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One gram of soil -- the weight of a little
packet of low-calorie sweetener -- can contain as many
as 10,000 species unknown to science, says Dr.
Handelsman, a professor of plant pathology at the University
of Wisconsin.
For more than a decade, Dr. Handelsman
had tantalizing glimpses of an elusive microscopic world she
could not enter. When she put samples of soil under the microscope,
she saw countless species of organisms she couldn't identify.
But efforts to isolate and grow these
microbes in the lab failed, and she couldn't learn much about
them. Except for one thing: Genetic and statistical analyses
revealed that these unknown organisms must make up 99.9% of
all the microbes in the soil.
Now, for the first time, she and her colleagues,
along with several other research groups working independently,
are learning to extract the DNA of these mysterious creatures
and clone it.
They are finding that the microbes differ
so profoundly from known bacteria that they could represent
entirely new kingdoms of life -- as different from other bacteria
as animals are from plants. That means that the proteins produced
by these creatures could have properties unlike any other
such substances known.
Most current antibiotics come from microbes
in the soil. They include streptomycin, the first treatment
for tuberculosis, and vancomycin, currently the drug of last
resort for the toughest infections.
By now, however, conventional bacteria
have been largely "mined out": Most of their useful
properties have already been exploited. Researchers say that
studies of the palette of novel biological agents Handelsman
and others are discovering could lead to a new wave of medicines,
anticancer drugs, insecticides and industrial enzymes, many
radically different from those already in use.
The research builds on earlier studies
of exotic microbes that live in boiling pools in Yellowstone
National Park, at steaming volcanic vents on the sea floor,
and in other forbidding locales.
These so-called extremophiles -- named
for their affinity for extreme environments -- were crucial
in the development of one of molecular biology's most useful
tools, a method of extracting and studying DNA called polymerase
chain reaction, or PCR.
In a report in mid-November at the annual
New Horizons in Science briefing in Tempe, Ariz., Handelsman
said she and her colleagues at Wisconsin have already identified
several new antibiotics from soil microbes, at least one of
which is also proving to be a powerful pesticide.
And in California, Edward F. DeLong and
his colleagues at the Monterey Bay Aquarium have found a distinctive
light-sensitive protein that could have applications in optical
computers. They expect these to be only the first of many
more such discoveries from a field of research known as metagenomics,
or environmental genomics.
Dazzling
Variety
The field has led, among other things,
to a new view of biological diversity. The dazzling variety
of tropical rain forests, it turns out, is dwarfed by the
unseen diversity in the microbial world.
To take one
example, a single gram of sediment on the ocean floor contains
1 billion organisms,
says one of the field's pioneers, biologist Norman R. Pace
of the University of Colorado.
Dig down about
one-third of a mile to an even more forbidding environment,
and the sediment still contains about 10
million microbes per gram.
The microbes in that 500-meter-thick layer
of ocean floor make up 10%
to 20% of all the biological matter on earth, Pace
says. They include uncounted numbers of species unknown to
science.
Even human intestines -- an environment
most people consider pretty familiar -- are home to perhaps
10,000 kinds of microbes. "I've been blown away by the
diversity there," says Pace, whose work was recognized
in October with a MacArthur Foundation Fellowship.
Indeed, one of the surprises in the decoding
of the human genome was that it contains more than 200 genes
that come from bacteria. Microbes not only keep us alive;
in some small part, we are made of them.
Pace is looking at how these largely unknown
microbes might play a role in Crohn's disease, an inflammation
of the small intestine. He has found that the makeup of the
mixed "community" of microbes in the intestines
changes in people with the disease.
A similar thing might happen with tuberculosis,
Pace says, leading him to wonder whether some diseases might
be caused not by a single dangerous microbe but by a change
in the microbial community -- an ecological imbalance inside
the human body.
Handelsman and Michelle R. Rondon, formerly
of the University of Wisconsin and now at Ohio State University,
have done most of their work with soil obtained from a University
of Wisconsin research station 15 minutes from their lab.
They devised a technique for isolating
long pieces of DNA from soil, something that other researchers
had assured them could not be done. Because soil is full of
contaminants that can interfere with the finicky chemicals
used to isolate DNA, it was a trial-and-error process -- and
in the beginning, it was mostly error.
Rondon's persistence paid off, however,
and the researchers learned to extract strings of DNA from
soil long enough to contain 50 to 80 genes. Some of this DNA
came from known organisms, of course, but most of it came
from the vast profusion of unknown organisms that couldn't
be grown in the lab. "This sent shivers down our spines,
because it was the first glimpse we had of the uncultured
world," Handelsman says.
Business Week
December 3, 2001 pages 61-62
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