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Polymath World # Episode 44 - Professor Keith Fox · Polymath World Channel

• Polymath World (00:01.192) Hello and welcome to the Polymath World Channel and we're back into genetics and biochemistry, my favourite subject with someone who I've long admired, someone whose research I've read and I've had the pleasure of getting to know a bit better in recent years. I'm joined today by Professor Keith Fox, who's Professor Emeritus of Biochemistry at Southampton University. Keith, thank you so much for being with me here today. Keith Fox (00:23.31) Thank you so much, a pleasure to be with you. Polymath World (00:25.938) Now for people who are in genetics, I'm really interested in how they got into it because genetics doesn't come up in learning about biology at school until later on. So what was it that drew you to biology and the life sciences? Were you like dreaming of being a doctor when you were a child? Keith Fox (00:45.138) Now let me give you a brief biographical stretch sketch from school days on. I wasn't one of those who from infant who knew that I was going to be a scientist. My family were all engineers and scientists so I suppose that was expected but I wasn't the sort of stared up at the stars or down a microscope thinking that's the career for me. So I was doing reasonably well. I went to a grammar school. got a free place there, an old-fashioned grammar school, 1967 when I went there. And I got put in the fast stream and to be honest I got bored and my distinction at school was not very good. was in my second, towards the end of my second or third year I was pretty much the bottom of the class in most things. not really knowing what I wanted. Science kind of interested me as did maths but I really wasn't enthusiastic about them. And then for me a chemistry teacher it was who inspired me that not only was chemistry interesting but I could do it and that was really important for me. So I'm really, grateful for a good chemistry teacher. So I came through that chemistry route. I could show you adjacent school reports where I was close to the bottom of the class in everything to one following where I was close to the bottom in everything except for chemistry where was top. it went as dramatically as that where things just kind of fell into place. I was never a biologist. I sort of scraped to biology O level as it was then, did maths, physics and chemistry at A level and then went on, I went to Cambridge University where of course it's natural sciences so you don't specialise in your first year. In that first year I did chemistry, physics, maths because you had to do maths. Keith Fox (02:47.298) with the intention originally of carrying on with physics. That was a foolish decision because I'd always known that I was better at chemistry. But as a make-weight subject, because I had to do an extra one, I chose to do biology of cells, as it was called then. And I did that because in my gap year, it wasn't a full gap year, I worked for the... what was nicknamed the CIDR Institute, the Agricultural Research Council Institute in Long Ashton in Bristol, where all I was doing was counting milge on apple trees. But looking at things down the microscope for that kind of interested me that maybe there was something in biology and I better pick it up. So that was my make-wake course in my first year. That took me to doing biochemistry in the second year, along with then advanced chemistry, the sort of double option chemistry for those who are going to be real. bona fide chemists. And at the end of my second year I was fascinated with biochemistry so that was when I did my finals in. And from then, what happened then, I mean I took a PhD. To some extent it was just happenstances to the PhD that I did. My director of studies had obviously had his eye on me as somebody he thought was reasonably bright and wanted me as a PhD student. and I suppose partly because it was easy and partly because it was interesting, I took a position in that laboratory in the Department of Pharmacology in Cambridge, which actually was novel because I'd never done pharmacology. I was a biochemist in the pharmacologist's department and I learnt a lot then. Polymath World (04:26.397) Thanks. Keith Fox (04:33.837) Because I was doing pharmacology, I kind of got roped into doing tutorials for pharmacology students. And I must be one of the few people who's taken the major pharmacological textbook, as it was then, to bed with me as bedtime reading so that I could keep up with one step ahead of the students I would be seeing the next day. So that's why... Polymath World (04:58.215) hope it was comfy. Keith Fox (05:02.535) So that's a practice in fast learning and keeping one step out of the students. also, I mean the advantage that I found throughout my career is that learning something fresh like that meant I saw it with the students eyes. Actually sometimes coming to it as a specialist, you don't see it in the way which an outsider does. You take so many things for granted. And my PhD was on a particularly unusual molecule that bound to DNA. everything sort of developed from that. did PhD in Cambridge and then stayed there, did a postdoctoral position, did two postdoctoral positions and was a research fellow at Emmanuel