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November-December 2007
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< previous | 1 | 2 | 3 | 4 The same could be said for microbes around the planet. There are a billion of them in a gram of soil, and a billion per liter of seawater, but we know neither what they are nor what they do. In the poetic conclusion to his 1994 autobiography, Naturalist, the great sociobiologist and Pellegrino University Professor emeritus E.O. Wilson mused on what he would do, “[i]f I could do it all over again and relive my vision in the twenty-first century. I would be a microbial ecologist...,” he wrote. “Into that world I would go with the aid of modern microscopy and molecular analysis. I would cut my way through clonal forests sprawled across grains of sand, travel in an imagined submarine through drops of water proportionately the size of lakes, and track predators and prey in order to discover new life ways and alien food webs. All this, and I need venture no farther than ten paces outside my laboratory building. The jaguars, ants, and orchids would still occupy distant forests in all their splendor, but now they would be joined by an even stranger and vastly more complex living world virtually without end.” The Limits of CulturesAs a practical matter, the Microbial Sciences Initiative (MSI) began in 2002 as a grass-roots effort among faculty members who recognized the unexplored ecology and potential of these organisms and wanted to share information about microbial research across diverse disciplines: biology, medicine, chemistry, engineering, geology, astronomy, and evolutionary and planetary history. The group held informal “chalk-talks” weekly, and in 2004 staged a day-long symposium with speakers from around the world. When President Lawrence H. Summers issued a call that year for initiatives that would bring people together from across the science and engineering disciplines, MSI was a perfect candidate, says Cabot professor of biology Richard Losick, a member of its steering committee. “I think there are few disciplines that lend themselves better to cross-disciplinary approaches,” he says, “and few subjects that have implications across a wider spectrum of sciences than is true for microbiology.” As a result, in 2006 MSI received four years of support, totaling $2.7 million, from the provost’s office. Sidebars:
“It kills me that people think only that bacteria are disease-causing,” says Cavanaugh, who studies the chemosynthetic symbiotic bacteria that make life possible for giant clams and tubeworms dwelling near deep ocean hydrothermal vents. Far from sunlight, they operate by mechanisms both similar to and much different from the photosynthetic organisms we see every day. “Although intracellular, these bacteria are helpful to their animal hosts,” she adds. “Like chloroplasts in plants [which evolved from symbiotic photosynthetic bacteria], the chemosynthetic symbionts turn carbon dioxide into sugars and proteins, feed- ing their hosts internally.”
Not much can be gleaned about the differences between these two microorganisms just by looking at them, but genetic analysis tells us that they are not even in the same domain. Left: Soil-dwelling Bacillus anthracis is classified as a bacterium. Right: Heat-loving Thermoproteus tenax is an archaean that lives in hot springs. But most people do associate microbes with disease. “Antibacterials” have been incorporated into all kinds of consumer products: soaps, sponges, toilet paper, towels, and cutting boards—even clothing. Kolter traces the origins of this “ludicrous” antimicrobial “scorched-earth policy” to the time of Louis Pasteur, who formulated germ theory, and Robert Koch, who developed methods for culturing bacteria. “Medical microbiology for almost 150 years has been driven by the idea that germs are the causative agents of disease. And there is no doubt that Koch and Pasteur were right, that Mycobacterium tuberculosis causes tuberculosis and Vibrio cholerae causes cholera,” says Kolter. But microbes have also led to most of our antibiotics, a development that Kolter calls “the most important advance in medical history.” Scientists had known that there are more microbes in an ounce of soil than humans alive on Earth, but that was just a measure of abundance. Pace’s discovery demonstrated something new, a previously unfathomed repository of biodiversity. Scientists began sequencing DNA from all sorts of environments. After looking at human gut microflora, they learned that each individual has his or her own characteristic set of a thousand species. “These represent three million genes that you carry,” points out Kolter, “as compared to the estimated 18,000 genes of the human genome. So you are living and exchanging [metabolites] constantly with a diverse pool of some three million genes.” Microbiologists continue to find new taxonomic divisions of microbes far faster than they can figure out how to culture them.
Their cell membranes outlined in red, individual Bacillus subtilis bacteria contain the biosynthetic machinery—shown as green dots—for making bacillaene, a newly discovered small molecule.
Colonies formed by the wild strain of Bacillus subtilis generate complex structures, as seen at left, while the domesticated strain—presumably selected for uniformity by generations of researchers who have used it in laboratory experiments for many decades—has lost nearly all colony architecture. The formerly limited view of the microbial world arose from what has turned out to be an inherently constrained approach to the study of bacteria: the practice of culturing them. For more than a hundred years, scientists had been mystified by what was called the “plate count paradox.” Whenever they tried to grow a sample of bacteria from the environment on a nutrient medium in a petri dish (an agar plate), only a few microorganisms grew and multiplied to form colonies, when there should have been at a minimum thousands of such colonies (based on the number of different species discernible just by looking through a microscope). Various explanations were offered—that 99.9 percent of the bacteria in the sample were dead, or that they must all be the same bacterium because they looked similar. 1 | 2 | 3 | 4 | continued >  
 
 
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