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Science Talk

Small Matters: Microbes In Us And The Environment

In this episode, Stanford's David Relman talks about the microbial life that lives on and in humans. Princeton's Andrew Dobson discusses the importance of parasites to an ecosystem. And former National Science Foundation director Rita Colwell mentions a low-tech practice with big public health implications. All from a conference on microbes and the environment at the American Museum of Natural History. Plus we'll test your knowledge of some recent science in the news. Websites mentioned on this episode include www.amnh.org/biodiversity.

Welcome to Science Talk, the weekly podcast of Scientific American for the seven days starting May 2nd. I am Steve Mirsky. This week on the podcast, some small talk—very small talk. We're going to talk about microbes. Last Thursday and Friday, the American Museum of Natural History in New York sponsored a symposium called, 'Small Matters: Microbes and Their Role in Conservation.' We have an interview with one of the keynote speakers, David Relman, who discussed all the little critters living on and inside us and we'll have short clips from two of the other keynote addresses by Princeton's, Andrew Dobson and former National Science Foundation director, Rita Colwell, plus we'll test your knowledge about some recent science in the news.

First up, David Relman. He came in from Stanford University where he is an associate professor of microbiology and immunology and an assistant professor of medicine in the division of infectious diseases.The human body has about 10 trillion individual cells—more remarkable, we are home to about 100 trillion microbial cells. I spoke to Dr. Relman after his talk, which was called "It's a Jungle in There: Microbial Diversity in the Human Body."

Steve: Dr. Relman, great to talk to you today.

Relman: It's a pleasure talking to you.

Steve: It's really quite amazing, we're one tenth us, talk about that a little bit.

Relman: Well! It's been known for sometime that we carry with us a huge consortium of microbial life. We're still confronting this very dramatic simple fact that we are 10 parts microbe and one part human, if you simply count the number of cells within the human body.

Steve: And those raw numbers are tenth to the thirteenth human cells and ten to the fourteenth microbial cells.

Relman: Very roughly speaking, yes.

Steve: So we're just, in some ways we're just a platform for the (laughs) microbes to live on.

Relman: Some have even argued that we are simply the victims of the chemical processes that these microbes are foisting upon us in order to control our behavior for their purpose. A bit far-fetched but you could certainly start rethinking what we have assumed to be the intrinsic parts of human physiology by now thinking about well what component of that physiology is really of microbial origin.

Steve: What do you get? Let's just limit it to say from a medical point of view, by adopting this way of thinking rather than the conventional view point that you are looking at an individual human being who is all human.

Relman: There are many ways in which you could answer that question or think about the issue. One is to take a perspective of looking at health and say how do we now begin to define what is health because this would lead you to think that the definition of health should include a census of the contributions made by the microbial world, not just the numbers, but what it is they are doing for us. And the importance of that for medicine is that to the degree that these microbes are contributing to health and helping us define health, we should be much more aware of these patterns as a target for treatment because, currently your physician, if you come to them sick, we'll treat you until signs of sickness resolve. This perspective would suggest maybe we as physicians should be treating people until the signs and the patterns associated with health reappear and are reestablished and those two endpoints may be some[what] different.

Steve: And is some ways the signs of health might be the senses of microbes, a restoration of the proper balance of microbes in the body?

Relman: Correct and I am using the word "census" in probably an oversimplistic way because it's not just who's there, but it's what they are doing. What we want to restore is the microbial community profile that reflects the functions they are providing to us into themselves, not just the names of the organisms that are there.

Steve: So, one of the things along this line that I was thinking about was, if you, for example, think of an infection as an invasion by a species that is not normally a member of this particular environment, right now the conventional treatment is to just try to kill the invader. But might it be possible to think of treatment modalities that are still completely faithful to the germ theory of disease, but you kind of boost the levels of the other[s to] somehow get the other microbes in your ecosystem to fight the battle for you. I mean in some ways that already does go on.

Relman: Absolutely. In fact, when you begin to think about disease now, in terms of community properties and the effects of community, it leads you in the direction you just described, that is thinking about ways to enhance the membership which might provide some resistance to invasion, so you could prevent disease even perhaps by supporting the community properties that prevent pathogens from invading the community and taking over. You could also think about restoring health by again boosting these beneficial community numbers or community structure. You could also think about a different set of very important diseases, which are really the product of a disturbed community structure—not the presence of one pathogen, but rather the presence of a very different set of organisms which together are causing disease.

Steve: Such as?

