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Our History - Timeline
Key events include:
- JIHI renamed the John Innes Institute to better encapsulate the plant, microbial and mammalian cell research in progress
- John Innes Institute moved from Bayfordbury to Norwich to form an association with the School of Biological Sciences at University of East Anglia
- Dr Roy Markham appointed Director; his ARC Virus Research Unit, Cambridge amalgamated with JII and most of it temporarily housed at the neighbouring Food Research Institute. The arrival of VRU staff nearly doubled the number of scientific and experimental officers at JII
The John Innes Institute is fifty years old. To celebrate the occasion 350 guests visit Bayfordbury on 8th July 1960. They are welcomed by the Chairman, Sir Frederick Stern, and Members of Governing Council and spend the afternoon in the grounds and glasshouses, and looking at exhibits set up in the laboratories. After tea, HRH the Duke of Northumberland KB presides over the Fifth Bateson Lecture at which Kenneth Mather, FRS speaks on ‘Genetics: Pure and Applied’. During the afternoon, the new building for the Department of Cell Biology is opened for inspection. When fully equipped and staffed it will provide research facilities for about twenty-five scientists.
The change of name from ‘John Innes Horticultural Institution’ to ‘John Innes Institute’ is announced by Sir Frederick Stern during the Jubilee celebrations. It is hoped that the new title will help to attract scientific staff to work at JII and will better describe the plant and microbial research that is now in progress. It is intended that the new name will signify to a new generation of research workers, who know nothing of the Institution’s past, or the scientific freedom that they would enjoy at Bayfordbury.
It is now nineteen years since Beadle and Tatum’s (1941) classic paper on the isolation of biochemical mutants in the red bread mould Neurospora crassa. By showing that the function of genes is to direct the formation of enzymes which regulate chemical events their work is often commemorated as the first in a series of fundamental advances that were to bridge the gap between genetics and biochemistry. Neurospora studies started with American mycologist B. O Dodge who influenced Carl Lindegren in the 1930s to study the genetics of Neurospora, working alone, at California Institute of Technology. When George Beadle and Edward Tatum started to isolate biochemical mutants there they started a ‘Neurospora revolution’ with geneticists around the world beginning to devote their research to microbes; in the UK John Fincham was a key figure in this move to fungal genetics.
Fincham trained in the Botany School at Cambridge, the UK’s original centre of Neurospora genetics. Here Harold Whitehouse had been the first to work on Neurospora under the supervision of cytologist and geneticist David Catcheside, beginning with some cultures of N. sitophila already available at the Botany School. In 1946 Catcheside obtained cultures of wild type and mutant strains of N. crassa and it was on these that John Fincham began work as a new PhD student. In 1948-49, on an Agricultural Research Council Scholarship to the California Institute of Technology, the stronghold of Neurospora genetics, Fincham worked on the biochemical genetics of N. crassa with Norman Horowitz and Sterling Emerson. Fincham’s work on am mutants that were deficient in a specific enzyme (glutamate dehydrogenase or GDH) provided very early confirmation (1950) that Beadle and Tatum’s ‘one gene-one enzyme’ hypothesis was correct. The study of am mutants and GDH was to become the central feature of Fincham’s experimental research.
Prior to coming to JII, Fincham had seeded a Neurospora group at Leicester University where from 1950 to 1960 he was a lecturer, then reader in botany. Catcheside had moved (from Cambridge, then Adelaide, Australia) to a new Chair of Microbiology at Birmingham in 1955, where he led another Neurospora group. Other centres of fungal genetics included Guido Pontecorvo’s Department of Genetics at the University of Glasgow which had established Aspergillus nidulans as a model microbe for genetic studies. Glasgow was the parent of off-shoot groups of Aspergillus researchers at Sheffield and, in the 1960s, in the Cambridge Genetics Department. By 1960 fungal genetics has reached a point in Britain where it is developing but is still a small endeavour compared with the genetics of plants and animals. Fincham’s appointment at JII, unsettling to some on JII Governing Council, is an acknowledgement that much really progressive work in biology is now done with microrganisms and is a strategic move by Dodds to give JII leadership in the field.
For a summary of Beadle and Tatum’s work and the Nobel Prize they shared with Joshua Lederberg, see:
For a post 1945 survey of UK genetics departments including fungal genetics:
J. R. S. Fincham, ‘Genetics in the United Kingdom - the last half-century’, Heredity, 71 (1993): 111-118.
On the growth of microbial genetics, see:
D. A. Hopwood, Streptomyces in Nature and Medicine, Oxford: Oxford University Press, 2007, pp. 51-57.
Head of JII’s Department of Plant Breeding Watkin Williams, resigns to take up a new post as Professor of Agriculture (Crop Production) at King’s College, University of Durham. Kenneth Dodds takes over as Acting Head and re-names the department Applied Genetics. The Department Dodds inherits has been working primarily on apple breeding (especially for scab and mildew-resistance), pear breeding, plum breeding, cherry breeding (including bacterial canker resistance), strawberry breeding (for yield, red-core fungus and mildew resistance), and tomato breeding. However, Dodds’ new Department has to operate in a new and challenging research environment and changes to the research programme are inevitable. The Agricultural Research Council is steadily transferring applied work to its other Institutes. Long Ashton (Bristol) and East Malling (Kent) are extending their research on fruit-breeding. The National Vegetable Research Station at Wellesbourne (Warwickshire) and the Glasshouse Crops Research Station at Rustington (Sussex) will between them cover most of the horticultural crops of commercial importance. When the tomato work is transferred from JII to Rustington (c. 1962) Dodds has to develop a research plan that will be unique to his Department to secure its future. He needs a crop that is genetically interesting but one that has not been claimed by any other of the ARC Institutes. Dodds settles on Pisum (peas) and re-introduces a pea genetics programme to JII. He begins by collecting a small number of lines from around the world to assess the range of variability. Brian Snoad later takes over the collection from Dodds and commences cytological and genetic studies. Pea research, by no means new to JII having been studied by Caroline Pellew from 1910-1941 (rogues, types and linkage), will become increasingly central to the work of Applied Genetics in the future.
