study specifically.

:woot: THANK YOU EVERYONE!!! :thumbsup:
I Phoned Columbia this afternoon. Add me to the tally. Izola
 
This study could be a very, very good thing for us. I also, and I believe Dr. Lipkin does to that the science and data from this study could reach way past ME/CFS patients well into other diseases with unknown cause. As well it could lead to better and more efficient treatments for many known diseases that currently have treatments available.

This is what I wish the NIH and CDC could envision and do what it takes to get this study completely funded now!!!!

I believe it is time to write my senator another letter! In the mean time I think I might have a yard sale to see how much I can come up with to make my contribution. If we have to build this road one brick at a time, then that's what we have to do. We should be use to it as we have done before in some form or fashion!

The NIH and the CDC could, but don't want to, envision anything for us except for us to go away.
 
I am happy to report that I just received an email from Columbia that says that yesterday (2/11/14) 66 gifts were received for the microbiome study for a total of $5,312. Thank you so much, everyone!! :balloons::balloons::balloons:
@Izola

I think this was the latest total we received, so as at Tuesday it was $5,312 :)


I believe Vanessa will try her best to keep this thread manually appraised on the total, until we can set something up that is more automatic.
 
If he is using the samples from his earlier study, then I think that may explain the unusually fast estimated turn-around time.

He has a reputation for results, though I haven't been keeping up with anyone for the past 7-10 years.
 
@biophile
I can't find it in the article itself (fatigued!) but I listened to Simon's recording of the interview several times and I know for a fact that at one point Lipkin answered Simon that he DID apply to the NIH for a grant for this study but was turned down. In short: with respect to microbiome work, neither the NIH NOR the CFI are giving him any money.


NIH wouldn't give us anything if we fell dead at their door. I forget who NOR and CFI are. Or maybe I didn't know in the first place.

Maybe someone could give the rest of us a clue. The alphabet stew and other non-usual references can confuse newcomers and those unable to be regulars.
 
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Thank you vli. That is not enough, of course.

I want to explore methods of doing online fundraising for this, but I can't put any effort into it today. I've spent my morning composing an email to a German reporter about the science behind the illness. Constantly trying to "enlighten" above and beyond the "depression" stigma.

Anyway. Segue, pardon me.
 
Whether or not Lipkin was officially turned down by the NIH is an interesting question.

When patients complain about a severe lack of funding, it is sometimes claimed that there has simply been a lack of quality proposals rather than a lack of available funding. I am not savvy in the complex politics of grant funding, but I have doubts that this reason alone can explain the severe lack of funding. Something else, such as politics or a lack of will, is also going on.

Are we supposed to believe that someone such as Lipkin is too incompetent to put together a quality proposal for a promising lead? Obviously application of a grant is no guarantee of success, but still, the reasons for rejection should be explored.
I had the same thought myself... its like they are talking out of both sides of their mouth.

1. Not funding because of lack of grant proposals.
2. Get a grant proposal from a well known, well respected, research lab at a major university to study a hot topic (microbiome) in an underserved and expensive (to society) illness.
3. DENY!

4. Instead give 1M to IOM against all expert advice.
 
Simon,

Well done on this article. I did some of my own due diligence and talked directly with Columbia to make sure that any money that I donated would go directly to Dr. Lipkin's project. I am confident that the majority of the money that I donate will go directly to fund this research and the amount going to overhead for the project will stay within the 10% ball park that I believe is an acceptable level for an organization to use for administrative and other overhead costs.

I just want to be sure that when others decide that they too would like to make a donation to this research project that they look at the donation page very carefully and make sure that their donation is earmarked to go directly to this particular project. Very excited to see another opportunity for patients to raise their voices up to be heard.

I also want people to know that if Dr. Lipkin's research project is not the particular research project that they feel ready to pull the trigger to make a donation to, they don't need to feel that they have been left out in the cold. They can hop on over to the Open Medicine Foundation and see what research projects a stellar group of MECFS physicians and scientists think would be worth funding. Note Mady Hornig works with Dr. Lipkin and she is on the OMNI Merit's list of collaborators. See, http://openmedicineinstitute.org/research-initiatives/mecfs-merit/. I plan to make donations to both of these organizations (directly to Columbia and directly to the OMI Foundation).