Relman: Examples would be gum disease, inflammatory bowel disease, perhaps certainly bacterial vaginosis, antibiotic-associated diarrhea, irritable bowel syndrome—there probably are a whole variety of disturbances that take place at our surfaces, where we have either skin or bowel or mouth disease, where the responsible party is not an organism, but it's a disturbed community structure.

Steve: Why is this kind of thinking about the body as an ecosystem—why is it sort of new? I mean it seems like its sort of new, is it just because we didn't have the techniques to really appreciate it before? We always knew there was flora, bacterial flora, but it just seems like there is a different appreciation for this ecosystem kind of thinking about the body.

Relman: You raise an important point, which is to reflect on the history of how this discussion comes to be today.In fact, for decades or even a century, there's been an appreciation for the fact that we do harbor microbes and for the fact that we might be able to manipulate the system to our benefit. Probiotics goes back quite some time—the idea of the beneficial value of yogurt or of purposefully ingesting microbes to alter the balance—that's been around for some time. I think what makes this discussion more lively and interesting and perhaps more robust today is that we have the tools to survey and understand and characterize our communities in far better detail to far better completion with more insight than we had before, and now we can really say, okay who really is there? Who really matters? Which communities are important for health? What parts of those communities and what properties and what are these organisms doing for us? And how can we enhance all of that health-associated phenotype.

Steve: You talked briefly about this really interesting study with babies and sort of observing the microbial colonization of babies.Can you briefly summarize that?

Relman: What we did—this is collaboration with my good friend and colleague at Stanford, Pat Brown—we designed what is now one of several different kinds of bacterial census-taking tools: it's a DNA microarray. We looked at fecal samples from the day of the birth through the first year of life for 14 babies; looked at many many samples over the course of that year and also looked at samples from these baby's moms at the time of birth and at the end of the year. And saw what as you might not be surprised to hear is an incredibly complex and very interesting set of dynamic pictures over the course of that year that, one: tell us a little bit about where babies pick up their microbiota in those first critical few days of life and weeks, but two: the fact that despite the difference in these historical accidents at the time of birth, there is this clearly emerging picture of individuality—every baby becomes more and more a story and picture unto his or herself.

Steve: John Donne was wrong (laughs).

Relman: Exactly!

Steve: Every man, every baby, is an island.

Relman: (laughs) To some degree, yes. I mean to the ecologist, this is probably an example of, you know, many replicated fermenter or incubator experiments that are, you know, might have been done in the classic ecology laboratory. Each of us is a segmented piece of what we as the human race contain, but each with its own slightly different story that starts from the day of birth.

Steve: And you did see in that study some similarity in the set of—Was it fraternal twins?

Relman: Yes.We had two twins. They were by far more similar to each other than any baby was to another baby.

Steve: In terms of the microbes they were harboring?

Relman: In terms of the microbes they were harboring. Now we don't know whether it's genetics or environment, because, of course, these twin babies were living and being fed in very much the same environment, but it does suggest that we ought now to be doing this same kind of study in the same or greater amount of detail with many larger numbers to really build out this picture of how much of it is genetics and how much of it is environment.

Steve: So there is a lot of talk about individualized medicine and, you know, the thousand-dollar genome some day, not too far away—even where you get your own genome sequence. But that's not going to enough, you really need the whole metagenome sequence to really understand what is really going on with you.

Relman: Absolutely! Absolutely—in fact there is now lot of interest finally among some of our national funding agencies to do just that on a very large scale.

Steve: So we are really going to see a lot of developments in this area in the coming years?

Relman: I think so.

Steve: It's really fascinating. It just changes your whole way of thinking about who we are? (laughs) Who you are? Who I am and I don't know. I find it kind of fun to think: Well how can anybody be lonely again?

Relman: Exactly! You never go to bed at night alone.

Steve: Great to talk to you.Thanks very much.

Relman: My pleasure.

Steve: All the talks from the conference are scheduled to be archived as both QuickTime movies and MP3 audio. They were not up when I checked on May 1st but they should be soon at the Web site of the American Museum of Natural History. Go to www.amnh.org/biodiversity then hit the link for spring symposium.More from the conference in a moment.

Now it's time to play TOTALL.......Y BOGUS.Here are four science stories, all about food, but only three are true. See if you know which story is TOTALL.......Y BOGUS.

Story number 1: Bananas are being touted as the optimal delivery system for a new hepatitis B vaccine.

