Second Part

0:05:07 I had the great privilege in my research career of being in an area that when I started was non-existent; it rapidly became rather hot and everybody was doing it, and I got out; I got a Junior Research Fellowship at Christ's and my plan was to do a post-doc in America; I would then come back and take my fellowship to molecular biology, to Max Perutz, and I would spend a year doing NMR of proteins; it seemed to me that the future of chemistry was in biology; then my supervisor got a job somewhere else and a vacancy came up in the chemistry department in Cambridge and I got the job, so I never went to molecular biology; but I have always been inspired by biology so in everything I have done I have either used chemical techniques to solve the problems of biology or used biology as an inspiration to do things in chemistry; everything I have done seems to have been by accident; I had a phone call once from Addenbrookes from somebody who said he had a problem with how certain kinds of drugs worked, and that led to a whole project; I had a phone call from Max Perutz in the late 1970s with another problem, and that led to a nice collaboration and paper; I haven’t actually ever initiated anything; problems come to me and then we make unexpected discoveries; most of what I have done that has been successful has been things that other people have said can't possibly work, but I have done it without knowing that; my advice is always to find an area that looks different from anything anyone else is doing; if there are a hundred research groups trying to synthesize a particular molecule there is no point in being the hundred and first group; I don't think there is any point in doing any research that is not going to have some kind of impact; partly you do it for your own satisfaction, but there is not point in doing it unless you can publish it and it solves a problem; that is not to say that I am doing applied research; almost nothing I have done has been applied in the sense of being picked up by a pharmaceutical company and used to create new drugs or patents; it has happened, but it has not been my motivation; I like to understand things, and help the world understand things, I like to develop techniques which solve problems in a way that people have not been able to solve them before, then other people can use them; when I was a PhD student I sat next to a visiting American professor who said he had been in the same field for fifteen years and was writing a book; I worked in NMR for a long time, I wrote a book, and then went on to other things; when I stop taking PhD students and post-docs the plan is to write another book that summarizes the last thirty years

5:33:22 My plan was to move from chemistry into molecular biology, but a junior research fellowship versus a proper university post in chemistry meant that I chose the latter; I went to Chemistry in 1973 as a demonstrator, an assistant lecturer; by the time I got there my supervisor had decided not to leave after all so there were two of us in the department who knew about NMR and mass spectroscopy; I was under huge pressure then from the professors to leave as they felt they didn't need two such people in the department, but I got tenure and I am still here; my first project - I had thought about a way of doing NMR spectroscopy of big biological molecules which I thought was rather clever; I got a grant, but it turned out to be completely impractical on 1970s equipment; it is actually now a technique that is around but it was not possible in the 1970s, but when I came back to Cambridge for this demonstratorship, I was sharing an office with my predecessor who did not get tenure, which was very uncomfortable; I did some experiments with him, published a couple of papers; he had discovered a reaction he didn't understand and I suggested using NMR to look at the reaction to see if we could find what was going on; all the lines in the spectrum went a funny shape, but we gradually understood what was happening; there were electrons hopping from one molecule to another in the solution, and the electrons hopping led to the NMR lines broadening; these tell you how long the electron is spending on which piece of the molecule; that seemed to be rather an interesting thing; just at that time in 1974 it was coming clear what the role of chlorophyll, the green pigment in plants, was in photosynthesis, the capturing of sunlight and turning it into chemical energy; one of the things that happens is that chlorophyll absorbs sunlight and it gives one electron away and that electron drives a whole lot of biological machinery; that leaves chlorophyll one electron missing, and what nobody knew was where was that one electron; we had just rediscovered using the NMR technique - a technique invented by physicists; the physics literature is full of techniques for doing things with NMR that chemists and biologists don't know about; we rediscovered one of these by accident and realized that this technique could tell us where the electron was that was missing from the chlorophyll; my first PhD student started in October 1974, we bought a packet of spinach seeds, the Botanical Gardens grew them for us, the student isolated chlorophyll from the spinach, and we did experiments and found out where the odd electron was; that led me to ask whether it was possible to make molecules which mimic the behaviour of chlorophyll in photosynthesis, absorb light, get rid of an electron, take an electron from somewhere else, and then generate chemical power; the whole of biology is driven by sunlight captured by biology, and being used to separate the electron from the chlorophyll, then that electron finding its way back home, drives the whole of biology; the question in 1976-77 was whether you could build molecules that behaved like chlorophyll in photosynthesis; I set my third PhD student onto making molecules like that; the third, fourth and fifth worked on that; we never made molecular machines in the way that I described, nevertheless we did discover some interesting things about how electrons move from one molecule to another; we did that for several years but it got too difficult; I realized by the mid 1980s that there were twenty groups all making artificial photosynthetic systems; what they were discovering was that their own systems didn't bear any relationship to anything else; using the same kind of molecular building blocks we switched to making model enzymes which could bind molecules inside their cavities and do chemistry inside cavities; that kept us happy for another ten years; along the way I had some wonderful PhD students including one who is my first to be an FRS, Chris Hunter, who in making these molecules suddenly had the understanding of how two molecules stack on each other; we published a wonderful paper in 1990 which has been cited many times; it got me into the Royal Society and now him; so you see, I work in an area for some time, get bored with it, and suddenly see a new area that we can move into; that is what keeps me young; I have a research group, and frequently have two or three strands going; so the phone call from Addenbrookes in 1977 led to a whole stream of doing spectroscopy on live cells, and we ended up understanding how some molecules get metabolised inside cells, also something about the biophysics of biodegradable polymers; I keep moving fields within the broad spectrum of chemistry - organic, inorganic, biological; I taught organic chemistry for twenty-five years; when I got a Readership, you have to choose a title, and I chose to be Reader in Chemistry; in 1996 we had a Chair of inorganic chemistry which we couldn't fill; I was by then FRS and had chair offers from elsewhere but was still a reader; David King was Head of Department and I asked to be made a professor as my molecules were just as inorganic as organic; they gave me the Chair; the inorganic chemistry community has never forgiven me, the organic chemistry community sees me as a traitor; the great advantage of this is that the Royal Society of Chemistry has left me alone; until recently it has been tribal - organic, inorganic, physical - and I am not interested in that kind of tribalism

