Saturday, April 18, 2009

are we organisms or living ecosystems?

SeedMagazine | To find a biological answer to the question “Who are we?” we might look to the human genome. Certainly, when the Human Genome Project first produced a draft of the 3 billion-base-pair sequence, it was touted as a blueprint for human life. Less than a decade later, however, most experts recognize that our genomes capture only a part of who we are. Researchers have become aware, for example, of the influence of epigenetic phenomena — imprinting, maternal effects, and gene silencing, among others — in determining how genetic material is ultimately expressed. Now comes the notion that the genomes of microbes within us must also be considered. Our bodies are, after all, composites of human and bacterial cells, with microbes together contributing at least 1,000 times more genes to the whole. As we discover more and more roles that microbes play, it has become impossible to ignore the contribution of bacteria to the pool of genes we define as ourselves. Indeed, several scientists have begun to refer to the human body as a “superorganism” whose complexity extends far beyond what is encoded in a single genome.

The physiology of a superorganism would likely look very different from traditional human physiology. There has been a great deal of research into the dynamics of communities among plants, insect colonies, and even in human society. What new insights could we gain by applying some of that knowledge to the workings of communities in our own bodies? Certain body functions could be the result of negotiations between several partners, and diseases the result of small changes in group dynamics — or of a breakdown in communication between symbiotic partners.

Recently, for instance, evidence has surfaced that obesity may well include a microbial component. In ongoing work that is part of the Human Microbiome Project, researchers in Jeffrey Gordon’s lab at the Washington University School of Medicine in St. Louis showed that lean and obese mice have different proportions of microbes in their digestive systems. Bacteria in the plumper rodents, it seemed, were better able to extract energy from food, because when these bacteria were transferred into lean mice, the mice gained weight. The same is apparently true for humans: In December Gordon’s team published findings that lean and obese twins — whether identical or fraternal — harbor strikingly different bacterial communities. And these bacteria, they discovered, are not just helping to process food directly; they actually influence whether that energy is ultimately stored as fat in the body.

Even confined in their designated body parts, microbes exert their effects by churning out chemical signals for our cells to receive. Jeremy Nicholson, a chemist at Imperial College of London, has become a champion of the idea that the extent of this microbial signaling goes vastly underappreciated. Nicholson had been looking at the metabolites in human blood and urine with the hope of developing personalized drugs when he found that our bodily fluids are filled with metabolites produced by our intestinal bacteria. He now believes that the influence of gut microbes ranges from the ways in which we metabolize drugs and food to the subtle workings of our brain chemistry.

Scientists originally expected that the communication between animals and their symbiotic bacteria would form its own molecular language. But McFall-Ngai, an expert on animal-microbe symbiosis, says that she and other scientists have instead found beneficial relationships involving some of the same chemical messages that had been discovered previously in pathogens. Many bacterial products that had been termed “virulence factors” or “toxins” turn out to not be inherently offensive signals; they are just part of the conversation between microbe and host. The difference between our interaction with harmful and helpful bacteria, she says, is not so much like separate languages as it is a change in tone: “It’s the difference between an argument and a civil conversation.” We are in constant communication with our microbes, and the messages are broadcast throughout the human body.

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