This is an odd story. Any story that starts with jellyfish would be, I suppose. But since we are now sliding into the icy gloom of January, the Body Scientific has decided to do a story about light.
You might suppose that jellyfish have little interest, but that would be wrong. They have a primitive nervous system and if you have ever been stung, you know how effective it is. But it is another property that interests us — they fluoresce. Shine blue light at them and they emit green light. In an aquarium, one of the most popular exhibits entails shining a black light at jellyfish and making them glow. There are sea creatures that produce similar proteins that glow in different colors — blue, cyan, cherry, or red.
In the 1960s, Osamu Shimamura, working in Woods Hole, Mass., wondered how organisms such as jellyfish, glow worms or fireflies produce light. There are a number of biochemical methods by which this happens, and Shimamura became well-known for studying them.
But by chance, he came upon a protein that fluoresced. If he shined blue light at a test tube of the purified stuff, he got back green light. It was a simple protein, which is to say a string of smaller molecules — amino acids — linked in a particular order. Why did he do this? He probably just thought it was interesting. But wait, this story has a good ending.
In the years after Shimamura isolated his green fluorescent protein, now called GFP, it became possible to isolate the genes that code for proteins and to reinsert them into cells. When the genes that provide the instructions for making hemoglobin or insulin are placed into cells of another species, those cells make hemoglobin or insulin.
It was not until about 1992 that Douglas Prasher isolated the jellyfish DNA that provides the instructions to make GFP.
Microscopes cannot distinguish objects that are too close to each other just as you cannot distinguish the two headlights of a distant car. But if one of the car lights was green and the other red, you could.
As he tells it, Marty Chalfie, professor of biology at Columbia University, was sitting in a seminar around noon on April 25, 1989 (he took notes). A visiting scientist was speaking about light-emitting organisms and mentioned GFP, which Marty had never heard of. He immediately realized that if he had the gene, he could insert it inside a cell or even in the middle of some other gene, and the cell would be green. Small objects would be easier to see.
He paid no attention to the rest of the talk. It was not until 1992 that he and Prasher got together and inserted the DNA for GFP into the experimental bacteria E. coli. When the experimenters shined ultraviolet light at them, the bacteria emitted green light.
The Chalfie laboratory is interested in how we feel things that we touch or how we keep our balance — and to study the basis of mechanosensation they use a small worm called C. elegans. This creature has many experimental advantages — not least that it is transparent. There are nerve cells in its head that help it sense where to go in the soil (it eats the slime molds we discussed a few weeks ago).
The Chalfie lab had been studying genes that turn on in these nerve cells and so they inserted the GFP DNA sequence into one of these genes and the nerve cells fluoresced green, so that they could be seen against the background of unlabeled cells. The cells, importantly, were not harmed.
This result created a sensation in the biological world. Since these experiments were published in 1994, the GFP gene has been used to solve thousands of biological problems. New versions have been recovered from other organisms, primarily by the laboratory of Roger Tsien, so that we have a pallet of colors. Thanks to GFP we can see what we could not see before and in living cells.
This research was motivated by curiosity, but now GFP is also essential to clinical research. Chalfie is a champion of basic research. We have not discovered all of the basic biology of life and it is worth hearing the speech he gave when he accepted the Nobel Prize he shared with Shimamura and Tsien in 2008. Google “Martin Chalfie� and you can hear it — a good-humored 30 minutes and (mostly) understandable to the non-scientist. One of his messages is that all that work with simple organisms does pay off. If you are talking from that podium in Stockholm, somebody believes you.
Richard Kessin is professor of pathology and cell biology at Columbia University. He and his wife, Galene, live in Norfolk.
