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.
Excerpts from his interview with Mindi Kitei at CFS Central:
Lipkin: 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?
Lipkin: 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.
Read more: Candid Conversation with Dr. Ian Lipkin
