The mesa is a little darker today. Roger Tsien 1952-2016.
September 1, 2016 8:15 AM   Subscribe

UCSD Chemistry Nobel laureate Roger Tsien dies. Amongst many other achievements, he is most well known as co-discoverer of Green Fluorescent Protein, which, as well as making headlines with glow-in-the dark rats, initiated a field that revolutionized biology and our understanding of the molecular and genetic basis of disease and life itself. More reaction and links from In The Pipeline.

It's worth noting in particular that while this man was a colossus in science - he was humble and treated his coworkers and students with respect, kindness and empathy. An example of this behavior was with Doug Prasher.
posted by lalochezia (14 comments total) 11 users marked this as a favorite
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posted by Dashy at 8:29 AM on September 1, 2016 [1 favorite]


I hope it's not too much hyperbole to say that nearly every biologist of this generation has made some discovery thanks, in large part, to GFP and by extension, Tsien.
posted by Cold Lurkey at 8:34 AM on September 1, 2016 [6 favorites]

It is impossible to overstate how important GFP is. Simply put, it lets us see things that would otherwise be effectively invisible, or at least indistinguishable from the masses around it. It's hard to imagine how one does biology at the scale of cells or below without his work.

As an aside, he also is critical to modern neuroscience for a second reason. He developed the first dyes that could be used to watch neuronal activity by having fluorescence intensity vary quickly with calcium concentration, which allows fast imaging of large populations of identified neurons. Nowadays we tend to do this with genetically encoded calcium indicators, but the principle remains.
posted by Schismatic at 8:44 AM on September 1, 2016 [11 favorites]

I saw him give a lecture at UCL maybe 5 years ago, when they awarded him some sort of prize. As well as being a good speaker he came across as a friendly and humble guy with wry, self-deprecating humour, and plenty of time and thought for the people asking him questions afterward.

It's hard to imagine modern biology without his work which, at the time, wasn't a hotly contested area. For a lot of science, if the person credited hadn't made the breakthrough then almost certainly one of their competitors would've got there within a month or two anyway. But Tsien chose his subject specifically because few others were going in that direction; someone would have got there eventually, sure, but without Tsien it would've been much later.
posted by metaBugs at 9:06 AM on September 1, 2016 [4 favorites]

We need a convenient way to be able to identify GMOs...why don't they use this protein to mark them?
posted by littlejohnnyjewel at 9:09 AM on September 1, 2016

For those who don't know, GFP (and the gene that codes for it) is essential for developmental and molecular biology. In a nutshell, say you have found a new gene but don't know what it does. Attach the GFP gene to it, and any time that gene is expressed (is active, makes protein) it will also make GFP and you have a handy glowing marker of exactly when and where that gene is expressed. I have an ex who is a developmental biologist who used it while studying kidney development in mice, specifically the gene Sprouty (which is a gene that is used all the damn time in development...any time a thing branches (or 'sprouts') fingers, blood vessels, air passages in the lungs, kidney vessels, you name it...sprouty)...he actually made some pretty amazing animations of the vessels in the kidneys branching over time by growing them in a petri dish and examining with a fluorescent light every hour for a few days straight.
Anyway...this is sad news...

posted by sexyrobot at 9:34 AM on September 1, 2016 [8 favorites]

Oh...also this has helped to discover the purpose of certain genes we have that are expressed in early development for literally like 10 minutes, and then never again as long as you live...and yet these genes are so essential that if we didn't have them our development would fail completely or we would be born with severe genetic disorders...and many genetic disorders have been isolated using this method.
posted by sexyrobot at 9:40 AM on September 1, 2016 [2 favorites]

You down with GFP? Yeah, you know me!
posted by exogenous at 9:40 AM on September 1, 2016

We need a convenient way to be able to identify GMOs...why don't they use this protein to mark them?

0) No, we don't. But...

1) Do you want more foreign protein in your GMOs?

2) Most people would not want to eat food that glowed green, nor animals that had eaten food that glowed green. This would negatively affect GMOs perception by the public regardless of any other positive or negative effects they had.

3) It would be a waste of resources for the plant, possibly leading to reduced efficiency of the protein that the plant was genetically modified to produce in the first place. This might sound trivial, but in order to get USDA approval of a GMO crop you must show that its performance is agronomically comparable or superior to non-modified crops. A plant already expressing a foreign protein might not have extra energy to also make GFP, so it could be detrimental to the health of the plant.

4) In fact, not all proteins tolerate GFP tag. Some enzymes would not work at all. GFP is actually a fairly bulky protein.

5) Enzymes are targeted to be expressed in specific tissues. (Your kidneys don't make the same proteins as your skin.) In many cases the protein engineered into a GMO is not express in part of the plant that would be visible.

6) GFP only glows when exposed to ultraviolet light so again, only proteins expressed to the surface of the plant would be visible.

7) Honestly, I don't know how GFP would react with chlorophyll. It's probably a neutral effect - the chlorophyll should be reflect most green light anyway.

8) GFP could attract insects or animals to the crop at a higher rate.

That's just a quick, unresearched take on it. (Sorry to sound so negative.) But it was an interesting thought experiment, so thanks!
posted by maryr at 9:43 AM on September 1, 2016 [7 favorites]

I didn't interact with him much in graduate school, but he was giving enough with his time to teach the Intro to Giving a Scientific Talk course to a bunch of incoming first-year chemistry PhD students. I'm sure he had the pull to get out of that obligation if he so desired, but he was willing to sit through our terrible unfocused powerpoints and give a few key points of constructive criticism to every one of the forty or so of us. We definitely all appreciated that. Even more so after he won the Nobel Prize five or so years later.
posted by Existential Dread at 10:42 AM on September 1, 2016 [8 favorites]

posted by allthinky at 12:40 PM on September 1, 2016

I started working with GFP just after Dr. Tsien's point mutation version came out in 1995. Of course, GFP was several factors larger than the protein signal I was trying to track, so things got kind of clogged up.

RIP Dr. Tsien. Your contributions accelerated the work of a generation.
posted by NoRelationToLea at 1:13 PM on September 1, 2016 [1 favorite]

I just gave 3 lectures this week showing my students many examples of the beautiful imaging you can get using GFP and its derivatives, and the wonderfully detailed analyses and mathematical modelling that it had enabled. It has transformed the biological sciences and for me there literally is not a working day where I am not looking at and trying to extract information from GFP imaging whether it is to to understand trafficking of proteins in cells or the development and structure of the kidney. I was recently lucky enough to be involved in some research where we discovered a protein that had been previously been implicated in Parkinson's disease was being mistrafficked to the wrong location in the cell, which may be part of the disease, and we observed that directly with a confocal microscope and GFP tagged proteins.

R.I.P. Roger Tsien, every day I benefit from and use your discovery.
posted by drnick at 3:39 PM on September 1, 2016 [5 favorites]


one hundreds times .


This man was an example of what makes homo sapiens worthwhile.
posted by brambleboy at 11:33 PM on September 1, 2016 [2 favorites]

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