Leland Hartwell

Interview

Interview, July 2007

Interview with the 2001 Nobel Laureate in Physiology or Medicine Leland H. Hartwell, at the 57th Meeting of Nobel Laureates in Lindau, Germany, July 2007. The interviewer is Adam Smith, Editor-in-Chief of Nobelprize.org.

Lee Hartwell talks about how a high school physics teacher stimulated his interest in science, the unusual path that led to him studying biology at the California Institute of Technology (11:13), what attracted him to studying cell growth and regulation (13:12), and his views on the desperate need to develop better diagnostic tools for improving treatment of cancer and other diseases (28:46).


Interview, December 2001

Interview with the 2001 Nobel Laureates in Physiology or Medicine, Tim Hunt, Leland H. Hartwell and Sir Paul Nurse, by science writer Peter Sylwan, 12 December 2001.

The Laureates talk about paradigm shifts in biology; reductionism (6:42); hard questions in bioscience (15:01); the important bridge between scientists and society (18:26); managing good science (26:341); and ethical issues in bioscience (29:32).

Interview transcript

Welcome to this interview with this year’s Nobel Laureates in Medicine or Physiology as it’s called and welcome to you gentlemen, Paul Nurse, Lee Hartwell and Tim Hunt and of course once again congratulations to the prize, you must have heard it thousands of times. What about your stay in Stockholm?

Sir Paul Nurse: I think we’ve all had a wonderful time.

Tim Hunt: Yes, we’ve been treated like royalty, it’s been like living in fairyland.

But is it true you are the royalties is of a scientific community for one year now or for the rest of your life?

Leland Hartwell: Certainly feel it during this celebration here.

Sir Paul Nurse: But of course, science moves on so in fact the Kings get changed very quickly.

Oh yes, those days, no scientist is happier as the one which can prove that the professor was wrong.

Sir Paul Nurse: Correct. That’s one of the beauties of science that it does move on and there isn’t a received wisdom that just stays in one place with one person.

Tim Hunt: But at the same time there were giants present here, this week, I’m thinking people like Jim Watson, I’m thinking of people like François Jacob, thinking of people like Günter Blobel, they haven’t been disapproved, they put a new big step on our constant stairway of knowledge.

But does that mean that science actually really is coming closer and closer to reality? There are some truths that remain truths even throughout the centuries.

Sir Paul Nurse: This is quite complex philosophically because we tend to work in certain paradigms and for a while in fact we put these bricks in the wall as Tim was alluding to within that paradigm, but then you can get a real shift which takes you into a sort of different area altogether. That’s certainly been the case in physics at the beginning of the last century with quantum mechanics and relativity there was a real shift from Newtonian paradigms of the previous two and a half centuries. In biology it’s sometimes a little bit more difficult to see that.

Tim Hunt: That’s really happened in biology, you know, the establishment of the cell theory and then Pasteur proves that there’s no such thing as spontaneous creation, these are sort of universal truths.

But what differentiation that everyone thought that higher animals could never be cloned and then all of a sudden there’s a Dolly. Isn’t that a major shift in how you perceived DNA?

Sir Paul Nurse: I think that not sure so much in the sense that was a technical achievement but it had been achieved with frogs actually that particular …

But not with high animals.

Leland Hartwell: Frogs are very high animals …

Tim Hunt: The frog is a high animal. What do you mean, were you trying to despise the poor frog?

Sir Paul Nurse: You’re talking to a …

Tim Hunt: You’re talking to the wrong people of course, we love frogs. They are called low organisms, but we love them.

Sir Paul Nurse: You’re talking to a CO and two /- – -/ here and frogs are something up there, very complex to us.

Leland Hartwell: But in terms of paradigms we are in an era now, from about the last 30 or 40 years, where we are sort of enumerating the molecular pieces, we’re making catalogues of who the players are in different processes and we’re already beginning to see the end of that era and a new era of you know, what are the properties of assemblies and modules and circuits of these groups.

Tim Hunt: Emergent properties ensemble of all of those subunits, sorry sub-assemblies.

But anyway, if you excuse me, in one way you have solved the easy problem and now you come to the real difficult problem.

Sir Paul Nurse: I think Lee, I mean this is why I was referring to paradigm shifts with physics which is clear, because I have a feeling there will be a paradigm shift in biology. I like to think of it a little bit like this a metaphor is that we’ve been identifying the actors in a play and we now have to write the script, and we’ve been identifying a lot of the molecules, the elements but actually putting it all together is in the symphony analogy or the play analogy requires maybe different sorts of thinking I actually am beginning to wonder.