Story number 2: Most people rank diet colas as tasting more like nondiet colas than diet lemon-lime sodas taste like their nondiet counterparts.

Story number 3: Study subjects who saw a package of cookies touch a box of sanitary napkins were less likely to accept a cookie offered to them an hour later.

Story number 4: Foods aimed at kids that say something like, good source of nutrient X on the label are still usually filled with some not-so-great ingredients.

We'll be back with the answer. But first, Andrew Dobson, he is a professor for ecology and evolutionary biology at Princeton. He delivered another keynote address at the museum conference called "The Role of Parasites and Pathogens in Food Webs" and that was part of the session called, "Can't Live With Them: Diseases and Other Harmful Microbes, but Are They a Necessarily Evil?" Here is a highly edited version of his half-hour talk.

Dobson: What, I am going to talk about is curious given the general theme of this afternoon about, "Can't Live With Them," because I am going to suggest that, that if you go and look at healthy ecosystems, a sign of how healthy they are is how many parasites are in them. And the fact having lots of parasites may be a sign of good health providing you have a nice diversity of parasites.We have problems when one or two of those parasites get an advantage and begin to explode and that's when we get epidemics.

What if we looked at an ecosystem such as the salt marsh down in Baja, Mexico? If we look at it as ecologists what do we see there? Well the sort of the most fervor ecologists are the birders and they would go and say, "Wow it's full of all this [these] cool birds" and then if you are a bit more hard core, you'd say, "Lets go fishing, it's full of fish, really quite cool fish, slightly more exotic," not fully appealing to the birders. And if you have seriously hard core you'd start looking at some of the invertebrates that are the sort of slimy things that are and not as appealing to the general public but really appeal to the ecologists. But there is one thing that all of those species have in common: every single one of them is parasitized. And in some cases every individual in the population is parasitized, so when we do our traditional ecological look at the salt marsh, we may be missing a lot, so we wanted to adjust the question—Why do people ignore parasites? Is it because they are so tiny, is it because they don't always have dramatic effects, and could we try and get around that by trying to quantify the abundance of parasites in three particular marshes?—just to see if we got consistent results. And can we somehow get around this question: is that Are parasites and small things ignored simply because they are small and people think that small things aren't important? Or are they ignored because they're harder to detect and therefore just perceive[d] to be unimportant? So we wanted to try and get into that and see why have the ecologists ignored parasites, and initially that effect is paradoxical, because if we look at ecosystems that have been studied for a long time—one of the other places I work is, is I think is still the most beautiful place on earth, the Serengeti—if we look at the Serengeti, we again get that perception that its dynamics have [been] dominated by the huge charismatic vertebrate species; but if you actually look at the data, the most important species in the Serengeti probably doesn't have a mass bigger than this glass of water. It's a virus called rinderpest closely related to measles. It came through in East Africa in the 1890s and completely eradicated to, almost completely eradicated many of the artiodactyls, the wildebeest, the buffalo and the domestic cattle. When we had a vaccine, simply by vaccinating the cattle you could remove the rinderpest from the system, and then you got this huge eruption of the wildebeest going from the original counts when the groomings first went there—about quarter of a million up to of the order of one and a half million—so one viral pathogen completely changes the abundance of the dominant vertebrates in that system and indeed that leads to knock-on effects that effect the burning cycle, the ratio of the woodland to grassland in ecosystem, so we know that specific pathogens can have huge effects that shed right through the ecosystem. I think the bottom-line is that if we go and look at these three marshes, they are all we thought that the three healthiest marshes we could find, they are rich in parasites and that parasite richness is an indicator of how healthy those places are.

We've got another set of disturbed marshes. If we go to those marshes different types of invasion or eutrophication doesn't only disrupt the living fauna, it massively disrupts the parasitic fauna and creates opportunities for one or two really nasty species. So a healthy one is one that has got lot of parasites but once it is doing well.Second thing is that the biomass, the parasites in the systems isn't trivial. It is at least of the order of 10 percent and it's distributed all through different species probably as the major regulators of the abundance of the other species. One of the things we've have learned a lot about in theoretically cultured over the last 10 years something realized that the predators are actually pretty useless in regulating their prey because they are constrained by handling time, functional responses, and having to reproduce slowly. If you are a virus or even a trematode, you are not constrained by any of those things. You can reproduce like mad and go and infect lots and lots of different people. So you are much better regulating populations than predators are.When we look at the biomass, it's also what they say quite substantial may be of the order of 10 percent and that's at the resolution which we could see it if we would go further down into the mud that may well creep up. So parasites aren't always the bad things, [in] some case[s] they are a wonderful thing.