A report to the government entitled ‘The Management and Control of Research and Development’ is published on 5th July 1961. The Committee, chaired first by Sir Claude Gibb and then by Sir Solly Zuckerman, considered, among other matters, the minimum size and location of government-funded research stations in relation to their viability and efficiency. They were concerned that some of the stations of the Department of Scientific and Industrial Research and the Agricultural Research Council (ARC) were too small and too isolated to ‘inspire much hope in their continued success’. The ARC had itself been worried about the relative isolation of the John Innes Institute, especially after the severance of formal links with the University of London in 1957 and had already mooted the idea that JII move to associate with a university. The Zuckerman Report gives further impetus to the re-location proposal though not everyone is convinced by the arguments put forward to support the move, as the JII is only 15 miles from the University of London which by 1965 is itself undergoing reform to restore recognition and co-operation to research institutes in the London area.
For background on the report see also:
Office of the Minister of Science, The Management and Control of Research and Development, London: HMSO, 1961.
Based on experiments with bacteria, especially their own work on enzyme synthesis in Escherichia coli, François Jacob and Jacques Monod at the Pasteur Institute in Paris describe a model for the regulation of protein synthesis. Their model envisages that the mechanisms which regulate the synthesis of proteins do not operate in the cytoplasm but act directly on the genes by governing the transcription of the DNA into RNA (the ‘genetic operator model’). Their study of the control of expression of genes in E. coli provides the first example of a transcriptional regulation system.
F. Jacob and J. Monod, ‘Genetic regulatory mechanisms in the synthesis of proteins’, Journal of Molecular Biology, 3 (1961): 318-56.
Sydney Brenner of the Medical Research Council Unit for Molecular Biology in Cambridge, François Jacob at the Pasteur Institute, Paris and Matthew Meselson at the California Institute of Technology (CalTech), publish their hypothesis that mRNA is the molecule that takes information from DNA in the nucleus to the protein-making machinery in the cytoplasm. The hypothesis is based on their experiments on phage-infected bacteria which were initiated while Brenner and Jacob were guest investigators at CalTech.
S. Brenner, F. Jacob, M. Meselson, ‘An unstable intermediate carrying information from genes to ribosomes for protein synthesis’, Nature 190 (1961): 576-581
When Henry Harris takes charge of the Cell Biology Department in 1961 he inherits three biologists who know a great deal about plant cells (Len LaCour, John McLeish, and Norman Sunderland), a biochemist (R. G. Stickland) and a physicist (John Crawley) with a special interest in advanced microscopic techniques. Harris sees at once that they possess skills that could be useful to his research but does not immediately seek to change the direction of their work. In addition, Harris has the collaborators he brought from Oxford (Marianne Jahnz and John Watts), and several newly appointed staff with expertise in biochemistry, physical chemistry and microbiology, making this by far the largest of JII’s departments, with 20 scientists by 1963.
Harris’s team quickly begin work investigating what Harris regards as the most important question in the field of RNA metabolism: where in the cell is the short-lived RNA broken down? With the methods available at the time this is a ‘fiendishly difficult’ task. Watts refines methods of separating the individual RNA components in the cell and they soon find that short-lived RNA is broken down within the cell nucleus. This phenomenon of great biological importance (i.e. turnover of RNA in the nucleus of animal cells) initially met with a sceptical response. The result was either disbelieved or regarded as an experimental artefact. Robin Holliday witnessed heated exchanges at a meeting in Cambridge (1962) where Sydney Brenner and Harris were both speakers. Scientists were ready to accept that there was an RNA fraction in the cell that turned over rapidly, following the discovery of short-lived messenger RNA in bacteria by Brenner, Jacob and Meselson (1961), but Harris has difficulty convincing them that the short-lived nuclear RNA which he has observed in higher organisms isn’t the messenger.
To provide experimental evidence to back his views Harris turns to a marine unicellular green alga, Acetabularia. He sends Marianne Jahnz to the Max Planck Institute of Marine Biology in Wilhelmshaven and she returns to JII with seed cultures of Acetabularia and the skills to grow them. Their experiments lead them to another discovery: the synthesis of RNA in the cytoplasm of Acetabularia. They are able to demonstrate that the template (the messenger) for protein synthesis is regulated by mechanisms that operate in the cytoplasm and not in the nucleus. This opposes the doctrine that protein synthesis is governed solely by gene switches that work through unstable, short-lived messengers. Harris’s findings do not upset the status quo, however, because scientists assume that Acetabularia is a special case.
Harris’s team discover that the relationship between nuclear and cytoplasmic RNA is very complex and they are led to explore another ‘heresy’: the idea that RNA can be synthesised in the cytoplasm. Natural features of cell division in plant cells make them more suitable for pursuing this investigation than animal cells. Harris is able to tap into the expertise of Len LaCour who suggests that he use growing root tips of the broad bean, Vicia faba. They are able to show convincingly that RNA synthesis continues in the cytoplasm during the period that synthesis of nuclear RNA is suspended. The continued opposition of other scientists means that Harris has to devote ‘almost three years to defensive, scholastic experiments’ rather than making progress in understanding the biological significance of the phenomenon he has discovered. It is only in the late 1970s when introns (non-coding regions of genes) are identified that Harris’s discovery of nuclear RNA turnover is understood. The turnover process is part of the elaborate mechanism that eukaryotic cells have for editing introns out of RNA. Once editing is complete the RNA passes out of the nucleus to a ribosome to be translated into protein.
