It’s Great to Glow Green

Discovery Used in All Facets of Biological Research

Martin Chalfie calls it "the most beautiful molecule I’ve ever seen."

Its aesthetically pleasing appearance also belies the unique and important role it has played in modern science.

The molecule that the 2008 Nobel prize winner in chemistry described is green fluorescent protein (GFP), and its actual molecular structure resembles a lantern, which is fitting, since when the DNA that encodes the protein is inserted into living cells, they “light up” green. Chalfie described his research as “hanging a lantern” on a protein to see what it does and where it goes.

That might sound like an entertaining parlor trick, but the use of GFP has been ubiquitous in better understanding such diverse phenomena as cell division to the development of neural networks.

Chalfie, William R. Kenan  Jr. Professor of Biological Sciences at Columbia University, spent two days at the Pratt School of Engineering to not only deliver the keynote address at this year’s annual symposium of the Fitzpatrick Institute of Photonics (FIP), but also to meet and chat with students – from those at Pratt to local high schools.

He also received the 2011 Pioneer in Photonics Award from FIP director Tuan Vo-Dinh, R. Eugene and Susie E. Goodson Professor of Biomedical Engineering and professor of chemistry.

Chalfie described the series of events that led to his ground-breaking discovery. As a geneticist, he had been working with the transparent worm known as caenorhabditis elegans (c. elegans), a well-studied animal model with exactly 302 nerve cells. Chalfie was particularly interested in how the simple animal responded to touch.

On the other side of globe, Japan's Osamu Shimomura, one of two other scientists who shared the Nobel with Chalfie, had been studying a certain species of jellyfish that was able to generate its own "light." The project had been going nowhere until Shimomura disgustedly threw, as Chalfie described it, jellyfish guts into a sink, turned of the lights and got ready to leave the lab. When he glanced back, he noticed a green glow in the sink. He later discovered that the calcium in seawater in the sink was the key.

"As I heard him describe this serendipitous event at a conference, I had that ah-hah moment," Chalfie said. "I too work with transparent animal model, and I might be able to use GFP in my research."

Chalfie went back to his lab, and before long, had used GFP to visualize in real time the development of the nervous system in the c. elgans worm. Not only that, but he could document actual cell division within his model. Shortly after Chalfie published his first paper, labs across the world started using GFP to highlight a vast array of life processes.

Over the next two decades, he has published more than 200 journal articles about his work with GFP and c. elegans, with the first being among the most highly cited in the field.

"As it turned out, GFP turned out to be such a powerful tool," Chalfie continued. "The gene has the advantage of being inheritable and has no negative effects on the organism. It can also be seen in living cells in real time."

By further manipulating the GFP gene, the third co-awardee of the 2008 Nobel, Roger Tsien, developed mutant versions that caused glowing in a rainbow of colors.

The use of the GFP gene has even transcended the laboratory and jumped into popular culture. An American artist, Eduardo Kac, had a transgenic rabbit created that glowed green when in the presence of blue light, and another company created a line of transgenic zebrafish whose bodies exhibit different Day Glo colors.

Chalfie left his audiences with the impressions he has gained from toiling in the laboratory for more than four decades.

"It's been my experience that many discoveries, like Shimomura's, turn out to be accidental," he said. "As many of you probably already know, grad students and post-docs are the real innovators in laboratory. And just as importantly, basic science and research is the essential driver of innovation."