Outside column: Protein is the light of his life

Posted: Friday, October 10, 2008

As is the case with most great scientific discoveries, it all started with a bit of curiosity. In the 1960s, Osamu Shimomura wondered why crystal jellyfish gave off green pinpricks of light. Now, half a century later, Shimomura has been awarded for his curiosity with the Nobel Prize in chemistry.

Shimomura was fascinated by the chemistry involved in bioluminescence and collected more than 1 million jellyfish from Washington state's Friday Harbor (on San Juan Island) in the '60s and early '70s. He spent the next 40 years meticulously examining the proteins that made them glow. In a crystal jellyfish's approximately 300 photo-organs, Shimomura found a protein he named aequorin that produces blue light, which subsequently is converted to green light by green fluorescent protein, or GFP.

Yet it is hard to imagine that even Shimomura understood the potential for the little protein that glowed.

In the decades since Shimomura isolated it, GFP has revolutionized stem cell research, cloning, organ transplants, neuroscience - and everything in between. That's because GFP can be attached biochemically to proteins within a cell, making a formerly invisible protein fluoresce beneath blue light. Proteins are extremely small and cannot be seen, even under an electron microscope. But attaching GFP makes a protein fluoresce: It's like seeing headlights from the window of a plane even if you're too high to make out the cars.

Proteins in human cancer cells have been tagged with GFP, and the resulting fluorescent tumors have been implanted in mice. As cancer cells break from the tumor and begin to metastasize, or move about the body, they continue to fluoresce, and scientists can watch the cancer spread.

Four other scientists are largely responsible for making this curious glowing protein into the most useful modern imaging technique available. Douglas Prasher cloned the GFP gene and was the first to think about using GFP as a fluorescent protein tag. Sergey Lukyanov won the race to find the first red fluorescent proteins, which he found in corals in a Moscow aquarium, and his research led to the discovery of fluorescent proteins in many other marine organisms.

Unfortunately, the Nobel can be shared among only three people, and these two worthy scientists were denied a slice of the $1.4 million prize.

The two others, however, join Shimomura as the new chemistry laureates: Marty Chalfie, who was the first to use GFP to light up bacteria and worms, and Roger Tsien, who has been in the forefront of fluorescent protein research since 1994 and has created a series of fluorescent proteins whose colors span the spectrum.

Many more continue to contribute to GFP research. GFP has been used to show how HIV travels from infected to noninfected cells. In another study, scientists created a mouse with fluorescent neurons that connect its whiskers with its cortex. By replacing part of its skull with a glass window, they have been able to observe how the mouse rewires its brain to cope when half of its whiskers are removed. This fluorescent window into the brain is being used to study the effects of aging and neuro-degenerative diseases.

In 2007 alone, more than 10,000 research papers were published about studies that relied on the glowing protein.

GFP is the microscope of the 21st century. It lets us see things we have never been able to see before. And, like the microscope, it has completely changed the way we think about science.

Green fluorescent protein has been floating in the ocean for more than 160 million years, but it took an inquisitive scientist, fascinated by bits of green light, to begin unlocking its potential.

Wednesday's recognition highlights the importance of his discovery and reminds us that all great discoveries originate with a healthy dose of curiosity.

• Marc Zimmer is the chemistry department chairman at Connecticut College. He is the author of "Glowing Genes: A Revolution in Biotechnology."

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