Henry Harris, The Balance of Improbabilities: A Scientific Life, Oxford, Oxford University Press, 1987, pp. 139-156; 177-184.
Robin Holliday, ‘The early years of molecular biology: personal recollections’, Notes & Records of the Royal Society London, 57, 2 (2003): 195-208, on p. 203.
The Governing Council of JII begins discussions with the Agricultural Research Council (ARC) about future research policy, although privately this has been under discussion since 1958. A dilemma faces the Institute. Should they follow the ‘problems of greatest academic interest’ which in 1960s genetics are centred in the study of bacteria, fungi and viruses, or do they continue to work on the genetics of higher plants? Microbial genetics is fundamental to biology but does not help agriculture in the short term; the plant breeder must still rely on classical genetics and biometry to help in selecting the best genotypes. With research moving to the molecular level, the Institute’s ability to play a part in modern genetic research and meet its shorter term obligations to agriculture is in question, as is the place of JII in the general pattern of state-aided research institutes. It is in 1962 that the ARC first suggests that the direction that JII has taken is too ‘academic’ and that its research programmes might fit better within a university with funding from the University Grants Committee. In June 1962 the idea that JII should form an association with the newly established University of East Anglia is proposed and a move to Norwich contemplated. JII Heads of Departments are told confidentially about the plans but most of the staff do not take rumours about relocation seriously until the move is officially announced early in 1963.
Henry Harris, Head of Cell Biology, has had daily contact with John Fincham, Head of Genetics, since the summer of 1961. This opportunity to observe Fincham’s bread mould Neurospora crassa has concentrated Harris’s mind on the sexual and parasexual processes of mycelial fungi, in particular the way in which the fusion of hyphae brings together within a single cytoplasm nuclei of different genotype (heterokaryosis). This natural phenomenon stimulates in him the idea of producing heterokaryons in somatic animal cells. The prospect of doing this is immensely attractive because it promises to make available to researchers on mammalian cells genetic techniques that are fruitful in the study of bacteria and fungi. Guido Pontecorvo had already pioneered the idea that parasexual cycle genetics could be applied to human or other animal cells in culture (Pontecorvo 1958, p. 134) and had started work on human genetics in 1959 at Glasgow University, but Harris’s inspiration for thinking about cell fusion by his own account drew from his local circumstances at Bayfordbury.
Later in 1962 reports from Japan of virus-induced cell fusion provide Harris with a laboratory method. Harris will not pursue this lead until after he has left the John Innes Institute; his first report on man-mouse heterokaryons (with J. F. Watkins) is published in Nature in February 1965. The news that an inactivated virus could be used to fuse together different animal species and that the hybrid cells produced in this way are viable grabs the attention of newspapers around the world. Harris’s subsequent research on cell fusion secures his international reputation. Harris later explained that the lack of an animal virologist in his Department at John Innes, there was no-one there familiar with the standard techniques of virus culture, isolation and titration, was a contributory factor in his postponement of research on cell fusion. More important, however, was his overriding pre-occupation at JII with his work on the metabolism of nuclear RNA.
For Henry Harris’s personal account of research on cell fusion see:
Henry Harris, Cell fusion, Oxford, Clarendon Press, 1970.
Henry Harris, The Balance of Improbabilities: A Scientific Life, Oxford, Oxford University Press, 1987.
For Guido Pontecorvo’s major contribution to genetic analysis in human cells see:
G. Pontecorvo, Trends in Genetic Analysis. Columbia Biological Series, New York & London: Columbia University Press, 1958.
Bernard L. Cohen, Guido Pontecorvo (“Ponte”), 1907-1909, Genetics, 154 (20000): 497-501
Discussions on future research policy have made it clear that the Agricultural Research Council will not continue to support the John Innes Institute in isolation at Bayfordbury. An agreement is reached that JII will be associated with the University of East Anglia (UEA) in Norwich. At this stage in the negotiations it is intended that JII will retain its separate identity and continue to undertake research in genetics, and plant and microbial science. To derive full benefits from this alliance it is decided that JII will move to Norwich. The John Innes Trustees are in the process of acquiring a new site of about 30 acres close to the University (at Colney) on land adjacent to the site on which a new Agricultural Research Council Food Research Institute will be built and populated by scientists moving from the Low Temperature Research Station in Cambridge. The JII site will be large enough for buildings, glasshouses and most of the field experiments required, but a separate Field Station will need to be found for the fruit-breeding work. By 1964 the purchase of the site at Colney is completed, together with a small farm of about 165 acres at Stanfield, 20 miles north-west of Norwich, for fruit breeding. Initially it is envisaged that the new Institute will be erected on the University Campus where Professor T. Bennett-Clark has established a School of Biological Sciences. The plan will bring to the Norwich area a hub of scientific and University institutions that is expected to be mutually beneficial and that over time will attract other scientific initiatives. The association is furthered by the Trustees’ agreement in 1965 to provide funds for three John Innes Chairs at UEA in Cell Biology, Genetics and Applied Genetics. These positions are later filled by Roy Markham (1967), David Hopwood (1968), and D. Roy Davies (1968) respectively. UEA, founded in 1963, is one of the rising new Universities and is among the first to abandon the old subdivisions of biology (botany, zoology and microbiology) in favour of an imaginative, integrated approach.
