Transcript from an interview with Sir Gregory P. Winter

Interview with Sir Gregory P. Winter on 6 December 2018 during the Nobel Week in Stockholm, Sweden.

I’m Greg Winter. I’m the Nobel Laureate for Chemistry, one quarter share.

When did you decide that you wanted to become a scientist?

Sir Gregory P. Winter: I started to take an interest in chemistry because I think I was very good at it. I found it logical but it wasn’t absolutely mathematical. I liked the way it was taught which was very much based on evidence. We had a historical approach going through how all the scientific experiments were done that led us to our understanding of matter and the way elements came together, and I found that evidence, that trail of evidence, very satisfying, always thinking about what evidence you needed to justify any particular statement. But in fact, my real interest was also in biology as well and when I went to university I hadn’t been sure whether I’d be a biologist or a chemist but what happened was, about in my second year in university, I still preferred chemistry as a subject but I thought that, for research, the biologists just had the more interesting questions.

So chemists seem to have got themselves lost, in my view. They were exploring things that really didn’t interest me. They were kind of more mathematical, so endless dealing with equations, which I could do, but I didn’t get any pleasure out of them. To me a mathematical equation is just a tool for solving a problem. I had no interest in the beauty of mathematics as such. I was much more interested in some of the big problems in biology and I became particularly excited by … There was a book by Melvin Calvin about early evolution and which was published around that time, which was the late 80s, perhaps early 70s, and in that book was a description of how the prebiotic soup was formed and the way in which that is thought to have bootstrapped its way into life as we know it and I thought, now that’s really interesting, it’s all combined my interest in molecules. At the same time it made me think about the bigger biological question of evolution. In a way that theme has underpinned everything I’ve done at some level since then. It’s that deep interest in evolution, but also interest in the chemistry of how that evolution is achieved.

What is it that you love about chemistry?

Sir Gregory P. Winter: We had a couple of very good teachers at school but, they were very good at teaching, neither of them were role models in the sense that they explained the subject in very different ways. The chemist was very competitive. We were always making us compete against each other to get the top grades, to answer faster than the next person. The biologist was more measured but again he would go out of area, he would get us to look at things that weren’t on the syllabus, went much wider than the standard school syllabus. So from both of them I learned quite a lot in very very different styles but they weren’t people I myself wanted to emulate, I had no model early on for the kind of scientist I might like to be. Only later when I started doing research did I start picking up ideas of the kind of people I’d like to be, the style I’d like to follow.

Who has inspired you?

Sir Gregory P. Winter: It’s a combination of role models. My own PhD supervisor was a northerner and he was very blunt and I’ve borne in mind some little teachings that he’s given from time to time. One of them was I happened to say that an experiment I was proposing to do or a subject I can’t remember the exact issue, was really interesting and he said: “Bugger interesting. Is it important?” And actually that got me thinking, yes, he was right, it was interesting to satisfy your curiosity about something but no, he was right, it wasn’t important and so actually that was a guiding principle I incorporated to try to work on things that were important. Of course you have to judge what you mean by important and as my own research developed I realized the importance was very much in the eye of the beholder but for me importance started to become increasingly utility, in other words the ability to use certain things for the common good and to my mind, that’s what I started to think about as being important and that’s what I nailed my colours to in the end.

How did you react finding out the news of being awarded the Nobel Prize?

Sir Gregory P. Winter: When I first got the news I was very tired and I didn’t really take it in. It wasn’t expected and it didn’t really compute. I just felt it was a bit unreal and I think that continued for quite a long time actually, so people said: “Didn’t you feel elated?” No, I didn’t feel remotely elated. I felt just in shock. I’ve had other prizes and I felt elated but this didn’t fill me with joy, it filled me with an unease. I think the unease being that actually inevitably I would become much more of a public figure which is not something I really wanted.

What are your favourite applications of your work?

Sir Gregory P. Winter: The applications I get the most pleasure from are the applications that where people have benefitted. There was a big impact from a patient that … I’d made an antibody against a mark on white cells and this antibody was given to the patient and I wasn’t involved in making a decision as to whether to give it to her, but we did not know what was going to happen. In fact, there was some unease that it might be so powerful it could give very unpleasant side effects. In fact, there were very few side effects it turned out, and in fact the large accumulation of tumours she had in the spleen started to regress and on about the fifth day I was taken round by the scientist to meet her and I was told: “Well, to get in there, you’ll have to look like a junior doctor, put on a white coat, it shouldn’t say medical research council on it because it looks like you’re going to experiment on people, just a white coat. There’s a stethoscope, put it round your neck! Everyone will think you’re a junior doctor!”