Leland Hartwell: What’s easy and what’s hard depends on the era, I think when we began our careers and were interested in dissecting some of the complexity of cell biology that was considered very mysterious and difficult and impossible but we’re moving beyond that era now and now people see that as relatively straight forward but how all things work together now appears to be a big mystery.

Tim Hunt: I think one of the curious things … I mean I never really seriously thought in my lifetime to see so much progress and developmental biology. I think Eric Wieschaus and Christiane Nüsslein-Volhard – this was extraordinary what they did – that was one of my favourite prizes of recent years actually, because the deep deep mystery and suddenly it’s all plain.

But nevertheless do you think there is need for a total new concept? Because you made a wonderful metaphor at your banquet speech about the cell being a symphony orchestra. You could maybe add that life was the music and you could have included the audience and even if you can analyse the conductor, could you then explain the symphony orchestra by looking at the details?

Leland Hartwell: I think that’s a metaphor of the transition that’s taking place is that as we learn more and more of the individual musicians, if you will, and what it is that they do as individuals we don’t yet understand how the whole assembly creates something that is as beautiful and mysterious as a cell dividing or just a cell metabolising or any of the wonderful things that cells do. That’s the era that I think most biologists, molecular biologists would say we’re moving into now, is how does the properties emerge.

Tim Hunt: It’s becoming much more … I’m so pleased that we have a prize for physiology because I think that’s exactly where we’re going, it’s molecular physiology from now on by which I mean that how things work together, right. It’s all very well having … we’ve sort of come out of a chemical phase almost and I think we’re entering a real physiological phase.

But I mean science is per definition reductionistic. How you look at structures, you look at details, and life is time- and spacedependent and dynamics and interactive. You have looked at frozen moments of details, can you ever understand system …

Tim Hunt: Oh sure, look at the way that muscles and nerves work for example, was done a long time ago. It’s funny, sometimes things are done from the top down and sometimes done from the bottom up.

Sir Paul Nurse: I often think too much is made of this reductionism holism difference. Of course science has to explain in terms of basic components or elements or sub systems but nearly all of us working at a holistic framework looking at the overall system. The challenge we have now is in particularly in the life sciences is that these systems are actually quite complicated, in fact very complicated and unlike for example in chemistry and physics where you have lots of objects behaving identically like atoms, what we have is lots of objects which don’t behave identically

Tim Hunt: Which interact and each feedback positively and negatively with each other. It’s very complicated and the trick of doing successful science is from isolating the simplicity out of that complexity otherwise you’re lost. It’s all very well to look at a dividing cell and going, ‘Gosh, this is marvellous’! but it doesn’t help you understand what’s going on behind the scenes.

Sir Paul Nurse: I think that’s absolutely right, but now we’ve got to start thinking. We have all this individual components, behaving in different ways, interact in different ways and we’ve got to somehow extract the general principles from that behaviour and try and get … You can use these words like emerge and properties or whatever, they often raise more heat than light when you use these terms, it must be said, but I think there is a challenge there and describing the dynamics of this in real space and real time. which we’re just beginning to do in cell biology. I think a brave new world is going to come from this, I’m an optimist I must say, but I think that it’s very exciting times.

Leland Hartwell: I think there’s another thing too to say about reductionism is that you take some global property and you try to explain it at the next level down and the next level down may just be cell society. We’re now very concentrated on the molecular level but as we start asking how cells behave the right description may not be in molecules, the right description may be in circuits or modules or certain properties, so creating the right concepts to go the next level down is sort of the nature of reductionism and the creative part.

Which means that you can find some very precise detail in hierarchy that is really governing the next level

Tim Hunt: Yes, the clue to the whole thing.

Sir Paul Nurse: I think there’s two ways actually to answer that: One is, which is perhaps what we’ve done, which is to focus on certain components and elements which are crucial and critical and I think that that falls naturally out of our analysis. I think a second way of viewing this, which I think is what Lee was hinting at, is could we describe general properties of these systems, are there rules that would govern general properties which don’t require going down to specific behaviours of individual components but when in a certain assemblage give rise to behaviours that are interesting. I think that’s perhaps what you were getting at.

Leland Hartwell: Exactly, we have our signalling system, cells respond to signals for example and they may respond over a certain concentration range, they may respond by flipping states or by a gradual transition. These are sort of dynamic concepts that don’t necessary require molecular explanation but require some kind of probably creative conceptualisation that may be different than anything we think of right now.

