[applause] thank you. The plan today is to have a talk about the book. We will chat 25, 30, 40 minutes depending on how it goes on at which point we will turn things over to the audience and have them provide some questions. We havent rehearsed anything. He doesnt know what im going to add, so im sure that he has nervous expectations. Sometimes it is hard to write a book and they often call it a memoir which might be a recollection of the theory that led to the result the recollection of the entire life i think that you have chosen to focus on the centerpiece of the less work and that is his efforts to help elucidate the structure of the gene machine protein manufacturing apparatus. He doesnt really tell us much about his early life. In fact, the book begins by saying when i left india but nevertheless, we definitely associate. If you were trying to say what it was all about and how it helped to shape you, tell us about that because we dont hear much about your appearance or how you live those first 19 years of your life. I was told by both publishers not to make it an autobiography. Some people might be interested in the science and what it does, stick to the signs science and we dont want to know about the childhood and stuff like that. I was in Southern India that has at least 13 major languages like europe i was standing at the edge of a playground and couldnt understand a word the other children were saying. He gave me a sense of what it was like to be an outsider and then at eight or nine i went to australia because my father was oddly enough a biochemist and went on a fellowship to australia so there was a bit of an outsider again and i came back and had a very strong australian accent that they couldnt understand in india then i finished my school please silence your cell phones. Another kept persuading schools and made me skip a grade. I had no interest in biology because i thought biology and chemistry involved lots of rote memorization and simply wasnt intellectually challenging unlike mathematics and physics the torso of a dent and beautiful. So i had my heart set on being a physicist. And when i graduated, my parents were spending a sabbatical in urbana illinois. So instead of staying on to get a masters which is what most students do, i decided the very last minute to apply to a few places and most places wouldnt even look at me because i havent taken the grd and the Physics Department said we will take you but we wont give you a fellowship. But then when they found out i was only 19 and had no humanities as a part of my work, they said okay. We are sorry we couldnt give two years of College Graduates to be a co credit to the then t wasnt really an option. So, it was the only place that could give me a fellowship and admission. One of the things that would strike most readers if you arent readers already have this terrific book when youre nobel prize was announced you seem to recall when many people especially newspaper editors wanted to embrace you and i think the business of identity is very complex especially with people that have wandered all over the world and are somewhat ruthless in a way that i am. So, i was already ruthless being a south indian growing up in the northwestern, western india, then i come to america and i sort of made it back in my home you only can tell fro controe book by reading closely learned russian as a teenager. You have read the book closely. [laughter] i was interested because i wasnt hedging my bets. I was interested in chess is interested in russian culture and the university had evening courses that you could take so i ended up studying russian and continue to study and ohio. If you wanted to get a phd in science you have to take a foreign language. Its one of the intriguing features and something that permeates the book. You are sitting in the business seats and these things are influential in developing a concept. In some way, he wrote a memoir. I would like to move on to think about your attitude because you said at one point that you are not a be a leader in this idea that there are heroes and you sometimes wonder whether people who make this discovery are agents of the discovery that would have been anyway. And yet, throughout the book there is a fierce sense of competition. You know that somebody is going to have a three or two or one and a half picture and you want to be one of the people that does that. The reason i say they occur at a certain stage and certain individuals have made it other people voted, the reason i say that is the remarkable coincidence we have throughout history of major advances. For centuries there is no calculus and suddenly within the same lifetime, to individuals come up with the idea simultaneously. All these people come up with ideas and even a special theory when we talk about the contraction isnt einstein. They had already come up with a formula for those things and so the ideas were there, and individuals almost seem like agents. If it hadnt spend those few bew people, if you wait and probably not even that long, it could have been some other few people because the stain of knowledge had reached a certain point where the next steps would become apparent. In the context of ideas where i think that many of us would say the ideas have been there for a long time. I point out how computing and all sorts of advances in technology detectors, all of these have been. They were not invented the plaintiffs once they were there, people could see it actually off to be possible now using the techniques that are very powerful. If three or four of us headed down this, other people would eventually. A classic story is dna. There are so many people maybe it wouldnt have come out double helix plus the base pair. They capture the essence of the whole problem do you see an equivalent . Who i dont think so because first of all it is far more complex and different parts have their own sort of