Read the full report by Brookdale Consulting (2013)
Transcription
Read the full report by Brookdale Consulting (2013)
Impact of the John Innes Centre Brookdale Consulting 7 Brookdale Road Bramhall Cheshire, SK7 2NW Donald@brookdaleconsulting.co.uk 0161 440 8290 07813 892090 th Issued 28 June 2013 Contents Executive Summary 1. Introduction 2. Background to JIC 2.1 Overview of JIC 2.2 Evolution of JIC’s Research 2.3 Market Failure 3. Impact of JIC Research 3.1 Wheat 3.1.1 Improving Wheat Yields 3.1.2 Reducing Wheat Diseases 3.2 Oilseed Rape 3.2.1 Reducing Pod Shatter 3.3 Nutritionally Enriched Broccoli 3.4 Industrial Biotechnology and Synthetic Biology 3.4.1 Antibiotics 3.4.2 High Value Chemicals from Plants 3.4.3 Vinca alkaloids 3.4.4 Molecular Pharming 3.5 Nitrogen Fixation instead of Fertilisers 4. Operating Impact of JIC 4.1 Direct Impact 4.2 Indirect Impact 4.3 Induced Impact 4.4 Summary of Operating Impacts 5. Wider JIC Impact 5.1 Knowledge Exchange and Commercialisation 5.1.1 High Impact Journal Articles 5.1.2 Collaborative Research, Consultancy and Company Engagement 5.1.3 Intellectual Property 5.1.4 Spin-Out Companies 5.2 Learning, Teaching and Training 5.2.1 Inspiring the Next Generation 5.2.2 Scientists of the Future 5.2.3 Career Development and Continuing Professional Development 5.3 Influence, Networks and Public Engagement 5.3.1 Local 5.3.2 National 5.3.3 International 5.3.4 Public Engagement 6. Summary and Overview 6.1.1 On-going impacts 6.1.2 Gross Research impacts 6.1.3 Net impacts UK 6.1.4 Net impacts globally and long term UK 2 4 5 5 5 7 8 8 8 10 12 12 13 14 14 16 17 18 21 23 23 24 25 25 26 26 26 26 27 28 29 29 29 30 30 30 31 32 34 35 35 36 37 38 Page 1 Executive Summary Brookdale Consulting was commissioned by the John Innes Centre (JIC) to produce an 1 updated socio-economic impact assessment of the Institute . JIC’s research has a global focus, contributing to all of BBSRC’s grand challenges and 2 addressing market failures in UK and global agriculture, food and biotechnology research. On-going Impacts JIC’s operating impact (from staff and supplier spending) supports 636 jobs and £30.4m of Gross Value Added (GVA) across the UK economy per year. JIC’s work has been key in supporting plant breeders in delivering £373m-£445m of gross wheat yield benefits per year at the UK level compared to 1982 yields. This includes the benefits of yield improvements and reduced cereal diseases. At the global level, gross productivity increases supported by JIC’s research could currently be worth £8.7bn. JIC’s work in antibiotics has supported additional global sales revenue potential of £247m per year for actinomycete-derived antibiotics, forecast to grow to £306m by 2017. Future Impacts In addition to the gross impacts above, net additional impacts of £223m GVA and 408 jobs are forecast over the next 10 years at the UK level. The value for money of the JIC research areas considered is £11.99 of GVA at the UK level. Given JIC’s global leadership in many science areas and the long-term nature of its research, over a thirty-year period, there could be a further £15.7bn of GVA and 12,433 jobs globally through JIC research if the areas reviewed are successful. A summary of the main gross impacts arising is set out below. Crop Improvement Improving wheat yields – In addition to the on-going impacts above, for every 1% increase in yield achieved, the JIC share of impact will be £3.67m at the UK level and £38.7m at the EU level per year. Reducing cereal diseases – JIC’s long-term work in cereal diseases supports the UK and global industry as set out above. By enabling breeders to produce varieties with half the current level of septoria disease losses (3%) it is estimated that the future impact attributable to JIC could be £3.3m at the UK level and £70m at the EU level per year while work in take-all could ultimately lead to reduced costs for UK wheat farmers of £60-340m per year. Oilseed rape – JICs work to reduce pod shatter in OSR could increase yields by 15%, worth £165m at the UK farm gate or £1.7bn if implemented across the EU. 1 2 This work was to update a previous impact report Economic Impact of JIC 2008 See Appendix 1. Page 2 Enriched Broccoli – Beneforte is now on sale in UK and US supermarkets. It has the potential to reduce cardiovascular disease and prostate cancer and work to support a health claim is on-going. Potential benefits of £38m per 1% reduction in disease can be anticipated at the UK level. 