Harris describes the plans to move JII to Norwich as ‘a worm at the heart of present happiness’. He is opposed to the plan and is not prepared to move to Norwich with JII. When Howard Florey resigns the Chair of Pathology at Oxford University leaving a vacancy Harris makes his decision to leave. Between 1963 and 1965 the Department of Cell Biology will lose another 12 members of staff.
Henry Harris, The Balance of Improbabilities: A Scientific Life, Oxford, Oxford University Press, 1987.
John Fincham and Peter Day publish the first edition of Fungal Genetics (Oxford: Blackwell Scientific Publications) a title that will run to a second edition in 1965 and a third in 1971. Fincham invited Day to join him in writing the book in 1961. Day wrote drafts of the chapters on the biology of fungi of genetic interest; the induction, isolation and characterization of mutants; the comparative genetics and physiology of mating type and sexual development; extra nuclear inheritance, and the genetics of pathogenicity. Fincham wrote the chapters on the chromosome theory as illustrated by Neurospora; chromosome mapping; the genetic consequences of changes in chromosome number; the gene as a functional unit; the fine structure of genes and the mechanism of genetic exchange, and the biochemical analysis of gene function. Throughout the months of writing both are greatly in debt to Robin Holliday for his help and constructive criticisms.
Robin Holliday in the Genetics Department at JII proposes a model of DNA-strand exchange that attempts to explain on a molecular basis the major features of crossing-over, gene conversion, and post-meiotic segregation that had been documented in several fungi. He chooses what seems to him to be the very simplest molecular configuration capable of explaining most of the facts. This new model of genetic recombination is based on the breakage and reunion of DNA chains, the formation of hybrid (heteroduplex) DNA, and the correction of mis-matched bases. Holliday is working on DNA damage and genetic recombination in Ustilago maydis (corn smut) and the yeast Saccharomyces cerevisiae. His most important experimental work at JII is the isolation of radiation sensitive, repair deficient mutants of U. maydis, which are the first in any non-bacterial organism.
Holliday’s model incorporates the cross-stranded (or cruciform) DNA structure that later became known as the ‘Holliday Junction’ (a mobile junction between four strands of DNA). These junctions have been found to occur from prokaryotes to mammals and are central intermediates in the process of homologous recombination. Holliday’s junction has been a cornerstone of recombination models since its introduction, although the original 1964 paper was rejected by Nature and Genetics before it found a publisher in Genetical Research, and it was cited infrequently for about 12 years (Holliday 1985, 1990; Stahl 1994; Liu and West 2004). Visualization of cruciform structures by electron microscopy from 1973 and other molecular studies began to persuade geneticists that this recombination intermediate might be real. Forty-five years on the Holliday Junction is still celebrated and investigated, although the model within which it was embedded has evolved from its original statement to fit the present picture of DNA recombination and repair. For a long time the study of DNA repair in U. maydis was carried out only in Holliday’s laboratory; now there are many laboratories using the organism.
R. Holliday, ‘A mechanism for gene conversion in fungi’, Genetic Research, 5 (1964): 282-304. For his 1985 commentary on this paper see:
R. Holliday, ‘The history of the DNA heteroduplex’, Bioessays, 12, 3 (1990): 133-141.
R. Holliday, ‘Early studies on recombination and DNA repair in Ustilago maydis’, DNA Repair 3 (2004): 671-682.
F. W. Stahl, ‘The Holliday Junction on its thirtieth anniversary’, Genetics, 138 (1994): 241-246, see:
Y. Liu and S. C. West, ‘Happy Hollidays: 40th anniversary of the Holliday junction’, Nature Reviews Molecular Cell Biology, 5 (2004): 937-946, see:
Brian Harrison, an Experimental Officer in the Genetics Department at JII, from the late 1950s had been studying the genetics of Antirrhinum majus (snapdragon), with a particular interest in mutable or unstable genes. Rosemary Carpenter has recently become his assistant in this work, soon after joining JII straight from school in August 1962. Harrison’s experiments have not been published but are of great interest to John Fincham who is well aware of the work of Barbara McClintock (1956) in the USA on unstable genes in maize, which many regarded as bizarre at the time. Fincham was one of the few geneticists who fully understood her complex publications. Fincham and Harrison begin to collaborate on an investigation of instability at the pallida locus of Antirrhinum. A normal wild type Antirrhinum flower is fully pigmented and has a magenta colour. Antirrhinum flowers with the unstable mutant allele pallidarecurrens (palrec) lack the overall magenta colour and have randomly distributed red sites (spots, stripes or flakes) representing cells or cell lineages in which reversion to wild type has taken place. Fincham and Harrison take advantage of the existence of illuminated, controlled-temperature rooms at Bayfordbury to show in the first of a series of papers (1964) that the level of instability is extremely sensitive to the temperature at which the plants are growing at the time of bud initiation and that the temperature effect on instability is also manifested in the germline. Between 1964 and 1968 their studies of Antirrhinum will establish important features of genetic instability and they identify a single gene unlinked to pal as responsible for the difference between ‘low’ and ‘high’ unstable lines (1968). Fincham and Harrison discuss their findings in the light of McClintock’s (1956, 1965) studies of maize, finding many similarities to the controlling elements she described (elements that had the capacity to move from one location in the genome to another). The importance of their work on Antirrhinum in the 1960s is only fully realised 20 years later when molecular techniques introduced at JII enable the transposable elements responsible for the observed instabilities to be isolated.