Tim Hunt: I know there’s an economist might describe an economy, sort of abstractable principles.

Leland Hartwell: Exactly, yes.

Does that also mean that you are looking for inspiration from other areas of science, like scientists who are dealing with the mathematics, the complex system, dealing with the scientists from economy are trying to do mathematics for complex systems.

Leland Hartwell: Yes, very much. I think one important area that we can learn a lot about molecular circuits from, or from electronic circuits in order to understand a complex circuit, what you’d really like to have is a very detailed description of the input/output characteristics, as you perturb the system how does it respond. We don’t usually have that for many of our biological circuits, we know what the components are but we don’t know how the input/output are related in any quantitative terms.

Sir Paul Nurse: Because I’d like to push that metaphor even further. It may be by knowing the sorts of components that you have and by knowing that they can be connected in certain ways. In fact all the huge variety that is possible may not actually be occurring because it may be that the only linking certain components that behave in certain ways in particular ways that may only generate certain stable operating systems and that we’re not actually faced with immense complexity we’re faced with a few solutions. If we can identify the rules for getting those solutions, we’ll simplify the problem.

But given that you’re right, what will the implications be? Finding the simple rules that govern complex systems, you said ‘brave new world’, it really sounds something in that direction, Tim?

Sir Paul Nurse: He’s more sceptical of …

Tim Hunt: I think, it’s very interesting. Paul likes theoretical biology and he has some good friends who are rather good theoretical biologists but my own view is that these approaches so far have not been very successful. Partly because we don’t even know the parts, secondly because it’s very difficult to measure accurately the properties of those parts. There are certain kinetic constants about how fast things happen and the values of those parameters are rather critical when it comes to building a model and so far the modellers have been quite good at describing what they know is the right answer because they knew that to start with. They’ve not been so good, in my view, about saying well you know about this component a, b, c, d, e, f and g, but without factor x it won’t have the behaviour that we know that it does have and it would be very helpful if they came in and said you’re missing the x factor and we said oh my goodness we can go and look for that. Actually that’s not the way it works and in fact, what happens is that the geneticists start having a kind of lucky dip and then some biochemists come along and analyse it and we keep on finding the various components, the key components of these systems completely by luck, well not completely by luck, but I mean going and looking for them, never by predicting sort of …

Leland Hartwell: I think we ought to look at history here. For example take gene regulation. This is an area where it might have been simple in Paul’s terms where it makes good sense to control a gene by turning on or off its message. But in fact, nature has used every single step of information transformation from turning on the gene, from getting the message part way started, the stopping it, from once it’s made degrading it, from starting the translation of a protein. You could every single step of information transfer from the gene to the protein and the activity of the programme is utilised by itself.

Tim Hunt: If you conceive a bit controlled somewhere, it will be controlled somewhere.

Leland Hartwell: Yes, and I have a feeling that that’s the level of complexity we’re going to be faced with and everything as anything that could happen will have been used somewhere.

Sir Paul Nurse: But it may be that it doesn’t matter where it’s regulated, in the sense that one can get an explanation by just understanding that this module if you like, will lead to regulation and it may be that when you’re trying to describe the higher order phenomena you do not need the detailed understanding of exactly where that regulation occurs.

But given that your optimism is real and you are getting some correct on the system, what would you like to explain by this, what are the really hard questions in bioscience today that you want to get to.

Sir Paul Nurse: Can I jump in there because there’s a new problem that really is interesting me which is how biological systems generate form, spatial order, because I think this is an interesting issue because, knowing within three-dimensional space, the positions of different objects and components within that is not a trivial problem

Tim Hunt: Theoretical everything should be spherical and they’re not.

Sir Paul Nurse: And that’s what I …

Tim Hunt: /- – -/ was wrong.

Sir Paul Nurse: I’m really fascinated by this because I’m thinking about it in terms of a single cell just because it’s such a simple system to approach. It may be the rules that are important, there are not the same rules that generate the shape of my nose for example, but simply understanding spatial order in any system I think is an interesting challenge.

Maybe we should change the perspective a little. You are all dealing in the frontier size, you are looking into unknown territory and coming back and telling the stories to the audience what you see in these unknown territorial, always or very often creates fright, a scare. People are really getting scared of what you’re doing.

Tim Hunt: I don’t think people are scared of us actually.

Why you’re part of it.

