Ian
Lipkin, professor of epidemiology and neurology at Columbia, recognized for his work on SARS
and West Nile virus, science consultant to the film Contagion, has been at work on what he admits may be his toughest
project to date: research into ME. From the Chronic Fatigue Initiative, Lipkin received funding, and his work so far has shown cytokine activation in the disease. Now he's in need of a million dollars
for ME research into the gut biome and is making his
plea directly to patients. To donate to the research, click here or here.
Dr.
Lipkin and I had a candid conversation about his ME research, the government’s
thinking when it comes to ME and how to secure more research dollars.
Mindy
Kitei: Where can people donate to your
research?
Dr.
Ian Lipkin: Donate to our research. We’re all in the same
boat. We’re trying to find solutions to
an important problem, so I want to be very clear to your readers that it is their project. It was organically developed in response to their needs, and their wishes, and we’re eager to serve.
The
idea here is that we believe there is an infectious trigger... that initiates
immune activation and results in a number of different abnormalities, which
results in turn in this debilitating fatigue and cognitive dysfunction, and all the other symptoms that are associated with this disorder. Very
similar to what you have with a low-grade but persistent infection, typically
with a virus, but can also occur with some bacteria.
The
idea is to find out what sorts of agents might be implicated in this syndrome. We have looked at peripheral blood
mononuclear cells, where we haven’t found anything as of yet, although we’re still
looking, but the area that is obvious to consider is the gastrointestinal tract because the gastrointestinal tract is so important in modulating immunity and has been implicated
in autoimmune disorders, not only those associated with gastrointestinal
disorders but outside....
Kitei: How is your gut research different from other
researchers looking at the gut, including Dr. Chia and Dr. DeMerlier?
Lipkin:
We have a very different approach than most people. There are people who are experts in viruses
or bacteria or fungi, there are people who focus on specific microorganisms
because they’re persuaded that this particular microorganism or that
microorganism is the one that’s important.
We approach this with the notion that this is really discovery. We don’t have any preconceived notions about
what we’re going to find and as you’re probably aware, our group has expertise in
looking for bacteria, viruses and fungi. Our approach will be comprehensive, it
will be vigorous, it will be quite deep.
We
will use methods designed specifically to find viruses, fungi and bacteria, so as long as it
falls into one of those three categories, we should be able to find it in the
materials we collect and analyze.
Kitei: Which is in stool?
Yes. We
are not going to do muscle biopsies or liver biopsies. Believe it or not, but I’ve been in meetings
where people have talked about doing brain biopsies, which shocked me.
Kitei: Unless you had cadavers.
Lipkin: Well, cadavers are very difficult place to
look for materials, unless somebody has an acute illness. People have been doing
that in MS and other disorders. So we do a lot of cadaver research. But I’m not aware that there’s a large
biobank of people with chronic fatigue syndrome from whom one could get such
materials even if we wanted to pursue that.
Our
intent is to look at people who have active disease and people who’ve recovered
and to look at their stool and their oral pharynxes as well and to test whether or not we can
find differences in the populations of bacteria, viruses and fungi in their mouths
and in their fecal flora. Whatever we
find by way of differences between populations, we will test for the relevance
and the acuteness of the infection by using serology, by testing for the
presence of antibodies in the blood that will react with those specific
agents.
Kitei: Is it possible that by the time you get to
the stool the pathogen is not detectable? I believe Dr. Chia has said that
tissue is a more effective place to find pathogens....
Lipkin: Depending on whom you speak to, people will tell you the culprit is a herpes virus in peripheral blood mononuclear cells, someone else tells you it’s an enterovirus in the wall of the bowel, other people tell me that it’s a stealth virus that’s lurking in the central nervous system. I mean there are many hypotheses that people have put forward. To get biopsies from the intestine of an individual is not something we can easily do. That requires people who are willing to have that done, number one. Number two means that you have to collect those biopsies. And third, I don’t know if an institutional review board would allow intestinal biopsies on people who don’t have intestinal complaints. That would be very difficult certainly at Columbia....