College at one stage in that as well. And then, if you like, happenstance again. The first real job that I got was a lectureship in Southampton. Well, it was a lecture in molecular pharmacology in a department that was physiology and pharmacology. And I had no physiology in my background either. So it was an exercise in fast learning. And then as departments... get rearranged and restructured. What was originally the Department of Physiology and Pharmacology became part of the School of Biological Sciences and within that I was sort of biochemical pharmacologist, moved through that and at the end of it, well not the end of it, but I ended up being head of the Department of Biological Sciences having almost no qualification in biology, formal one, but having picked up through the biochemistry and the pharmacology that I'd done and a real background in chemistry, an appreciation for biology. because I was working on DNA, if you like genetics is the, but again, I never had formal training in genetics, but you can't be working on DNA unless you've got a fair understanding of what it does. Polymath World (07:02.845) I love how, and a lot of people have said this, it was a really good teacher who took interest in you and saw your potential that is the turning point in the story. I mean that comes up a lot and that must have made a big difference to you when you became a lecturer and then a professor yourself. Keith Fox (07:23.149) Absolutely. When I became a professor, I was in the days when they used to give inaugural lectures, it was a public lecture where you would talk in layperson's terms as far as you could about your academic background, the science interests. And I pretty much dedicated my inaugural lecture to that chemistry teacher. I let him know what I was doing. He couldn't come. was too old to come. And that was before the days of videos and Zooms and all the rest of that. So he wasn't involved in it, but it was dedicated to him. And I... I always enjoyed lecturing. mean, I came to my position mainly as a researcher. I love research at the bench doing things, but yet I'm supposed, unusual to some degree, I actually enjoyed lecturing. I know lots of lecturers who get there by virtue of their research and that lecturing is a necessary evil, but I actually enjoyed doing it. And the process of engaging the minds of 20 to 21 year olds. I enjoyed doing that. I have to say, so partly inspired by what a good teacher did for me, I think actually it made a difference to my teaching when I realised, when my own children went to university. And instead of looking out on a sea of faces, 250 students, The penny dropped and actually each one of those was an individual. And each one of them, in the same way as I was rooting for my children who were at university, almost certainly everyone there had somebody, a parent, a guardian, a friend, whatever it was, who would be rooting for them at university. And so they, while they were still a mass of students, my attitude I think changed a little. That they were individuals, they're people, persons. Polymath World (09:26.909) That's wonderful, I love that. I'd like to get into your research because I'm interested in that and you've researched a lot of things that I'm not particularly familiar with myself. So you conducted a lot of research on sequence specific recognition. So macromolecules recognising very specific sequences of DNA for different purposes. Can you tell us about that, what it looked like and how it came about? Keith Fox (09:56.63) Yes, I mean, was essentially the molecule I did my PhD in. It was a DNA binding agent. It didn't have great selectivity, but it had some. And it raises questions that I think are still out there. You've got, for instance, the human genome is three billion base pairs. And some proteins particularly bind to very specific sequences. There are two major questions. Why do they bind to that sequence and nothing else? So what's the mechanism by which they target a particular sequence? And I think we know quite a lot about that now. The question I think is still out there is how on earth do they find it? Finding their preferred sequence, like finding a needle in a haystack, how do they, by process of random collision, which is when you might look at it, end up zooming in on the particular sequence that they are particularly going to interact with? And I think that's still an open question. So the molecules that I worked on didn't have great specificity. Some of them would just bind to sequences of A and T rather than G and C. But there is still that question. So if you look at a DNA molecule from the outside of it, you can't actually just by looking at see what the sequence is. You've got to get right down into the molecular details of the atoms that stick into various parts of it. So if you just look at those sort cartoon models of DNA, the right-handed double helix, one bit looks exactly the same as another. Keith Fox (11:37.515) So how is it that small molecules, what I worked with, can particularly target some DNA sequences and not others? What are the mechanisms by which they might be able to do that? What are the things they're recognising? And sometimes it's by virtue of the DNA sequence itself, what functional groups are pointing out in what positions in