Tim Hunt: I don’t think what we did was at all scary, it simply explained what was …

Bioscience today is generating a lot of fear, so what is your role in this perspective, what is /- – -/ science

Tim Hunt: Trying to explain clearly, for example take genetically modified food for example. I just simply don’t understand why this bothers people, but it turned out on interrogation a lot of people don’t realise that with every mouthful of every food whether it’s a plate of fish and chips or a big fat steak they take in billions of DNA molecules. People really thought that only the genetically modified corn contained DNA and that was dangerous somehow, I mean it’s just absurd ignorance on the part of the public.

Leland Hartwell: I think there’s another side to this which is as explores basic discoverers bring back knowledge that illuminates mystery in the world and I think everybody enjoys that. That’s an experience of awe over nature and astronomy is a terrific science in a sense because it is almost all that level of appreciation, but the other aspect that scientific knowledge brings in is the possibility to apply it in some way. It’s the application phase, particularly with respective biology and medicine and human life that fear is created and I think we are all afraid. For example just the transition from being not knowing what the sex of a child was until it’s born to being able to determine at an early stage and decide whether or not you want a child of that sex, that really changes human culture and make life in a very profound way.

Paul Nurse, in this debate on science and society there has been much talk about public understanding of science but maybe there is a reverse of that question, science understanding of public, do you think that is crucial?

Sir Paul Nurse: I think there is a bridge that we have to construct between scientists and society and it has two sides to that bridge and one is the public understanding, the point Tim emphasised, we have to explain these things so that society has a proper sense. Quite often, just to expand on that briefly, quite often the real debates are not actually about science but they’re about politics and in fact the GM foods debate is as much to do with large corporations controlling the crops and having economic control over issues as much as the gene transfer issue and it all gets mixed together and that’s why it creates so much fire and I think we …

Tim Hunt: It’s sort of eased a demonise some giant corporation …

Sir Paul Nurse: We need to separate those debates so that there’s a clear scientific issue and a political one because you may find people are on one side of that debate with one issue and on the other with the other. But back to this bridge between science and society, I think there it is also important for the scientists to be listening to the public and to be aware of what their issues are and to be aware of the sorts of questions they want answered and the sorts of approaches that should be taken. Sometimes we may get divorced from what the ordinary person or the politician’s thinking, and that I think is truly potentially dangerous because we can become a priesthood and separate it off as some sort of witch doctor class and I think that is a real danger for us.

Tim Hunt: It’s so important that the public should really trust us as far as we’re trustworthy, otherwise everything will break down.

They might not lay their trust on you, unless you understand them.

Leland Hartwell: It’s not there to understand what our roles are, our role is to provide new knowledge and insights but it’s really society’s role to decide how to use those. Science may identify stem cells and provide ways in which they could be used, but it’s really society’s role to decide whether to make use of that or not.

Tim Hunt: Yes, and in what circumstances they should be used and what circumstances should not.

Leland Hartwell: And scientists should not … their role, we should not say what society should do or not.

But if you pick up one thing that Paul said that if you separate roles, you might find out that what people are really scared of is not the DNA, it’s the companies.

Tim Hunt: Yes, yes.

And you might be if …

Tim Hunt: Then you can set up … I would say it’s none of our business, but we cannot just take care of the DNA issue.

But somehow you are advisors to the companies and some of you work inside the companies, and you are funded by money from the company. How do you look upon your credibility when it comes to funding in this respect.

Sir Paul Nurse: This is another huge area of course.

About ten minutes left.

Sir Paul Nurse: This is a huge area about funding and accountability and these issues. I think that there are a number of misconceptions and I think that often many of the general public think that many scientists are funded simply by private capital and they have this sense that we’re in the pockets of a big industry. That is very often not the case. We have received most of our support from Government funded work, mostly at the front end of work which is available to everybody and indeed one of the nice aspects of science is making that information, that knowledge available for all the societies in the world to make use of, so I think we do have a role here in explaining how work is funded and our accountability within that.

Leland Hartwell: But there also is a conflict of interest thing that we need to be very cautious of and within our Institutions we have rules for dealing with conflict of interest, for example if you have an interest in a company, you cannot be involved in clinical trials in a direct way that are testing products that you have a financial interest in and when we make pronouncements to the public about some area of knowledge if we have a financial interest in it we should disclose that.

I mean have an interest in thing is not only financial interest. Today I think almost every research is interest driven, you have strategic interests, you have environmental interests, you have commercial interests, you have carrier interests, so what about the credibility of a scientist when they are all driven by interests.