special nature like the transfer center that we focus on so it was more diffuse than dna. But you could split it into two parts how do you get two of something from one of something, that is what the instructor showeshowed, but the second pars it took a very long time and required several people to elucidate that. I want to get back to the question of the reiteration and the theme of who did what and what does it mean to elucidate. The writer i writers writer is r scientists to the new work placing a lot of emphasis and speaking very frankly about the nature of the prizes, and i think that its widely known as your work came out there would be major prizes for the work on the ribosome. Reading about your discourse and you imagine putting them together too many are satisfied. The rule of three is to accept the idea of the rule of three. Your analysis of the potential prize brings up the difference between a certain approach to behavior that emphasizes the biochemistry and the molecule doing the work as opposed to figuring out where all the atoms are and how the proteins have this role leading to the better understanding of how the antibiotics work. Even from the perspective of some of the organizations, they might be appalled by the fact that you have recounted organizations in which we talk to the jury members who asked you to try to explain how things should go together. Its not a frowned upon activity. My reading of the book, your deception is the structural and functional part. Im not sure that i agree about the structure versus function because the only reason to do structure you your self say we already knew, so heres how i saw it if you look at the early biochemistry, the early biochemistry established the lights after the transfer etc. Those were all done before the generation who kept working the last 20 years or so even when they arrived on scene. Many of these things are already known again. Those were the things that hold you what it did and how it worked. So then the question was how does it do it and what the biochemists were doing im sure they were fond of one or two of these to take issue, but i am absolutely sur firm in my opinin about this. They were trying to do structure using the biochemistry. So they would say isnt it interesting this protein is next to this piece of our name. Its put together with how it works. This is next to this without knowing the context. Nearly all that work was done by the early 90s. There was no talk of it getting a good price in the early 90s because the early work was done by lots of different people each person contributing something to figure out what it does. It really didnt get us any closer to understanding it as a complex, so i think it is the structure that made possible to understand how this works. How to stop them. How do they get hydrolyzed by the ribosome and trigger the movement and so on and so the structure is what led to more detaidetailed and functional understanding. Its the desire to understand how the antibiotics work. Thats a lot of money into the production of antibiotics do you see ways in which it influences . The colleagues started a company in new haven. At some point, they decided to try to go public and they withdrew the Public Offering it was only a small fraction of what people invested in the company. Around the same time, the company was named the product as the ability to exchange photographs and fake news with hundreds of billions and so how do you see that . Part of the problem is the way that the antibiotics work it feels like a new patient because they will only give it to people in sections that are resistant to standard that is a small patient pool. You only needed for a week or two and thing then you dont haa customer anymore. Then they are not sources of income so the profit motive is failing and that is why we havent had a good new class for decades. We have to remember one of the first biological antibiotics wasnt funded by the Public Company but the British Government in response to world war ii and a fun di at this at oxford to develop penicillin is a useful medicine. So maybe we need to go back to that model did have the governments and the organizations develop this. Talking about the difference between the mode of support, which we continually apply for grants, not just the ones we did get, but also the ones we didnt get. We get money for a few years and come back with more preliminary results where certainly people were working in the british system more generally and in a much less datadriven fashion where you dont need to make as many promises about what you want to achieve. 3 miles down the road at the university you have a grant he would be in the same position. You would be in a similar position and reviewed every few years and so on to recreate the revolutionary war here, im just trying to get us back to the position of defending the uk. You are an american citizen. [laughter] but i just want to get back to the question of being these days of tension its something i do want to get back to in a broader sense i want to pick up on your comment about the government supporting the development of penicillin. Theres always a problem. If you find institutions and dont make them highly accountable, you have complacency that could lead to stagnation etc. The reason they have survived for several generations now is people who set a leadership at the top, and it has to know the difference between when someone is wasting their time or just goofing off or when someone is actually working hard but wasting their time, and when someone is actually making progress but it isnt progress that you can publish or have some sort of big breakthrough. They seem to be on the right track even if they are eliminating dead end. And that makes a judgment on the part of the people running the show. And i think that as a sort of many of the intramural institutes have done quite well. Marshall