Kitei: But there are many people who do have intestinal complaints.
Lipkin: But there are many people who don’t who also have chronic fatigue syndrome.... I’ve met the man [Dr. John Chia] at a conference in
San Francisco.... I've been down this path many times before when people who are clinicians try to shift and do certain types of laboratory work. And it's always a concern for me when they make a report of this type because I don’t know what kind of
controls he uses to make certain he doesn’t have artifacts. We went through this with [Dr. Andrew] Wakefield,
as you may remember, with MMR and autism.
We went through this with XMRV in prostate cancer and then in chronic fatigue
syndrome….
It
seems very unlikely that if you have a virus which is growing inside the bowel
that as you shed the lining of the bowel—which happens continuously—that you’re
not going to have viral particles that will also be present in feces. We’ve done so much work with fecal material from bats to
camels to people to gorillas that I’m confident that if there’s something
present within the bowel that we will be able to see it as long as it reaches a
certain threshold for concentration, and that threshold for concentration we know, and most people don't know that number.
Kitei: How many subjects will you have in the study?
Lipkin: At present we're not nearly where we need to be in terms of funding to do what we need to do. Ideally we would like to have a minimum of
200 subjects. My view on chronic fatigue
syndrome is that there are likely to be multiple pathogens that are implicated
and when you do discovery, sensitivity is not as good as when one uses a specific assay. Specific assays exclude all other material
that may be present in a sample, and sensitivity frequently is an order of
magnitude or 10-fold higher than the discovery methods that we use. So all we need is to find a couple of
candidates, and then we’ll develop specific assays and then go back into the
rest of the population to see whether or not we can chip away at the
problem.
I
would not be at all surprised if there were multiple agents implicated in
chronic fatigue syndrome. But if we can
identify 10 percent of people with herpes viruses and another 10 percent with Borrelia pathogens and another 10 percent with enteroviruses, and so
forth, we can develop specific tailored
approaches for dealing with these problems. It’s no
different from dealing with cancer. In
[1971], you had Nixon declaring the war on cancer as though it were a single agent
and we now know that even if you take adenocarcinoma of the lung, there are very
many different variations. Some are
associated with very specific mutations and if you can exclude or include those
mutations you can tailor therapy specifically for an individual that’s nontoxic
and highly effective.
And
my thought is that there is final common pathway for chronic fatigue syndrome,
but there may be multiple triggers. So
our objective is identify as many potential triggers as we can, and then begin to move
toward some sort of clinical trial so that we can help people with specific
management recommendations.
"Vulnerable people who do not have others looking out for them are most at risk for not getting the science that’s needed to address their problem."
Kitei: When is your study on biomarkers coming out?
Lipkin: Mady Hornig spent last weekend with Dan Peterson in Incline Village pulling together a study on spinal fluid and that is the first one that’s going out for publication.
The second one, which concerns cytokine measurements in chronic fatigue syndrome in peripheral blood will follow that probably by about a month. We’ve presented that data in public forums, because we felt it was important to get out.... But the actual publications in print will take a few more months.
Kitei: And in what publications?
Lipkin: No one knows. You submit and then move on.
Kitei:
Did you look at natural killer cells? That
seems to be one thing that most patients have a problem with. Either too many that are not functioning, or
too few.
Lipkin: No, we have not. It would be very difficult to use that as a
biomarker. It’s very complicated
laboratory research. We’re hoping to
develop a biomarker that going to be inexpensive and simple, rather than requiring
people to culture cells. I’m optimistic
that we will get there, but that doesn’t really tell me why the NK cells are
abnormal or why the cytokine patterns are abnormal. That's what I'm focused on. Identifying biomarkers is going to be useful
primarily for persuading insurance companies that patients are not
malingering. I have no doubt that people
are not malingering, but that’s not going to tell me necessarily why people are
getting sick and what to do about it.