B.J. Harrison and J. Fincham’s series of papers on instability in Antirrhinum majus can be found in Heredity, 19 (1964): 237-258; 22 (1967): 211-224; 23 (1968): 67-72.
R. Holliday and R. B. Flavell, ‘John Robert Stanley Fincham 1926-2005’, Biographical Memoirs of Fellows of the Royal Society, 52 (2006): 83-95, on pp. 89-91.
Information on Barbara McClintock’s work on what we now call transposable elements, for which she received a Nobel Prize in 1982, is available at:
Rosemary Carpenter’s historical summary of research on genetic instability in Antirrhinum majus (part of her claim for the Degree of Doctor of Science, University East Anglia, 1998) is available in the John Innes Centre archives.
Director Kenneth Dodds’ Annual Report for 1964 acknowledges that the planned move has resulted in ‘lively’ discussion among the staff and he reports that ‘it was accepted with good grace’. Behind the scenes, however, there is considerable staff unrest not least because of months of uncertainty about whether the proposed move will take place. In April 1965 Bayfordbury and grounds are advertised for sale and a decision is reached at ARC headquarters to reduce JII to only two departments: Genetics and Cell Biology will transfer to the University of East Anglia to form part of the School of Biological Sciences while the other departments will be discontinued. Anger is expressed about the prospect of the ‘complete disappearance of the John Innes Institute as an independent research establishment with its own special facilities, traditions and research programme’. Critics also complain of an ARC plot to divert funds from research to education. The senior staff mount an active campaign to reverse the decision. From May to July 1965 the removal is discussed in the House of Commons, Sunday Telegraph, Gardeners’ Chronicle, the Grower, The Times, the Observer and the Eastern Daily Press. In June twenty-five senior members of the Institute’s staff circulate a protest to the ARC, John Innes Trustees and Governing Council, MPs and leading scientists about what they see as a ‘proposed closure’ or break-up of the Institute. In response, the Genetical Society pass a resolution at their AGM saying that they are ‘gravely disturbed’ by these reports and urging that this ‘unique centre for genetic research’ be maintained in its integrity. During the summer and autumn Cyril Darlington at Oxford (former Director of JIHI) helps mobilise university professors of genetics and fellows of the Royal Society to protest, and musters support from the President of the Royal Horticultural Society, the Director of Kew, and the Principal of Wye College. Meanwhile Dan Lewis tries to speed up reform measures at the University of London that would have fostered better relationships between it and JII, in the hope that this might remove one of the justifications for the move. The uncertainty about the Institute’s future results in considerable staff turnover, including the loss of Heads of Department John Fincham, Norman Simmonds, and Henry Harris. By September 1965 new proposals for JII at Norwich are agreed; these include the establishment of a Chair and Department of Applied Genetics in addition to the two departments already planned. Colonel James Innes, Chairman of Governing Council, announces that the following principles are being adhered to: first, that JII will ‘remain as an identifiable entity’ and secondly, that fundamental and applied work ‘should be and be seen to be interdependent’.
Shortly before joining JII John Fincham and his student John Pateman at the University of Leicester working with am mutants of Neurospora crassa found to their surprise that some mutants deficient in the enzyme GDH, and therefore presumably in the same gene, when combined in a heterozygote would regain their enzyme activity; in other words they were ‘complementing’ each other. Allelic complementation occurs when the active enzyme consists of a pair of, normally identical, polypeptide chains – ‘a dimer’. Certain pairwise combinations of mutant forms can make good each other’s defect and give a partially active enzyme.
Fincham had obtained indirect evidence that such allelic complementation occurred at the protein level during his year at the Massachusetts Institute of Technology (1960) where he also worked out methods for purifying wild-type and mutant enzymes. Fincham continued to work on complementation at JII with post-doctoral colleague Alan Coddington (a biochemist); their first results were published in 1963. At the time their research on genetic complementation posed a challenge to gene theory because mutations in the same gene were supposed to affect the same polypeptide and never to complement each other. That they could demonstrate complementation raised questions of great importance concerning the definition of the gene and the relation between the polypeptide chains, presumed to be the primary products of genetic translation, and finished proteins. Fincham’s research and interest in complementation encourages him to write this comprehensive review of the genetics and biochemistry of all types of complementation. His summary concludes that allelic complementation is basically irrelevant to primary gene action (‘except in so far as it confuses the investigator’!) but that it is of considerable importance in providing an insight into protein structure and function. The book becomes a ‘citation classic’.
For Fincham’s reflections on the origin and impact of his book see:
Head of Department, Norman W. Simmonds leaves in September to become Director of the Scottish Plant Breeding Station in Edinburgh where the potato work will continue. Dr R. K McKee also leaves to take up a post in the Ministry of Agriculture and the Chair of Plant Pathology at Queen’s University, Belfast, Northern Ireland. The remaining members of JII’s Potato Genetics Department are transferred to Applied Genetics. The Commonwealth Potato Collection, which was being maintained by the Department, is transferred to the Scottish Plant Breeding Station. Between 1954 and 1965 the Potato Genetics Department has contributed to the classification of wild and cultivated potatoes, furthering understanding of variability, incompatibility relationships and cultivar evolution. Expeditions made by Kenneth Dodds and Norman Simmonds to study cultivated potato origins in South America have added to the stock of biological material in the collection. The Department has also undertaken biochemical pigment research and disease resistance studies (common scab, late blight and virus Y) with a view to breeding improved and disease-resistant varieties, together with other investigations of problems associated with potato improvement.
