Seeing the shimmer of biology in action

Creatures that glow lend their proteins to biomedical research

Leigh MacMillan, Ph.D.
Published: February, 2006

Field of fireflies near New London, Conn.
Courtesy of James E. Lloyd, Ph.D., University of Florida
It’s a scene that says summertime—sparks of light in the gloaming and children darting after them, Mason jars at the ready. The captured fireflies might be released or they might be tortured. They are sure to be admired.

The glow of fireflies—called lightning bugs in some regions of the country—is a source of wonder to children and adults alike. Over the past decade, scientists have discovered how to harness this biological glow, called bioluminescence, to reveal secrets from inside living animals. The chemical reaction that produces light can be used to follow cancer cell metastasis, stem cell migration, gene expression, and protein activity, all as they are happening in vivo.

Bioluminescence imaging is part of the burgeoning field of molecular imaging, which aims to “see” not just anatomy, but specific molecular or cellular processes, says Sanjiv Sam Gambhir, M.D., Ph.D., director of the Molecular Imaging Program at Stanford University.

“The goal is to do this as non-invasively as possible so that one can interrogate a living subject repeatedly over time,” Gambhir says. “Ultimately, we want to fundamentally change the way in which we diagnose and manage disease by really looking at molecular information.”

Let there be light

Fireflies are not alone in their ability to generate light—marine organisms including jellyfish, sea pansies and squid, along with various worms, fungi and bacteria all possess the biochemistry to shine. They glow to signal interest in courtship and mating, lure prey, defend, camouflage, and respond to stress.

Light production depends on the presence of a protein enzyme called a luciferase, from the Latin “lucem ferre”—bringer, or bearer of light. The luciferase performs a biochemical reaction on its substrate—luciferin for the firefly protein—usually requiring energy, oxygen and other co-factors, with the end products including the release of a single photon of light.

Of the wide variety of luciferases, the protein from the firefly has been most commonly used in biological research. It was first purified and characterized 30 years ago, and it gained widespread exposure as an “optical reporter gene” for cells in culture beginning in the late 1980s.

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