 Hello and welcome to NewsClick. Today we have with us Dr. Satyajit Rat of National Institute of Humanology. Satyajit there has been a recent study done by Northwestern University in Ecuador which has talked about that the local population in the Amazonian rainforest seem to have much less what is called Tronic inflammation than what is found for instance in the developed countries. How significant do you think this is with respect to the fact that if you do not you are not exposed to early infections then you tend to get much more problems later on. It is an interesting study but we need to deconstruct it a little bit. So in the first place it is a study by the University of Oregon and Northwestern University in the United States. It is a study based in a tribal community research field station in Ecuador and what they are really trying to test is not something amongst the tribal community as such what they are trying to test is a hypothesis generated by community studies in the United States. So the hypothesis is that if you have chronic inflammation then chronic inflammation leads to resetting of your metabolic and immunological baselines so that you become much more prone to obesity, to cardiovascular disease, to heart attacks, strokes and so on. So in the United States a particular immunologically relevant molecule in the blood called C-reactive protein CRP is used as a marker in the United States to identify people who have chronic inflammation. Now the problem in this from our point of view all of us would appreciate is that if you have an ongoing infection supposing you have a throat infection cold in cold is your CRP level going to rise of course it is going to rise is that normal yes it is normal it is beneficial because it is part and parcel of your immune response. So when you test people to see if they have chronic inflammation you take a blood sample and measure CRP. How do you know whether they were suffering from some infection which did not quite come to the level of giving symptoms but nonetheless increased the CRP level because if that is why the CRP is higher then that is not an indicator of chronic inflammation that is an indicator of acute infection it will all get well fairly rapidly. So people have done this in the United States extensively and they find that in the community people actually partition the community partitions between I forget the exact ratios but some half and half or two-thirds and one-third of people who have chronically increased one-third one-third is figure that chronically increased CRP and it is this group that epidemiological data suggests is particularly prone to obesity diabetes cardiovascular disease and so on and so forth. So what they tested amongst the Shuar people the Shuar tribal community in Ecuador is if you bleed people serially every week do the people with high CRP in the first blood sample maintain high CRP over subsequent blood samples if they do then that is exactly like the United States the short finding it is a modest study the short finding is that they did not maintain. In other words people had infection that may or may not have led to actual symptoms but people had infection were clearing it had infection were clearing it and CRP levels were going up and down and up and down rather than a single high CRP level being indicative of chronic inflammation a single high CRP level amongst the Shuar was not meaningful. Honestly all that this means if one wants to be a little dismissive about it all that this means is that the level of infections amongst the Shuar is much greater than in on Northwestern University campus or in Oregon that is self-evident all sudden done infection related mortality rates in the United States are of the order of 2 or 3 percent infection related mortality rates in Ecuador not sure about whether this is Shuar or not or of the order of between 10 to 20 percent. So those are large differences it is no wonder that there are ongoing infections and that therefore a single CRP measurement is no indicator of chronic inflammation in the Shuar beyond this it really the study by itself doesn't really say anything particularly BP meaningful. You do not think that it shows that the one-third kind of group does not exist in the Shuar population and therefore chronic inflammatory conditions are not met over there. This particular study is of 50 odd people followed over a month or six weeks or something like that weekly samples of blood drawn that's really not a sample size that allows you to say whether there were or were not people with chronic inflammation in this group that were significantly different from what they find in American contexts. However it does connect in everybody's mind to the possibility that having regular exposure to infections which is the state of all poor economies all communities in poor economies being regularly exposed to infections somehow prevents chronic inflammation and really the subtext of the excitement about this relatively modest finding is that that if you are particularly hygienic in your surroundings then you are at risk of a whole different set of inflammatory disorders. Basically the immune system does not perk up enough to do a certain set of things particularly if you are not exposed to infections in the childhood that is the argument I presume that's been given by what you are calling the hygiene hypothesis. Right so the hygiene hypothesis is the term that's been used for many decades now and the hygiene hypothesis is a peculiarly attractive hypothesis particularly in South Asia because it's a hypothesis that comes perilously close to our glorious philosophical traditions. Every time you falsify one version of this hypothesis a new avatar crops up. So it's endlessly entertaining and it provides many jobs for academics. Joking aside there is a certain amount of rational to the hygiene hypothesis. What's really problematic is that there are so many possible explanations for how mechanism wise hygiene or lack of hygiene can lead to either an inflammatory disordered situation or a low inflammatory disorder likelihood situation that it's very difficult to come up with mechanisms that are actually mediating these possibilities in the community and really what we are looking for is intervention. Now if we don't know the mechanism then what intervention are we going to do? I have a slightly different question to ask you of this hygiene hypothesis. It seems to argue that if you sanitize your environment too much that you get into problems. Now the question is that if you really take an Amazonian rainforest kind of ecosystem in terms of disease it's actually fairly free of disease unlike the urban situations for instance in South Asia where you have much more disease much more chances of infection. Evolutionary terms the human society really starts seeing disease after you start settling down close to each other and