Tsien, who comes from a family of scientists and engineers, is more modest. Slender and self-effacing, with close-cropped black hair turning gray and wire-rimmed glasses, he quickly notes that he did not discover fluorescent proteins, nor has he used them to reveal profound biological truths.
“I'm the guy who makes the tools,” he said.
Those tools, however, have arguably changed science. Before the advent of fluorescent proteins, known as FPs, in the early 1990s, biologists and others seeking answers to some of life's mysteries – from basic cellular functions to how neurons stored memories – were often forced to employ disruptive or destructive methods of investigation, from injecting dyes into the cells (which frequently killed them) to actually grinding them up to examine their contents.
In 1992, however, Douglas Prasher at Woods Hole Oceanographic Institute successfully cloned a gene encoding green fluorescent protein, or GFP, from a jellyfish. When exposed to visible light, the protein glowed green. It offered scientists a way to see inside living cells without causing harm.
Chalfie took the next step, proving GFP could function in other organisms.
“One of the wonderful things about fluorescent proteins is they can be made by any modified cell,” said Martin Chalfie, a molecular biologist at Columbia University who first demonstrated the usefulness of GFP as a research tool in the mid-1990s.
“You don't have to add anything to the cell except light. Activate it with light of a certain wavelength and it says, 'Here I am.' You're not really interfering with the cell. Just feeding light in and getting light out.”
Tsien's contribution was to make this useful but relatively untested tool much, much better.
“He played a seminal role,” said Jennifer Lippincott-Schwartz, head of organelle biology at the National Institute of Child Health and Human Development, part of the National Institutes of Health. “By demonstrating the creative potential of GFP-based reagents and then making them available to the cell biology community, Dr. Tsien has contributed enormously to the direction and progress of cell biology.”
Combining talents in both chemistry and biology, Tsien found ways to make GFP glow more brightly and consistently. He then created a vast, new palette of FP colors: yellow, blue, cyan and orange among them.
In the words of Ellisman, it was “the whole Crayola box.”
“I've always been attracted to colors,” Tsien said. “Color helps makes the work more interesting and endurable. It helps when things aren't going well. If I had been born color-blind, I probably never would have gone into this.”
With many colors to work with, researchers can use FPs to track more than one cellular function at a time. They can tag different proteins-of-interest with different colors, then watch where they go and what they do.
But Tsien didn't stop there. He made FPs even more useful by creating versions that change colors as conditions around them change, such as acidity or calcium levels. For example, if one color-tagged protein interacts with another color-tagged protein, a new color emerges, providing researchers with even more detail and information.