nerenberg was at nih as a scientist and so, i would say you need both models, but you do need a few institutions in each country where you are encouraging risktaking and the longterm vision rather than this sort of turning. Back to risktaking, i would like to think a little bit about your own curvier path in relation to what many young people, some in the audience today who are very anxious about the competitive atmosphere and the need to publish the journals getting the academic places and getting their first grant. You have a very long Trading Program and looked around for the program biology then you moved a lot several times and you even talked about utah. These are things people often discourage to take on because theres nervousness about continuing to plot out with what you have been successful in doing. How do you think that this is going to affect the progress over the next five or ten years quick i think that the scientists it is this hyper competitive atmosphere today that is a bad thing. People dont feel encouraged to work on these unfashionable problems or problems that take a long time. You might switch technique as i did because i it isnt really getting you anywhere and you need to learn something else, which means taking a year off and relearning something. So, i think we need somehow to encourage that. I dont know how to did in the n the context of these three to five year grants. Institutions make expectation and expose himself. Im against any enforcement and science because ultimately science is individualistic. So to an expectation without doing that. We create expectations trying to get out. I can tell you, how things work at the lmb, someone came in with a certain background and simply started turning up more papers based on what they had done as opposed to what they had to offer. I think the colleagues would say, wait a minute what are you doing. Why are you doing this. What is the goal. I think to just ask somebody why are you doing this, thats a very powerful question and if they want to answer that, they have to articulate where theyre going. So i think often works. How do you create an atmosphere. Id be fearful if you looked at my current work and said where are you going with this. [laughter] but i think you should have some sort of goal. Im sure you do. [laughter] otherwise what happens, you simply end up doing the next feasible experiment in the next feasible. And before you know it ten years have gone by and youve done in bunch of incremental stuff that is not new leaning towards something. Its a different between a directed random walk in a completely random walk. It is still random but there is a biased that takes you towards a certain goal and i think that is what more should be like. Another life and science comes across strongly in her book, his attention between collaborative activity and competitive activity. There is no doubt your driven by competition. And people you share the price of and you been nervous with your good friend tom is doing not to mention what theyre doing. In a number of occasions in which people you did not know, total strangers were crying and provided you with clues. I like to say to represent a microcosm of humanity. There is no reason why the range of behavior among scientists should be really any different from the range of behavior of humanity as a whole. And humanity you see selfishness, competition, egos, ambition all of that stuff. And some of it is useful to drive science forward and other times you see people i tell you my father about ten days ago fell down while walking on the streets of cambridge. About five people immediately stopped what they were doing and helped him to call the ambulance and so on. They were not saying i have an appointment, i have to go somewhere. They were instinctively reached out to help him. They had all these special rearrangements, you cannot even make them. You need a special expertise to make these clusters and so on. They had no idea who you are but they want to help you, they are so thrilled that theyre able to help somebody advanced science in some way. You wrote someone in argonne that didnt respond for a long time. I dont want he is very nice fella. [laughter] so this is a very interesting story because it shows you two things about science. So when we had reached the limits of what we could do at the instruments we were using, we wanted an instrument that had hightech intensity but also the ability to perfectly align crystals at will so symmetry related spots would appear on same image as we collected a fraction picture. It was a technical reason for this. There is a technical reason for this. And the only instrument at the time was Argonne National law. It was a newly commissioned be lined in a row to this person in october of 1999, i got a reply saying i am very busy now, we dont have any time but we could probably review time early next year or get back to you. A month later there is no reply. So i sent another email, another month later now into december, i called the person, left messages on his voicemail, still no reply. Then in january, peter writes that the group has cracked and we were stuck and we had no feeling on how to proceed. So i wrote to peter and i said you guys have collected data in argonne, was it good, he said yes better than anything we had. I immediately knew i was correct. So i wrote to peter and i said can you talk to your colleague who happened to be on the committee that oversaw this in the person running it was former. So i had him intercede on our behalf and peter wrote back and said all talk to paul which comes biblical. [laughter] and then the next day he said ive spoken to paul, paul will talk to those guys in the next day he said paul has talked to the people and theyre going to get back to you. The next day i get back in answer saying i been busy for the last few months but we give you some time at the end of