What motivated you to work in the agbiotech space? 

I’ll try to give a short answer to this – but it won’t be easy.  At high school I studied maths, physics and chemistry – but I sensed that the world was heading for an ecological crisis (Silent Spring had just come out, and I was one of the early subscribers to an ecomagazine called The Ecologist). I felt the last thing the world needed was more physicists so I attempted to switch to biology. With hindsight this was not smart and I wished I’d had some better career advice – look at how transformational solar panels and wind turbines have been for the world’s energy supply. Anyway, I ended up doing a degree in Botany from Cambridge, and it still amazes me that plant and algal conversion of solar radiation and CO2 into sugars underpins all life on the planet. During my PhD at the Plant Breeding Institute in Cambridge (now unfortunately privatized), I developed a keen interest in how genetic improvement of crops provides a societal benefit. After a postdoc on symbiotic nitrogen fixation with Fred Ausubel at Harvard, I joined the first agbiotech company to go public: Advanced Genetic Sciences in Oakland CA. At the time there was great excitement about how delivery of DNA into plants via Agrobacterium- which I will call “the GM method” – could be put to good use.  The subsequent neurosis about use of the GM method had not yet kicked in. The engineering of Bt for insect resistance was a clear win, and its deployment to reduce insecticide use for cotton protection from major insects pests was and is a triumph. I even had an early (and not particularly successful) project on disease resistance by engineering expression of a bacterial chitinase. However, eventually I and my wife-to-be (Caroline Dean) moved back to the UK, starting positions in Norwich in September 1988.  I’d developed genetic methods to clone Mendelian genes from plants using transposons, and I got the job at The Sainsbury Lab (TSL) because I could overcome the big challenge in the disease resistance field which was cloning disease resistance (R) genes.  The next 15 years were spent trying to make the most important discoveries about how plant immunity worked, but by the mid-noughties, I felt we knew enough about immunity to start bringing these insights to public use by deploying R genes in crops, using the GM method to stack multiple R genes to maximise the durability of the deployed resistance. I certainly haven’t abandoned discovery science and I think we still make some useful contributions, but my emphasis has shifted towards using what we know to solve problems in the field.

 

The purple tomato has recently gained significant public attention. Being involved in this project since its inception, could you elaborate on the journey and what it means to you for it to now be available to farmers and consumers after so many years? 

By the mid noughties, anxiety about use of the GM method had kicked in. I saw Cathie Martin (in 2006) give a talk about the purple tomato, with its very credible health benefits and beautiful appearance and thought, what if we could combine consumer pull (the purple trait) with disease resistance (to benefit farmers and the environment)? Cathie and I founded the company Norfolk Plant Sciences (NPS) in summer 2007 with this purpose in mind. We’ve had to keep the faith since then and it’s been a long and winding road (and a big shout out to then President of 2Blades, Eric Ward, who joined the NPS board and has contributed enormously to making NPS and its US subsidiary Norfolk Healthy Produce a success). Supporters of NPS have had to dip into their own pockets to keep it going over the last ten years while we waited for the regulatory path to clear. It was a great thrill last summer when I had lunch at a fancy restaurant in Boston where purple tomatoes were on the menu. It’s extraordinary that 13,000 home growers in the US have ordered seeds to plant for themselves. There is still a long way to go but there will be purple tomatoes on supermarket shelves this year, which is amazing.  I’m excited now because the project has identified a significant demographic of people who are quite comfortable growing and consuming a crop improved with the GM method.  This means that there should be no consumer concern about additional improvements with the GM method, such as disease resistance to rugose virus or spotted wilt virus, to Xanthomonas, Ralstonia or Pseudomonas bacterial diseases and to Phytophthora. I am working currently to add these traits to the purple tomato.

 

What technology/innovation are you most excited about in the next 5-10 years? 

Site-specific nucleases (SSNs), such as CrispRs and TALENs, provide a valuable method to fine tune the alleles of any gene in any crop; this will be extremely useful.  It would also be useful to be able to use SSNs to make DNA breaks that drive homologous recombination to insert specified DNA sequences at a defined location.  For crop improvement more broadly, I see gradual accumulation of good alleles of many genes – whether for disease resistance, stress tolerance or simply complementing deleterious alleles – at a single locus will free up plant breeders to combine good alleles at other loci without the distraction of also trying to retain independently segregating alleles of resistance genes and other genes.