you start getting much more infections. So is in fact the hygiene hypothesis therefore in evolutionary terms not a problem is not a problem when you see that you know what you are talking about is a very specific kind of scenario which is the Amazonian rainforest it's very different from South Asia or the third world in general. So I know that some streams of anthropology have made this assertion that isolated hunter-gatherer or at least sort of semi agro-pastoralist communities all sudden it's done the shuar that we were talking about or not a hunter-gatherer community they're an agro-pastoralist. And they're today in the modern world so they are open to infections from surroundings which is not the evolutionary situation they would have been say 15,000 years back. Now the issue here is in a sense very simple the argument is that if you live in large crowded communities you transmit a lot of disease to each other because microbes tend to get adopted to a particular host species and that's when they work best from their point of view and those are the microbes that we keep transmitting amongst each other and therefore we get a lot of disease. You know that would imply for example that solitary cats, tigers would have much less infection than say gregarious cats like lions. There's no evidence that that is the case. In fact the current evidence is that that's not the case although you can always say that the data are incomplete but such evidence as there is doesn't really support this. One can always imagine scenarios of very different kinds for how microbial pathogens would adopt themselves to host species with solitary lifestyles quite differently from host species with gregarious lifestyles. So it's not clear to me that this is very solidly evidence supported hypothesis. Given the fact of the lifespan in hunter-gathered communities, admittedly hunter-gathered communities that have been in contact with modern societies with all the attendant transmitted ills, it's not clear that they were enormously healthier than agricultural communities. That said the fact of do we have as economic individual economic betterment happens, do we have a lower and lower exposure to pathogens? That's really a question of general modern society and that's clearly true, we do. Are there attendant ills along with that and the answer tentatively epidemiologically in a correlative sense seems to be yes. What the mechanisms are is the great black box of the hygiene hypothesis and we can talk about what the possibilities are if you like. You do not think that it is more the parasites, the worms and so on which are the major causative agent which really boost our immune system as distinct from infections which are more modern in that in my argument of the case. It's interesting that we are talking about this today because only a few months ago, I forget February, March, something like that science the journal published a study in mice and in this study what they've done is they've taken germ free mice that have absolutely no microbes at all in them and they've taken ordinary mice and these are not ordinary mice that are exposed to infections, they're only ordinary mice that are exposed to the normal bacteria that live in all our guts, mouse guts different bacteria. Between these two groups, they have demonstrated very clear immunological differences, a particular kind of immunological cell type that is over prominent in the germ free mice in the lungs and in the gut and that appears to contribute to exacerbation of inflammatory disease that goes down with commensal gut bacteria, with gut bacteria that are not really as you say disease causing gut bacteria but simply the normal gut bacteria that all of us acquire when we are born from our mothers and we live with them all our lives. Those bacteria seem to make a substantial change in how our inflammatory immune responses function so that supports exactly what you're saying. It goes even beyond having to invoke a specific type of parasite like worms. On the other hand, it is also true that worms modify the immune responses of the host in ways that are conducive for their own survival and some of those ways actually suppress the inflammatory response of the host body. So very interestingly, worms like the returus or worms like the roundworm nicotin have begun to be used in worm therapy of chronic inflammatory diseases so that you actually use the worms, you actually infest somebody with worms, patients and even though this is scattered in early stage stuff, there seems to be suddenly in experimental animal systems, there is a clear cause and effect relationship. So what you're saying is the hygiene hypothesis tentatively seems to have something going for it but specific examples, mechanisms etc have to be really searched out and at the moment it's too early to really conclude anything on what the mechanisms could be. That's perfectly true but a real problem with the hygiene hypothesis is it begins to imply that people who are well off and who live in sterile and beautifully pristine surroundings actually have problems and therefore it is better for us, those of us poor mortals who live in ordinary dirty surroundings to count our blessings and not to aspire to that and I suggest very humbly to you that this is something of a problem. Well, at the same time you must accept that if nature strikes back at the wealthy, it's not something that I would you know instinctively react to but that's a social outlook if you will. That's an argument for another time. But the point is that it does seem to appear that there will be elements to hygiene hypothesis without accepting the hygiene hypothesis in total. There will be certain elements in this which is worth looking. Oh no, so not simply would I agree with you, I'd go one step further. I do not mean to give the impression that there is something dodgy about the whole notion of the hygiene hypothesis. My skepticism is that we keep finding individual research groups, keep finding ways by which they think the hygiene hypothesis works as a mechanism. There are so many different mechanisms that it's currently unclear how to decide which of these myriad of possible mechanisms is actually functional in a given situation where the hygiene hypothesis is showing a correlation. That's the real problem and that's what most of us who want to try to figure out something about how the hygiene hypothesis works are trying to. In other words, we don't really have to keep disease alive in order to fight inflammation. So what we should really look at specifics of how it works because then we can recapitulate by interventions rather than having to invite disease back into our systems. Thank you Satyajit. I think that's been a very interesting discussion and hopefully we will see positive results though it's been 20 years since the hygiene hypothesis has been around. Thank you very much.