the DNA. And sometimes it's even by virtue of the shape of the DNA. We might come to talk about different DNA shapes and structures. So it's fascinating the way in which all that links together. Polymath World (12:12.561) Yes, it's hugely important because obviously in a 3.1 million letter chain you're going to get the same patterns showing up in multiple places and so you want to make sure that it's binding to the right spot in the right place rather than the right sequence but in the wrong place and that's very important with things like CRISPR-Cas9 and off-target effects, know, it's a concern obviously. Keith Fox (12:15.298) you Keith Fox (12:35.981) Oh, absolutely. Until you get to something that's 15 or 16 base pairs long, statistically, there will inevitably be more than one copy of that within the genome. As soon as you get into 18, 19, 20, they're on the basis of probability, it's probably unique. Polymath World (12:55.548) Right. Keith Fox (12:55.585) does not say it is, it could recur. how do you get, you mentioned CRISPR-Cas, how does that recognise one particular sequence in the DNA so as to be able to do the fantastic genome editing that's available these days and not bind somewhere else? And of course, somewhere else, if it did, would lead to off-target effects, probably be... be damaging to the cell if not carcinogenic. Polymath World (13:27.047) Yes, yeah, absolutely. Let's talk about DNA sequences then. Sorry, DNA structures. You did some research on the formation of more unusual DNA structures, including triplexes and quadruplexes, which is not something I know much about. So can you tell us about your research on those? Keith Fox (13:41.804) Yeah. Keith Fox (13:47.691) Yes, mean, everybody knows, of course, that DNA structure is a double helix. It's an iconic structure. You find it all over the place. And just in case there's any misunderstanding, I'm not challenging that as a structure of DNA. Overall, time average, it's that beautiful double helix that was discovered by Watson and Crick and Franklin back in the early 1950s. But if you think of what happens during the process that DNA is used, as it's copied or as it's read, those two strands have got to be pulled apart. So for some part of it, for some part of some bits of the DNA, are always going to be single stranded because you've got to read them. Now, there are all kinds of proteins that bind to those to stop any damaging events, stop the DNA falling apart. But once you've got single stranded DNA, those strands can actually fold back on themselves sometimes forming what internal base pairs rather than with the complementary strand it's supposed to. So the very un-pairing of the DNA gives the opportunity for it to fold in transiently into all kinds of unusual structures. And it's been known since actually the late 1950s, at least in at least in what I would call test tube experiments, in vitro, just a bit of synthetic chemistry, that if you mix DNA strands with the right sequence and the right ratios, you can form three-stranded DNA. So instead of having an AT-based pair, which is what we're used to, the... If you look at a model of DNA, I should have had one with me, but I don't. There are two grooves in it, what's called the minor groove and the major groove, never mind about why they arise. The major groove is big enough actually to sit another strand of DNA within that forming a three-stranded structure. And sometimes DNA can adopt that three-stranded structure. Transiently, maybe... Keith Fox (16:00.621) during replication, maybe during the time when the DNA has been single stranded, can fold back on itself and form these remarkable structures. The reason why I was interested in triplex DNA is that Because the addition of that third strand is very sequence specific, so in the same way as A only pairs with T, the third strand, T, only pairs with an AT-based pair. So you could design a third strand that recognizes a specific sequence of DNA to wrap around that sequence. And if you did that, then any protein bound to that sequence would be blocked. It couldn't get to its target site. So I was looking at, if you like, can we use these three-stranded structures as a means of switching genes on or off. So that's three-stranded DNA. Four-stranded I could wax lyrical about as well. Polymath World (16:56.347) Yeah. Polymath World (17:01.245) Well, please do actually, because I'm a three-stranded DNA, I can picture and understand from how you described it before, that sounds really quite rare and remarkable. Keith Fox (17:14.187) Yes, actually four-stranded DNA is something, again, that's been known for some while. It is actually, it only forms with some sequences. If you take a sequence that's very rich in Gs, guanins, the guanins can actually, they... put it in the chemistry term, one edge of it has got hydro-bond acceptors and one bond's got hydro-bond donors, and you can fit those together in a nice square where they're actually head to tail biting each other. So you form what's called a G quartet. And they're very, very stable structures with these G quartets. And it turns out that blocks of Gs that could transiently adopt these sorts of structures are very common within the human genome and they're especially common within the control regions of lots of