familiar names. During a 150-year span in the sixteenth and seventeenth centuries, they led the scienti\ufb01c revo- lution 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 scienti\ufb01c revolution in biology that, in its repudiation of anthropocentric
In 1977, Woese (pronounced \u201cwoes\u201d), a professor at the Univer- sity 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 mi- crobes, and also the denizens of the human-scale world with which we are familiar: the \ufb02owers, 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 \u201ckingdoms\u201d of Plantae, Animalia, and Fungi almost disappeared, shrinking to \ufb01t on a small, trifurcating branch of his tree. In their place were three vast \u201cdomains\u201d: Bacteria (single-celled microorganisms that lack a distinct nucleus and organelles); Archaea, or Archaebacte- ria (similar in appearance and simplicity to bacteria, but with no- tably di\u2260erent molecular organization); and Eukarya (all organ- isms whose cells have a distinct nucleus\u2014or, simply put, everything else). Life on Earth, Woese\u2019s model showed, is over- whelmingly microbial. In fact, the extent of microbial diversity is so great that scientists have di\u221eculties estimating its actual size. Some estimates place the number of microbial species in the
In light of this new understanding of life, scientists with ad- vanced research tools are focusing anew on microbes, which, fol- lowing the great discoveries of penicillin and other antibiotics in the mid twentieth century, had largely been consigned to the con\ufb01nes of pharmaceutical research.
\u201cOur planet has been shaped by an invisible world,\u201d says Roberto Kolter, a professor of microbiology and molecular genet- ics at Harvard Medical School (HMS). He and Je\u2260rey professor of biology Colleen Cavanaugh of the Faculty of Arts and Sciences (FAS) together co-direct Harvard\u2019s Microbial Sciences Initiative, which serves as a focal point for researchers in the \ufb01eld from all over the University. \u201cMicrobes mediate all the important element cycles on Earth, and have played a de\ufb01ning role in the develop- ment of the planet,\u201d 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 \u201cprimary producers\u201d that use sunlight, water, and carbon dioxide to form the broad base of the food chain, and to- gether with plants make up the earth\u2019s 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 num- ber 10 trillion, but that pales by comparison to the estimated 100 trillion microbial cells that live in and on you. \u201cWithout them, you would be in trouble,\u201d Kolter says: animals experience abnormal
growth and become sick if deprived of their micro\ufb02ora during de- velopment. 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
In the poetic conclusion to his 1994 autobiography,Na t u ra l i s t, the great sociobiologist and Pellegrino University Professor emeritus E. O. Wilson mused on what he would do, \u201c[i]f I could do it all over again and relive my vision in the twenty- \ufb01rst century. I would be a microbial ecologist...,\u201d he wrote. \u201cInto that world I would go with the aid of modern microscopy and molecu- lar 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 build- ing. 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.\u201d
crobial Sciences Initiative (MSI) began in 2002 as a grass-roots e\u2260ort among faculty members who recog- nized the unexplored ecology and potential of these organisms and wanted to share information about microbial research across diverse disciplines: biology, medicine, chem- istry, engineering, geology, astron- omy, and evolutionary and plane- tary history. The group held informal \u201cchalk-talks\u201d weekly, and in 2004 staged a day-long symposium with speakers from around the world. When President Lawrence H. Sum- mers issued a call that year for ini- tiatives that would bring people to- gether 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. \u201cI think there are few disciplines that lend them- selves better to cross-disciplinary approaches,\u201d he says, \u201cand few
subjects that have implications across a wider spectrum of sci- ences than is true for microbiology.\u201d As a result, in 2006 MSI re- ceived four years of support, totaling $2.7 million, from the provost\u2019s o\u221ece.
