Laurence Hurst, Professor of Evolutionary Genetics at Bath University and Director of the Milner Centre for Evolution.
Laurence studies the evolution of genes and genomes both at a fundamental and, most recently, at an applied level.
In broad outline I am interested in two related things. First, when we think about how genes work we often think that all is perfect – the gene is expressed and controlled just as it needs to be. But it is becoming increasingly evident that a core problem that all organisms face – especially species like humans in which selection is inefficient – are errors at every stage. Genes are expressed when they shouldn’t be and they are processed incorrectly at every stage. What are the devices that selection builds in to reduce or mitigate these errors? What are the consequences of these errors? The second issue – and indeed partially the way I got into this problem – is the extent to which apparently innocuous mutations are under selection. It turns out that there are hidden layers of information for controlling errors that are impacted by these seemingly harmless mutations – we thought they were innocuous just because we didn’t understand how the system worked.
A major theme of my current work is to translate this new understanding to making for better healthcare – what you might call applied evolution. We are for example designing improved (error reduced) genes for gene therapy, defining locations in the genome that are relatively error free and so good for the introduction of these new genes. Our first attempts to design a new gene, for gene therapy for age related macular degeneration, outperformed the commercial alternative. The same understanding can also improve diagnostics as it allows us to highlight previously ignored mutations that turn out to be causative of genetic diseases. The effects are not small either: we recently estimated that 25-45% of disease-causing mutations have their effects by disrupting the error control mechanisms.
I have also initiated a program to study via large scaled controlled trials the best way to teach evolution. We recently showed after a 5 year project that teaching genetics before teaching evolution can make about a grade level difference at GCSE, compared with teaching evolution before genetics. It is such a lovely result as it suggests a significant, minimally disruptive and cost-free change to teaching that makes a big difference.
What was it that got you interested in a career in science, where did it start?
Looking back I think I always had the brain for science. Even in primary school in Truro I enjoyed the logic of science and the fact that there was a correct answer and one that could be shown to be correct (I enjoyed maths for the same reason). Much later at secondary school I learnt to enjoy thinking about arts but was frustrated by the inability to determine whether an “interesting” answer was in any sense correct. For the most part my early education was not so important. I don’t recall being enthused by my school science teachers (although from age 15 I had some superb chemistry teachers). But I recall when I was 12 or 13 I read Freud and was immensely impressed by his ability to explain what I thought was unexplainable. I was particularly impressed by his “Psychopathology of everyday life”. I soon realised that much of Freud was absurd (or at least untestable), but at the time I wanted to be a psychologist.
In retrospect, this idea of the compact narrative to explain the unexplainable I think has always been an attraction to all the parts of science I have gravitated towards. I have never been attracted to ecology or neuroscience – too complex! So I always gravitate towards the simple but interesting. At University (Cambridge) the domain where strong simple ideas could explain much more than by rights they should be able to explain, was in the study of the evolution of animal behaviour. When it came to choosing a PhD subject (at Oxford), however, my instincts kicked in and I wanted to take these simple evolutionary ideas to explain less complex paradoxes – why have two sexes, why are some genes only inherited from one parent? I like genes and single celled organisms – simple but not too simple. The human genomes is so much more messy than that of yeast.
Was there an event or person that inspired you to pursue a career in research?
At school, for a long time everyone (myself included) assumed that I was going to be a medic. I had a place at Guy’s to read medicine. Before going I had a summer to think and decided that what I really liked about science was the intellectual challenge – I was curiosity driven. I would have made a dreadful doctor and thank my former 18 year old self for having that vision. Fortunately my A levels were good and Churchill College offered me a place to read Natural Sciences. Once at Cambridge the real eye opener were the second year lectures by Nick Davies on evolutionary approaches to behaviour. Why had no one told me that evolution could be so interesting? Before that I considered it a rather dull obvious subject – how many times was I told that black moths on a black background are eaten less than white moths on the same black background and that somehow this statement of the obvious was a great insight!
Nick recommended me to one of the greats of the field, WD (Bill) Hamilton in Oxford to do a PhD. By enormous good fortune Bill took me on and he and my co-supervisor Alan Grafen (one of the clearest thinking people I ever had the pleasure to meet) had a large influence on me, in no small part by letting me be independent.
In between Cambridge and Oxford I was fortunate to receive a fellowship to go to Harvard for a year. I worked with Stephen J Gould for that year and had a blast – with an English accent in Harvard you can get away with blue murder. But I didn’t get much science done. The energy of the place was, however, amazing and it was a real eye opener to see how others saw the intellectual pedigree I had grown up in.(Gould referred to it as the “English School” of evolution).
Have you had any other science related jobs before settling in at the University of Bath?
I have had a blessed career. After my PhD I won a Junior Research Fellowship at Queen’s College Oxford and could again work independently. After two years I was awarded a Royal Society Research Fellowship and moved to the Department of Genetics in Cambridge – I worked out that if I was to work seriously on the evolution of genes and genetics systems I should learn some genetics. After just three years of that position Bath offered me a Chair and I have never looked back. It must have been a massive risk for Bath to offer a Chair to someone so young and inexperienced (I was 30 when they offered me the position). So I have never worked for anyone else – I have always been my own boss and determined what I wanted to study. I also never needed to go through the normal academic stages. As I said, mine has been a enormously lucky and blessed career. Before going to Uni I worked in the local water authority’s chemistry labs. I’d like to say that this was a seminal experience, but I’d be lying (although I did learn that I would like an intellectually stimulating job).
What is the most interesting thing you have worked on in your career?
That is such a hard question – rather like good music, your favourite piece is the one you just heard. I have worked on so many interesting problems. I have been a bit of a scientific magpie working on many problems because they interested me (and often I only see the connections after the event). I remember the excitement of discovering that the genetic code is amazingly well structured to minimize the impact of mistranslational errors. We had one paper where we started with the hypothesis that these error-control devices might impact on how our proteins evolve – and every test just fell into place like a jigsaw completing itself. We knew then that we must have the right answer and one that had remained hidden. But to say which question is the most interesting is like having to choose one child over another. Recently for example, I just followed my instincts in looking at a set of genes that are all sequence related and all expressed in early human embryos – and we ended up discovering what others have called the holy-grail of stem cells.
What are your favourite and least favourite parts of your job?
I love doing science. I like it when I can hide away and do programming. The ability to corral all that data with a few lines of well chosen code never disappoints. But I love best talking science with my graduate students – I have had so many phenomenally good students. It has been a pleasure to help them mature to independence and then let them fledge. I am very proud of their achievements. I think my great strength is to be able to see the possible story in the mass of data – it is always very satisfying when “the story” emerges from the data.
What do I like least? Marking. I’m also not too keen on paperwork but I take the view that if I agree to something I should do it properly. But I’m not someone who wants power or its trappings. I like the quiet life.
What recent science news (not directly related to your own work) do you think has been the biggest breakthrough in the last year or so and why?
The most recent big changes in genetics tend not to be conceptual but practical. A few years ago there were massive leaps in the technology to sequence DNA. Before that PCR was revolutionary. More recently the big leaps have been in editing DNA (the CRISPR-Cas system). This enables us to do experiments that were either unimaginable or just incredibly slow and tedious. We are already seeing the first study to delete every gene in the human genome to look at their effects. Knocking out one gene was classically a long PhD project – years for one gene.