Steve: Rita Colwell is distinguished university professor at the University of Maryland, College Park, and at the Johns Hopkins University Bloomberg School of Public Health. In 1998 she was named the 11th director of the National Science foundation. Her talk was called "Microbial Diversity, Biogeography, Climate and Health." Here is a very brief clip about how a very low-tech methodology filtering water with folded up sari cloth made a big public health impact in Bangladesh.

Colwell: We hypothesized that if we could remove plankton from the water that alone would be enough to reduce the cholera incidence and with, you know, [a] three-year study, we were able to show that by training the women, educating them to filter the water they collected each morning in their kalashes—these aluminum pots to bring up to their homes for the families—by folding the sari cloth four times you get [a] 20 micron filter that we determined that by electron microscopy, and we were able to reduce cholera by 50 percent. What's very reassuring is that the Thrasher Foundation gave us some funding to go back almost five years later and see if they are still filtering. Seventy percent continued to filter and this includes even the controlled villages, which of course makes it difficult for us to do our calculations of the actual effect on cholera, but the overall cholera rate has been significantly reduced for the Matlab area in Bangladesh.

Steve: Again, all the talks are scheduled to be archived soon at www.amnh.org/biodiversity.

Now it's time to see which story was TOTALL.......Y BOGUS. Let's review the four stories.

Story number 1: Bananas could be the best hepatitis B vaccine vehicle.

Story number 2: Diet cola tastes more like the real thing than do diet lemon-lime sodas to most people.

Story number 3: People who saw a cookie package touch a box of sanitary napkins were less likely to later want a cookie.

And Story number 4: Fortified kids foods are often still healthfully challenged.

Time is up.

Story number 1 is true. Researchers publishing in the June 1st issue of the American Chemical Society Journal, Biotechnology Progress, will report that bananas are the best candidates for delivering an oral hepatitis B vaccine. Researchers have engineered several plants including potatoes, carrots, lettuce and tobacco to produce the orally ingested vaccines but the banana has them beat. It could be a pill in a peel.

Story number 4 is true.Just because the package says [it is a] good source of nutrient X doesn't mean the food is healthful. That's according to a study reported at this week's experimental biology meeting in Washington. Researchers looked at over 7,000 products aimed at kids and touting their nutritional benefits and found that 60 percent of the products were also high in saturated fats, sodium or added sugar. Hey, give the kid a banana.

And Story number 3 is true. An hour after seeing a sealed box of cookies touch a sealed package of sanitary napkins, subjects were still less likely to accept the offer of a cookie. That finding was part of a study to see how influenced people were in their reactions to products by what was next to that product. Pretty influence[d], it turns out. For more, check out the May 1st edition of [our] daily science podcast 60-Second Science.

All of which means that story number 2 about diet colas tasting more real than diet lemon-lime sodas is TOTALL.......Y BOGUS. Because for most people diet lemon-lime sodas taste better than diet colas or really feel better. Researchers at the University of Illinois found that mouth feel is really important to your perception of soda taste and diet colas have a really different feel from full sugary colas due to the lack of high fructose corn syrup. Even though the artificial sweetness is pretty close, lemon-lime flavor, however, has a stimulating effect on the mouth that appears to somewhat cover up the thinness of the diet drink.

A couple of notes: First Atul Gawande, our guest on the April 18th podcast has an article in the April 30th issue of the New Yorker, on the challenges the aging population poses to medicine. Also on the last episode, I mentioned the finding that microwaving your kitchen sponges can sterilize them pretty effectively. Then I got an e-mail from one of my fellow SciAm editor, Steve Ashley, who wrote, "It sounds like you're unaware of the controversy surrounding the idea of microwaving sponges. It seems that some people cook them to the point that they ignite it, so there has been an effort in the New York Times and elsewhere to discourage the practice—you may want to put in a warning somewhere yourself." Indeed, so here is the warning: "Do not microwave your sponges as they apparently may burst into flames. Putting them into dishwasher with a drying cycle still seems fairly foolproof."

Well that's it for this edition of the weekly Scientific American podcast. You can write to us at podcast@sciam.com, check out news articles at our Web site, www.sciam.com and the daily SciAm podcast 60-Second Science is at the Web site and at iTunes. For Science Talk, the weekly podcast of Scientific American, I am Steve Mirsky. Thanks for clicking on us.

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