\u201cIt kills me that people think only that bacteria are disease- causing,\u201d says Cavanaugh, who studies the chemosynthetic symbi- otic bacteria that make life possible for giant clams and tubeworms dwelling near deep ocean hy- drothermal vents. Far from sun- light, they operate by mechanisms both similar to and much di\u2260erent from the photosynthetic organisms we see every day. \u201cAlthough intra- cellular, these bacteria are helpful to their animal hosts,\u201d she adds. \u201cLike chloroplasts in plants [which evolved from symbiotic photosyn- thetic bacteria], the chemosyn-
thetic symbionts turn carbon diox- ide into sugars and proteins, feed- ing their hosts internally.\u201d
But most people do associate mi- crobes with disease. \u201cAntibacteri- als\u201d have been incorporated into all kinds of consumer products: soaps, sponges, toilet paper, towels, and cutting boards\u2014even clothing. Kol- ter traces the origins of this \u201cludi- crous\u201d antimicrobial \u201cscorched-earth policy\u201d to the time of Louis Pasteur,
who formulated germ theory, and Robert Koch, who developed methods for culturing bacteria. \u201cMedical microbiology for al- most 150 years has been driven by the idea that germs are the causative agents of disease. And there is no doubt that Koch and
1: In terms of gene content, humans
and potatoes are more closely
related than these two bacteria are
to each other\u2014one measure of
bacterial diversity. On the left,
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.
\u201cThere is so much beauty every-
where we look,\u201d says microbiologist
Roberto Kolter. 3: A strain of
and agriculture. When starved,
these bacteria take on a \u201chairy\u201d
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 strepto-
mycin, colorful antibiotic-resistant
mutants ofStreptomyces coelicolor
spring up and form colonies.
Pasteur were right, thatMycobacte rium t ube rc ulosis causes tuberculosis andVibrio cholerae causes cholera,\u201d says Kolter. But microbes have also led to most of our antibiotics, a development that Kolter calls \u201cthe most important advance in medical history.\u201d
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 mysti\ufb01ed by what was called the \u201cplate count paradox.\u201d Whenever they tried to grow a sam- ple of bacteria from the environment on a nutri- ent 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 di\u2260erent species discernible just by looking through a microscope). Various explanations were o\u2260ered\u2014that 99.9 percent of the bacteria in the sample were dead, or that they
\u201cBut then in 1990,\u201d says Kolter, \u201cscientists showed that the DNA complexity in a typical soil sample meant that there had to be thousands of times more diversity than was being plated.\u201d Norman Pace, a professor at the University of Colorado, began to wonder if scientists simply lacked the basic knowledge needed to grow most of the bacteria on the planet\u2014if perhaps we were so ignorant of these bacteria that we could not culture them. He hit on the idea that he could instead analyze a sample of soil or water for its DNA content in order to ascertain how many species it contained. \u201cPace went to Yellowstone National Park, to some of its famous hot springs, where the water was nearly boil-
ing, and collected a sample of sediment,\u201d Kolter explains. \u201cHe extracted the DNA, cloned it, and put it into a little bacterium that he knew how to grow.\u201d Then he sequenced the genes. \u201cIn that one little gram of sediment,\u201d Kolter notes, \u201cPace discovered more diversity than we ever knew existed before, when using our traditional, cen- tury-old techniques for cultivating bacteria.\u201d
Earth, but that was just a measure of abundance. Pace\u2019s discovery demonstrated something new, a previously un- fathomed repository of biodiversity. Scientists began sequencing DNA from all sorts of environments. After looking at human gut
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.\u201d Microbiologists continue to \ufb01nd new taxonomic divisions of microbes far faster than they can \ufb01gure out how to culture them.
The world of animals\u2014from elephants to ants\u2014is divided into 13 phyla (vertebrates are one phylum, insects another). In the mi- crobial world, their equivalents are called, for the time being, \u201cdeep-rooting branches.\u201d In 1987, 13 of these big divisions were
Not much can be gleaned about the differences
between these two microorganisms just by look-
ing at them, but genetic analysis tells us that they
are not even in the same domain. 1: Soil-dwelling
The modern \u201ctree of
life,\u201d based on genetic
analysis, shows that
the bulk of Earth\u2019s bio-
diversity resides among
the Archaea, Bacteria,
and that portion of
the Eukarya that does
not include plants,
animals, and fungi.
classified all unicellular
organisms lacking nuclei
(archaea and bacteria)
as Monera. The nucleat-
ed eukaryotes compris-
ing plants, animals, and
fungi were thought
to represent the bulk
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