march. If you look at the beginning of october to the end of march that is six months in a tight race. And four days after this paul died of a heart attack on his way to work. So this struck me in two ways, one, i knew somebody who knew somebody who knew someday, i was in an intercircle. If i had been outside the inner circle, there was nobody i could write to to intercede. I dont know what wouldve happened. And i point out, the fate, if i wouldve waited two weeks there would not of been one to talk to. I just think, we all think science is a logical thing that flows along but it flows inosine with waves that cast you in whatever direction. So there is a lot of circumstance in fate. You spend a lot of time talking about nature in the history and how its interpreted. And you also talk a lot about them. His hithere is a kind of discond seems between, even at this stage what seems to be almost happenstance and then you have an incredibly beautiful structure that emerges. The problem is the theory of kristi auger free is very well defined and developed, its elegant. But the theory of crystallization, the physics of how molecules can come togethe together getting a signal and changing heavy metals. , the physics of how to coax a particular molecule without knowing it structure and even if you know it structure, if you give somebody a structure of a molecule answer i want to to predict and what condition this will crystallize. They wont be able to do it. So the physics of what happens to persuade molecules to stack up in a very regular array is a complex and undefined and so likely what we do now, we dont set up thousands of conditions by hand, we have robots. And we now even have robots to screen crystallization conditions so its still a hit or miss random process. So that brings up an obvious question, what is the future of crystallography and is everything becoming cry mom cry. Even in 1985 Richard Henderson had written a paper showing that audit be possible for atomic structures from electrons. A few people at the time actually believed although they cannot find any fault with its paper. People had to figure out how to get signal in the line and particles and get structures from them. He was one of the leaders. Until about 2012 or so the technology had not reached a stage where you could get structures. And now you can. But i have to tell you its not all panacea. The problem is, the particles are not constrained in any way. That is both good and bad. You see the range of dynamic constellation so they can have. It means and you cant get a High Resolution picture of the three or four parts of the martyr under molecule. Often many molecules will fall apart when you make the grade. Were reaching another black box area which is the preparation and the goo. People dont reallyd solution for that. One of the things telling a story always brings up is ending. And in one sense it feels like there were two indians to a story and one the moment when you publish on these papers and you, and tom and theres nine years of going to meetings in the sense of what the prizes will be awarded in the combination moment when you receive your trip to stock compared and then theres a sense of a new phase and you had some reflections about what its like to go through that phase and you talk about the syndrome. [laughter] but i want to get your reflections that you have done some things that i consider to be but i know of you. You came ahead of society. Not everybody expected that to happen. Tell us what happened. Well go back to matthew chapter 13 versus 12. Which for those of you are not biblical, is says to him who have more shall be given and he shall have more abundance. And they shall be taken away even that. A rather cruel paragraph. And when i cynically was saying, if you get a recognition like the nobel prize, they want to give you recognition but they never wouldve considered without those other awards. Its a way of success that creates more success. Or nothing succeeds like success. So you know, suddenly i get a phone call which says would you consider becoming treasure of society. I was astonished because here i was, somebody who become to britain and i become a british citizen only a few years before. But i came to britain later in life as an american citizen and i had no net worth, i parachuted into this lab which is almost its own world and i did not have a Broad Network in britain, did i did not have political click interconnections, no cohort i could rely on, no managerial experience. I was a lab rat at the lmb in no managerial experience. Suddenly i was asked if i wanted to be the president. That sort of says something im sort of touched in a way which is they did not care about all those other things. They really only want to look at you for your scientific credentials. But of course theyre looking at it in a particular way. If i had not had the phone call there is no way that the society wouldve said this guy does great work, lets make him president of the society. Theres no way they wouldve done that. So i had a choice to make, i asked a few people and i said, i am nothing but paul nurse. Though no exactly what i mean. And they said, aaron did it, so you ought to be able to do it because aaron if anything is more introverted and so shy and im not that introverted or shy. Which i have not been shy of the president. At a very critical time you might want to Say Something about the threat you have to ask why did i take it. Why have i just been interested in doing the next problem i had very clear goals. I have to admit i was flattered. It is an honor is so different from everything ive done. It might be interesting to do for five years because the single fiveyear term. So i said yes and i talked to him and he said no problem, you can do it two days a week. Paul had done this he was my immediate predecessor. No problem, i have been building the institute in two weeks is