The Unit of Nitrogen Fixation, which became one of the largest of the Agricultural Research Council’s Units, originated in a report commissioned for the multinational petrochemical company Shell in 1961 on state of the art research on nitrogen fixation. Shell decided that commercial prospects for such research were too remote but passed the report (by K. R. Butlin) on to the Agricultural Research Council which was interested in its proposals for a dedicated research group to investigate the basic chemical processes in nitrogen fixation. Biological nitrogen fixation represented a chemical enigma and there was no centre in Britain in a position to pick up on the lead given in this field by the US industrial giant, Dupont. Joseph Chatt, a leading inorganic chemist, was chosen to direct the new Unit, and John Postgate, a chemist turned microbiologist, was appointed Assistant Director to take charge of the biological side of the research. The plan was for the team to comprise equal numbers of chemists and microbiologists. The Unit started work in temporary accommodation in London with the chemists based at Queen Mary College where Chatt had been offered a professorship in chemistry, and the microbiologists at the Royal Veterinary College several miles away. Difficulties with the site at QMC led to the consideration of other options for expanding the Unit. Chatt accepted the offer of a professorship at the new University of Sussex which had plenty of room. A common research space was created at the University of Sussex in 1965, albeit in pre-fabricated huts initially. The Unit moved into purpose-built labs in the Chemistry building in 1968. Chatt and Postgate developed independent but interlocking research programmes and within a few years the Unit was widely admired for its interdisciplinary approach and its research on the fundamentals of nitrogen fixation.
The Unit of Nitrogen Fixation moved to Colney in 1987 as the Nitrogen Fixation Laboratory.
Fincham’s extensive work on Neurospora, which included studies of glyoxylate metabolism (with student R. B. Flavell) as well as allelic complementation, resulted in his lab at the John Innes Institute becoming a leading laboratory for the study of this fungus. According to Flavell, Fincham also ‘helped establish and sustain fungal genetics in Europe to balance the larger interest in the topic in the USA. His book with Peter Day, Fungal genetics, was the most comprehensive and influential in the world’ (Holliday and Flavell 2006, p. 89). However, after these few highly successful years, fungal genetics at JII began to unravel. Peter Day left to take up a position at Ohio State University in 1963; Fincham announced his decision to leave in 1964, when he secured the Professorship of Genetics at Leeds, but he did not take up the post until August 1966 because temporary buildings had to be constructed to house his new department. In September 1965 Robin Holliday left for a post at the Division of Microbiology, National Institute for Medical Research in London, and Alan Coddington went to the University of East Anglia as Lecturer in the new School of Biological Sciences. Fincham, Holliday and Coddington’s decisions to leave were directly related to the anticipated disruption and political upheaval of JII’s planned move to Norwich.
For Fincham’s biography see:
R. Holliday and R. B. Flavell, ‘John Robert Stanley Fincham 1926-2005’, Biographical Memoirs of Fellows of the Royal Society, 52 (2006): 83-95.
Over the course of several years, Marshall Nirenberg, Har Khorana and Severo Ochoa and their colleagues have elucidated the genetic code – showing how triplet mRNA codons specify each of the twenty kinds of amino acids in proteins. In 1968 Khorana and Nirenberg share the Nobel Prize in Physiology or Medicine with Robert Holley for their interpretation of the genetic code and its function in protein synthesis.
In February, Kenneth Dodds takes up a post in Turkey under the Food and Agricultural Organization of the United Nations. As an interim measure, the Governing Council arranges for Dr E. E. Cheesman of the Agricultural Research Council to help administer the Institute. Cheesman continues as Acting Director until the appointment of a new Director in 1967.
The Institute’s move to Norwich is completed in June 1967, a year since building operations began. The temporary buildings at Colney were partially occupied in March, and the move proceeded in stages over the following months. Equipment was moved in between March and June and all the scientific staff have transferred to Norwich by October. The Bayfordbury estate is taken over by Hertfordshire County Council in July, with provision for JII staff to return until the end of the year to remove plants, trees and shrubs of scientific or botanical interest needed at the Institute’s new home in Norwich. The original plan following the move to Norwich is for JII’s permanent laboratories to be built on the University Plain a mile away from the Colney site. It is intended that Colney will be used as temporary accommodation and later for the plant work and to house the Department of Applied Genetics, an arrangement that if carried out will split up the ‘pure’ and ‘applied’ sections of the Institute.
The Agricultural Research Council (ARC) remains unwilling to specify the extent of their financial support to JII after the next five-year period. They wish to see how the association with the University of East Anglia develops but at this stage their commitment to the Genetics Department looks most at risk. In the long-term (and particularly after 1977) the ARC envisages a re-assessment of its contribution to JII with some of its responsibilities transferring to the University Grants Committee. The exception to this general proposal is Applied Genetics which, subject to an agreed programme, will remain the responsibility of the ARC and receive substantial funding.
Dr Roy Markham, FRS takes up his new appointments on 1st October 1967; he brings with him the Agricultural Research Council Virus Research Unit (VRU) which he has directed since 1960. VRU originated as the ‘Potato Virus Research Station’, founded as part of Cambridge University’s School of Agriculture in 1927 with help from the Ministry of Agriculture. The founding director R. N. Salaman had been a friend of William Bateson and Sir Daniel Hall and under him the work of the Institute involved the development of virus-free potato varieties and general plant virus studies, especially those relating to potatoes (including Potato Virus X). In 1939 Kenneth M. Smith succeeded Salaman as director of the Institute which was later taken over by the ARC in 1947 and re-named the ‘Plant Virus Research Unit’ to reflect Smith’s wider interests in plant viruses. Smith’s interest in insect viruses engendered a further name change to ‘Virus Research Unit’. Markham first joined VRU in 1940 (with a first degree in biochemistry) as Smith’s assistant.
