NEW LONDON

SOMETIMES THE DIFFERENCE between a $10-an-hour job at a car dealership and winning the $1.4-million Nobel Prize can be smaller than one-millionth the breadth of a hair. That was the case for Douglas Prasher, courtesy shuttle operator at Bill Penney’s Toyota, in Huntsville, Ala.

This year, Osamu Shimomura, Martin Chalfie and Roger Tsien won the chemistry Nobel Prize for their discovery and development of the green fluorescent protein (GFP). Both Chalfie and Tsien acknowledged Douglas Prasher’s contribution to their research. “[Prasher’s] work was critical and essential for the work we did in our lab,” Chalfie said. “They could’ve easily given the prize to Douglas and left me out.”

Very few people know Prasher’s story and how close he came to getting the Nobel Prize. It was Prasher’s 1994 GFP talk at Connecticut College that got me interested in this amazing protein, which has since become such an important part of my academic career. It’s been four years since I last spoke to Prasher, and I was stunned to learn that the man who missed the Nobel chemistry prize by 20 DNA base pairs is now driving a courtesy shuttle at a car dealership. This is not a soap opera, but a real-life tale of life’s cruel twists and turns.

While working at Woods Hole Oceanographic Institute in 1987, Prasher wrote a grant in which he proposed to isolate the GFP gene and clone it from a jellyfish. Essentially, Prasher was trying to find the “recipe” for GFP, so that he might copy it and program another organism to make it. The American Cancer Society granted him $220,000 to undertake the project. Prasher’s ultimate goal was to connect the glowing GFP to otherwise invisible proteins, so that scientists might be able to see when and where they are made.

In the late 1980s, molecular biology was still in its infancy, and cloning a new protein was a painstaking and tedious process. Eventually, Prasher found the GFP gene, sequenced it and cloned it in E.coli, but could not express the fluorescent protein in the bacteria. He came to the conclusion that the bacteria could make GFP but didn’t have the machinery to make it glow. Then his grant ran out. He applied for more funding, but it was denied. Prasher gave up.

If Prasher had had a little more time, he might have realized that what was preventing his bacteria from glowing was only a tiny oversight. When Prasher copied the GFP gene, he also copied 20 additional base pairs before the gene, and it was this little bit of DNA — shorter than one-millionth the breadth of a hair — that was responsible for the GFP folding incorrectly in the bacteria and preventing it from emitting its signature green glow.

Both Chalfie and Tsien requested a copy of Prasher’s GFP gene, and he gave it to them. “I could have hung onto the gene,” Prasher told the Huntsville Times. “But when you’re in that environment and losing public funds, you’ve got an obligation to share.”

Chalfie cleaved off the extraneous DNA and managed to make fluorescent GFP in both bacteria and C. elegans. It was the crucial experiment that showed the potential GFP had as a marker protein. And so Douglas Prasher missed the Nobel Prize by less than the skin of his teeth, and ended up working for a car dealership.

Shortly after giving Chalfie and Tsien copies of his GFP gene, Prasher left Woods Hole for a job researching plant pests for the U.S. Department of Agriculture. Then, after a minor heart attack at age 51, Prasher took a position with AZ Technology, a NASA subcontractor in Huntsville, Ala., developing hand-held sensors designed to detect harmful bacteria in spacecraft. Again, Prasher’s project lost its funding, and he spent a year looking for employment in the science sector in Huntsville. But after a year of searching for a position appropriate for a PhD biochemist, Prasher felt a need to productively occupy himself. That’s when he dropped his car off at Bill Penney’s Toyota, saw an advertisement, and became possibly the world’s most over-qualified courtesy van driver. Ironically, the dealership is on University Drive.

Prasher’s story is a sad one, but a happy ending might still be a possibility. Without him, science would not be the same today, and it is my great hope that Douglas Prasher will finally get the recognition that he so richly deserves.

Marc Zimmer ( mzim@conncoll.edu) is Chemistry Department chairman at Connecticut College and author of Glowing Genes: A Revolution in Biotechnology (Prometheus, 2005).