So
our focus is on the origin of the syndrome. That's the place where we can make the largest contribution.
Kitei: I’ve read that you found in 85 percent of
pooled samples possible evidence of retroviral infection, but that you
believe that’s not related to ME. Why do you believe it’s not related to ME?
Lipkin: We also find it in controls. We need to find something that’s going to be
specific.... All the studies we do are very well controlled because we're involved with clinics where they see hundreds of patients a year, like Nancy Klimas, Cindy Bateman, Dan Peterson, Jose Montoya and Sue Levine.... These are the people we have selecting our patients and controls, collecting materials and working very closely with us.... We decided to go with the blue-chip group so that there's no question when they send us a patient....
Kitei: Are you going to be using the Canadian
Consensus Criteria?
Lipkin: We use all the criteria: the Canadian
Consensus Criteria, the original Fukuda criteria, the criteria used by the
programs run by Nancy [Klimas] and Dan [Peterson], Tony [Komaroff] and others,
we use the most stringent criteria. We also try to emphasize whenever possible those people who give us a history of a viral prodrome because that also suggests that these people have the agent present. And whenever possible we try to get people who are having an acute relapse….
A paper coming out in the not to distant future about which I’m very encouraged
has to do with RNA profiling host response in those with chronic fatigue
syndrome and controls and these are individuals from the original NIH XMRV
study.
Kitei:
And what have you found?
Lipkin: I can’t say yet. I’m not trying to be coy. We’re still in the process of analyzing
it. It’s an enormous amount of
information. When you start doing
genetic sequencing, it can take months to analyze the data. It’s like building a house. So, at the end, when you’re slapping on the
paint and polishing the floors, it goes very very quickly, but before that it
just looks like chaos.
Kitei: German researchers found Epstein Barr
virus-encoded small RNA DNA in 11 out of 20 patients, compared with 3 out of 20
controls.
Lipkin:
That’s such a small number of patients that I don’t think it’s meaningful.
Kitei: Is it something that should be repeated with
more patients?
Lipkin: It’s certainly interesting. There’s so much
scatter everywhere. One of the reasons
why we’re doing it the way we’re doing it is that we don’t go into specific
bias. We think what we to do is the same thing that has been done for discovery
in any number of diseases. The patients
deserve that. The field deserves
that. One of the problems we have is to
a carpenter with a hammer everything looks like a nail. We don’t have that approach.
Kitei: Do you believe ME is contagious and/or
infectious?
Lipkin: I don’t know that, but I do think there's an
infectious trigger. It’s ultimately
going to be a gene environment interaction, and we’re going to have to explore
the genetic susceptibility issues as well as the environmental triggers....
Kitei:
Do you believe this is a hit-and-run agent?
Lipkin: In some cases it may be. I don’t know that
that’s the case. We haven’t proven
anything as yet, except that we know that some people have an indistinguishable
illness that reflects infection with borrelia species or herpes viruses. If you talk to Konstance Knox, you think
everything is HHV-6. Some people think
it’s HHV-6, some people think this is EBV, some people think it’s Borrelia,
some people it’s another bacterium, some people think it’s a “stealth” virus,
some people think it’s a retrovirus, there are a number of possibilities. They can all be right, and they can all be
wrong.
Kitei:
Following Koch’s Postulates, have you considered finding an animal model for
ME?
Lipkin: It would be very difficult to develop an
animal model right now. I’ve been
dealing with this for a long time in autism.
It’s a disorder in which people don’t make eye contact. What is eye contact in a rodent?
Kitei: There's some researcher [Dr. Robert Naviaux] who did this in autism
recently and came up with a drug [Suramin] developed in 1916 to treat river
blindness that reversed the autism in mice.
Lipkin:
I’m not persuaded. The only thing that
seems to work with these kids is applied behavioral therapy. What you’re doing there is starting very very
early and trying to socialize them….