plenty. And theyd be like being a cheerleader and you meet a lot of interesting people. And then six months into my term britain unexpectedly to be academic echo chamber that thought trump cannot possibly win. [laughter] the same sort of people. They voted to leave the european union. My job becomes extremely clinical. And i have to on the one hand persuade the european colleagues that british scientists have suddenly turned and changed their mind and want to collaborate, we want to exchan exchange, we want postop from europe and go to europe and all of those things. And at the same time we had to persuade even hard brexit tears in her government, why is British National interest to give money to the eu and reclaim it back. This is a hard sell. I have said why do want us to give money to this organization in brussels for your claims. Why dont we just give you the money. And its not just about the money, its all these intangible benefits. If you are part of the European Network you have a chance to influence science on a much bigger stage, you are properly network so you become european scientist and young scientist to come to europe and britain and vice versa. And you get a chance to influence the direction but european signs, you act as a magnet and they can then be a magnet for the talent, investment and so on. So once you try to explain in those terms, even the hard brexit tears are on board with the idea was that we should continue to collaborate. That i count as one of my successes. Here i have to say, the fact i was an outsider, the rightwingers love america and they would like to term britain into a trump like america. So they saw me as an outsider who come from america and they felt that i did not have an ax to grind. I was not one of the whining intellectual british academics. So i think theyre more willing to listen to me. That helped me. I like to turn to the audience and ask who have questions to come to the microphones on the side and while youre doing that i want to ask you a more literary style question, we always ask writers, who do you admire in your daily work as a writer, one of the things that always comes to mind and i read your book is double helix. That is the prototype of a book about a discovery. What other books would you recommend to the audience question. Not seen people at the microphones . Im happy to ask more questions but this is your opportunity. We are living in different times but i have to say when i was a physics students and consider biology to be boring and go to memorization, and 1969 this book made its way to india. And when i read the double helix and came as a revelation to me. I do not perceive at the time as the weight is perceived by some quarters now. So, i have to say in some ways the idea that science is about excitement, and about burning desire to know the answer and get their and competition. It did have a strong sense of narrative and what ive tried to do in this book is to capture the frankness of the double helix but without some of the necessary divergence in the double helix and i think i hit sweet spot because he says you can think of ronald is a nice jim watson. And thats the other books, i love literature. Slightly intimidated about sending you the book because i know you have a degree in English Literature and i thought you take a red pen and go through it. [laughter] is a related question. When did you decide you wanted to write the book. What was your writing process, your dimension some books that inspired you but was there a moment that you said i have a story i have to tell and who did you want to tell it to . You have to remember i dirty read the double helix but id also read a hero of mine was Richard Feynman and i read his autobiographies which were frank and quite engaging. In wall the race was developing, you could see how people were behaving and how the field was evolving and i said, there is going to be a story in here someday. And by original title was going to be the race by someone who also ran. In that book would never be published because publishers do not like somebody who has a bunch of sour grapes to write about. But it occurred to me while it was happening and the result of that, i stored away all sorts of remarks, incidents, encounters that a normally mighty forgotten. But to me they sit with the narrative that was going on in my head. So when the time came, which is probably around 2009 or 2010. I thought it was time to tell the story. The fac facts were already ther. And is extremely unguarded and frank and all of my emails. So i would not want to publish those i would say. [laughter] so i had a very detailed record of events as they were happening and how i felt while they were happening. But it turned out my memory was quite accurate when i went to the emails. You describe herself in the book as an inveterate gossip. It comes clear, its a good thing to be a gossip. That your interest in other people i will be a spoiler and describe how you deal with some of the people you have these feelings, but they come out very clearly in the book and that is one of the humanizing attractions. You spoke about success, i was curious about failure. And i wanted to ask you, about the biggest mistake you have made in your career or big mistakes early on and how that influenced your trajectory or what you learned from that. I think you could regard me as a failed physicist and someways. [laughter] because they went into graduate career in physics and very quickly into my phd realized that i was not really interested in what i was doing and had to bail out and go to graduate school all over again. Describe the episode after Thesis Committee where they ask you what you read recently. It was really terrible. Physics graduate courses were slightly different from biological. The first year or two is filled of coursework then you have a big comprehensive exam that covers all of physics. At the