50% of these are attributed to JIC. Nitrogen fixing cereals – If JIC’s work on N-fixing in maize is successful, it could improve food security for 0.436 billion people in sub-Saharan Africa and provide an alternative to synthetic fertilisers. Industrial Biotechnology and Synthetic Biology Tunicamycin – JIC is working to reduce toxicity of Tunicamycin so it can be taken up by the pharmaceutical industry as a new class of antibiotics. Antibiotic resistance is a major policy priority in the UK and EU. Every 10% reduction in the costs of antibiotic resistance at the EU level will conservatively deliver £125m. Super Hosts - JIC has just developed a series of Streptomyces strains that can be used as ‘Super Hosts’ to reduce drug development costs where every 1% saving is worth £5-£10m. High Value Chemicals from Plants - Improving yields of vinca alkaloids will have a significant impact on the industry, reducing costs and increasing availability. A 10% increase in yield through JIC’s research could save the pharmaceutical sector £9.4-£18.8m annually. 3 Molecular Pharming – JIC’s plant molecular production system CPMV-HT produces a wide variety of novel substances. It could revolutionise vaccine screening production, yield novel metabolites and is licensed to industry. If the technology results in more effective and rapid vaccines reducing incidence of flu by just 1%, then it would save the UK economy £13.5m per year. A 1% reduction in costs of HIV treatment and care through the technology would save the UK £10m per year. Wider impacts of JIC include: • • • • • • • • independent ranking with the Sainsbury Laboratory as number one in the world for 4 academic citations in 2009 engagement in £5m of current industrial collaborations spin-out companies with increased investment, turnover and employment training scientists from school age children and students through to JIC staff JIC is active in the public debate around science, food security and GM, informing government and society about the direction of scientific research. important contributions to the Global Food Security programme and around 330 active JIC global collaborations. The JIC-China Centre of Excellence represents a substantial research collaboration that will have global impact. For example, more than 100 JIC alumni have academic positions in China. Norwich Research Park impacts of 1,300 net additional jobs and £566m GVA over 10 years estimated by Brookdale Consulting as attributable to JIC. 3 Cow Pea Mosaic Virus – HyperTrans Plant and animal science see: http://www.timeshighereducation.co.uk/story.asp?storyCode= 411170§ioncode=26 4 Page 3 1. Introduction Brookdale Consulting was commissioned by the John Innes Centre (JIC) to produce an updated impact assessment of the Institute. This report highlights the range of quantitative and qualitative impacts generated by the ongoing research and activities of JIC. The report reviews and updates the previous impact report of 2008 as well as highlighting the wide range of new areas that JIC is actively researching. JIC receives three quarters of its revenue from BBSRC and contributes across all three of BBSRC’s grand challenges: Food security - maintaining a safe, affordable and nutritious food supply for UK citizens and achieving global food security to feed nine billion people by 2050. Work to improve wheat yields, N fixation, flowering time in brassicas, crop biotech and improved nutrient content of legumes are examples of JIC contributions here. Sustainable bioenergy, chemicals and renewable materials from bioscience through industrial biotechnology, developing options to lessen UK reliance on fossil carbon; making the low-carbon/green economy a reality. The potential of crop biotech, synthetic biology to produce high value compounds and high oleic acid oilseed rape are examples as is temperature sensing. Enhancing lives and improving wellbeing - through fundamental bioscience, particularly as the proportion of UK society living beyond 65 continues to increase dramatically. Molecular pharming, enriched broccoli, antibiotics and other high value compounds are all examples here. • • • The structure of the rest of the document is as follows: • Section 2 - sets out the background to JIC and describes the evolution of the Institute since the previous impact report • Section 3 - presents the impact of JIC research • Section 4 - sets out the operating impact of JIC • Section 5 - presents