"I have been in competition now twice to get funded, and the people there who reviewed me gave me abysmal scores. And the critiques of my work were unfair, and one of the people who critiqued my work said, in fact, that this is a psychosomatic illness. I was floored."
Kitei:
If you did find the cause of ME, would you become involved in finding effective
treatments?
Lipkin: Yes. That’s job one. We’re not in this for intellectual
interest. We’re trying to make
differences. I’m a physician. I saw some of the first cases of chronic fatigue
syndrome in the early 1980s when I was at the University of California at San
Francisco, referred to me by Dan Peterson.
It’s been a long time. We need to
bring some clarity.
Kitei: There’s been so little funding. You have Dr.
Fauci’s ear. He has talked about this
disease being psychiatric. That was
documented in Osler’s Web.
Lipkin: No, no. I don’t think that’s fair. I know Tony Fauci extremely well. And there’s another thing people misquote. [People misquote] William Stewart, surgeon general in 1967, when they said [that he said] that the era of infectious
diseases is over. There’s no evidence that he ever said that. My esteemed colleagues... continually misquote
him. I’ve never heard Tony Fauci say anything like that [that ME is a psychiatric disorder]. The fact that it's in Osler's Web doesn't mean he said that.
Kitei: She's [Hillary Johnson] a good reporter. Have you talk to Dr. Fauci about your theories [of ME]?
Lipkin: In fact I have spoken to him about it. That's why I can't understand why people think this is the case.
Kitei: There’s no federal money for ME research. Year after year there’s no money, and more is
given to male-patterned baldness than to this disease.
Lipkin: Let’s backtrack and examine how these
decisions are made. First of all, the
National Institutes of Health gets money from the Congress. The Congress will mandate what it is they
want people to do. The Department of Defense has funding for autism, for a number of other things that people push,
including, as you mentioned, some disorders that are
specifically male.
One
of them is prostate cancer. The Department of Defense has been running programs on prostate cancer for decades.
Why? Because men in the position to make
those decisions have wanted research focused on prostate cancer, so
they allocate money for prostate cancer. The NIH doesn’t allocate money for
specific disorders. Those kind of monies
are allocated in response to congressional mandates.
Now, Tony Fauci doesn’t have the ability to start a brand-new program on chronic
fatigue syndrome. This is what I want to
do. He’s continually being pushed to
work on influenza, HIV, bio-threat agents, things of that nature. And there is
a portfolio for chronic fatigue syndrome, which, as you said, is quite
small. There are not many people working
in this field.
I
have been in competition now twice to get funded, and the people there who reviewed
me gave me abysmal scores. And the
critiques of my work were unfair, and one of the people who critiqued my work
said, in fact, that this is a psychosomatic illness. I was floored. I protested, and for reasons that are obscure
to me this same individual wound up back on the study section, and I got a
similar unfundable score. Am I upset
about this? Absolutely. Do I think Tony
Fauci knows about this? No. And if Tony
Fauci were to find out that people said that he claimed this is a psychosomatic
illness, he would deny it because he doesn’t believe that’s true. I’m sure he doesn’t believe that’s true....
[In the first set of critiques I was also
told] that everybody knows that this is a herpes virus infection of peripheral
blood mononuclear cells so there’s no reason to look at the gut. This is the
nature of study sections. You can’t
control what people are going to do when they get on…. They do the best that they can, but that
doesn’t mean they’re up to the task and it doesn’t mean that they’re
appropriate.
One
of the challenges is that there aren’t enough people doing credible research in
the field. Period. If there were more people, you’d have better
study sections, better work and we’d be further along in terms of sorting out
this problem.
Kitei: But it’s a vicious cycle. If you can’t get funding—
Lipkin: It’s not the leadership of NIH. That’s not the problem. The problem is that you need a champion in
Congress who's going to go ahead and say, I want money allocated for chronic
fatigue syndrome research. That’s the
way it gets done. That’s the way HIV got
done, that’s the way breast cancer got done, and so on. It has to be somebody who has some ability to
influence the purse. And if that happens, the NIH would only be too happy to
take the money and to allocate it and get the best science done. That’s all the NIH cares about.