genes, particularly cancer genes. So the formation of these structures transiently probably plays a role in gene control. and switching genes on and off. It's one of those regions, one of those areas of science where it's a good demonstration of sometimes scientific prejudices. So three-stranded and four-stranded DNA, of course those, there are many people who say, DNA is a duplex. Forget it, this is a bit of, it's just playing around with bits of DNA in a test tube. It will never form in vivo. Having seen the way in which science has developed, particularly over the last, let's say, 15 years in DNA structure, I think you find very few people now who will say that DNA never forms a quadruplex in vivo. It never forms a triplex in vivo. So it's interesting how the science develops. Polymath World (19:16.497) Yeah. Keith Fox (19:16.823) that attitudes change and that what seems like a wacky idea, I mean it's not just mine, there were others involved in it as well, slowly become scientific dogma. We still don't know enough about what these sequences do, but there's enough evidence now to say that they, at least transiently, they exist within the human genome. Polymath World (19:39.686) Yes, and especially those attitudes will change when you can see the clinical potential. obviously, the sequence is really, important in terms of what proteins are doing and reading and finding and how gene expression is regulated, but also structure as well. You mentioned minor grooves and major grooves. are proteins that are looking for those spaces and recognizing those as well. We've known since Crick and Watson and Franklin and Wilkins that the the structure of DNA was really key to its replication and a whole host of other processes. So I'd love if you could tell us a bit about the clinical applications that might have come out of this and what sort of findings or relevance they've had to things like cancer. Keith Fox (20:31.253) Yes, so some of my earlier research on three-stranded DNA, the triplex is actually funded by what was then called the Cancer Research Campaign, has now got incorporated, it's called Cancer Research UK. And that would be with the idea of specifically being able to switch some sequences of oncogenes, the genes that are responsible for activating cells to divide in an uncoordinated fashion, if we could find some of the binds to the sequences within those to stop that activation. So that was the theory behind why this could be involved in some form of cancer research. I don't think it's ever made it, but that is the theory. And certainly too with the quadriplex four-stranded DNA, if we can find ways of promoting or inhibiting the formation of those structures as they're involved in gene control, so that again could be a way of either switching the right genes on or switching genes off that would be involved in cancer because cancer is basically a disease of DNA. Polymath World (21:44.601) So what was the sort of mechanisms you were looking for or could work with in terms of triplexes and quadruplexes? Keith Fox (21:55.661) Yes, so a lot of what I was doing was, if you like, a bit of physical biochemistry of actually looking at how these structures form, how we can develop their sequence recognition properties, whether they might form under the sort of conditions that are in the cell. And so very well doing in a test tube where you've got the particular. environment but when you're in within the cell of course it's competing with all sorts of other things and the inside of the cell is it's crowded with molecules it's like wading through treacle so asking questions about how do things behave in that very very thick environment within the cell Polymath World (22:42.237) Yeah, obviously that's the sort of stuff I work in, I'm very interested in that. But I'd like to talk more about your research because you held a very key role and position for a while. You were the head of the journal Nucleic Acids Research, one of the top and most important journals in biological sciences. And you were in that position for a long time. So for all those budding academics and researchers out there who are interested in this sort of stuff. How did you come to be head of nucleic acids research and what did that look like in terms of the sheer amount of research output? Keith Fox (23:23.733) Yeah, that was a tremendous privilege to be head of that journal. In nucleic acids, as a specialist journal, it is undoubtedly the top journal. And I say that with all due modesty and not because of necessarily any things that I did. So one of the things, of course, in all research is publication. and submitting your papers. I had a reasonable number of papers I was submitting and of course the more you submit the more journals come back to you and say will you referee papers for other people and I think that actually should be an obligation on scientists. If you're expecting to publish yourself you should at least be prepared to referee papers for other people to help them improve their science, improve their writing. So I'd always taken that very seriously and I had a I think a good reputation as a referee, that I'd get my reports back accurately and they'd be back fairly quickly. And I was approached by the senior editor at that time, Mike Gate, was in LMB in