Seeing the shimmer of biology in action  pg. 2

"The greatest contribution to human medicine that probably all molecular imaging approaches, including bioluminescence, will have is in refining and accelerating our animal models of disease, such that we can test and develop drugs more efficiently."
Christopher H. Contag, Ph.D., co-director of the Molecular Imaging Program at Stanford University
Such luciferase assays to study gene regulation in cultured cells were in full swing when Christopher H. Contag, Ph.D., got frustrated with the methods for studying infectious diseases. Contag, a virologist by training, was following mother-to-infant transmission of HIV by comparing viral genetic sequences.

“It turned out to be a very complicated analysis, and I said at the time, ‘wouldn’t this be so much easier if we could just watch the whole process?’” recalls Contag, now co-director of the Molecular Imaging Program at Stanford. “It occurred to us that we should be developing tools for watching complex biological processes in the context of living animals, and at some point in time, living humans.”

A search of the available imaging modalities and a fortuitously timed lecture by an environmental microbiologist about luminescent bacterial enzymes pointed Contag and his wife Pamela R. Contag, Ph.D., in the direction of bioluminescence.

“We figured that since animals and people don’t glow in the dark, if you put something in the body that does glow in the dark, you should get great signal-to-noise ratios since there should be relatively no background noise,” Contag says. We now know there are background signals—from biological processes in animals that produce small amounts of light—but for bioluminescence imaging, he notes, “the signal-to-noise ratio is really extraordinary.”

For their first studies, the Contags and their colleagues followed bioluminescent bacteria in a mouse.

“When we saw the first images of glowing bacteria in the intestines of a mouse, I said, ‘Every biology lab in the world will want to use this; this will be fantastic,’” Contag recalls. The team published its findings in 1995, and Contag anticipated that use of the technology “would explode.” It took a little longer than he expected, with adoption by many laboratories occurring only in the last five years.

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