15:03:08 On PhD students, my research group is usually about 50% post-docs; I have been head of the Chemistry Department, Chair of the national RE committee, now head of the School of Physical Sciences; my technique is to set up a Laboratory, have very bright post-docs and students, set a tone of being exploratory, nothing is off-limits - I have published a paper on spiders' webs, tried to use NMR to look at wet sand, nothing to me is off-limits by way of experiments - as long as it is interesting, new, with a chance of learning something new; there is an overall way of operating where I have bright people who I expect to talk to each other a lot, and to talk to me when I have time; the best students do what I did when rejecting one idea for a better one; Chris Hunter started his PhD in 1986 and I gave him a paper I had just published on how porphyrin molecules, the flat red component of haemoglobin, come together; he said that the explanation was wrong; I suggested he went away and devised an experiment distinguishing my explanation from what he considered to be correct; that is what he did and it led to the paper that made us quite famous; I am very happy when my students come up with better ideas than mine; my technique as Head of Chemistry was always to try and appoint people who were better than me; I am taken with Harry Truman's suggestion that there is no limit on what you can achieve if you don't mind who takes the credit

17:58:13 During the 1980s we were making molecules that behaved like enzymes; what I realized by the end of the early 1990s is that people round the world invest a huge amount of time and money in building molecules that then don't work - drug companies do it all the time; they do that because we don't understand enough about molecular recognition, how one molecule recognises another; I took my inspiration then from biology, from the immune system; if you challenge a body with a foreign molecule then your immune system has lots of different antibodies in it, and if there is one that is successful in recognizing a foreign molecule then it gets amplified; what I have done is devise a chemical system whereby you don't know what successful molecules are going to be but you have a complicated mix of them, you add something that you would like to recognise, and the successful molecules are amplified; we call that dynamic combinatorial chemistry; that has been pretty successful; one of the unexpected spinouts from that three years ago, one of my post-docs, Dan Pantos, discovered a system that turns out to make nanotubes which have a diameter which is exactly right to fit C60; C60 is a molecule discovered by Harry Kroto - sixty carbons making a football - and it happens to be an intriguing, rather beautiful molecule, though it is not clear yet whether it has any importance in the world; it happens that it binds inside our nanotubes; what we are now trying to do is to use our nanotubes as chemical reactors with a very high concentration of C60 inside, and can you do chemistry with the C60 inside; it is not directly related to carbon dioxide in the atmosphere or carbon capture; sometimes I ask myself whether I feel guilty that everything I am doing is rather abstract and pure, and should I be switching my research effort to solving another problem - carbon capture, conversion of light energy to electricity; I know that strategically we need to do that; as head of the School of Physical Sciences I am saying that we need collectively to be tackling these big societal problems; I don't spend more than 20-30% on research now so I think it is too late for me to make that kind of switch as a leader, though I am happy to be part of a big group; my style of research is essentially random and exploratory and you never know what you are going to discover; it is quite cruel for PhD students - my way of doing research is brutally Darwinian in that research students who do really well, flourish; if they are not lucky or have flair, I don't have a systematic research project that they can follow to get a paper at the end; I am not good at doing strategic, directed research; it is for others to judge whether I have wasted millions of pounds of public money over the last forty years