So I went round and I got to walk straight in, no-one challenged me at all and went up to this lovely old lady, she was sitting knitting, and talked to her and I remember at the time, she asked me if I’d got any idea of how long this therapy was going to last and I said that we think you won’t react to the antibody because it was our first humanized antibody, but we don’t know for sure. And it, you know, frankly we’re just very glad to see the tumours disappearing but we don’t know just how long it’s going to go on for, you know, maybe it’s going to buy you a few days, a few weeks, a few months, a year or two. I simply don’t know. She said “Well, you’re very honest”, she said “It’s actually a pleasure to talk to scientists”. She’d been talking to medics and I suppose they were a little bit more circumspect, and she said “But all I really need is a couple of months.” I was startled: “Why do you need a couple of months?” And she said: “Well, my husband’s dying and I want to be with him when he dies.” I still feel choked up when I think about it now and I thought, this poor woman, there’s nothing she can do and yet we’ve done something that we can make a difference and you know we just have to … It actually gave me an increasing feel of worth for the kind of science I was doing and at that moment I decided I’d really got to make much more of an effort to focus my work on the practical application of those molecules.

What happened to the patient?

Sir Gregory P. Winter: Her husband died and she was with him and she’d also mentioned that the other two months, the rest of the time she wanted to acclimatize her granddaughter to the fact she was going to have two grandparents dying very quickly. But she lasted a year and then, unfortunately what happened is, the tumour came back. We had no more antibody to treat her, well, we only had one lot of antibody to treat her and it was all in the hands of medics and they decided to give it to a child who they said was more important or it was the ethical thing to do. As a scientist I didn’t agree with that, because I actually felt that this woman was valuable experimental material. She’d also been the first person to have it. It had worked well in her case and I actually felt that we owed it to her to give her another shot of the stuff. But they said: “Well, I’m afraid you know you’re taking the scientist’s perspective, we have to take the clinical perspective and the ethical thing for us to do is to give it to the child.” And they gave it to the child and the child died and so did the lady.

It was all very sad and it made me realize that one of the issues that we hadn’t dealt with, we simply couldn’t make enough of this antibody on the laboratory scale where, I say we, it was really my colleagues, Herman Waldmann in the Department of Pathology, they were making this antibody and just the amounts we could make of suitable grade to go into patients wasn’t suitable and it wasn’t sufficient and I realized that we will have to work with industry to do it. So I thought, well, we’d just better grasp that nettle. I need to find ways of working with industry so anything I get in the lab can be taken through and we don’t end up with these situations where we’ve got antibody and we just simply can’t. We’ve not got a route forward.

Why do you think scientists shy away from working across science and industry?

Sir Gregory P. Winter: Other scientists, I think they do their best but they probably … and it’s perfectly legitimate to say: Well, this is what I can do. I can do this bit and I need other people to take it forward. It’s true in my case. There’s a limit to how far I can go, but on the other hand I feel I should go as far as I can to make sure it is actually used and once it’s been picked up by industry that then, in fact, I don’t have to do anymore. I don’t have to keep to following it through. I don’t have to continue doing industrial stuff. So I actually would step back at that point. It’s quite exciting to see something going all the way through and I have always kept tabs on it but actually the most important thing for me has been to get involved to the point at which … If you’ve done something novel, you’ve got a new technology, then I can assure you industry doesn’t run over and seize it off you. You’ve really got to work quite hard to cross that gap to make them feel it’s worth picking up and running with.

How do you stay focused on your research?

Sir Gregory P. Winter: I realize now my research has gone in phases so what tends to happen is I’ll have a period where I make some discoveries. I try to apply that, I take it forward, then having done that, I step back and try and go back and think of something else I want to try and in fact, that’s happened two or three times. So I’m now working on, or trying to take forward something we invented in the lab in 2009 which was development of mini antibodies which we call bicycles, bicyclic peptides, and we’re lashing on toxins to those and also trying to use them in immuno-oncology so those are things which again, it wasn’t possible to take those forward in academia, you know. To get into patients and well, to do all the preclinical and to get into patients has consumed tens of millions which is the kind of money you don’t get from granting bodies. You have to go to the market to get that and so therefore I’ve tried to, least sell the technology to people, to investors so they will come in and we try to take that forward with a company to a point at which we can see these things applied and in patients. And we’ve now got in the case of the bicyclic peptide, so it’s 2018, we founded the company in the end of 2009 and so it’s nine years but with technology development plus developing individual molecules, we’ve actually got a molecule in a patient now in the clinic in London which we hope will work out well. I mean so far, they don’t seem to have any side-effects but who knows. The kind of things we’re using potentially could be very toxic.

How can we get more young people interested in science?

Sir Gregory P. Winter: I think a lot of things have happened, certainly in the UK since I grew up. I think one of the problems is there’s much less focus on experimental work. With my own children, I was astonished to hear them say that chemistry was boring and I said, “How can it be? It’s a wonderful subject, it’s so exciting all these things you can do.” And they said: “Well, dad, don’t you realise, the most exciting thing we saw was a nail rust.” I said: “You what?” It turned out for whatever reason virtually everything is frowned on for health and safety reasons and possibly other reasons as well, maybe there aren’t the teachers to do it but in the state schools there just isn’t this culture of experiment.