Leland Hartwell: Everybody’s driven by interests. If you don’t limit it to a financial conflict of interest, then of course we’re all interested in all sorts of /- – -/.

Why do we always distrust the science that are commercial driven interests and not suspicious about the idealistic interests?

Leland Hartwell: I don’t distrust scientists who have a commercial interest, I just want to know what their biases are, I want to know, that’s all.

Tim Hunt: There’s no reason to distrust companies. After all drug companies, the best thing you can do is produce a highly successful drug and the more people it cures the better, so I must say I think their interests and the public interests are one in the same. Where it comes bad is if they try and foist some imperfect product and exaggerate it’s properties, that’s a different matter.

Sir Paul Nurse: But you touch upon something which is not quite what you were getting at, but I’d like to draw attention to, which is actually a problem to do with managing good science, because in fact good science is carried out by creative individuals working within the scientific society because it’s very socially interactive but still with lots of freedom to follow their own ideas. Then sitting on top of that is some sort of scientific management that provides money and support which has certain strategic objectives and because we’re not paid as scientists simply to play in our laboratories, we like to think that we are, but in fact society supports us and we’re very expensive to support, because they expect something back. They expect something to increase the health or wealth of the nation and balancing this is actually a very difficult task and I don’t think anybody gets it quite right and it’s very very difficult to explain that to our political masters who would really be much happier sometimes with a very heavy strong strategic top /- – -/.

Tim Hunt: They would love to be able to say just solve this problem. In Britain for example BSE is a problem, we really don’t know whether sheep have it, we really don’t know whether humans eating this stuff are going to get it and they would love to be able to direct scientists to solve these problems and the trouble is that people like us are really not very good at behaving under those circumstances.

Leland Hartwell: There are a full range of possibilities though. It’s ok to have to fund areas of strategic direction that where you want problems solved and at that point they almost become engineering problems but if you don’t have a foundation of undirected investigation, it’s going to draw you up.

But given the path, the experience of the path of science you know that when you’re looking for one thing you always pop up with something else, so those who are going to finance you with a specific goal will probably find themselves financing some totally different knowledge not that they really knew they were looking for.

Sir Paul Nurse: That’s certainly the case, but there is, you know, science is a complex activity and there are roles of different sorts of people at different stages in that process. At the front end you need the explorers, a little later the explorers are no good at turning into practical benefit some of those, or not necessarily good at it.

Tim Hunt: And explorers maybe very good exploring mountains but rotten at the seabed.

Leland Hartwell: In one place you see this happening is in start-up companies. Very often start-up company starts up with a very specific idea and they get venture capital to go out and six months later they’re doing something entirely different because the first idea didn’t work and they’ve still got to be profitable and that’s an arena in which you see a lot of shifting around.

But that turns us into what might be the gist of science, the serendipity I mean you are always seeking for something else what you really found. What is the role of serendipity in science?

Sir Paul Nurse: I’ll kick off with this but I think we’ve all had our own experiences. I think that serendipity does play an important role but in a very particular context. We’re biologists, we’re trying to understand nature and we have to pay real attention to what nature gives us. If we try and impose too much our own thoughts on such complex system, we will either miss things or simply try and force it into a box that is not good for it. I think you have to be very aware of all the possibilities, you have to be very observant and then you can pick up on the serendipitous event, which has certainly happened to me on many occasions in my career and the way I like to think of it, is that nature is giving us the clue that we try and follow.

Leland Hartwell: I think there are actually two forms of approaches to science, both of which lend themselves to serendipity. One is Tim’s example which maybe he can amplify, where all of a sudden nature presents you with some observations say, My gosh that’s interesting, I wasn’t looking for that, let’s see what’s there. The other is more /- – -/ approach where we knew what we looking for, but we didn’t know quite how to find it and all of a sudden something popped up that said, Look over here and you might find what you’re looking for.

Tim Hunt: In my case it really was complete serendipity and I was really studying one problem but interestingly in a system where actually cell division was very much a part of the system, that’s what it was specialised for, but that aspect of it was just fun for me. It was fun to look at these things down a microscope, I never seriously thought I would make any advance, it was much too difficult a problem. Then suddenly I saw this protein go away and because I’d been sort of half thinking about the nature of the problem, worrying about things, it immediately announced to me what was going on. It was something that nobody for a century had even sort of remotely considered possible but once you see it, bang, it’s obvious. Then you go chasing after it because it leads you in that direction. But nobody would ever have even gone looking for the damn thing in the first place because, precisely, because theoretical biology hadn’t said we should be looking for this so, when nature sort of presents itself to you on a plate then you’re …

The secret is to really be open minded …

Tim Hunt: You’ve got to be terribly open minded and have …

… to the unexpected.