Cambridge, to say, you know, would I come on board as what was then called the methods editor. So they had a section of the journal that was specifically dedicated to novel methods in nucleic acids research, not necessarily the outcomes of the research, but the methods that you might apply. And I thought about that for a while. I well, yeah, I'll give that a go. That section of the journal was in itself was groundbreaking, is that the methods section was the first part of the journal to go online only. So was not published in the print, it was indexed in the print version, but all the papers themselves were just PDF files online, as rigorously refereed as anything else, but online only. And from being methods editor, I was then actually asked, would I become senior editor of the journal? I went through a process to become senior editor. And... Keith Fox (25:36.425) Not long in, if I was just before I became a senior register, the whole journal went online, no, so went open access, which was a novel departure for major, if I think we were the first OUP-owned journal, a major journal anyway, to go open access. So that meant there was no paywall to access the articles. Anybody could do that. And I'm passionate about that. One of the reasons is that I want science to be known by people. And in the olden days when you had to have a paywall and I wanted to be to read the articles, actually it... in terms of public understanding of science was really bad because all the cranks and the bits of witchcraft and the nothing that had no scientific basis to it was always free online. But the genuine science was behind a paywall. So that meant that if you wanted to research a disease you've got or a friend had, you could find all the quack recipes online for free. Polymath World (26:33.255) Bye. Polymath World (26:36.591) Yes. Keith Fox (26:47.425) but you couldn't get, unless you're part of a university and academic background, you couldn't get the genuine research. So it really is a change in mindset so that it is seen that publishing the research is an essential part of research and making it accessible to everybody. So the whole journal went open access. There are cost implications to that, obviously. Polymath World (26:54.225) So... Keith Fox (27:15.479) which that's a different debate. And then subsequently, after pressure to the publishers, who we went to online only. So the print version ceased to be. Publishers actually used to make quite a lot money out of the print version. And rightly so, they've got to survive. But eventually I think they were persuaded that... There was no point in going through printing, postage, all of that, when the vast majority of people can access things online, download PDF files. If you're open access, that's the way forward. So I played a small part in that process, but I think it was an important decision to do that. Being an editor of a journal is such a privilege. So nuclear-acid research... probably receives, I suppose, about 4,000 submissions a year, of which probably 1,500 to 2,000-ish get published. Those are rough figures. It's publishing an issue of the journal once every two weeks. There's a fantastic team of people, obviously, behind all that in OUP. So it ran like clockwork. As an editor, I would get first glance Polymath World (28:16.561) Wow. Keith Fox (28:40.621) all the articles submitted. Now I didn't make the decisions and do the referring, on many of them I had a team of probably a dozen what we called executive editors. I would parcel out. the papers as they came in to different editors. They were executive editors. They appointed referees. They made the decisions on the papers and would only come back to me if there was any query. I did my, obviously, enough of my refereeing and editor myself in terms of choosing referees, making decisions on papers. But it was a fantastic team internationally of great scientists. who had their own specialities within nucleic acids. So it was a tremendous privilege. Go on. Polymath World (29:26.321) just curious yeah were there any papers published in the journal that led to major prizes for anybody Keith Fox (29:40.973) gosh, that's an awful question to ask. There have been papers published which have been very, very highly cited. Nobel laureates were publishing obviously hundreds of papers typically and there have been a number who have published seminal work within nuclear encounters research. Polymath World (30:07.163) How many years were you the editor? Keith Fox (30:11.917) I think it was 12 or 13 years as senior editor. And then I did obviously a few years previous to that as editor. Polymath World (30:22.493) Terrific. I'd to... Keith Fox (30:23.797) And you see things about the way in which scientists think and the way in which they communicate their science. And again, that taught me the importance of good communication. As an editor, I obviously didn't have time as senior editor to read every part of every paper that was submitted before I parceled it out. I would often read the title and the abstract and say, does that look exciting? Has it communicated anything to me? And to be honest, if it hadn't of that, if they couldn't persuade me with the title and the abstract that it was significant, it was interesting, then it would go in a pile that was