Science Spotlight: Nobel Laureate Martin Chalfie

Nobel laureate and Columbia University Professor of Biological Sciences Martin Chalfie visited the College last Thursday, Oct. 16 to give two lectures. One talk focused on his research on the green fluorescent protein (GFP), which earned him the 2008 Nobel Prize in Chemistry, and the other on his current work on the molecular basis of the sense of touch.

In his first lecture, “GFP: Lighting Up Light,” Chalfie recounted the story of GFP’s discovery with humor, humility, and advice for aspiring scientists. Chalfie described GFP as a biochemical lantern and homing beacon that enables molecular biologists to watch the movement of proteins in living cells and organisms. Chalfie gave several specific examples of GFP’s use, including how scientists had used it to track the movement of viruses from cell to cell, the metastasis of cancer and the division of cells during embryonic development. There have been close to 160,000 published papers citing GFP.

The story of GFP began with the life of Chalfie’s Nobel co-laureate Osamu Shimomura. Shimomura, who was the first scientist to isolate GFP, followed an unconventional path to his life in science. When Shimomura was sixteen years old he dropped out of school to work in a paint factory to support his family. He moved from Nagasaki, Japan to a valley close to the city in 1945, fortuitously avoiding the blast of the atomic bomb. Shimomura decided to matriculate into the first college rebuilt in Nagasaki, which happened to be a pharmaceutical school.

Shimomura successfully isolated GFP in a marine biology lab, but when he attempted to illuminate the isolated GFP, it wouldn’t light up.

Chalfie explained, “This is where we depart from the scientific method and the standard story about science, because the experiment failed every single time he did it the entire summer. Nothing worked. One night near the end of the summer, he decided to go home because he’d failed once again. He took his prep, threw it in the sink and turned off the light. As he was about to leave the lab he looked back and found that it was glowing brightly. “I want to point out that in biochemistry throwing things in the sink or on the floor or the lab bench is often a very good procedure.”

It turns out that seawater has several important chemicals that enable GFP’s function.

Chalfie first heard about Shimomura’s work in 1989 at a lecture and immediately realized its potential importance. Chalfie worked on incorporating GFP into cells and fusing it to proteins, and in 1993 his work on GFP was on the cover of Science. Soon after, the scientific community embraced GFP as a powerful research tool.

Chalfie thought the story of GFP illustrated the cumulative, collaborative nature of science.

“Scientific progress isn’t something made by one great genius, but a cumulative effort, we as scientists take up ideas of others, modify them by our own experiments, and give them off to others,” he said. “What made GFP Nobel-worthy was not the work of the three of us, but the work of the thousands of people who made it a useful tool.”

Chalfie ended the talk by emphasizing the importance of funding basic research.

“Columbia gave me the freedom to do the experiments I wanted to do. I didn’t have to ask for permission or write a grant to do work on GFP. People outside of science misunderstand when we talk about the grant system. Grants are different from contract. They give you the freedom to go where the science leads you and not be tied up to a contractual obligation. I have found this to be very important, and it was really the only reason we were able to do the work on GFP that ended up working.”

Chalfie’s current work is focused largely on the sense of touch. Scientists largely understand the senses that are prompted by light, like sight, and chemical signaling, like taste and smell, but don’t understand how mechanical signals translate into touch sensation. Chalfie discovered that there are 17 important genes in the mechanosensory system and mapped their relationships with one another. He used them to investigate important questions in the field, including how we habituate touch and how we sense touch so rapidly.

When asked how the winning the Nobel Prize had changed his life, he said, “The first thing is that I get invited to give more talks like this. Before the Nobel, I never had the chance to give a general talk about science and how I thought GFP fit into it. This has given me a platform for me to do that. I’ve been able to interact much more with students. Eight months after the Nobel my niece’s daughter took me into class for show and tell, which was quite nice.”