Another egregious error from the Nobel Chemistry committee?

My old boss Jack Kaplan had a nice saying: "Everyone who wants to win a Nobel Prize should be given one." The Prize for chemistry was announced on 8th October 2008 as being given to Shimonura, Chalfie and Tsien for the discovery and development of green fluorescent protein".

There is a funny rule about the Nobel Prize that it can only be shared by 3 scientists. So this year Doug Prasher misses out. Prasher was at the MBL he sequenced the DNA for GFP. Shimonura was also at the MBL but apparently Prasher and Shimonura only met once (edit: see comment correcting my mistake about where Prasher worked, thanks Mark!). See page 123 of the book A Glow in the Dark, where Prasher is quoted as saying of Shimonura: "He didn't think if it was expressed, it would be fluorescent." My guess is that since all other bioluminescent molecules require co-factors, Shiminonura naturally thought GFP would too. Strictly speaking, of course, it does, but since oxygen is in every cell, we don't think of it as a "co-factor". {Note added 11 Oct: the final paragraph of Pasher's sequencing paper also says Praher himself did not think GFP would fluorescent on its own! "These results will enable us to construct an expression vector for the preparation of non-flourescent apoGFP." exphasis mine. Prasher says in the final sentence of his paper that GFP will require Aequorin to be fluorescent, at least I think he says this?}

Shimonura and co-workers reported their discovery of GFP in 1962. Probably because of his broad interest in bioluminescence, he did not do much more work on GFP. Though he did uncover the structure of the chromophore of GFP in 1979. It was not until the "DNA era" (i.e. the 1990s onwards) that fluorescent proteins took off as tools for biologists. Prasher had already sequenced in 1985 the "other protein" discovered by Shimonura, namely Aequorin. One of the kings of bioluminescence, Aequorin is consumed in a calcium-dependent chemical reaction, to give photons as product. (Many labs have tried to use this to measure intracellular calcium concentrations. This is a hopeless task, as the luminescence is dependent on too many other variables to allow quantification of calcium.)

Fast forward to 1993-4, when Martin Chalfie had the vision to see that GFP would be useful as cellular marker. He co-authored two papers with Prasher at this time. It seems that due to the lack of interest in funding this research by NIH or NSF, Prasher left the field of bioluminescence. Roger Tsien, already famous for making calcium indicators fura-2, indo-1 and fluo-3, also realised how useful such a genetically driven marker could be for cell biology. Heim, Prasher & Tsien co-authored an important paper in 1994 in PNAS in which they mutated GFP to make it useful for cell biology. Subsequently Tsien's lab have made many of the most important improvements upon the technology.

In 1997 the Nobel prize for Chemistry was awarded to Boyer, Walker and Skou for their work on ATPases. Skou got half the prize for his "discovery" of the Sodium Pump. The man who should really have won the prize for the Pump was Robin Post. However, since 4 cannot share the Prize, Post was screwed.It was Post who actually suggested the right experiment to Skou so he could make his discovery. Post also "taught us 80% of what we know about the Sodium Pump" according the my former colleague Carlos Pedemonte. In 1988 the Chemistry Prize was awarded to Deisenhofer, Huber and Michel for the crystal structure of the photosynthetic reaction center. Huber shared this prize even though he actually opposed the research, which was in fact supported by Deiter Osterhelt. Huber and Osterhelt were both Max Plank directors at that time. So did the Chemistry committee miss again? You be the judge.

I wonder how Doug Prasher feels this morning?

Update 14 Oct: There was an article on Prasher on NPR:
http://www.npr.org/templates/story/story.php?storyId=95545761
It is nice to know he can be "philosophical" about it.