the wider impact of JIC • Section 6 - summarises the findings of the report • Annexes contain supporting material and data. Brookdale Consulting acknowledges the significant contribution of JIC staff in working with the team to produce this final report. Page 4 2. Background to JIC 2.1 Overview of JIC JIC’s mission is to generate knowledge of plants and microbes through innovative research and to apply the knowledge to benefit agriculture, the environment, human health and wellbeing. In doing so, it trains scientists for the future and engages with policy makers and the public for the furtherance of science. JIC’s research has a long-term horizon over many decades and is the focus of fundamental plant and microbial research in the UK. An emerging area is its research into the potential for plants and microbes to produce new useful compounds, an area known as industrial biotechnology. JIC has four integrally linked Institute Strategic Programmes (ISPs) as follows: 2.2 • Sustainable solutions to crop disease and nutrition (BIO) – exploring resistance to pests and pathogens as well as the beneficial symbioses that micro-organisms can have on plant nutrient uptake and providing genetic alternatives to agro-chemicals. BIO aims to maximise yield by reducing crop losses. This ISP sees JIC scientists working closely with those at the neighbouring Sainsbury Laboratory. • Growth and Development Underpinning Yield (GRO) – most crops do not achieve maximum yield due to environmental limitations and disease. GRO aims to maximise yield by increased productivity to secure future food supplies. • Wheat Improvement Strategic Programme (WISP) – addresses UK and global food security by providing pre-breeding support for development of new high yielding, low input wheat varieties. This ISP involves a collaboration with scientists at the University of Bristol, NIAB, Rothamsted Research and the University of Nottingham. • Plants and Microbes: factories for food, bio-industry and health (MET) – exploiting renewable biological resources to provide new antibiotics, sustainable ways of controlling crop pests and diseases and ‘new to nature’ compounds. Evolution of JIC’s Research 5 The previous report highlighted the following aspects of JIC’s research: Crops • Research into wheat semi-dwarfing genes bringing global annual benefits of £3.4bn. • Mitigating cereal diseases to avoid losses in world wheat production of as much as £4.3bn per annum. • Synteny - JIC’s gene mapping helping to address world hunger, and supporting international research at IRRI (in the Philippines) and CIMMYT (in Mexico). • World’s first nutritionally enhanced fresh vegetable, Beneforte Broccoli, with possible benefits to cardiovascular health and reduced incidence of cancer. 5 Economic Impact of John Innes Centre 2008 Page 5 Antibiotics • JIC discovered the genetic basis polyketide of antibiotics, naturally produced by Streptomyces, a global market now worth $35bn per annum. JIC spin-outs • Novacta Biosystems - working on solutions to C. difficile and MRSA, which could add £194m to the UK economy through prevention of avoidable deaths. • Procarta Biosystems - developing a completely new approach to overcome antibiotic resistance that could have broad application. Cross Cutting Impacts • Intelligent breeding research, potentially reducing the time for breeding new plant varieties. • Income from commercial sources generating an additional £5.2m GVA in the economy per annum. • £171k per year of royalty income. This updated report assesses the on-going benefits of the discoveries highlighted above as well as research that could yield new impacts as follows: Crops • Significant further improvement in wheat yields and reduced diseases of wheat and barley. Developments in oilseed rape to reduce pod shatter thus increasing yield. • Beneforte ‘Super broccoli’ is now in supermarkets in the UK and USA and having its health claims assessed in relation to cancer and cardiovascular disease. • A whole host of new technologies are in trials under licence to improve yield of crops such as maize, soya, wheat and rice. • Plant microbe interactions is an important area of research that may yield useful discoveries to improve crop productivity Antibiotics • Further developments in Streptomyces could yield a whole new class of antibiotics, reducing resistance which is a major problem for policy makers • Development of a ‘Super Host’ could radically reduce drug development