I also realize some people may not have the resources to make a donation. So, I think it is important for each patient to know that they should not feel left out if they simply can't afford to make a donation. I am hoping that maybe we could even set up a buddy system, where those who can afford to donate (and I mean any amount to donate) could be paired with a buddy who would like to make a donation, but is unable to do so right now. It could be an anonymous pairing and/or an anonymous amount for the donation.

For instance if you would like to be my donation buddy, I am volunteering to make a donation on your behalf (pseudo names are fine with me) to Dr. Lipkin's study at https://giving.columbia.edu/giveonline/?schoolstyle=5881&alloc=21677. Alternatively, you can select one of the research projects listed on the OMI Foundation site at http://openmedicineinstitute.org/research-initiatives/mecfs-merit/. Or if you really are struggling to decide where you would like a donation to be made, I will split the donation between Dr. Lipkin's project and one project on the OMNI Merit list.

The donation amount that I will be willing to make for my donation buddy is $50.00 for one study or divided between two studies (i.e. $25.00 for Dr. Lipkin's microbiome project and $25.00 to one project that you select from the OMNI-Merit list). Leave me a message on my Forum member e-mail, if you would like to buddy up. I will come back and post as soon as I receive a buddy request and let you know if there are other buddy requests that have come through. If no one decides to be my buddy, I will be very sad :(, but I will still make a donation in honor of my namesake Wally, who is somewhere up in beagle heaven probably enjoying a fun day chasing bunny rabbits and squirrels.

Together let's make tomorrow a great Valentine's Day for our patient community!

Wally
 
Good points. It's reminded me that, at a CFSAC meeting or the FDA (patient stakeholders conference) meeting Susan Maier of the NIH said that the NIH wanted to fund more good quality research and that ME researchers should go directly to her for guidance on making successful research applications. Perhaps budget restrictions are the only reason for the Lipkin funding being declined, but it would be good to know the details. One of us should perhaps contact Maier to ask why the Lipkin study was declined. Does anyone know if she responds to emails, and would they divulge such information? (i.e. is it worth bothering?)
Bob I think this is a great idea. If for no other reason than to motivate a focused letter writing campaign.
 
I just gave, because I firmly believe that if anyone can solve this riddle, it's Ian Lipkin. If you haven't given already, PLEASE, find it in your heart to do so. Even a dollar will help. Whatever help you can offer will make a difference.

Thank you.

Drew
 
I forget who NOR and CFI are.
LOL I'm so sorry Izola.

CFI = Chronic fatigue Initiative

I meant 'neither NIH nor CFI are funding him...'.
 
I have read most of this thread, but may have missed this thought. Does anyone know of a list or some other way to solicit organizations and/or possibly companies (especially larger ones) to see if there is a way to acquire matching funds for the funds donated by patients or individuals?

So, the "Microbiome study" did not fall under the original "CFI" funding? Dr. Lipkin has not finished the CFI study has he?

Thanks
 
you can also donate to the WPI, where all the most cutting edge work is being done, under dr. Lombardi's team. they will solve this faster than anyone, I think.

if people are still angry over the xmrv thing or the mikovits thing, we need to get over it because they are doing some fabulous work over there.
 
@Daffodil . Any examples of the cutting edge work being done at the WPI? I don't think many people are going to get over the WPI's history so easily without a good solid reason, like a published paper which stands replication.
 
Name the campaign!

The Lipkin fundraising group is beavering away in the background (join us!) but we are struggling to find a snappy, memorable name - and we can't set up websites or social media until we have one.

So, please help us out if you can with a suggestion, or say if any of those below grab you. Thanks very much

Suggestions to date:

Million4ME

FundME

Hunting for a Cure


Big Bang Study 4 Gut Bugs
Million $ BIG BANG 4 GUT Research
The 1 million BIG BANG FOR GUT study


Lipkin's $1 million dollar appeal

The $1 million microbiome project
 
no luck for bug
no more luck for bug

But english is not my language - so maybe it doesnt sound good