IDEaS - Nobel Laureate Roger Y. Tsien

this ucsd-tv program is a presentation of university of california television for educational and non-commercial use only our last speaker is Roger Tsien winner of the Nobel Prize in Chemistry in 2008 for the discovery and development of the green fluorescent protein GFP Roger began his career in science when he was 6 or 7 years old his father bought him a chemistry set which led to his discovery of science books in the elementary school library this in turn resulted in his sketching experiment in a notebook when he was 8 years old although he was unable to get the notebook published the original now resides in the Nobel Museum Roger's career in science progressed nicely through high school in his senior year he won the first of his many honors by winning the nationwide Westinghouse Science Talent Search although he remains mystified how he won because he now considers his project to have been scientifically unsound of course it has been onward and upward ever since when it came time to go to college Roger went to Harvard interestingly he chose Harvard over Caltech in part because Harvard had a better music department and he did take music theory and chamber music performance classes there he also took economics classes but unlike Rob he resisted the temptation to pursue an economics career Roger decided to leave Cambridge Massachusetts for Cambridge University in England for graduate study where he also did his postdoctoral work because of Prime Minister Thatcher's austerity program there were few faculty positions available in England when Roger completed his postdoc so he decided to return to the US and found a position at UC Berkeley now public universities in the u.s. at that time were also dealing with financial challenges so Berkeley was unable to provide the research facilities that Roger needed as a result UCSD was able to entice him in eight 1989 join the chemistry and biochemistry department the department of pharmacology and the Howard Hughes Medical Institute all at UCSD in Rogers words UCSD was much younger roomier faster growing and less tradition-bound than Berkeley we are indeed indeed very fortunate that we could attract Roger to UCSD in the words of an anonymous reviewer his contributions have brought considerable claim to our faculty and institution moreover he has been an outstanding departmental citizen and a teacher who has shown an abiding commitment to academic endeavors that are not necessarily connected to his research please join me in welcoming roger chin I realize it's very late and I'll try to go through this quickly and hopefully I'm lucky that my research it tends to be fairly visual so I can just show you some movies so the first is to thank the creature that really perhaps should have gotten a Nobel Prize which is aquaria Victoria this jellyfish here shown swimming in an aquarium I have to confess though it's famous and its scientific role is because it glows when disturbed every so often here you see the flash that is not the flash of the jellyfish that has children pushing the button that changes the lighting at the Monterey Bay Aquarium and two of these guys are having a race to the bottom of the tank he see the other ones coming up fast in the inside lane as I said the jellyfish glows when it's disturbed and that attracted the interest of this man Osamu Shimomura and he was interested in the mechanism of glowing and that's what he mainly work done but in his paper that he'd first described a glowing protein a Koren he also mentioned that there was this contaminant in the jellyfish that actually was somewhat hard to separate and that this protein took the could absorb ultraviolet or blue light and turn it into green and a Koren actually glows blue originally so they worked as a could work as a pair and I don't have a picture of a Sun with from 1962 I have a picture of him from 2008 at the rehearsal where here is holding a tube of GFP he has perhaps the last tube in the world that was actually made out of real jellyfish and I believe there's about 20,000 jellyfish died to make this tube and here this is here if the you hand UV lamp that he uses to show how it the protein can glow the next major step was that this man in the middle here at Douglas pressure in 1992 cloned the gene for GFP which shimomura declined to do pressure was more of a molecular biologist and decided that he would find the DNA then encoded this protein and there's a long story of a tremendous personal irony here that Doug pressure did not make tenure at the Woods Hole Oceanographic Institution his grants were not renewed and he dropped out of science very shortly thereafter but he at least did publish the gene and the the cloning and the two people basically in the world read the paper with any care and one of them was me and the other was Marty Chaffee we are the ones who then took up the story but you might ask why pressure did not and the airing is a long story and perhaps have the fact to do with that he did drop out of science and that unfortunately the Nobel is never given to four people so Marty was the first one to show that pressures gene could be put into other organisms and would make a glowing protein and that was done in 1994 actually a month later Fred suji right here at sio