costs. JIC spin-outs • The number of spin-outs has increased. Cross Cutting Impacts • JIC contributes to national debate on science • Global influence has grown including setting up the JIC-China Centre of Excellence • Norwich Research Park is developing strongly • Royalty income has increased. New areas of research • Industrial Biotechnology and Synthetic Biology – new areas with potential of creating high value compounds from plants or microbes that can be used as drugs, vaccines, agrochemicals or ingredients for industry Page 6 • 2.3 Researching the potential for nitrogen fixation in cereals to reduce fertiliser requirements in developing countries and ultimately to potentially displace synthetic fertilisers in the long term. Market Failure JIC’s research addresses economic, policy and societal issues that are in the public interest and key to the future of the UK’s society and economy. They are not ‘goods’ that the market (i.e. private businesses) could be expected to deliver on its own without public investment. JIC also wins public funding competitively when it bids for grant funding against other potential providers (e.g. to the European Union Framework Programme and other research funding bodies). Market failure may still have occurred but competition ensures value for money for the public purse. In addition, part of JIC’s income comes from private sources, such as when individual businesses or trade bodies commission work specifically for them or their members. In this case, market failure may not apply but JIC’s expertise and reputation are important in undertaking the work and in ensuring adoption. Details of specific market failures addressed are set out in Appendix 1. Page 7 3. Impact of JIC Research This section sets out the calculation of final impacts for JIC under the following headings: • Wheat • Oilseed Rape • Nutritionally Enriched Broccoli • Industrial Biotechnology and Synthetic Biology • Nitrogen fixation instead of fertilisers The methodology is set out in Appendix 2. 3.1 Wheat The previous impact report on JIC’s science highlighted the need for on-going productivity improvements in wheat production. JIC is active in a number of areas that have the potential to improve significantly wheat production. 6 UK farm gate turnover of wheat was £2.2bn in 2011 , with 1,969,000 hectares grown, making wheat by far the largest UK cereal crop by value and area. Uses include milling to produce flour for baking, animal feed and distilling. JIC’s work has global impact. According to the Consultative Group on Independent Agricultural Research (CGIAR) there are around 1.2bn “wheat dependent” to 2.5bn “wheat 7 consuming” poor (living on less than £1.30 per day) . Investment in wheat productivity can benefit these people. The UK Foresight report suggests a 50% increase in wheat yields will be required by 2030 8 while the current level of investment from royalties is expected to deliver only 13% . 9 While developing world demand for wheat is expected to increase by 60% to 2050 , climatechange could reduce wheat production in developing countries by 20–30% due to temperature increases. There is a clear rationale for further investment in wheat productivity. 3.1.1 Improving Wheat Yields JIC has had a global role in contributing to the understanding of the genetics of wheat over many years. Discoveries include factors controlling bread making quality, Ppd1 (control of flowering time), Rht1 (control of dwarfing), Ph1 (major locus controlling recombination) and synteny. These discoveries have supported plant breeders in using and scoring these traits in commercial wheats. Whilst JIC also described Vrn1 (vernalisation), it was scientists in the US that finally identified it using synteny. The previous impact report highlighted a global impact of £3.4bn per year from the introduction of wheat dwarfing genes. These genes remain important to commercial wheat crops around the world so can be considered an on-going impact of the work of JIC, other 6 All Defra references in this section are from the publication ‘Agriculture in the United Kingdom 2011’ http://wheat.org/index.php/why-wheat/what-the-world-eats 8 Foresight project Global Food and Farming Futures final report and BSPB 9 The Future of Food and Farming: Challenges and choices for global sustainability 7 Page 8 institutes and industry. In 2012, using the same assumptions as the previous report, the gross value of these benefits globally is estimated to have risen to £8.7bn given increases in global wheat production. This includes the benefits from reduced disease set out in the next section. 