Squeezing the Gap

This past month, our lab picked up the latest version of a 'genetically encoded calcium indicator' known as GCaMP from the GENIE project at Janelia Farm. Below is an example of calcium levels changing inside of neurons. GCaMP utilizes GFP (green fluorescent protein) to fluoresce brightly as calcium concentrations rise and then dims as calcium levels drop (note the movie has been false-colored to improve contrast, and to look cool, of course):

GCaMP movie

After some intense left-brain activity, analyzing these data, I kind of just wanted to take a minute to think about the source of GFP, the crystal jellyfish. Some of the best crystal jellyfish stories are from the accounts of nobel-laureate Osamu Shimomura, who started his quest to understand the bioluminescent glow back in 1961 off the coast of Washington state. Shimomura's advisor, Dr. Frank Johnson, constructed a chopping device, so that they could plow through tens of thousands of these creatures. The unknown glowing substance was then squeezed out, as 'the squeezate', for further purification and analysis. Fifty years later, everything has been solved - the chemical details, genetic code and crystal structure of two molecules essential to the natural process: aequorin and GFP. Over the years, things have been shuffled around to generate brighter greens and better calcium grabbers.

Wait a minute, I just spent my time writing about the details of a tragic end to 50,000 mysterious creatures as they were scooped out of the ocean and slapped down onto the chopping blocks. Oh, my ... I need to make sure that this little organism is alive and well.

Claudia E. Mills at the University of Washington knows these creatures, Aequorea, in great detail and has some answers:

Aequorea facts from Dr. C. E. Mills

I am relieved to find that those fervent scientists of the 1960's were not responsible for a major depletion of our jelly friend. Reading through her facts, you will quickly notice an impassioned rant on the misrepresentation of Aequorea in the popular news media - things being false colored green for the most part. As it turns out, the glowing substance does not permeate the entire jelly, but precisely exists around the edge of his dome, hence the special chopping device that dissected out the rim. My first thoughts are 'well, this scientist is over-reacting - really what's the harm in a little photo-shopping to get the green-glow idea across?' Then I read her statement:

I am increasingly concerned that people studying green fluorescent protein recognize neither the animal from which it derives nor natural fluorescence when they see it. The "cool inner light" (phrase used in opening text of the Science News article, vol. 152, p. 55) of the above-mentioned photo was actually reflected light from the photographer's flash, not fluorescence. This article has inadvertently highlighted the growing gap between the reductionist and the naturalist in science. 

The 'growing gap'. As scientific finding builds upon scientific finding, we do become distanced from the organism itself. Perhaps the best discoveries by Shimomura were made when he was closest to the natural home of the jellyfish. For many months, he had a tough time deciphering the luminescent reaction. He finally developed the correct hypothesis after long hours, close to the sea, quietly thinking...

I often meditated on the problem on a drifting rowing boat under clear summer skies. Friday Harbor in summer at that time was quiet and peaceful, quite different from the present day, when it is saturated with busy pleasure boats and noisy seaplanes. Meditation afloat was safe but if  I fell asleep the boat was carried away by the tide so that I had to row for a long time to get back to the laboratory.

Aequorea has been silently drifting in the ocean for 160,000,000 years. To date, we still do not know exactly for what purpose these jellyfish glow.



Sources:
Mills, C.E. 1999-present. Bioluminescence of Aequorea, a hydromedusa. Electronic internet document available at http://faculty.washington.edu/cemills/Aequorea.html.
Shimomura, O., Journal of Microscopy, Vol. 217, Pt 1 January 2005, pp. 3–15
http://www.cooperlab.wustl.edu/PracticalAdvice/Shimomura2005.pdf

Preamble

                 A Statement of Purpose of Sorts

With the rapid progression of science, a new dominion has emerged, one where man can readily manipulate the beautiful underpinnings of the natural world. When existing in a society where whole organisms can be broken down into parts, molded to our liking and rebuilt, is it inevitable that we become irreverent of the natural world?

As a neuroscientist, I work in a field where we are considerably far from any complete understanding of our muse, the brain. It is possible to be in constant wonder of this organ as we have little knowledge of how the molecular details translate to complex functions. On the other hand, it is very easy as a scientist to become bogged down by the details (neuroscience has a barrage of those details!) to the point that one completely forgets how wondrous the whole thing is. 

So yes, even when practicing something as exciting as brain science, we can easily slide into a distanced state, risking our connection to the bigger picture.

What I have found most helpful, is taking time out each week to read, reflect and bring myself back to the enthusiastic state I had when learning neuroscience for the first time.

A neuron grows extensive branches along the surface of a plastic dish as it searches for neighbors to form connections with. (RE Mott, 2009)

I started this blog for that reflection, and to start a dialogue with others regarding neuroscience, scientific policy, the practice of science, and 'the bigger picture'.

So here it begins ....