did the same thing but he was a month later and our contribution was eventually to do many things but partly to change the color of GFP into this entire panel and to fix up the deficiencies of the original jellyfish protein which the jellyfish made for its own purposes and not to help biologists and it needed a lot of fixing up to do but yet that still one could regard all what we did is relatively derivative but you know for some reason they decided to include me and we came up with some fun names for all of these which these names these are all turns out from coral rather than jellyfish and some very clever Russians discovered that the corals also have homologs of the jellyfish - jellyfish never could get us beyond this yellow green but the corals got us to the rest of the spectrum and so this is where things stood in 2004 and if I can explain very in one slide you know who cares so what so you've got these colors well they are glowing enough you may have seen this picture here they've all been illuminated with other wavelengths of light they're not toxic and they're the key is that they are pigments that we can teach nearly any cell or organism how to make the only exceptions are those that you can't put genes into or that can't tolerate oxygen from the air the these colors then form labels that we can tag any protein just about any protein you want or any cell within an organism or even an entire organism if you can genetically modify and that way we can watch the living protein cell organism do its thing it's weak watched life history we can detect when genes are turned on and off and in a particular favorite of mine is that we can engineer these proteins to make them artificially sensitive to nearly any biochemical other biochemical signal inside cells such as the acidity the pH that is the calcium level the kinase activity this is enzymes that put phosphate groups on enzymes that tear proteins apart just any time an enzyme or a protein snuggles up and then to another one we can also see that by engineering these fluorescent proteins and I'll give you just two examples that are happened to be nice visual pictures I don't say that they're the most profound scientifically but for this audience I thought vision fun pictures are good so these are this is a zebrafish embryo that has been transfected we have put DNA in other in other words to teach this embryo of how to make a special molecule that will change color when it sees calcium ions and we're gonna watch this embryo as it begins to divide in its first steps to becoming a fish from just a single cell and if I can run the movie here the first thing that happened is that you notice it it when it began to divide a band of red spread across and that band is is maintained at the belt where it's tightening and in fact this is the signal to tighten the belt and as if I were to do this and tighten and tighten tight until I eventually was pinched into and calcium of the trigger for that and this keeps going and the next cell division which is going to be here once again the red color which is the high calcium press ages the formation of that cleavage furrow and then the next one is coming and that's spit here and here and we go into the eighth cell stage and next to the 16 cell stage coming up and then there's some more and at this stage it begins to just get visually muddy because there's so many divisions piled up on top of each other you can't resolve them any more but the procedure continues and this is really the beginning of life for all of us all vertebrates just happens the zebrafish are transparent and they make nice pictures and here's another example again from a former postdoc at sushi Milwaukee where he made a different set of molecules and now tell you whether a cell is getting ready to divide or have just divided or is finished and that's using our biochemical knowledge of the steps and triggering division vs. quiescent then going to division in other words the cells business cycle you might say except that we see it in color and he chose this as pretty colors he had some choice and so I think he made it nice and memorable green means go red means stop in quiescence and you know it could have been the other way around but traffic lights work this way so it's easier to remember and here are two cells and one of them is red which means it's taking a break and this one's about to divide and now I'm gonna show you one week's worth of data compressed into a few seconds as we watch and each one of these cells cycles between green and red and green and red and green and red as you watch them it is green just before it divides and then it goes into a red phase and then back into green and so on just as before it divides with intermediate colors of orange and yellow as it goes back and forth up and down and you see the date has gone from Friday to Thursday and you have this whole mix of cells at different stages now you may ask why did we need to see this after all if you have a complete movie in retrospect you can trace out when each cell divided because you could play the movie back and check but this tells you a prediction now it's almost like what we were just hearing about this will predict by the color whether it's gonna divide very soon or not and I think these business cycles