Discovering The Bugs Within

We are crawling with bugs. It might even be better to say that we are bugs. For every human cell in our bodies there may be ten or even a hundred other cells that aren’t human at all. Yet many of these microbes are entirely unknown to science. To change that, the National Institutes of Health has just begun a five-year, $115 million Roadmap initiative called the Human Microbiome Project. It aims to find out what these bacteria, viruses, archaea and fungi are, how they function, and the ways they can keep us healthy or make us sick.


“There have been some tantalizing findings that gut flora influence things like obesity and irritable bowel disorder,” says Jane Peterson, PhD, associate director of the Division of Extramural Research at the National Human Genome Research Institute and a program director for the project. “Ultimately, what we really want to understand is health as well as disease. What makes us healthy? Our microbes are a part of that.”


But learning about these bugs has seemed like an overwhelming undertaking. Part of the problem is simply numbers: thousands of different species of microbes swarm on and in our bodies.


A human gut microbe. This bacterium, Entercoccus faecalis, which lives in the human gut, is just one type of microbe that will be studied as part of NIH’s Human Microbiome Project. Courtesy: United States Department of AgricultureThe most obvious way to find out what they are is to understand their genomes. Unfortunately, sequencing these microbes is even harder than sequencing our own genome because most of the microbes have an obstreperous unwillingness to grow in isolation in a lab. They will only grow in the particular conditions of, say, our teeth, where they commune with a particular group of other microbes that create an agreeable environment.


Sequencing technology has been improving rapidly, however, bringing the task within reach now. “Metagenomic” techniques have been developed to study the genomes of many different microbes simultaneously, making it unnecessary to culture the microbes in the lab. In addition, modern sequencing machines can now produce millions of sequences in a day, compared to a few thousand in the past, and they do it less expensively.


The Human Microbiome Project has already awarded $8.2 million to research groups around the country in 2007, and they currently have six requests for proposals out, due between February and May. Analyzing the data from all these far-flung groups will require the development of new computational techniques. Genomic analysis already produces such vast quantities of data that it has pushed the computational capacity to make sense of it all, and the Human Microbiome Project will produce an order of magnitude more data than that. The project aims to coordinate the results from all the different groups, producing a single, publicly-available dataset.


The researchers involved in the project say the most exciting part is that they simply don’t know what they’re going to find. “You have to expect that there will be very many ways microbes are impacting our health that we don’t know and maybe can’t imagine at this point,” says George Weinstock, PhD of Washington University in St. Louis. “We’re hopeful it will have an impact on the level of the human genome project.”


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