Tim Hunt: Yes, absolutely, and all my career I’ve had things like that, you know, suddenly, it’s like walking down the street and seeing something shiny and kneel down and have a look and see whether it’s gold or not.

Let’s finish off then with some really easy questions.

Sir Paul Nurse: I suspect not.

It seems as if bioscience is getting into realms that before has been totally occupied by philosophers and theologians. We’re starting to ask those questions about when does a human become human and when do we finish being human. Take for example this stem cell debate and the debate of embryology. How do you look on your own science when you were really going into this field that raises so many existential questions?

Sir Paul Nurse: First of all you’re right, and this is why biomedical research is now becoming increasingly contentious because we now are addressing really critical problems about the nature of a human being, about the nature of identity when a human being begins and finishes, and this moves us really into the realm of religious thoughts and brings in fact scientists increasingly into a challenging position with well established religious thoughts. Not unlike I would suggest, the Copernican revolution in the 16th century with physics and the heliocentric, the sun centred world, and I have a feeling that biology and biomedicine is really going to take us into that realm which is one reason why I think this two way process of listening to the society and listening to what really bothers people is so important so that we can make a better go at this transition in the brave new world than maybe happened with astronomy and physics in the 16th century.

With the big difference that there is no death sentence for scientists these days.

Tim Hunt: I find these kind of ethical issues very difficult to deal with and I’m not really used to thinking about them, and I’m not even particularly well informed on the details for example of the stem cell debate which I’ve been asked about a lot. I myself don’t think there’s much wrong with it, I have to say, after all you know things like blood transfusions have been going on for a very long time, that doesn’t seem to bother anybody. I’m slightly confused, I don’t really understand, maybe again it’s a case of what Paul said I should be listening more to the public and finding out what’s really bothering them at the bottom because, scientifically, it seems to be only a good thing. If your leg drops off and you can make a new one from stem cells – who could possibly say that was a bad thing, I just don’t … am I missing something?

Leland Hartwell: It’s a moving target, I feel like the ethics and religious and things come up around areas of mystery where we try to develop some concepts about what’s going on and as knowledge accumulates and enlightens these areas, the sort of ethical questions have to move with them and that’s sort of hard. It’s always a difficult transition and as I look forward, one of the things that I see that looks scary to me, I don’t think I’ll live to see it, is the sort of combination of much more integration of machines with people. Now we wear glasses for example to correct eyesight, I don’t think it will be long before we have all sorts of little computer chips in us and you know …

Tim Hunt: Yes, you can get false ears that really say work like ears if you are deaf …

Leland Hartwell: … and that sort of bothers me you know, it’s going to happen, it’s inevitable.

Tim Hunt: Yes, and completely synthetic hearts.

Finally, many people are really getting scared about what is going to happen. One of the questions thar raises is when you really have managed to find the mechanisms of life, we feel, many of us, that life is also going to be instrumentalised as you decrease the respect for life. What is going on in your own mind when you see the details on how intricate the system is in biology. Are you getting more or less a miracle when you’re looking at it?

Sir Paul Nurse: I think the more you understand about this beautiful thing we call life the more wonderful it is. Again, it’s easier to look to history because it’s less contentious. Darwin’s theory of evolution by natural selection was such a beautiful idea that you could still have a sense of god who created such a beautiful process and still see it as a wonderful solution to that particular problem. I think if we look at today’s new understanding you can have nothing but a great sense of wonder that comes with that, I think it deepens, in a sense a spiritual understanding beyond simply ignorance and total mystery.

Leland Hartwell: I agree in a little bit difference sense. I don’t think we really ever understand anything. I think we only describe it. That we look and look at greater detail and we develop words and concepts to describe it and we’re all just describing the beauty of nature and it doesn’t become any less beautiful just because we describe it.

Tim Hunt: Yes exactly, as you walk through a forest, knowing what the trees are growing it doesn’t make it any less the more beautiful forest exactly as Lee says. Inside the cell you find almost every day more wonderful things and say, Oh, that’s how it works, it’s beautiful it’s really beautiful.

You are making mysteries into miracles. Thank you very much, gentlemen, for sharing your time and your knowledge and your views. Thank you.

Sir Paul Nurse: Thank you.

Leland Hartwell: Thank you.

Tim Hunt: Thanks.

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