are great but I wish I knew what was gonna happen next month that's what we would all wish and it's a lot easier to plot them in retrospect let me point out that fluorescent proteins are also good educational tools even down to the high school and elementary school classroom and we have helped launch a outreach program here from UCSD called bio bridge that tries to takes experiments like this out into the schools because these are pretty you know easy experiments and have a nice visual feedback the students can see in this case bacterial colonies glowing cherry stick read and by making a little change they can turn the red back into green or make it colorless or so on so they can see the principles of mutation genetic engineering biochemistry with their own hands and the fact that it made a recent Nobel Prize makes them happier because they feel they're at near the cutting edge and not just studying stuff that was discovered a hundred years ago by Mendel or someone like that so this is spreading through San Diego County I just want to mention that I want to be the first one to tell you the limitations fluorescent proteins have been good but they also have some bad and some ugly features not really nasty in the sense of society but though they revolutionized basic biomedical sciences and the way I just described there is one organism that is the most difficult to put DNA into and that is the human being it's not because it's scientifically difficult but it is ethically not something we're going to allow if you are sick and going to the hospital and I want to treat you are you going to volunteer to have DNA put into you which would be a form of gene therapy furthermore humans are too thick and opaque for fluorescence of the sort I showed you which is why we were our colleagues worked on zebrafish which are transparent so between the genetic engineering and thickness and opacity of most of us we have two for solving disease problems for actual sick people now this is distinct from under secrete to understand disease but to actually try to treat people we still need other non genetic methods and this is more of what I've gone back to in my career having had my fling with the genetically encoded ones and I'll just show you an example of what we're trying to do here is a mouse that actually has a tumor in there I'm sorry it's a bit dark but most of you would not be able to see where the tumor begins and ends it's really of course it's so dark you can't see anything at all but trust me it's not easy to see okay sorry there it's a little bit brighter and even then you wouldn't have an easy time seeing where the tumor begins and ends but when we switch into the fluorescence mode and this is a special types of dyes attached to peptides that we are injecting into the mouse this isn't not genetic this is not GFP anymore but we're trying to do the equivalent with things that can be done on human beings now you can see the boundaries of the tumor sort of they're not crisp because it sort of fades away at the edges but the bright fluorescence indicates where the enzymes are active in this cancer and then we go on with a little further now we can superimpose these two views and the fluorescence we false color green and superimpose it on the rest of the mouse and then it looks as if it had GFP in it but it really isn't it's something we injected and this helps the surgeon go along and cut out the tumor there's the regular white light view the surgeons have always had and now in the false color view with the green it becomes much easier to cut out the tumor relatively accurately because you just want to get rid of all the green stuff so if this is the white light view hard to know where the boundaries are here it's much better we're revealing the nerve here but unfortunately soon we're gonna see two branches of this nerve but in regular white light you don't know that there's an extra hidden branch the nerve that's here it's been visible in white light there's the white light view but only when we turn on the fluorescence can we see that there's this extra branch using a separate molecule that lights up the nerves and so we use the second molecule to tell us we're not the cut and the first molecule that finds the tumor to tell us what to get rid of and you need both that information so let me switch now to some pontificating my version is what are some lessons for young scientists try to put your neuroses to constructive use now what I mean by neuroses I didn't have time to go into is but one of them for example is that though I like to play the piano I am really not very dexterous in the lab especially with micromanipulators and my failure at that was a cause for a lot of this chemistry to find a way of putting dyes or colors into animals without poking the cells and trying to keep them alive while I injected stuff out of this super microscopic tip I'm not very good at that I hate it so I'm you know put Disney roses to constructive use also why am i ik m Estill it's partly because my father was a mechanical engineer and my older brothers were electrical engineers and they sort of took over all the sort of chemistry and the engineering and electrical spaces and so on and I was a sort of scientifically inclined the one thing that they all hated all of