Kitei: That’s a crazy way of doing things. If anybody should understand this disease,
it’s scientists.
Lipkin: But they don’t listen to scientists. Congress doesn’t listen to scientists. They listen to people who vote for them. I
was very involved in getting the autism bill passed, in the late 1990s and
early 2000s. And it was two parents and
a few of their friends who went down and lobbied on Capitol Hill and pushed
through this first bill that created the autism Centers of Excellence. And it was the parents who did it. The problem is with chronic fatigue syndrome,
and I feel bad about this, these are the most vulnerable people. They don’t have the energy or the resources
that are needed to go and lobby.
Whereas
if you have a child and you’re otherwise healthy, and you’re looking at this
child every day, then you’re motivated, you’re strong, you’re powerful and you
go down there and you complain, and push and squeak until you get the resources that you
need. The other people who have the same
problem are people with mental illness, and I am not saying by any means that
chronic fatigue syndrome is mental illness.
I’m just saying that these are also vulnerable people. Vulnerable people
who do not have others looking out for them are most at risk for not getting
the science that’s needed to address their problem.
But the solution for that is for the healthy
ones, the people who have recovered, or relatives and friends of those who have
these disorders need to push. I talk to
everybody. I do everything I can to
promote this. When people who are
scientists tell me they don’t believe this is a real disease, I refute it, I
refute it with facts, I talk to the media, but I don’t have any traction with
Congress because I live in a blue state.
And New York is in favor of scientific research and increasing the NIH
budget. And the problem is, when you go
into the South and the Midwest, you don’t have that support. The budget for the NIH has been cut
dramatically.
I’m on the advisory
committee for Francis Collins, and I can tell you that Francis Collins, the
director of the NIH, believes that chronic fatigue syndrome is a problem. He would love to have the resources to
allocate. The resources are going to
have to come because people push their representatives to provide that kind of
support. That's the only way it's going to happen. I’m sorry about that, because
believe me, the last thing I want to do is begging for dimes and quarters for
my work....
Kitei: You mentioned someone on the study section
said this was a psychosomatic illness. Can’t this person be educated?
Lipkin: I think this person has to be
eliminated. I pushed to have him
eliminated permanently from this study section. I’m
not going to tell you his name because it’s not appropriate, and I’m not
supposed to know it….
Kitei: That’s one person, and it would be great to
get him eliminated, but there’s a basic feeling in the government—certainly in
the CDC—that this is a psychosomatic illness....
Lipkin: I don’t think that’s true.
Kitei: I believe it is true at the CDC.
Lipkin: I don’t know who at the CDC you mean.
Kitei: Certainly [Dr. Beth] Unger, but she’s just
taking orders.
Lipkin: She’s in the process of doing biological
research.
Kitei: Have you read Osler’s Web? I would urge you to read it.
Lipkin: No. I’ve been given three copies of it.
Kitei: Well, maybe you should read it. Maybe someone
is trying to tell you something.
Lipkin: I’ve read Absence
of Evidence with the autism stuff and so forth. I’m sure people mean well. Hillary [Johnson] is a very nice individual. I like her. But I’ve also had people tell me that they’ve
never said the things she claims they’ve said.
This is a problem. I know some of
these people. I knew Bill Reeves. He was a problem. But he’s no longer on the
face of the earth. So that’s not an
issue. And Beth Unger does not believe
that this is a psychosomatic illness. She just doesn't. And Bill Switzer doesn’t believe that this is a psychosomatic illness.
So I don’t know where people get this.
And [CDC Director] Tom Frieden doesn’t believe this is a psychosomatic
illness. As I’ve said, the best way to
get results is to organize a grass-roots campaign to push the Congress to
allocate money for chronic fatigue syndrome research and treatment. That’s
really the way to go.
