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Norm Pace Finds New Ways to Map Microbial Tree of Life


Norm Pace discovered the invisible world around us when he was still in grade school.

"I was given a microscope at about the age of 10 or 11, and I found it really quite fascinating," he recalls. It was fascinating enough for him to decide to make the study of these tiny forms of life his life's work.

The University of Colorado microbiologist has journeyed in a bathysphere to thermal vents on the ocean floor to study microbes that thrive in these extreme conditions. He monitors the air in the subways of New York. He crawls on his belly in caves filled with poisonous gas, all to collect unusual microbes.

But even with the world's best microscopes, Pace says, some of those specks of life are hard to figure out.

"We're used to describing organisms in terms of arms and legs and leaves. But that doesn't do you much good in terms of the microbial world," he notes.

A focus on microbial DNA

A better way to describe the microbial world came in the 1970s, when National Medal of Science winner Carl Woese focused not on a microbe's appearance, but on its DNA. He says the genetic material revealed surprises. For instance, many microbes are more closely related to trees and humans than they are to each other.

"It's not like finding a huge animal in your backyard," Woese says. "But in terms of phylogenetic [evolutionary] relationships, these things are very distant from known things."

Studying a microbe's DNA requires growing billions of cells from one single microbe in a lab. Pace says this was groundbreaking work, but it missed the larger picture.

"One microbe alone probably won't be doing very well. In fact, if you see a single microbe in the terrestrial environment, it's probably dead or going somewhere."

Pace suspected that many species of microbes live together in diverse communities, in the same way that trees, flowers, fish, birds and bugs interact. He wanted to study this diversity, rather than one species at a time.

What's more, he says, most microbial species that thrive in the natural environment die when scientists try to grow them in the lab.

"If I go down to Boulder Creek and pick up a little water and look at in a microscope and count directly the number of organisms that are in that water, I'll see about a million cells per thimbleful. If I do what I can do to culture those organisms, I'm going to get about 10."

And because most microbes can't be cultured, new species couldn't be identified.

A crowded microscopic community

Woese says researchers recognized the problem but didn't know what to do - until Pace came up with the solution.

"What he deserves credit for," he explains, "is seeing that you can bring the sample from the environment to the lab and go directly after the genes, not after the organisms that contained them."

To do this, Pace stripped off a snippet of DNA from all the species of microbes in an environmental sample. Next, he attached those snippets to an easy to culture species of bacteria. As that bacteria multiplied, it also copied the diverse DNA. This allowed the genes of the entire sample to be analyzed.

It's now clear that hundreds - sometimes thousands - of microbial species often thrive in a drop of water, in an underground cave or in the lungs of a child with cystic fibrosis.

At Pace's research lab, Kirk Harris leads a study of lung infections, especially cystic fibrosis.

"It's a very bad disease," he says, adding that it would be nice to do more to help find a cure.

Traditional cultures of diseased tissue can generally spot half a dozen species of "bad guy" bugs infecting the lung. But Pace's gene mapping technique reveals that even healthy lungs sometimes contain hundreds of different microbial types. However, Harris notes, in the healthy lungs, no single species seems to dominate.

"That does seem to be the case - that healthy, diverse microbial communities represent the normal stable function, whether you're talking about the gut, or the lungs, or the skin, or whatever surface of the human body."

Grandfather of microbial ecology

Promoting this diversity may someday promote better human health and Woese says Pace's ideas for tracking microbes will lead the way. He calls Pace, "the grandfather of microbial ecology. Real microbial ecology, where you can ask about what is there rather than just see what comes out of the system."

As for how many microbes he's discovered in these ways, Pace estimates hundreds of thousands. "I'm mapping the tree of life," he points out.

For his contributions to that map, Pace was awarded a prestigious MacArthur Fellowship - the so-called genius grant - plus several lifetime-achievement awards from the world's leading microbial research organizations. And at the recent American Association for the Advancement of Science annual meeting, Pace was featured in a panel presentation, "Microbes in a Changing World."

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