my brothers and my father was chemistry so I as the youngest child I was forced to find the ecological niche there's a whole book on the subject by the way the effective birth order try to find projects that give you some sensual pleasure and you may have noticed that I do love pretty colors except that your batting average will be low hopefully not zero and that when you do succeed it's often for the wrong reasons you have to learn to make lemonade from lemons and sometimes persistence pays often if I had time I could go through example after example where nature gave fetes some disappointing result but fortunately we were able to use that to our advantage 'as prizes are ultimately a matter of luck so avoid being motivated or impressed by them you have to go for things that would you know please your own gut because the chance that you will get a prize is so low that's not an acceptable reward to risk ratio shall we say and of course you've got to find the right collaborators and exploit them in a kind way for a mutual benefit so let me go back through a little history some of which actually has to do with UCSD people are always asking Nobel laureates was it a complete surprise when you got the call from Stockholm and I have to admit it was not it was an extremely annoying thing because several days earlier the practice now this news agency called Thompson Reuters is to make their picks of who they think deserves the Nobel Prize at least in the physics chemistry and medicine subjects I'm not sure if they do economics they probably do and they had predicted these three people Charlie Lieber Christophe moshevsky and me now we work in completely different areas so we could never share it but they were hedging their bets and tried to pick three different areas and based on this was enough for reporters like the Union Tribune also already wanting interviews what does it feel like to be tipped as a Nobel laureate I see the answer is really go away I don't want you know to have any you know chickens counted before they hatch that's the surest way to make sure it won't happen right to have people count on it but UCSD public relations insisted they wanted to get ready they ordered a cake with green green icing you know in honor of GFP and you know I thought this is a really dumb idea because especially here and I had some you know day by day prediction I could check there the likelihood of their predictions on medicine as always announced on Monday and not one of their three candidates Thomson Reuters was right and then physics on Tuesday and again they struck out completely so you know the likelihood that they're gonna be right on Wednesday is pretty dismal furthermore I must admit that I had been forced to go through an audition in spring of 2006 where I was holed up in front of the Swedish royal of Academy of Sciences well I have to admit I you know I wasn't resisting that hard very few people turned down an invitation to speak in front of the Royal Academy of Sciences and after that talk which was you know a summary of what we'd done including that picture of all the colored tubes and then being taken out the dinner nobody would talk to me and they were all sort of sat there like bumps on a log and I tried to make polite conversation you know what areas of chemistry were they interested blah blah blah but no it was pretty sad failure so I was sure I'd flunked it and so it was pretty surprising then when I got a phone call at 2:25 in the morning on October 8th a warning that there would be a press conference in 20 minutes held in Stockholm that I would be participating by phone and I had to participate because of Samuel and Marty were not answering their telephones and they had advantage that it was 5:25 in the morning there and not 2:25 and I think they could have done their their their part but they really laid it all on me by you know sleeping through their alarm clocks or phones so groggily I had to you know rouse myself from a minute I had taken a sleeping pill precisely not to be bothered by all of this and I had to you know come up with something to say to the world's press it's a real challenge to keep the lab running I never really managed to acknowledge - congratulations properly and I really don't know how paul krugman who was the economics winner for that you had as hell does he managed to meet two or three deadlines a week for the New York Times he still managed to do it of course there's some strange moments like the traditionally American Nobel laureates get invited to the White House we were in wendy and i were in some doubt whether we should even go and you know go didn't meet this man but he had you know after obama had just a shake in his hand after winning elections so who were we to consider ourselves higher and mightier and the man does have I have to say mister Bush did have a very good sense of humor at one stage he put his arm around Paul Krugman who you know has attacked Bush vitriolic Lee in the newspaper and Bush said well and as the photic tog refers were clicking away he said professor Krugman I think your grandchildren will enjoy this picture or something like that and so here my pictures that's the King shaking my hand and I have just checked to his rom angle and we agreed and neither of us heard what the King