 

I also am excited about AI driven (specifically Alphafold and Alphafold Multimer) methods to extend and adjust the recognition specificity of plant immune receptors to enhance their utility, and other likely new methods to create synthetic immune receptors that can be designed to recognize any pathogen effector, prioritizing the most conserved and indispensable effectors for the pathogen.

 

But there is still a lot to do with the old technology of Agrobacterium-based GM methods to insert multiple genes at one locus. I’m still keen to do what I can to break down the public misperceptions of a benign and useful method for crop improvement.

 

Having been at The Sainsbury Laboratory since 1988, including two stints as its Head of Lab (HoL), are there particular moments or achievements that stick out when you look back at your career? 

Gosh, that’s a difficult one- there have been many great moments. I remember when we transposon-tagged Cf-9, a tomato gene for resistance to a fungal disease. We could select for lines in which Cf-9 was inactivated by transposon insertion; the lines we sought had somatic sectors in which the transposon had hopped out to restore function, and in our set up, these sectors were necrotic. When I found these seedlings, I knew we had tagged the gene in summer 1993; it was then just standard molecular biology for us to look at the gene sequence, which encoded the first cell surface immune receptor to be genetically defined in any eukaryote.

 

In my first stint as HoL, the best thing I did was to recruit Paul Schulze-Lefert to our faculty, initially as a junior investigator but he was very rapidly promoted. He was a fantastic colleague at TSL, and we were very sorry to see him go, though it’s hard to compete with an offer from a Max Planck Institute.

 

In my second stint as HoL I remember most the decision to purchase a then very new Solexa sequencing machine (one of the first purchased in the UK) which could achieve 1 Gb of DNA sequence data per run (!). We had to recruit to strengthen our bioinformatics team to make the most of the data, but it was clear at the time that better DNA sequence data acquisition was key to the future; this “risky decision” is now completely vindicated.

 

Other highlights include our collaboration with the de Wit lab which validated the guard hypothesis for Cf-2/Rcr3 recognition of Avr2; cloning late blight resistance genes from wild Solanums and then putting together stacks of them together to achieve essentially complete disease resistance; writing well-received reviews with Jeff Dangl and others and making new discoveries about how surface-receptor and intracellular-receptor initiated immunity mechanisms mutually potentiate to achieve robust disease resistance.  I also remember with great fondness our “triple stack” issue of Nature Biotechnology in June 2016 where we reported in three back-to-back papers the use of PacBio Renseq to clone Rpi-amr3, the map-based cloning (with many great colleagues) of a soybean rust resistance gene from pigeon pea, and (with Brande Wulff) cloning (with RenSeq) a rust resistance gene from wheat.

 

Following up on the previous question, what advice would you give to young scientists just starting out in their career? 

The most important thing is stay really focused on the science you are most excited about and to address what you think to be the most interesting and crucial questions. Of course, you must be aware of what others are doing in a competitive landscape, and to try to define your comparative advantages and play to your strengths and create a niche for yourself. It’s more important to prioritize questions than methods. You have to dare to follow the science even it leads you out of your comfort zone into territory different than what you expected. Have the courage of your convictions. And don’t be intimidated.

 

What attracted you to 2Blades and your involvement on its Scientific Advisory Board?  

I’ve always wanted to not only make scientific discoveries but to also see them brought to public use, particularly for elevating crop disease resistance. 2Blades’ interests and mission and mine are entirely congruent.

 

What are you reading/listening/watching right now? 

Just read Michael Mann’s “Our Fragile Moment” – a very interesting read about the history of the Earth’s climate as context for understanding our anthropogenic departure from the preindustrial state. I read Joseph Barr’s “A Line in the Sand” to better understand the current tragic situation in the Middle East (and British complicity and ineptitude during the path to where we are now). I listen to podcasts in the car and on the rowing machine – The Rest is Politics and The Life Scientific are good.

 

What keeps you busy outside of work?  

These days my six grandchildren provide a major distraction most weekends – they’re exhausting but it’s a good problem to have! I used to run 15k a week but have an ankle problem that restricts that, but I also race Laser sailing dinghies when I can.  I bike to work and at weekends get on a rowing machine to try to maintain some level of fitness.