questionable as to whether this is not suitable for the journal. So as an academic, I would teach my own PhD students and other PhD students. I'd give them advice on getting papers published. My advice, the first thing is make sure you get the title and the abstract right. Because if you can't excite people with the title and the abstract, you won't excite anybody to read the rest of it. It's so important. Polymath World (31:37.565) Yeah, absolutely, Looking ahead to the future of biology, given your experience both as a professor, as a lead researcher and as head of a journal, what are you particularly excited about and where do you think biology is at right now? Keith Fox (32:01.085) There are all kinds of ways in which biology is moving and I think our understanding of the genetics of the way that DNA operates, the way in which it's controlled is very, very important and a fast moving field. There's an awful lot that goes on what might be called bioinformatics. We know a lot of things about DNA sequences. The ability to sequence organisms almost within a day is just so easy now to compare organisms. And so I think there's a lot that's going to go on in that. My fear of some of those things is that the area of what I call computational biology within DNA, comparing DNA sequences, is that we never actually get around to doing the experiments to say what's it actually like rather than what do we think it's like on the basis of the theory. And I'm a great believer in using those computational things to predict things and then going back out and doing experiments. Otherwise we run the risk of thinking that we know how biology works on the basis of a few computer algorithms which are very, very powerful and then going back and saying, does it actually work actually when you put it in real life? So I think there's a lot to be learned about DNA sequences, comparing DNA from different organisms. I think the power of things like CRISPR-Cas of being able to modify DNA as we want, maybe for therapeutic principles, maybe just to learn more about how the cell works, being able to switch things on and off to change sequences at will. I think that's such a powerful technique. Polymath World (33:53.936) You have raised concerns on this as well. You've dipped your toe into the waters of ethics in writing a few times. In fact, I'll put it in the description for this video, but we had quite an interesting discussion on the show, Unbelievable, about the ethics versus the potential of gene editing and synthetic biology. You wrote the book Modifying Our Genes a few years ago now. Just explain to the audience what your concerns are when it comes to genetic engineering and the new era we're in. Keith Fox (34:35.405) I mean, it's a very powerful technique that could be used for curing diseases, genetic diseases particularly, being able to take a damaged cna sequence and repair it. The problems with that is if we do that in, if you like, an adult in a somatic cell, it doesn't get passed to the next generation. If you do that in an embryo, which of course is the most powerful technique, it's there forever and gets passed down the gene line. which could be great if you make a mistake. Of course, it's tragic. But it also raises the question of what is normal and what is abnormal. Defining what is normal is actually very, very difficult. What is normal for one person or what is abnormal for one person actually becomes a strength for another one. So you can take various... Let's take for example autism, for which we know a little bit about the genetics now. Is that abnormal? Or those who live with autism? Do they have characteristics and abilities that some of us might call abnormal, but actually it's normal in a different way? That's one example of that. And we end up, if you like, having social constructs as to what a human being is like. And we're very good at doing it in other ways. A silly example is beauty. Why, I mean men do it as well now, of having cosmetic surgery. It started, this was something that was done largely to, as a form of surgery when people have had serious accidents, and then it moves through to nose jobs and ears and buttocks and all the rest of it. Why do people do that? It's because some things are seen to be beautiful. Well, who says what's beautiful? Keith Fox (36:44.461) And we have a social construct of what it means to be a human being and to be a functional human being. And the danger with that is that we put to one side people who aren't like us and effectively say, we're not interested in you. Or if we go down a line of curing some genetic diseases. For those who have suffered for that disease, are we actually saying to them, I wish you weren't here. I wish we had the opportunity to modify your genome earlier. And what value do we put on, if you like, a disabled and who says what's disabled and what's abled. And I fear for what that might do for human enhancement as well, for giving us properties that we don't normally possess. and what that says again for just being different individuals with different skills. I mean, you could modify, you could have modified my genome so I have athletic skills. I don't have the right kind of muscle mass for being neither a shot putter or a long distance jumper or a fantastic sprinter. But I'm