Markham’s early training consequently includes practical plant virological methods, for example, diagnostic work and routine monitoring of virus-free stocks of potatoes. He has since become an expert in biochemical and biophysical investigations of plant viruses including turnip yellow mosaic virus, among others. He is also by temperament an inventive engineer. At this stage in his career he is recognised as a distinguished virologist and since 1964 has been a keen and active member of the Governing Council of JII. Recently he has been working intensively on the ultrastructure of viruses (their detailed architecture revealed by electron microscopy) and has begun to explore diffraction techniques. Getting Markham to leave Cambridge and accept the appointment is a major triumph because as yet JII has little to offer by comparison. Newly settled at Norwich, the Institute has no permanent laboratories and in May 1967 the total senior staff, including the Librarian and Secretary, number only 17. Professor Sidney Elsden (first Director of the Food Research Institute at Colney and an old friend of Markham) later documented the decisions waiting on the start of Markham’s Directorship:
‘… on the location of the Institute, on its design and on the appointment of the John Innes Professors of Genetics and Applied Genetics. Markham realised that if the Institute was built on the University Campus the laboratories would be separated from the glasshouses which were at Colney Lane and that this would be extremely inconvenient for the staff. He persuaded the John Innes Council and the Trustees to build the Institute on the Colney Lane site and at the same time he persuaded the Trustees to provide funds for a much larger Institute than was originally planned and which would include substantial facilities for research on ultrastructure’ (Elsden 1982, p. 21).
In addition, Markham proposed (in 1970) a large lecture theatre and recreational facilities for the staff; these included a swimming pool ‘on the grounds that the founder, John Innes, like him, was a keen swimmer’. Integration of the Virus Research Unit (VRU) with JII has to wait until the building of additional accommodation is completed in 1970-1. Once Markham’s plans are pushed through, Markham will preside over the best designed and equipped centre for research on plant and microbial science in the United Kingdom.
S. R. Elsden, ‘Roy Markham, 29 January 1916-16 November 1979’, Biographical Memoirs of Fellows of the Royal Society, 28 (1982): 318-345.
R. E. F. Matthews, ‘Roy Markham: Pioneer in Plant Pathology’, Annual Review of Phytopathology, 27 (1989): 13-22.
J. W. Davies and H. W. Woolhouse, ‘The John Innes Institute’, Biologist, 33, 4 (1986): 189-194.
For archives relating to Kenneth Smith, Roy Markham and VRU see:
The decision to move the ARC Virus Research Unit from Cambridge to Norwich means that the John Innes Institute will possess three high resolution electron microscopes, two from Cambridge and one from Bayfordbury. Markham is keen to exploit this as an opportunity to open an electron microscopy section, capable of running postgraduate courses. He appoints Robert W. Horne, formerly Senior Principal Scientific Officer at the ARC’s Institute of Animal Physiology at Babraham and before that a pioneer electron microscopist in the Cavendish Laboratory in Cambridge to lead the section. Horne’s microscopic images attracted BBC TV coverage in the 1950s and his 3-D models of animal tumour virus and human Adeno virus have recently (February 1965) featured on the front pages of the New York Herald Tribune. Over a period of 18 months Horne helps to plan and design the new electron microscopy and photographic building (with special structural and technical requirements) to accommodate up to five electron microscopes and the vast amount of enlarging that will be needed for the electron microscopy work. The new building will have a large classroom for teaching embedding, sectioning and staining techniques as well as the interpretation of electron micrographs. Few EM laboratories in the UK and Europe are designed and constructed specifically for electron microscopy, which presents the Institute with a unique opportunity to build something special, and also attract interest.
Transcript of an interview with Professor Michael Whelan by Bernadette Bensaude-Vincent, Oxford Materials Department, December 12, 2002. Describes Horne’s work at the Cavendish Laboratory in Cambridge.
A. C. Steven and W. Baumeister, ‘The state of the art’, Journal of Structural Biology, 163, 3 (2008): 201-207 provides a biographical summary.
Robert W. Horne, ‘Biographical Notes’ (c. 2000). Typescript available in JIC archives.
David Hopwood, formerly a lecturer in Genetics at the University of Glasgow (1961-68), takes up his new appointment as Head of Genetics in July 1968 and moves to Norwich on 1 September. He is an expert in Streptomyces coelicolor, which belongs to a genus of bacteria that, unusually for bacteria, grows mycelial colonies with sporulating aerial hyphae. Streptomycetes are also of interest because they are important natural antiobiotic-producers. When Hopwood first took up the study of S. coelicolor as a Ph.D. student in the Botany School at Cambridge nobody else in the world was known to be working on Streptomyces genetics. Indeed, bacterial genetics was still in its infancy and ‘appeared bizarre compared with the genetics of plants and animals’ (Hopwood 2007, p.51). Pioneering work by Hopwood in the 1950s and 1960s has established S. coelicolor A3 (2) as the model system for the genus. His work has involved developing the basic genetics of S. coelicolor A3 (2) and devising a novel method of linkage analysis (1959), a procedure that later proved useful for genetic studies of other microbes. Hopwood had had a productive collaboration with Giuseppe Sermonti and his wife Isabella Spada-Sermonti in Rome and had spent sabbatical periods there in 1960 and 1961. They continued to collaborate after Hopwood’s move to Glasgow, but Sermonti gradually lost interest in practical science and moved to philosophical studies, eventually becoming Italy’s strongest advocate of creationism.
