I just came from a wonderful talk by Nobel Prize winner Marty Chalfie at the conference I am attending at UCLA (the International C. elegans meeting...more commonly called "the worm meeting"). Hearing a talk from a recent Nobel Prize winner is always wonderful, because they usually still have a sense of wonder at not just their own accomplishments but the fact that their accomplishments are part of a flow of science that depends on past efforts and has meaning in the context of future accomplishments by hundreds of other scientists. I have to say hearing from people who have gotten their Nobel Prizes a long time ago is often less inspiring because they have come to terms with greatness and take it for granted. New Nobel Prize winners have not and so their perspective is generally most inspiring.

I work in a somewhat obscure, to most people, field studying a small worm that normally grows in soil. I can generally explain my work easily by saying that I study the role of insulin signaling in the development of the reproductive system. People understand that. But it is hard to convey just why studying a worm, a so-called "model organism," is meaningful or the intricate complexity that even this one study involves, linking to dozens of less commonly heard of signaling systems like TGF-beta, Tor/Raptor, etc. And it is even harder to convey why science is so exciting.

My work, like almost every bit of work done by scientists, does have applications for medicine, agriculture and industry...but usually that is not why we are scientists. Yes we think about those applications and the implications of our work, but most of us become scientists because we want to understand how life works on all levels. And the thrill of discovering how live works--how molecules interact to make a cell function and how cells interact to make a functioning organ and how organs work together to make a functioning organism--is what I love about science.

Marty Chalfie shared the 2008 Nobel Prize in chemistry with Osamu Shimomura and Roger Y. Tsien for the discovery and application of a jellyfish protein named "Green Fluorescent Protein," GFP for short. Since about 1998 GFP has been an integral tool I have used for studying first mammalian cells then worms. When these three individuals won the Nobel Prize for working this protein out, everyone felt it was well-deserved, because it revolutionized biological research in ways that non-scientists would have a hard time understanding. This protein allows us to tag almost any protein in an organism and watch in a live cell or live worm or live whatever you want just where that protein goes and what it does in real time. All my best papers to date made use of this technology.

In today's lecture by Marty Chalfie, he told the story of the discovery and application of this protein, some of which I knew, and put it into context. One of his main points was that this Nobel Prize was a real recognition of the collaborative nature and cumulative nature of science. Osamu Shimomura was the first to study this protein in an attempt to understand the chemistry of bioluminescence, how living things can produce light. Chalfie gave a brief biography of Shimomura, expressed with some awe. Shimomura was born in Kyoto, Japan, and at age 17, in 1945, was told he couldn't go to school anymore because he had to go work in the next valley in a factory. The city he had to leave to go work in a factory was Nagasaki. So he got to see the flash of the atomic bomb from a distance rather than be in the middle of it. (Coincidentally I just finished a book on Nagasaki and the end of WWII which I will be reviewing soon). Shimomura finally went to college and went to the US to work. He was given a project to isolate the protein that made this light in the jellyfish:

(image from US News, which also has more info)

Not being told that it had already stymied two other researchers Shimomura promptly isolated it. This was accomplished in 1962.

The cDNA (basically the simplest genetic structure of the protein, a direct code for the protein sequence) was worked out by Doug Prasher in 1992. Marty Chalfie, who had heard of Shimomura's work from yet another scientists in a lecture, had been eager to get a hold of that cDNA so he could find a way of expressing the protein in the C. elegans worm to use it as a tool for looking at the structure of the nervous system. Prasher and Chalfie collaborated and a graduate student in Chalfie's lab made the first ever construct artificially expressing GFP (initially in bacteria). Another student expressed it in worms and yet another collaborator showed that the emission spectrum in bacteria was the same as in the jelly fish. This was in 1994...though Chalfie had already published it in an informal journal received by C. elegans researchers (called "the worm community") called "The Wormbreeder's Gazette." It was the following year I first heard about GFP, though it was 4 years before I started working with it. But many, many biologists started working on it early, using it as a tool to study how proteins worked in cells, and developing the technology further. Roger Tsien is one of the scientists who developed the technology into a whole series of molecules fluorescing with different colors and excited at different light wavelengths so that many proteins could be studied at once in living cells. This includes the amazing Brainbow:

(image from the Royal Society of Chemistry)

Not to mention my own, much humbler work in a previous lab (see for example this book chapter).

The Nobel Prize recognized the contribution of the person who first isolated the protein in 1962, the main researcher who found a way, in 1994, to put the protein into another organism as a tool for studying proteins and cells, and the researcher who more than anyone turned it into a tool that has revolutionized biology. Science is a collaboration and, as Chalfie put it tonight, cumulative. You can read about these three scientists and see film of their Nobel speeches and presentations here.

But Chalfie made another critical point in his talk. These days science is seen as only valuable if it can be directly justified by an application to human disease, agriculture or industry. Basic research has become under appreciated. This is largely due to a misguided cost-benefit approach to funding research. GFP and the variants developed by Tsien has revolutionized all aspects of biology including medical research, agricultural research and pharmaceutical research. And yet every step that has been honored by this Nobel Prize was pure, basic research. The study of how light is produced in a jelly fish led to someone using the results of that work to study how neurons work in a worm and that led to someone else developing newer and better tools for other basic researchers to study their own systems. Without basic research, and the driving curiosity that drives basic researchers simply to understand how things work, this wonderful tool would never have been developed and later applied to translational research (where basic research is "translated" into a medical or other practical application). That translation was not the reason for the initial work by these Nobel Prize winners, though they certainly would have been aware of the potential applications.

Chalfie put it this way:

"Basic research is essential."

This basic point is under appreciated by American society and government.

Chalfie told a story of the head of an agency from the previous president's administration who told a crowd of researchers that we don't need basic research anymore because we understand everything and so we can move on to applications like curing cancer.

This was a stunningly ignorant statement.

It reminds me of a talk my wife heard in climatology where a representative from the same previous president's administration told a bunch of scientists that we didn't need to study earth anymore because didn't we all just want to leave earth anyway.

Another stunningly ignorant statement from what was a stunningly ignorant administration.

This also reminded me of what in some ways is an extension of this level of ignorance. Ronald Reagan's Secretary of the Interior, James Watts, made the statement that we don't need to conserve our resources because the second coming is at hand and so we should just use up our resources as fast as we can.

This was what was most appalling to me about Bush's presidency, and before that Reagan's presidency. Both, but particularly Bush's, glorified ignorance and denigrated knowledge. A stunningly stupid thing to do.

I have heard criticisms of Obama, saying he isn't doing enough. Well, that is fine. Even great presidents need people to badger them to do what they should do. But when people claim that there has been no change since Bush left I get angry. Because I have seen a fundamental change: science and knowledge is once again valued and decisions are no longer being made through the glorification of ignorance. Republicans are still clinging to that ignorance, but Obama has in every way shown he values knowledge and science, putting excellent scientists in positions of making policy.

I want to thank Marty Chalfie for his excellent talk tonight (as well as making the tool that I have gotten my best work from!) and reminding me of just why I am a scientist and just why the change from Bush's leadership based on ignorance to Obama's leadership based on understanding and knowledge matters so much to me.