not... There's more to being a human than having those sort of attributes and we start to define people by what their genome is. So those of you like are tasters as to why I have hesitation about what that might do. I think it's a tremendously powerful technique. I'm not knocking it in terms of its great therapeutic potential. I think it's for some diseases, it's a form of healing and a form of medicine and therapy. which I would enthusiastically endorse. But it's then, where is the fuzzy boundary between what is therapy and what is enhancement for what is necessary and what is a social construct? Polymath World (38:47.267) Yes, that boundary is extremely fuzzy now. I say to students, we live in a crisper world. There's no putting it back in the box. we've now got base editing and prime editing as well. There's other ways of doing it that are so cheap and accurate and well proven could be done in a high school lab. But I encourage people to read the book. I found it very interesting and very helpful. read it in the summer holidays and also to listen to our Keith Fox (39:07.233) No. Polymath World (39:16.965) other discussion on Unbelievable about this. Finally, the very first time I came across you actually was listening to a debate on Unbelievable that you had against a Young Earth Creationist. And I just felt so sorry for you because it was such a horrible, horrible discussion. Your opponent was most unpleasant and I just, I, yeah, my heart went out to you but it appears to happen a lot for people who debate creationists. But, Then when I met you for the first time a few years ago, I found out about your faith. And now you... have you just been ordained or are you getting ordained? Where in the process are you? Keith Fox (40:00.865) Yes, I was ordained 18 months ago. Can I go back to the creationists first of all and then talk about all the nations? Yes, I have over the years, I'm not the only one who debated with creationists who take a literal view to what the Bible says and I think an incorrect interpretation of Scripture and what the Scriptures are there for and what it's trying to say. I have admiration for them in sticking by their principles but I think they're just wrong and some of them can be very rude. Polymath World (40:08.924) yes, of course. Keith Fox (40:36.445) I actually enjoy debating with people who rude because all you've then got to do is smile and be reasonable and the audience realise that you've won the argument. And the same goes for debating with really atheists, the new atheists that they've had their day now, but those who are almost rude in their atheism. And again, all you've got to do is smile, say some nice things, crack a few jokes, and you've got the audience on site. All right, you then do have to present sensible arguments. But and I think you've helped me with one of those with Peter Atkins, hardened atheist, who can be quite rude. that really doesn't faze me at all. Polymath World (41:26.205) Really lovely guy without the microphone. Keith Fox (41:32.715) he's charming. He's a real Oxford gentleman. But in debate, he can be a little aggressive, shall we say. So I enjoy those. I'd rather dialogue than debate. Debate has winners and losers. I'd rather be able to present an argument and actually say to somebody, well, you've got a good point there. Let me think about that one for a while, rather than try to counter everything they say. I think the best way to deal with error is to put it out there in the public domain. Let's talk about it. And truth will out eventually. That's always the way in science. Erroneous science or fraudulent science eventually will be discovered because truth will come out. So let's have an honest debate and see what's... what's right. And maybe some people might then change my mind in the process of debate. A scientist with a closed mind is a sad case. We have to be open to new discoveries. mean, all of science really is provisional. The science that's there is actually only there because it hasn't been disproved. So it's inference to the best explanation all the time until somebody comes with a better explanation. That's not to you should question whether most of the scientific facts we know, but they're only facts until somebody thinks of a better theory. So that's my take on creationism and as I've debated the other way as well. Ordination. Throughout my scientific career, and I think I'm not the only one, Polymath World (43:10.994) Hmm. Keith Fox (43:19.457) who would occasionally stop and say, am I doing anything worthwhile with my life? Just teaching undergraduates, doing a little bit of research that 10 years after I'm gone will have been forgotten. Am I doing anything worthwhile? And I kind of toyed with ordination through that. I've been a Christian since my teens and my faith has meant a lot to me. Actually, my Christian faith came alive at pretty much the same time as my academic background in chemistry came alive. So those two have always ran in parallel for me. So explored that at various times and it was clear that to put it in these terms that I was called to be a scientist in a research environment. That was my duty in life. That was my calling, my vocation, if you like, those sorts of words. Various things came up. Christians in Science I was very