A broad view: Dick Flavell
Year: 2021
Type: article
Abstract: At the 20th anniversary of the publication of the first sequenced plant genome, it is hard to imagine conducting plant genetic research in its pregenomic form (Arabidopsis Genome Initiative 2000). The tools, resources, and institutions we have today were developed painstakingly by the pioneers of the field. One such trailblazer, Richard (Dick) Flavell, has been leading the charge almost from Day 1, as one of the world’s first plant molecular geneticists. Dick has combined his genial personality and openness to opportunity into a meaningful career in plant genetics, spanning academia and industry over five decades. One sunny morning in November, I had the pleasure of meeting Dick over Zoom to discuss his remarkable career and his vision for the future of plant biology. Dick Flavell in the greenhouse Raised in the city of Birmingham, United Kingdom, by parents who hailed from the English countryside, Dick grew up appreciating English gardens and the care and keeping of flowers, but he did not initially consider the field of agriculture or plant biology for a career. Indeed, as a teen he set out to study chemistry, but in 1960 a life-changing informational interview with a prominent chemistry professor sent him down a different path. Dick recounted, “He said, if I was having my time all over again, I wouldn't start chemistry. I'd go into what he called ‘Microbiology’. And that actually ended up being something much closer to microbial genetics… So as a 17 year old, I said, OK, that's what I'll do.” Dick ended up at The University of Birmingham, where this relatively narrow undergraduate field of study launched his career at the cutting edge of science. He joined a department with only four students, who were privileged to be doing interrupted mating and phage rII mutation experiments with Escherichia coli and Bacillus subtilis genetics at an early stage of their careers. From there, Dick continued on to a Ph.D. at the John Innes Institute and the University of East Anglia under the tutelage of John Fincham, with whom he isolated and mapped mutants of the Neurospora crassa glyoxylate shunt (Flavell and Fincham, 1968a, 1968b). “I felt even as a graduate student and as a postdoc I belonged to a small group who knew the same literature and were addressing the same kinds of questions… I felt privileged and excited to be in this microbial world.” He did a productive postdoc describing the function and regulation of the enzymes of the Neurospora Krebs cycle with Dow Woodward at Stanford (Flavell and Woodward, 1968, 1970a, 1970b, 1971b, 1971a). After his postdoc, Dick looked forward to a promising career in microbial genetics. How, then, did he end up studying plants? When the time came to look for faculty positions, Dick’s open-mindedness proved key to the transition that lay ahead. The Plant Breeding Institute in Cambridge, United Kingdom, was looking for someone with expertise in molecular genetics, and Dick came highly recommended. In 1969, he made the pivotal decision to join the Department of Cytogenetics, known for successes on the frontiers of wheat chromosome manipulation and wheat genetics. He reflects, “It felt the right thing to do- if you're going to build a career of inquiry in microbes, it seemed to me a little bit distant from society. Because how many people walking in the street could tell you what a bacterium is or a virus or even a fungus? But they would have some recognition of plants and agriculture.” At the time, plant molecular genetics was in its infancy, and it took people like Dick crossing the aisle and bringing new technologies previously implemented in model organisms to bring a rush of groundbreaking discoveries about plants. “It suddenly became pretty lonely, when I first took that job. But if you've been once taught how to grow E. coli, when recombinant DNA comes along and you need to grow E. coli cultures, you're well equipped, you know, you don't fear it… so it gave me a head start, taking the plunge to convince people in a plant breeding institute that we should start pulling apart chromosomes.” The wheat researchers of Cambridge were progressive cytogeneticists, changing the chromosomes of wheat and even making stable plants with rye chromosomes integrated and describing their phenotypes (Chapman and Riley, 1955; Riley and Ewart, 1970). However, Dick still had something to contribute to the team: “I started isolating DNA, and then the floodgates opened because of what we discovered so soon after. We used what were the frontier technologies of the day to address what is it? What is the DNA in the chromosomes?” By observing the kinetics of DNA renaturation, his group soon published major findings about the high degree of repetitive DNA content of cereal genomes (Smith and Flavell, 1975), and interspecies DNA–DNA hybridization allowed them to extend their findings to the evolution of cereal chromosomes, demonstrating the rapid evolution of repeated DNA sequences (Smith et al., 1976; Rimpau et al., 1980). He also put his training in bacterial genetics to work, cloning the first plant DNA sequences in the process of describing the different families of cereal DNA repeats (Bedbrook et al., 1980; Flavell et al., 1980), and some of the first plant cDNAs while studying the contents of barley endosperm (Forde et al., 1981). It was an exciting time for plant genetics, as Robert Goldberg reflected in Plant Physiology in 2001, “A pioneering principle was established—plant DNA was similar to that of all other organisms and could be manipulated using the same enzymes, cells, and vector systems” (Goldberg, 2001). Early in his time at Cambridge, Dick realized the genetic limitations of species that had evolved for purposes other than to feed humans. “I believe that genetic variation has to be the source of improvement, and if we've more or less exhausted the natural variation … transgenes are an obvious source.” To aid in the creation of transgenic plants, the group prioritized technology development, publishing one of the first uses of the Agrobacterium Nos promoter to drive