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Transcript of Undiscovered Planet
The Undiscovered PlanetMicrobial science illuminates a world of astounding diversity. by JONATHAN SHAW
opernicus, kepler, galileo, newton these are
familiar names. During a 150-year span in the sixteenth and seventeenth centuries, they led the scientic revolution that placed the sun, rather than the earth, at the center of things astronomical. But have you ever heard of Carl Woese? He set in motion a scientic revolution in biology that, in its repudiation of anthropocentric views of life, is proving no less profound. In 1977, Woese (pronounced woes), a professor at the University of Illinois at Urbana-Champaign, drew a terrestrial family tree that showed the genetic relatedness of all living things on this planet. Using modern tools of molecular biology, he sampled the known single-celled, microscopic organisms we call microbes, and also the denizens of the human-scale world with which we are familiar: the owers, trees, and shrubs; the animals; and the fungi. His map of all this new information revealed that taxonomists of ages past had been looking at the world through the wrong end of a telescope. The formerly great kingdoms of Plantae, Animalia, and Fungi almost disappeared, shrinking to t on a small, trifurcating branch of his tree. In their place were three vast domains: Bacteria (single-celled microorganisms that lack a distinct nucleus and organelles); Archaea, or Archaebacteria (similar in appearance and simplicity to bacteria, but with notably dierent molecular organization); and Eukarya (all organisms whose cells have a distinct nucleusor, simply put, everything else). Life on Earth, Woeses model showed, is overwhelmingly microbial. In fact, the extent of microbial diversity is so great that scientists have diculties estimating its actual size. Some estimates place the number of microbial species in theNov ember - December 2007
range of billions, exceeding the number of species of large organisms by several orders of magnitude. In light of this new understanding of life, scientists with advanced research tools are focusing anew on microbes, which, following the great discoveries of penicillin and other antibiotics in the mid twentieth century, had largely been consigned to the connes of pharmaceutical research. Our planet has been shaped by an invisible world, says Roberto Kolter, a professor of microbiology and molecular genetics at Harvard Medical School (HMS). He and Jerey professor of biology Colleen Cavanaugh of the Faculty of Arts and Sciences (FAS) together co-direct Harvards Microbial Sciences Initiative, which serves as a focal point for researchers in the eld from all over the University. Microbes mediate all the important element cycles on Earth, and have played a dening role in the development of the planet, says Kolter. They form clouds, break down rocks, deposit minerals, fertilize plants, condition soils, and clean up toxic waste. Among their ranks, explains Cavanaugh, are the photosynthetic primary producers that use sunlight, water, and carbon dioxide to form the broad base of the food chain, and together with plants make up the earths largest source of biomass. The earliest life on our planet was entirely microbial, and if life exists on other planets, it is surely microbial there as well. In the realm of human health, microbes help us digest food and produce vitamins, protect us against infection, and are the main source of antibiotic medicines. The human cells in your body number 10 trillion, but that pales by comparison to the estimated 100 trillion microbial cells that live in and on you. Without them, you would be in trouble, Kolter says: animals experience abnormal
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growth and become sick if deprived of their microora during development. Although a few microbes are known to cause disease, the precise role played by the vast majority is essentially unknown. 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 twentyrst 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.
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 provosts oce. It kills me that people think only that bacteria are diseasecausing, 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 sun1 light, they operate by mechanisms both similar to and much dierent 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 chemosyn1: In terms of gene content, humans and potatoes are more closely related than these two bacteria are to each otherone measure of bacterial diversity. On the left, Vibrio cholerae; on the right, Mycobacterium tuberculosis. 2: From the billions of bacteria in a soil sample, these few cells landed on a nutrient medium where they could grow and form colonies. There is so much beauty everywhere we look, says microbiologist Roberto Kolter. 3: A strain of Streptomyces that produces several antibiotics widely used in medicine and agriculture. When starved, these bacteria take on a hairy appearance as they initiate growth of aerial structures where protective spores develop. The pigmented areas consist of small molecules, often with antibiotic properties. 4: In the presence of the antibiotic streptomycin, colorful antibiotic-resistant mutants of Streptomyces coelicolor spring up and form colonies.
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The Limits of CulturesAs a practical matter, the Microbial Sciences Initiative (MSI) began in 2002 as a grass-roots eort 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 fewAl l i m a g e s c o u r t e s y o f R o b e r t o K o l t e r, unless other wise noted
thetic symbionts turn carbon dioxide into sugars and proteins, feeding their hosts internally. But most people do associate microbes with disease. Antibacterials have been incorporated into all 4 kinds of consumer products: soaps, sponges, toilet paper, towels, and cutting boardseven 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 andHarvard Magazine 45
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. 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 mystied 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 dierent species discernible just by looking through a microscope). Various explanations were oeredthat 99.9 percent of the bacteria in the sample were dead, or that they
ing, and collected a sample of sediment, Kolter explains. He extracted the DNA, cloned it, and put it into a little bacterium that he knew how to grow. Then he sequenced the genes. In that one little gram of sediment, Kolter notes, Pace discovered more diversity than we ever knew 2 existed before, when using our traditional, century-old techniques for cultivating bacteria. 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. Paces d