involved with. The Faraday Institute in Cambridge I was involved with. And on retirement, that whole thing came back to me again. Was it right to be ordained? I came across through a Christian ordained friend, pointed out there was something offered through St. Malaitis College in London, which was a one-year fast-track course to ordination, or rather training for one year. for those who had already had considerable experience. It wasn't that sort of fast route in for those who were in their twenties and thirties, but in those days minimum age 55 and I kind of beat that by quite a long way. Polymath World (45:02.396) you Keith Fox (45:03.337) And so I did the course. ran in parallel with the Church of England's rigorous discernment process, which asks, you are you right for this? And so in June 24, I was ordained and now serving in the church, what I've been part of for some while. So now technically Reverend Professor, but don't anybody dare use those titles together for me. Polymath World (45:18.983) Yeah. Polymath World (45:31.439) Okay, okay, I'll stick with Professor Ameritius. Keith Fox (45:35.371) And the reason for that is, as I am a reverent, I am a professor, but my professorship is not in theology, it's in science, whereas the reverent is so, it kind of muddies the water to put both of those together. Polymath World (45:42.567) No. Yes. Polymath World (45:49.086) I just find this fascinating. My first doctorate is in history and philosophy of science and did quite a lot about George Lemaître during that. The Belgian priest who discovered the Big Bang off the back of Einstein's equations and of course he was a fully ordained priest and a professor and a lecturer and an astrophysicist involved in research. that you know it's that these Keith Fox (46:01.947) yes. Keith Fox (46:09.079) Mmm. Polymath World (46:17.381) amazing people, they always interest me and of course more recently Sir John Polkinghorne, a colleague of Stephen Hawking and president of Queens College Cambridge of course was a really renowned mathematical physicist who was also ordained so he some pretty good precedent to go there with you, Keith. Keith Fox (46:25.569) Yes. Keith Fox (46:36.141) I like the quote that's attributed to the Metro which is that there are two ways of following the truth. I decided to follow them both. Polymath World (46:45.544) that is a good quote. Keith Fox (46:48.493) I haven't got it exactly word perfect, but it's along the lines of that. Religion, Christian belief and practicing science. Some people naively think those are contradictory, but actually being able to put them together and follow those and explore the way in which the world works. For me, from a Christian perspective, this is... This is the world that God one way or the other has brought into being and exploring how that works is, as a Christian, I think it's a great privilege. Polymath World (47:28.497) Yeah, well those are the ideas that founded the the Royal Society in this country, aren't they? With Francis Bacon and Robert Boyle and then of course, you'll see Isaac Newton. I mean that was the idea in the beginning, wasn't it? And we've been reaping the benefits of modern science here in Britain ever since with that. I'll put... Sorry, Keith Fox (47:48.011) Yes, those two ways, the two books, the book of nature and the book of scripture, both revealing different aspects of God, and they cannot contradict each other if there is a God who's behind it all and just simply exploring the way in which the world that he has made works. So if there is a God, those two cannot be contradictory. Polymath World (48:15.97) Yeah, you Keith Fox (48:15.979) Now sometimes at the surface they might appear to be, and we need to work on that. And sometimes because I've misunderstood scripture, and sometimes it's because I've misunderstood science. And sometimes I've misunderstood both. Polymath World (48:29.437) I was going to say Keith, think you're in danger of making creationists mad again. They'll come after you again. But that's nothing you aren't used to. Apart from putting up a link to your book and of course the discussion that we had and a few others, if people want to find out more about you or about your writing or your research, where should they go? Keith Fox (48:41.517) And what? Keith Fox (48:56.164) That's a good question. There are probably things about me on the Christians in Science website, on the Faraday Institute website. Google search me, you'll find out about my academic research. Southampton University, they're fairly good at making sure that people's publications are well listed. So yeah, any of those. Google search Professor Keith Fox. Beware there is one other Professor, Keith Fox, who's a cardiologist in Edinburgh. So make sure you get the right one. It's Keith R. Avanara is my middle initial. But Google and you'll find me. Polymath World (49:36.217) Excellent. Yes, when talking to Kenneth Miller, we had to be aware that there were about three different Professor Kenneth Millers. Brilliant. Thank you so much. It's always a pleasure speaking to you and I've long admired your work and it's been a pleasure talking to you today. Keith Fox (49:43.351) Yes. Yeah. Keith Fox (49:52.674) Great thank you, it's been great talking to you, thank you for the opportunity.