10 At the UK level, a report on the impact of plant breeding on the UK highlighted £373m£445m of gross yield benefits per year due to yield increases over the period 1982 to 2008, JIC being key in supporting plant breeders in delivering these benefits. JIC is actively working to deliver further yield improvements. For example, JIC is leading the 11 £15m 6 year Wheat Improvement Strategic Programme (WISP) with five partners . The programme aims to develop new germplasm that will be useful for plant breeders to develop new high performing wheat varieties. Three complementary methods will introduce more genetic variation and therefore potentially find ways of increasing yield in new varieties. Key targets for improvement are yield traits, nutrient efficiency and resistance to Take All, aphids and bulb fly. The project will have international relevance in providing germplasm to support new wheat varieties globally. JIC’s Germplasm Resources Unit (GRU) curates germplasm collections of a wide range of cereal and legume crops and their wild relatives. It is a National Capability for the research community, which is unique for the UK and is formally registered under the International Treaty of Plant Genetic Resources for Food and Agriculture operated through FAO. Small grain cereals are the most widely grown crops in the world. Access to extensive genetic variation in the GRU is useful for identifying traits to cope with climate change, disease resistance and improved productivity for crops. It is vital to JIC on-going research. In addition to WISP, other JIC research has identified Quantitative Trait Loci (QTLs) that stabilise yield under different environmental conditions. Research was undertaken up to the 1980s on single gene traits and has recently re-started as there is significant new potential to be gained, based on other research such as mapping the wheat genome. JIC is providing the tools to select useful QTLs in breeding programmes. If more QTLs can be identified, it will be possible to make much more accurate crosses that combine the highest yielding QTLs of different varieties together. At the moment, breeders do not generally have this information when they select their crosses. Ten or so QTLs have been identified as contributing to yield to date but the process takes a long time given the complexity of the traits and because it is only possible to do one field trial per year. 10 11 Economic Impact of Plant Breeding in the UK, 2010. JIC, University of Bristol, NIAB, Rothamsted Research and the University of Nottingham Page 9 JIC estimates that each yield component identified is worth a potential extra 1-2% yield minimum. For every 1% increase in wheat yield at the UK level, the additional revenue to the farming industry will be £22m (assuming all other factors such as inputs and price remain constant). As the plant breeding industry is constantly introducing new lines, the research will not increase costs to the industry. Impacts from WISP can be equally attributed to the five partners and the plant breeding industry that will implement the findings of the research. Assuming the same attribution for QTLs, JIC’s research could realistically deliver several percentage point increases in yield. On this basis, for every 1% increase in yield achieved by WISP and QTLs, the JIC share of impact will be £3.67m at the UK level. Given the significance of this work and the international nature of plant breeding, it is likely that yield improvements resulting will also influence EU-27 wheat production, and possibly wider global production (except in areas where other factors such as water may restrict production). Therefore, at the EU level where wheat production was 139m tonnes in 12 2011 , a 1% increase would generate 1.39m tonnes of additional wheat at £167 per 13 tonne generating £232m, the JIC share of impact being £38.7m at the EU level. 