Talking to Sir David Hopwood

We sat down with Sir David Hopwood to discuss his life and career.

What made you want to come to the John Innes Institute in the first place?

I was in Glasgow, as a lecturer in Genetics – it was an inspirational department – the head was Guido Pontecorvo, a really charismatic individual. He put together the parasexual cycle in non-sexual fungi, and then moved on to the idea of human somatic cell genetics.

I did my PhD in Cambridge and stayed on as a demonstrator, working on Streptomyces and then I took that to Glasgow, but as a family we felt it was time to move. I had a postcard from two people I knew [at UEA and the Food Research Institute] pointing out an advertisement for a Professor of Genetics, and it seemed a unique opportunity.

Nowadays a big part of the John Innes Centre is teaching the next generation…

Well I had quite a bit to do with that if I might say so. The John Innes Institute had virtually no graduate students, and, if you like, an ageing population. I set out to change this as much as possible, to make it as much as possible like a university department, without heavy responsibilities in teaching, but with graduate students, post docs and visiting scientists.

I had an obligation to teach because that was part of the contract, but I encouraged other people in the institute to give a few lectures, because I think that everybody benefits by doing a bit of teaching. The students benefit because they get access to cutting edge research, and I’m quite sure that it is a symbiotic relationship.

What was your abiding first memory of the Institute when you arrived?

I thought that things needed changing.

First, there was no media kitchen. In Glasgow in the Department of Genetics there was a very good provision of media both for human cell culture and microbiologists. Pontecorvo thought that project leaders shouldn’t be wasting their time making their own media, so it was a very good set up for sterile glassware and media – and so we needed to set that up here.

There was no ‘stores’. There was a room in which you could go and rummage – I think obviously everybody realised there had to be stores.

And we put a stop to the idea that the institute would finish at 3.45pm on a Friday. It was so inconvenient. People would phone up and there’d be nobody around…it wasn’t terribly popular, but it had to go that way.

One thing that I was impressed by was the quality of the students at UEA, and I began to get quite a lot of satisfaction from giving lectures. At one point I was doing first, second and third year lectures in genetics, all on the same morning, so quite often I’d have nine lectures in one week. I was determined to act as a university professor.

People speak of your career as being hugely successful, but did you always get that sense or is it only looking back on it that you see how far you came?

No, it didn’t feel terribly successful until, I suppose, the beginning of the molecular era of Streptomyces when a lot more people got interested.

The first plasmid work was in the mid-1970s. Mervyn Bibb discovered how to introduce DNA by transformation into Streptomyces protoplast in 1978, the first genetic engineering experiments were in 1982, we began to isolate antibiotic biosynthesis genes at that time, in the early 80s, so that’s when we began to feel we were getting there.

Were there any underlying principles that guided your work?

It started as fundamental curiosity.

When I started, somebody in the Botany School at Cambridge, a guy called Lewis Frost, said to me, here are streptomycetes, people don’t know whether they’re bacteria or fungi or something in between, why don’t you see if they have any genetics, because already at that time bacterial genetics and fungal genetics were clearly extremely different.

At the time, bacterial genetics and molecular biology was very collegiate. I mean there was competition but not cut-throat competition, and that was what I tried to foster.

I don’t claim that we’ve changed the world of antibiotic production because it’s extremely hard to discover or to develop novel antibiotics that are better than what nature has already produced. You can certainly make changes, medicinal chemists can make changes, sometimes that sort of modification of an existing antibiotic could best be made by genetic engineering, but otherwise it might need twenty steps in an organic chemistry lab.

What I did think had more of an effect is our discovery of protoplast fusion where you strip the cell walls off two strains in an osmotically stabilising medium and make protoplasts, and then fuse them together with polyethylene glycol. You get a complete mixing of the genotypes, incredibly high recombination frequencies doing this so this was a way in which people interested in strain improvement could take two divergent lines and very easily mix them together, and hopefully get strains that were better.

Now there’s no doubt that technique was used in industry, I think to quite a degree, but of course it’s never published and you never hear about it, so in that way it’s unsatisfactory. A company isn’t going to patent that because that would mean releasing details they want to keep as know-how, and in any case it would probably be hard to patent.

You’ve always been keen on collaboration. Is that something that was encouraged in the scientific culture at the time, was it normal?

Yes. Well it certainly was in the golden age of bacterial genetics, there was a lot of sharing. It’s not unique to my approach. I mean collaboration is universal.

I think you have to go where the collaboration is natural, because, I’m not sure whether this was expressed, but there was the idea that perhaps there are chemists at UEA and chemists at the John Innes Centre, so why am I collaborating with people in Tokyo, or Stanford in the chemical work that we were doing?

It’s because they were interested in that class of compound and there was nobody doing the chemistry of polyketide antibiotics in the institute; the expertise was where we went and sought it. I’m sure that’s not unique to this field

Is there anything that stands out in your memory as being unique or a special moment in your time at the John Innes Centre?

Well in terms of science, the hybrid antibiotic stands out, because that was a sort of Eureka moment, and of course it had a picture with it.

It’s a fantastic place to work. I mean I had job offers elsewhere as people do, but I stayed here.I It was the perfect job really, because you could get student contact, which I liked, but very little in the way of university chores.

You always had to be a little bit clever about how to go about getting funding. Now I gather people can apply almost anywhere, even to the Wellcome Foundation; we couldn’t apply to the Wellcome Foundation, because we weren’t medical.

The whole saga of getting the money to fund the genome sequence, that was exciting and when we got the money that was a high point.

£1.5m had been earmarked by the BBSRC for microbial genome sequencing and I had chaired a series of earlier meetings, but then at the last meeting Debbie Pool, who was the administrator, asked somebody else – Nigel Brown – to chair it.

On reflection, I think that was a useful move, because it meant that I could talk about Streptomyces as a project which if I’d been chairman would have been difficult. Within half an hour they had decided they were going to devote the whole £1.5m to Streptomyces coelicolor. That was a high point.

What was your reaction to being knighted?

I’d been to Stanford for a week discussing writing papers and flew back into Norwich Airport at 4pm. My wife Joyce picked me up, and we realised it was election day, so we went and voted. When we got home it seemed to be time for supper, but Joyce suggested I look at the mail and there was this envelope from the Prime Minister’s office. It said the Prime Minister was recommending me [for a knighthood], and I thought well, what am I going to do, I’ve always been rather rude about the honours system, so could I accept this?

Alec Jeffries, the pioneer of genetic fingerprinting, and Ken Murray, a pioneer of phage genetics, had accepted knighthoods. I mean there were obvious people who must have been offered knighthoods and hadn’t [accepted], but Streptomyces was less known scientifically, and it would probably be good for the subject to accept, so I ticked the acceptance box and sent the form back.

It had more effect on my wife, who was doing a lot of voluntary work. She was on the East Anglian Regional Health Authority and she was Chairwomen of the Norfolk Probation Committee, and they were delighted that she was now Lady Hopwood.

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