end of this is an oral exam and they want to probe you to see what youre going to do. And what have you read interesting about physics lately. In fact i had not read anything. And i could not tell them a thing. It was embarrassing. When Francis Crick talks about the gossip factory you can tell when a person is interested by what they gossip about all the time. I can tell you there is a figure in the book which shows my obsession that was made by a former graduate student of mine. It is called the fal thought prs in the flowchart. And you can tell for four or five years it got so bad that the r word was forbidden from a house in my home. So you can tell when somebody is really interested. Thank you for letting us listen to the great conversation. I also had a question about your physics background. I know that doctor was influenced by his english background, how did physics help you in your career . I think what physics does teach you is how to think quantitatively. That is becoming increasingly important in biology. Biology is increasingly a quantitative discipline. When you learn physics you become fluent in mathematics, not afraid of equipment, computers and you have a strong sense of the signal you might expect an experiment. So one of the key things that i did was a fairly simple calculation to use a method that i believe i saw a method pioneer by hendrickson on a scattering. And i did a calculation which ask, could you get a signal with certain types of atoms from the crystal of the ribosome. If i had not had that physics training, im not entirely sure that i would have done that and then been confident that actually if you did the experiment the signal would be there. At some point in the conversation you made the comment that science is ultimately a process what would be your position or reaction about what the american institutions you know this as well dont encourage often to come together and do the science together and you patient there are two aspects. First of all, a lot of science involves large collaborations. But when i say individualistic, what i mean is one should not impose an individual scientist as a choice. Individuals want to join an experiment and discover vegetation always, thats an individual choice they make it within the corporation, they are individuals and making individual contributions to a larger effort. So they are not the same as somebody working in an assembly plant. In an automobile factory. That is a different kind of team effort. They are making creative contributions but as part of the large scale collaboration. However, if the science gets to a stage where really you need a lot of individuals to turn the crank, then i would say that is more engineering or an industrial kind of effort. My question is kind of similar to what was asked. How do we make it so the rate of discovery increases in science. To increase the amount of people involved in science or put the right people in the right places . I think it is very hard to measure things like rates of discovery, often a single idea can respond a change in science. And on the other hand lots and lots of discoveries you might say are actually if you cut the number of papers in the field then have hundreds of papers so the field is going fast, that is not necessarily true. Measuring these rates is not so easy. But there is a recent paper in nature which lies different types of science, large scale groups, large groups, small groups and it turns out the smaller groups often make big breakthrough changes and in fact, if you look at things and ask what work had they rewarded and what groups exist and when the key experiments were done, they may have grown later but when they were done they were not big groups. So i think small groups tend to be more dynamic and think creatively. Once the initial break there has been made in order to exploit it, you may need to expand or have larger efforts. I think what i would say is science needs to be flexible. You cannot say, fashion, everything has to be collaborative and Large Scale Enterprises institutions coming together et cetera. That is just a corporate industrial style. That is not going to lead to creative breakthroughs. I think you need to balance both of those. Im sorry to say our hour is coming to an end. Before we conclude and go to the lobby for refreshments and the chance to speak directly to him, i want to post one last issue. I mentioned, the acts of finishing, finishing the papers, receiving the nobel prize, what you did after. We do conversation on a walk in new york a few months ago about the ending of a career and you said at the age of 70 often stop that. In the u. S. We do not have that particular mechanism and many of us continue to we were away perhaps not as well as we once did. Tell me what do you think will happen when you have to be acknowledging that you had to hang up your sneakers. Will you build a vote in your backyard . Or will you do something more adventurous . I dont know, but i do know i dont think i want to hang around and publish a bunch more papers. That take up space that i think a younger person might use more creatively and boldly to launch off in a new direction of science. Or new area of science. But people with my experience could help another ways and serve the science communities in various ways. One possibility, i take a Popular Science writing and see where that goes. The book has not been such a fun because my publishers book has passed me when i want to publish more books. That is a sign that at least they will tolerate one or two more books from me. So that is another thank you very much for subjecting yourself to this. [applause] [inaudible conversathistory of. Your watching live coverage on book tv. [inaudible] im going to get started here. Welcome everyone. The scientific look at the elements that create our world. Thank you everyone for coming especially at 4 30 p. M. When its not