3.1.2 Reducing Wheat Diseases JIC’s efforts are focused on identifying durable resistance and highlighting potential trade-offs between resistance to initial target pathogens and other traits such as yield or resistance to other pathogens. The previous impact report highlighted the potential value of reducing global cereal diseases as being worth £4.8bn annually and JIC’s key role in supporting industry to deliver disease reductions. One disease where JIC has had significant involvement is Septoria in wheat. Over the past 20 years, JIC has worked in collaboration with industry to understand the genetic inheritance of Septoria resistance in wheat. JIC discovered that plant breeders had inadvertently introduced increased susceptibility to Septoria in the 1980s and that they were relying on a limited number of resistance genes. Septoria alone can lead to yield reductions of 20% depending on variety. According to 14 NIAB , the difference in yield between the historic worst performing and current best performing varieties for Septoria is around 18%, though not all farmers choose to grow the most resistant varieties. JIC’s historic work, together with industry, has contributed to reductions in Septoria with each 1% being worth £122m per year at the UK level and £1.4bn per year at the global level. These benefits are included in the overall wheat yield improvement impact in the previous section. New disease challenges keep emerging so this is an area that requires on-going investment. 12 Eurostat Based on Eurostat figures for 2011 at €200 per tonne changed to £ at €1.20/£1. 14 Personal Communication, Dr Rosemary Bayles, Principal Cereal Pathologist, NIAB 13 Page 10 JIC continues to provide valuable tools for plant breeders. For example, DNA markers linked to all three of the known eyespot resistance genes are currently deployed in European wheat varieties. JIC continues to identify and characterise resistances to some of the most important cereal diseases in close collaboration with UK and mainland European plant breeders. Breeders are using JIC markers to assist in their decision-making processes at precommercialisation stage. JIC’s research is continuing to add to the knowledge base on Septoria resistance. 15 JIC is part of the WAGTAIL consortium led by NIAB. This £962k project aims to increase or maintain wheat yields through disease resistance as EU legislation may lead to fewer fungicides being available in future. JIC’s funding is 10% of the project total. The project involves all major wheat plant breeders in North West Europe, will phenotype a panel of 500 elite UK winter wheat lines for Septoria, yellow rust, brown rust and mildew, and run association studies with 90,000 markers. The scale of the project is only possible given advances in DNA marker screening technology that would not have been possible even 5 years ago. The WAGTAIL consortium estimates that 6% of wheat production is currently lost to the four target diseases despite fungicide control. 50% of the UK's pesticide usage is applied to wheat, accounting for 20% of farmers’ operating costs. Changes to EU legislation removing 16 certain fungicides from the market could result in yield losses of 20-30% if no action is taken resulting in additional losses to the UK wheat crop of £154m-£264m based on 2011 production. Benefits of WAGTAIL will be: • clear understanding of the trade-offs between disease resistance and yield • improved all-round disease resistant varieties without yield penalty • fast application of the results in UK and EU breeding programmes • reduced carbon emissions and pollution through reduced need for fungicides. By enabling breeders to produce varieties with half the current level of disease losses (3%) it is estimated that the impact could be £33m at current levels of fungicide usage in the UK, the JIC share being £3.3m based on its 10% funding share. At the EU level, the impact could be £696m, the JIC share being £70m. Alongside traditional breeding, transgenic approaches could provide a strategy to introduce novel resistance and make a step-change in wheat productivity. An example of this is the control of take-all, a fungal, soil-borne disease that affects the growth of cereals. The fungus is found in most wheat growing areas. Severity of the disease is affected by weather, soil type and management. Resistance to take-all will produce a major increase in yield. HGCA estimates that half of UK wheat crops are affected with average yield losses of 15 Wheat Association Genetics for Trait Advancement and Improvement of Lineages (WAGTAIL) is a BBSRC funded project of £481k, £383k to NIAB, £98k to JIC and £481k industry match funding (2012June 2015). Total project costs are £962k. 16 http://www.bbsrc.ac.uk/pa/grants/AwardDetails.aspx?FundingReference=BB/J002542/1 Page 11 17 5-20% . The cost to farmers is estimated by HGCA to be up to £60m a year for wheat alone 18 while industry estimates suggest higher figures of £80-340m . JIC is pioneering transgenic approaches to introduce resistance to take-all in wheat. The project could result in the following benefits: • Trialling of GM approaches – the work will test a new GM approach and its potential to deliver disease resistance. The platform developed will also have relevance for other traits such as nitrogen fixation and will inform the policy debate on GM approaches. • Improved nitrogen efficiency – since take-all reduces nitrogen uptake by the plant roots, a reduction in disease will also reduce the amount of fertiliser required to achieve the same yield. • Reduced costs – if introduced in the UK in the longer-term take-all resistance could save £60-340m per year. 3.2 Oilseed Rape Since 2006 farm gate turnover of oilseed rape (OSR) has increased by 250% to £1.1bn in 2011, with 705,000 hectares grown making it the third largest UK arable crop by area but 19 second largest by value . A total of 2.8m tonnes of oilseed rape was produced in the UK in 20 2011 , representing 10% of the total volume harvested across EU-27, which was 29m 21 tonnes, harvested from 11.4m hectares . Uses include crushing to produce rapeseed oil, animal feed and increasingly biofuels. 3.2.1 Reducing Pod Shatter Premature pod shatter is a major problem in oilseed rape (OSR), resulting in average yield 22 losses of between 15-20% . The problem is a global issue made worse by weather variability. Producers try to overcome pod shatter by either spraying the OSR with glue, or cutting the crop early and letting it dry in the fields. JIC understands the genes responsible for causing fruit to open and has translated this to OSR to stop premature pod shatter. JIC has patented part of the technology. With grant funding from BBRSC, and collaborations with plant breeders, JIC is now transferring the technology into OSR to create pre-breeding material. It is likely to be 4-6 years for any new varieties of OSR to reach market. Benefits will include: • • increasing the OSR yield by an average of 15-20% improving production efficiency by reducing the need to spray or swathe the crop; and eliminating the need to spray fields of subsequent crops to eliminate rogue OSR caused by pod shatter JIC is utilising a non-GM approach suitable for UK and EU markets. Assuming JIC’s technology is bred into commercial crops in the UK and EU, an increase in OSR yield of 17 HGCA - Take-all in winter wheat - management guidelines. Based on combined views of plant breeders KWS, Limagrain, Elsoms, Syngenta and RAGT. 19 Defra 20 Source: FEDIOL 2013 21 FAS EU 27; http://www.thebioenergysite.com/reports/?category=39&id=355 22 Price JS, Neale MA, Hobson RN, and Bruce DM (1996) J Agric Engng Res 80, 343-350 18 Page 12 15% would equate to an increase in UK farmgate value of £165m based on 2011 prices or £1.7bn if implemented across the EU-27. There will also be environmental benefits from reduced need for spraying. 3.3 Nutritionally Enriched Broccoli In 1990, JIC began to research disease and pest resistance of Brassica. The research included investigation of the role of glucosinolates, and the discovery that they were potent inducers of detoxification enzymes with potential consumer health benefits. It was found that by crossing cultivated broccoli with a wild plant B.villosa there was potential to increase the level of glucosinolates in broccoli. A diet rich in glucoraphanin may reduce levels of cardio-vascular disease and cancers such as prostate cancer. PBL filed patents for JIC for the high glucosinolate broccoli and in 1999, it was licensed by PBL to Seminis as the world’s leading supplier of broccoli seed (now Monsanto). In October 2011, enriched Broccoli was launched in the UK in Marks and Spencer stores under the brand name Beneforte achieving wide media coverage. In July 2012, it became more widely available in certain other UK supermarkets. Prior to its UK launch, it was launched in the USA in 2010 and is now being sold in all US states. Following its original inception at JIC, the work transferred to IFR to develop an understanding of the human health benefits necessary to support consumer communications. A human intervention study at IFR aims to validate heart health benefits of Beneforte. Another study is looking at benefits for prostate cancer. Including Beneforte in a healthy diet, also involving reduction in salt and saturated fats