expression of a selectable marker for transgenics, which Mike Bevan then extended into a collection of plant transformation vectors broadly used in the first transgenic plants (Bevan et al., 1983; Bevan, 1984). In 1987, after almost two decades building up the Department of Plant Molecular Genetics, which he founded at Cambridge, Dick transitioned to a new role as the director of the John Innes Institute, Norwich. He led the merger of the John Innes Institute with the Cambridge Laboratory and the Nitrogen Fixation Laboratory into the John Innes Centre (JIC). This merger helped to usher in a new era of British plant research, capitalizing on the movement beginning in plant genetics to embrace a model organism for plant research, Arabidopsis. Dick was excited about the power of the emerging model plant, working on it in his own lab, and encouraging its use more broadly. “Because of who I am and because of my baptism into plants through the Plant Breeding Institute, I always saw Arabidopsis as a model and not as an end in itself… I passionately believed that you needed stories that were good enough to go onto the leading international stages because they were on the frontiers. They were revealing, they were provocative. And you also needed stories that really resonated with the future of agriculture, and if you lost either one then I believe the group was poorer for it.” He swiftly put this principle into action, drawing on his decades of experience in cereal genetics to inform hiring decisions at the JIC: “The big things that had made a difference to [wheat] yield were the dwarfing genes and flowering time. So, it was no accident that when we launched Arabidopsis, we hired somebody to get to the bottom of dwarfing genes and flowering time.” As a result of this initiative, Nick Harberd published his seminal study identifying the Green Revolution dwarfing gene as the wheat homolog of the Arabidopsis gibberellin signaling gene DELLA, and Caroline Dean published her acclaimed body of work describing FRIGIDA, the major determinant of flowering time in Arabidopsis (Clarke and Dean, 1994; Peng et al., 1999; Johanson et al., 2000). Although it may seem like an unlikely path, Dick’s history of leadership at the Plant Breeding Institute and the JIC set the stage for the next phase of his scientific career; in 1998 he transitioned to the role of Chief Scientific Officer of the California-based plant genomics company Ceres Inc (Dicks time in academia culminated in his election to the Royal Society of London for services to science in 1998.). “If you get involved in application, you inevitably require multidisciplinarity… I've always been interested in a broad view, for many reasons, but that fitted me to go into industry and collect around me whatever one needed in order to move the plant biology in an applied sense further forward.” With Ceres, Dick contributed the sequencing of an Arabidopsis cDNA library used in the early annotations of the genome, produced many transgenics in Arabidopsis and crops, and participated in the filing of a number of patents related to plant genomics (Haas et al., 2002; Alexandrov et al., 2006). This major change coincided with one of the lowest points of Dick’s career, when the global response to transgenic plants became clear. He hoped a move from the EU, which effectively banned the permitting of new transgenics in 1998, to the more permissive the United States would allow him to continue to contribute to the essential pursuit of crop improvement (Davison, 2010). Dick has spoken widely and penned a number of impassioned defenses of transgenic plants (Flavell, 1999; Flavell, 2016). To Dick, plant breeders will require a toolbox of solutions to solve the global agricultural productivity crisis, incorporating transgenics as well as editing and novel breeding techniques. “We have to fight back as a scientific community and show the world that every living organism is a product of remarkable genetic change, and that we only stay alive on this world, food wise and disease management wise in crops, through the deployment of extraordinary genetic variation. If we as a scientific community don't push back sufficiently far to be able to win the deployment, then there is going to be far more tragedy than there need be.” So, what has Dick turned his attention to today? He has set out to address one of the last remaining serious bottlenecks to scientific and human progress: the translation of research findings into agricultural application. “That's another one of the challenges that I believe should be put right, not to stop the discovery for its own sake, but to just do something with the discoveries beyond writing a great paper.” As the chair of the Scientific and Impact Executive Board of the International Wheat Yield Partnership (IWYP), he hopes to model a purposeful way forward for scientific research funding, integrating grants directly into a development pipeline through plant breeding institute “hubs”, the first of which is a CIMMYT (Centro Internacional de Mejoramiento de Maíz y Trigo) field station near Ciudad Obregon in Mexico. This exciting arrangement allows streamlined testing of academic findings, such as new germplasm, genetic markers, tools, and phenotyping systems, by application experts. It also includes a framework for feedback to researchers throughout the process, from proof-of-concept through to prebreeding. Since its inception, IWYP has developed 38 such projects; in Dick’s vision, this system would exist for a variety of crops, with hubs throughout the world. “And then the outputs of the research labs would not just stay as great papers, but also the tangible pieces would be going to where they can be assessed for their utility.” For Dick, keeping the joy of scientific discovery while honoring his commitment to crop improvement has been a recipe for a fulfilling and productive career.
Source: PLANT PHYSIOLOGY
Author: Sophia G Zebell
Institution: Howard Hughes Medical Institute
Language: English
Subfield: History
Field: Arts and Humanities
Domain: Social Sciences
Open Access status: green
OpenAlex ID: W3146047740