In fact I remember going back a few years later to my old school where I’d done chemistry, and this was probably about five years after I’d left. I’d gone through Cambridge and I went to see my old chemistry teacher and he was surrounded by a class of 14-year-olds with Bunsen burners and things leaping out of the ends of tubes and things going pop and he was sitting there unconcernedly marking things and all round him there was kind of mayhem of boys doing this and that and adding things they shouldn’t have added and I realised you probably have to be quite brave if you’re a chemistry teacher but he kind of presumably knew all the various kind of serious risks. Occasionally a boy would burn their fingers or singe their hair and you know he’d quickly administer first aid and tell them to do what he told them to do in the first place, but I remember thinking this is what chemistry was. The room was full of smells, probably all toxic, it was full of boys doing things off stage and playing little jokes on each other but actually it got them excited and they really looked forward to chemistry and I remember thinking, what a shame that we’ve destroyed that.

Is education in experimental science too timid? Is the focus on safety concerns legitimate?

Sir Gregory P. Winter: I’d like the things I’d like to see people taking … Well, it depends on what you mean by legitimate. I mean I think providing that, you know, I think people should wear safety glasses and obviously you make sure that you couldn’t actually blow anybody up in a lesson but I think people are far too safety conscious, is my impression, but I can’t say I’ve been in lots of schools and I’ve seen lots of things. All I can do is to report back from my own children in state schools and I can tell you that there was a reaction I had many years ago to a biological experiment I did in school. I got invited to my children’s primary school many years ago to show them, you know, parents were asked to come and say something about their work and so for example it was easy for a carpenter to come in and show how they did, carved a piece of wood or whatever. But I went in and I thought I’ll show them an experiment but I needed to make it a couple of days’ worth.

So what I did was, I took petri dishes on one day and I agreed I’d go in the next day and I took samples of bacteria and we had a great time because it was a school in the country and we went round taking samples from the bottom of people’s shoes, from down their ear, up their nose, round the back of a young boy’s neck, on the school climbing frame by swabbing these different areas. I then also mixed this in some school disinfectant to see how that worked and then we plated the bugs out. We plated out the cultures and I’d done some initial ideas of titrations myself earlier on something, so I had an idea of the kind of dilutions you might need to make and anyway took the things home, put them in the bottom of the Aga oven which is a nice 37 degrees or so. The following day they were colonies on these different plates so I wrapped the plates up carefully in cling film and took them in and we scored the plates and we had a sort of big chart on the blackboard with the different sites, named the bottom of Johnny’s shoes, who always used to come from a sheep farm and he’d always trod on sheep shit, that’s just why the girls wanted to have that back of someone’s neck, someone’s hands, the school climbing frame, the school, the effect of the school disinfectant and there were certain things that ended up being very unexpected. First of all the school climbing frame was not the filthiest thing which I had assumed it would be. Nor was it the bottom of Johnny’s shoes, which clearly did have discernible pieces of sheep shit on them. It was the back of the boy’s neck and these things came up. I just couldn’t believe the number of colonies that came up. The other thing was that the school disinfectant had no effect on anything. So we produced this chart and I have to say the children loved it, particularly the boys. Two of them cut out: “Can I be a scientist when I grow up, sir?” They were transfixed by the idea that you could discover things that you didn’t know because they said: “We didn’t know what the answer would be because we’d had a bet and we realised everyone was wrong.” They’d all bet it was actually the bottom of this boy’s shoes and it wasn’t.

Of course the next thing that happened is, I have a nasty letter from the headmistress saying apologizing for the school disinfectant but saying the mother of the boy Johnny had been humiliated by this and this poor boy was going to get his neck thoroughly scrubbed and furthermore there was a hell that I should have done a health and safety assessment on the possibility that there could have been pathogenic organisms on these plates which children had scored and I said: “Look! The plates are sealed.” I had sealed them all round so they couldn’t open them and I thought to myself, these poor little children under that kind of culture. You know, this shows the dead hand of health and safety and bureaucracy in schools. It was such a shame because those boys were really enthused. I thought it was actually quite a good experiment, relatively harmless.

What would be your advice for young researchers starting their career in academia?

Sir Gregory P. Winter: My tips for a career in academia: Work on something important that matters. That matters to you but also most preferentially will matter to other people as well and that someone’s going to put some money into it. I would say you will have to work extremely hard, harder than you have ever known before. You need to forget about work-life balance, you will have none.

Could you explain your prize awarding discovery in 30 seconds?

Sir Gregory P. Winter: The prize was given for making antibodies using a filamentous bacteriophage and I’m going to explain it by analogy and I’m going to explain it by the analogy of a master thief. Let’s imagine that we want to make an antibody against a cancer cell. Imagine the cancer cell is being the lock and the antibody is being the key. If you’re a master thief, what you would do would be to create a huge number of different keys and then you would try those keys out on that lock and that’s effectively what we did. We found ways of generating a huge number of keys and then we found an automated way which was the use of the phage to be able to do many locks in parallel.

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