has to say and I've heard that mother laureates as well that he mumbles something and we're guessing we are told that probably what he's saying is don't drop it it's heavy it looks embarrassing if you drop it in front of a few thousand people there's the three of us and I'm looking particularly morose because I hate dressing up in this penguin suit here the beautiful Royals and the king the Queen the the beautiful princesses and the prince and the laureates the chemistry laureates and their spouse of course just corresponding pictures for the other subjects then there's this fancy banquet during the Swedes sure know how to throw a party and I had the fortune to sit next to a princess Madeleine who's a rather charming lady on her other side was Paul Krugman she is shown in this picture talking to me which was actually a relatively rare event during this dinner because if you are a beautiful princess who is not a scientist who would you rather talk to one of the world's most famous experts on economic crises 2008 who can explain to you what's gonna happen to the Swedish auto industry and who's really good at explaining things to laypeople because he right does it every day twice a week for the New York Times would you rather talk to somebody about jellyfish but here we actually are talking to each other and what we found in communists that she of course as the youngest of three and I am the youngest of three and when she found out that Wendy is the youngest of three she asked do you think that youngest children and their families are meant for each other because her boyfriend was the youngest of three and I apply yes yes unfortunately that boyfriend has subsequently proven unfaithful and has it's broken up so that's sad Wendy could not complain I had a beautiful young lady to a top two because she had a pretty good-looking guy this is Prince Carl Philip and she had can monopolize him because on his other side was the Japanese the wife of one of the Japanese physicists and she didn't speak either English or Swedish or anything that he could communicate with so Wendi had him all to herself for the entire evening and the evening does go on a bit because one thing if I dare say I inside secret you are not allowed to get up from the table as long as the royalty is seated so you are well advised and they do advise you make sure you visit the rest of the room beforehand because it's going to be a quite a few hours so here is the inside of the dining room during this fantastic banquet this I guess is the top table I think and halfway down there is the King and half was somewhere around there or us and these are the waiters bringing in the dessert which traditionally has these fireworks associated with it so each one of these is a sort of a sparkler that they carry and we've they carried a whole thing down the length of the whole way while this thing is blazing away some other side pictures you do get to sign a big book with other people's names in it and they do allow you to ask who do you whose previous signature or picture you want to look at and you might not be surprised that we asked to see Albert Einstein's picture there they make us give lectures at schools and here was a young man who was so excited about meeting he me that he insisted that I sign my name on his torso in ink it's not easy to do if human flesh is not a very easy thing to write on actually this is the actual weather and that shows you Wendy on the day after noon no bail during the daytime this is Stockholm city hall weather ceremonies are held this is the testament of nobel himself and it's a really pretty chicken scratchy document he really had lousy handwriting and a really bad organization you see it's all scribbled in the margins and all of the things that have grown up and tradition are the interpretation of just these two pages in his will and finally here is a picture of the paper mache giant green frog with which the Stockholm University students roast the laureates those who are willing to at least hang around to be roasted and we stayed and was we are inducted into the order of the ever smiling jumping green frog which is what we're wearing around our necks and it takes four people to hold the four legs of a frog and in this case I happen somebody took a picture of me at the front Tsutomu Shimomura son of Osama represented his dad who wasn't feeling well enough there's Marty Chafee at the back and I'm sorry it's partially obscured there is Douglas pressure and I'm really glad to say it and it takes four people to hold up a frog and that Douglas as our guest Marty's and my guest was able to contribute there at least and finally this is our interpretation of a sunset with a green flash as you might see it had we been a little closer to the edge of the cliff we actually can't see the sunset from our lab but it's not far off and this is all dream drawn of course with fluorescent bacteria so this is the actual living pigments used as our paint and these are the people in the lab who did the various things that I've mentioned none of it by me by the way thank you

Channel: University of California Television (UCTV)

Views: 11,496

Rating: 5 out of 5

Keywords: Tsien, Nobel Laureate, IDEaS

Id: sPe-EPNqh6U

Length: 28min 34sec (1714 seconds)

Published: Thu Jun 02 2011