In 1967 Hopwood, still working with a very small group, has just established a detailed circular linkage map of more than 100 S. coelicolor genes. A recent sabbatical at New York University with Werner Maas, who since 1956 has been investigating the regulation of arginine biosynthesis in Escherichia coli, has provided him with a comfortable grounding in biochemistry and skills that will be of use in the more molecular aspects of genetics in the next decade. Though still only 34, Markham recognises in him the ability to establish a more substantial group and to shape the future of genetics at JII. Hopwood will go on to develop an exceptionally successful blend of plant and bacterial genetics over the next three decades though not without a struggle. Hopwood has to contend with the difficulty that the Governing Council of JII has little understanding of microorganisms and with Agricultural Research Council fears that they will be paying only for a topic - Streptomyces – that they believe will have no relevance to agriculture. There are also challenges associated with continuing uncertainty about the long-term future of genetics at JII; the ARC has not made an ongoing commitment to fund it after the move to Norwich and it still faces the possibility of being detached to join biological sciences at UEA.
When Hopwood joins JII he brings four members of his Glasgow group including Alan Vivian (postdoctoral fellow) and Helen Ferguson (later Wright and now Kieser) his young laboratory assistant. Helen had left school at 16 and joined the Department of Bacteriology at Glasgow, gaining a thorough grounding as a technician in the teaching laboratories. Hopwood had been fortunate enough to have her assigned to his laboratory when he applied to Glasgow University for a technician to assist him in his research in 1965 and valued her work so much that he persuaded her to move to Norwich with him. She will work alongside Hopwood for the next 30 years and much of the later development of Streptomyces genetics as an international field of study will be due to her skill and personality.
Keith Chater, ‘David Hopwood and the emergence of Streptomyces genetics’, International Microbiology, 2 (1999): 61-68.
D. A. Hopwood, ‘Linkage and the mechanism of recombination in Streptomyces coelicolor’, Annals New York Academy of Sciences, 81 (1959): 887-898.
D. A. Hopwood, ‘A circular linkage map in the actinomycete Streptomyces coelicolor’, Journal Molecular Biology, 12 (1965): 514-516.
D. A. Hopwood, ‘Genetic analysis and genome structure in Streptomyces coelicolor’, Bacteriological Review, 31 (1967): 373-403.
D. A. Hopwood, Streptomyces in Nature and Medicine, Oxford: Oxford University Press, 2007.
D. Roy Davies comes from the UK’s Atomic Energy Research Establishment at Harwell where his group were initially concerned to establish the feasibility of exploiting induced mutations for crop improvement. As many claims proved to be over-optimistic, the group’s work changed to studies of the induction and repair of radiation damage in a range of biological systems, notably Chlamydomonas, a genus of green algae. His primary concern on taking over Applied Genetics is to put together a research programme that will satisfy the Agricultural Research Council in the long term. In particular he must define those plant breeding problems that exist in the horticultural industry and which are not being catered for elsewhere by State-supported research organisations. This will mean scaling down some of the existing fruit-breeding work. Future programmes in Applied Genetics will centre on the exploitation of leafless and semi-leafless peas since there is no State-supported work on this crop; physiological and pathological studies will be supplemented by biochemical investigations as opportunities arise. In the interim Davies also hopes to fill other gaps in research in the horticultural industry by including the production of certain commercially important flower crops (including Carnation, Chrysanthemum, Poinsettias, Freesias, Anemones and F1 Antirrhinums).
Studies of genetic recombination in the bacterium Streptomyces coelicolor by David Hopwood, Richard Harold, Alan Vivian and Helen Ferguson strongly suggest that some kind of mating is involved. At this time the only precedent for bacterial conjugation is the system discovered by Joshua Lederberg and Edward Tatum in Escherichia coli (1946). It was Lederberg who between 1946 and 1952 launched bacterial genetics by showing that certain strains of bacteria reproduce by mating, combining their genetic material. His experiments overturned conventional opinion that bacteria were primitive organisms not suitable for genetic analysis. Since then Bill Hayes at the London Postgraduate Medical School, whose work and personality especially inspired Hopwood as a young PhD student, Luca Cavalli-Sforza in the Lederbergs’ laboratory at Stanford University, USA and other researchers around the world had made significant advances in the study of fertility in bacteria.
The most pressing problem for Hopwood’s group on arriving at Norwich is to try and make sense of the mating system of Streptomyces. Hopwood’s team have recently (1969) identified a class of fertility variants in S. coelicolor A3 (2) called ‘ultra-fertile’ (UF). These variants differ strikingly in their sexual capabilities from the strains that they have previously worked with. Fertility variants in the better-known bacterium E. coli have led to the elucidation of its sexual process. Using these insights, Hopwood’s team devise methods for attacking this problem in Streptomyces. By 1969 they are able to present the first firm evidence for a fertility system controlling mating in Streptomyces.
D. A. Hopwood, R. J. Harold, A. Vivian and H. M. Ferguson, ‘Non-selective genetic analysis in Streptomyces coelicolor’, Heredity, 23 (1968): 628.
D. A. Hopwood, R. J. Harold, A. Vivian and H. M. Ferguson, ‘A new kind of fertility variant in Streptomyces coelicolor’, Genetics, 62 (1969): 461-477.
D. A. Hopwood, Streptomyces in Nature and Medicine, Oxford: Oxford University Press, 2007.
On Joshua Lederberg’s experiments see:
On the history of bacterial genetics:
T. D. Brock, The emergence of bacterial genetics, New York: Cold Spring Harbor Press, 1990.
R. H. Davis, The microbial models of molecular biology: from genes to genomes, New York: Oxford University Press, 2003.
For a summary of early work on bacterial conjugation: