Medical research is about to be revolutionized. Not by a new kind of computer or a new type of drug, but by a bright-green glow.

In Stockholm last December—as the world’s scientific elite met to discuss the future of 21st century medical science at the Nobel Centennial—it seemed appropriate that in a country where the winter sun sets just after noon, the hottest topic of conversation would be molecules that light up like beacons to guide researchers to discoveries.

Now that the human genome has been sequenced, scientists have a “parts list” which details the contents of a human cell. It’s now estimated there are from 30,000 to 40,000 genes in each cell, each of which encodes at least one protein. The number of these “parts” is equivalent to the population of a small town, says Roger Tsien, a professor at the University of California at San Diego. The goal of medicine in the post-genome age will be to track each member of this genetic “town”—and to be able to identify and correct those townspeople who are misbehaving, who put the town in danger of spiraling out of control—leading to cancer, for example.

Tsien’s Nobel Week lecture focused on striking new methods that his laboratory is developing that allow scientists to keep better tabs on the population of this genetic town.

The prevailing way that scientists keep track of proteins is by using green fluorescent protein (GFP). Naturally produced in jellyfish, GFP glows bright green under the microscope when illuminated with ultraviolet light. By linking GFP to a protein of interest, a biologist can track that protein’s movement throughout the cell. In the case of diseases like cancer, GFP’s green light acts like an ankle transmitter on a convict, alerting a researcher to the location of a misbehaving gene.

“The green fluorescent protein has been wonderful for us,” said Tsien, “but it has some major problems and limitations.” One concern is that GFP is too big, being composed of over two hundred amino acids, making it as big or bigger than some of the proteins it is designed to monitor. “Using GFP,” said Tsien, “[is like having] a policeman literally chained to the subject under observation.” Another problem is that the light from GFP is too diffuse to be seen under the electron microscope.

Tsien’s groundbreaking solution to this conundrum was to bypass GFP altogether and to change the fundamental structure of the protein under study.

Using simple genetic engineering techniques, Tsien’s group added a small tail to a protein called actin, which makes up the skeleton that keeps a cell’s shape. This tiny modification creates a hook-like shape (see sidebar) that is so small that it doesn’t interfere with the actin protein at all.

Tsien then flooded the cell with a special dye his team constructed. The dye—which contains arsenic—binds tightly with the special tail. When illuminated under the microscope, the dye glows. But not just green—Tsien’s group has made a whole rainbow of different dyes that fluoresce in different colours.

Because the dye molecule is so small, it goes right into the living cell and interacts with its target protein in real time. And since so many colours are available, scientists can immediately and accurately follow how the proteins in cells behave, for example, when stimulated with stresses that cause cancer. Previous techniques that track these behavioural changes have required the cells under study to be killed and fixed—destroying the natural environment so crucial to a proper understanding of disease mechanisms. So why had no one attempted Tsien’s remarkable technique before? His arsenic-containing dye may have had something to do it. “Arsenic, of course is famous for toxicity, and that scares people…and that was why no one else was crazy enough to try it.”