23:18:06 On great ideas, the other big date that is etched on my mind is 17th September 1992, the day after the pound fell out of the European monetary system; that week the Royal Society of Chemistry had its annual congress in Dublin; the day after that I was giving a lecture and it was the first time I had lectured about doing chemistry inside these cavities that I have described; a wonderful student, Harry Anderson, who is now professor in Oxford, had made this beautiful molecule, the cavity; then the next PhD student, Chris Walter, made two molecules which bind inside the cavity and react with each other - it was something I had imagined for ten years; on that day it was the first time that I gave a lecture on it; in the audience were two people I admire, Chris Hunter and Fraser Stoddart; I had lunch with them after when they said they liked it, but that it was not a general solution to the problem of molecular recognition; one student had take three years to make the cavity, another had taken three years to make the components, and we were lucky it worked; as we talked over lunch it became clear that there was something fundamentally wrong with the conventional chemist's way of making molecules click things together in an irreversible way; when you make Lego you can always take it apart; the conventional way that chemists make molecules is like a glued model airplane; we realized that the general solution to the problem was to make big molecules in a way that mimicked Lego so that you can proof read, so if you have the molecule you want to recognise and you offer it a large library of different molecules, it will find the correct one; once found, that stabilizes that one; if you now let all the others keep falling apart and remaking then you will get more and more successful molecules than unsuccessful; that is what I call dynamic combinational chemistry; the Royal Society has given me the Davy Medal this year for it; it is a very powerful idea, and I went home from that meeting really excited; by the end of the week I had sketched out the whole grant proposal and knew what we needed to do in intellectual terms; then I wondered why nobody else had do it and I still don't know; it is obvious, which is how people react when told about it; people had done experiments along those lines to solve particular problems, but nobody had done what I did; independently Jean-Marie Lehn who had the Nobel Prize for chemistry in 1987, came to the same conclusion; Jean-Marie and I both realized that this was a general solution to a problem; that is the only really good idea I have ever had, and it came out of a discussion; I am not good at sitting in a darkened room or walking the hills, with or without music, and coming up with an idea; my ideas come from sitting and discussing with PhD students and post-docs, and it is in the to and fro of the conversation that I get ideas; I have two very good post-docs now who have done some lovely work on these nanotubes; when they write a paper, they give me the draft, and we discuss the exact meaning of what has been written; that is when a lot of the hard work of interpreting begins, deciding what we have really discovered and what it really means; I am not hypothesis-driven in the way that now conventional biology is; in the words of Laurie Hall, listen to what the science is telling you, and that is what I do

30:35:22 Cambridge has been very good for quirky individuals; when I first came here as a junior demonstrator, whatever I needed I could go to my head of department and get; now heads of department don't have that resource; nobody asked me when I was appointed what science I was going to do, how I was going to fund it, or what was my strategic plan for the next ten years; not all the appointments made in that way turned out successfully, but quite a lot did, at least in chemistry; what was going on then was that they were somehow picking talent and giving talent some freedom and resource; it is increasingly difficult for us to give resource; very talented people now are in great demand and can demand huge start-ups; we are in competition with American universities which give huge start-ups to chemists at the beginning of their careers; if we can't compete with that then we will lose out; if we do compete then we will get a set of people who are very determined, very focussed, very ambitious - they are very good for themselves though not necessarily ideal for the community; although Cambridge has often been a ragbag of quirky individuals there has also been a sense of community; it was there when I started but I don't see it any more; it is not a problem just in Cambridge, but everywhere; if you appoint people who are good enough to go out and get million dollar grants they are usually people who are very focussed; people like that are rather hard to manage; if you ask them to do something for the university or the college they will make implicit or explicit calculations whether it is time well spent for them; that is going to make it particularly difficult in future for colleges; in some ways we are better placed than other institutions; if we can all give up a little bit of our individuality for the common good, to get in a big grant to look at sustainability, or look at new materials for photovoltaics etc., if we had a big grant that covers ten people, then within the protective envelope you can afford to have individuals who are not necessarily team players; it may be that by putting people in together in big consortia you have got enough space to protect the individuals who really to the creative things but who don't necessarily flourish in our present target orientated society

36:22:24 To me it has been very important to have a happy and stable home life; I have been very involved in bringing up my children; have a son now thirty-two who is an assistant professor of physics in Mexico, and a daughter, now thirty, who is the academic administrator at Somerville in Oxford; my wife is a biologist although she is not currently working; all of that dimension is pretty important to me; the only thing I do around the house is cook, and I do the shopping