Kitei:
But then they do psychosomatic research, personality disorders.... Beth Unger’s [name] has been on the studies that do this. Or they do an exercise study, and instead of
doing a two-day test—because it takes two days to see the problems in the recovery period—they only do a one-day test because they say it’s too hard on the patients. But patients are willing to do this.
Lipkin: I’ve had physicians say they can’t get a
rectal swab because it’s too painful for patients.
Kitei: There are plenty of patients who would be
willing to do it.
Lipkin:
There are all kinds of things people will say, and I don’t want to fight with
you.
Kitei: No, no. I don’t want to fight with you either.
Lipkin: I’m fighting for you. What I do want you to appreciate though, is
that our enemy is not that the people we’re talking about. It just isn't. These people, we may disagree with them, we may think that their strategies are insufficient, we may want to do things differently but none of the people whom you mentioned think it’s a psychosomatic illness or think it’s
overstated. That’s just not who they
are. I know these people. I’ve worked with them for years…. Beth Unger
was desperate for me to be involved in these conference calls, and she was very
happy to hear about cytokine abnormalities, and she would like to do more work
on genetic responses and so on, all of this she’s interested in doing. She’s interested in a biological
solution.
Kitei: We’ll agree to disagree on that. How can people donate to our research?
Lipkin: We are eager to move as rapidly as
possible. We will be as frugal as we can
be. We deserve the same kind of work
that I do for the Saudi government, trying to figure out the origin of MERS or
anything else. I want to be working for
[patients]. And the problem we have at present is that I’ve gone as far as I
can go before the institution says, look you can’t pay your bills. That’s where we are at present. I need to be able to pay for the work….
There
are some people who have herpes virus infections. We can define those, we can detect
those. Those people should be diagnosed
because they can be treated now. The
same thing is true with Borrelia infections.
We’ve created a series of multiplex assays to detect those infections….
And those people can be treated, and maybe that takes care of 10 percent of
people. We need to deal with the other 90
percent. And that’s why we need to look
for other sources of infection, other ways in which things get triggered. And it’s going to be a wide range of
things. Some people it’s going to be
infectious, some people it’s going to be toxic, some people it’s going to be
hit and run. All of these things need to
be understood, dissected, addressed, and we will chip away slowly at the
problem. This is like cancer…. Some people need radiation. Some people need this drug, or that drug or
the other drug.... It has to be
personalized medicine.
Kitei:
But how do you know that yet? There might be a common-denomination
pathogen, like what hit Incline Village and Lyndonville, New York, when all
those people came down with it.
Lipkin: I wish I could get samples from either of
those outbreaks. I can’t. They don’t exist. We’ve been asking for them for years.
Kitei: [Dr. Daniel] Peterson doesn’t have them?
Lipkin: He’s sending us some materials. Maybe we will find something. There’s some mantle cell lymphoma. He’s got
very few samples, because most of it went to WPI [Whittemore-Peterson
Institute], and they refuse to return it to him. Believe me, we are doing
everything we can. It’s an incredibly depressing,
humbling experience. It’s so much more difficult than 99 percent of what I do
day-to-day.
A Clarification by Dr. Lipkin Concerning Osler’s Web by Hillary Johnson:
On occasion during this interview, Ms. Kitei brought up the book Osler’s Web by Hillary Johnson. I wish to make clear that I never meant to imply that any quotations in that book, of statements by government scientists or any other sources, were inaccurate. As I mentioned in the interview, I have not read the book. And I do not have any reason to believe that Ms. Johnson misquoted anyone. If anything I said in the interview could be construed to have made such a suggestion, that was not at all my intention.
W. Ian Lipkin, MD
This article, "Candid Conversation with Dr. Ian Lipkin” is copyright © CFS Central 2014. All rights reserved. Unless you receive permission to quote more, you may quote up to 100 words from this article as long as you link to this article and indicate in the body of your post (as opposed to a footnote or an endnote) that the excerpt is from CFS Central.
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