could result in a reduction in cardiovascular disease (CVD) and prostate risk, resulting in benefits for the individual, cost savings for the NHS and benefits to the UK economy. CVD causes 50,000 premature deaths per year in the UK and affects more than five million people with annual costs exceeding £30bn. 80% of premature CVD (i.e. occurring before age 75) is avoidable. Reducing cardiovascular events by just 1% would result in savings to the health service worth at least £30m a year compared with no additional 23 intervention. Prostate cancer is the most common non-skin cancer for males in western countries. About 24 41,000 men are diagnosed each year in the UK . One study found that prostate cancer costs the UK economy £800m per year, comprising health care costs of £400m, economic costs of 25 £200m plus the cost of informal care of another £200m . A 1% reduction in prostate cancer in the UK, would deliver £8m of savings (NHS savings £4m, lost workdays £2m and informal care £2m). 23 Barton P et al (2011) Effectiveness and cost effectiveness of cardiovascular disease prevention in whole populations: modelling study British Medical Journal 343, 4044 24 Data Table: Incidence cases and rates for males, females and persons in the UK, England, Wales, Scotland and Northern Ireland, Cancer Research UK, December 2012. 25 The economic burden of cancer across the European Union, Jose Leal, University of Oxford, NCRI conference paper, Nov 2012 Page 13 Potential benefits of £38m per 1% reduction in disease can be anticipated at the UK level. 50% of these are attributed to JIC. Monsanto sees products such as Beneforte as key to its growth plans. Along with other major agricultural and biotechnology businesses, Monsanto is now seeking to deliver consumer benefits directly through food rather than simply focusing on increasing yields of commodity crops for growers. 3.4 Industrial Biotechnology and Synthetic Biology 3.4.1 Antibiotics JIC’s historic work in antibiotics and Streptomyces in particular has been extensively reviewed 26 in a previous assessment in 2010 , which highlighted substantial on-going impacts including: • additional global sales revenue potential of £247m per year for actinomycete-derived 27 antibiotics, now forecast to be £306m by 2017 through market growth • £46m global sales potential for cephalosporins (a class of beta-lactam antibiotics) • supporting development of new anti-cancer and immunosuppressant drugs likely to exceed £120m per annum in the long term • Increasing antibiotic productivity of £44.7m per year and 28 • Potential animal health drug discoveries, leading to additional annual sales of £60m . The focus in this report is on new developments that have emerged since the last report. JIC’s work is focused on understanding biosynthetic pathways of Streptomyces and related actinomycetes such that new useful compounds can be produced in sufficient quantities to be commercially viable. There are two key areas of research that have emerged with potential commercial prospects, firstly Tunicamycin - a potent antibiotic and secondly an enabling technology known as a ‘Super Host’ for the discovery and potentially industrial production of antibiotics and other natural products such as natural herbicides and insecticides. JIC has a commercially confidential on-going project to develop natural herbicides. There have also been developments in JIC spin-out companies Novacta, Procarta and Inspiralis, which are discussed in Section 5. 3.4.1.1 Tunicamycin JIC is working with the University of Oxford to produce new derivatives of Tunicamycin. JIC’s expertise in molecular genetics and molecular biology is complementary to Oxford’s expertise in natural product chemistry and enzymology. 26 Economic Impact of Streptomyces Genetics Research, BBSRC, April 2010. Antibacterial Drugs: World Market Prospects 2013-2023 28 Economic Impact of Streptomyces Genetics Research, BBSRC, April 2010. 27 Page 14 Whilst Tunicamycin is a very potent antibiotic, it is very toxic to humans thus preventing its use. By understanding how it is made, JIC aims to change its biosynthetic pathway such that its antibiotic properties are maintained but human toxicity reduced to acceptable levels. By manipulating the biosynthetic gene cluster, JIC is now able to produce Tunicamycin variants that can be assessed for efficacy and toxicity. Nevertheless, it will be a couple of years before any of these candidates could be subjected to pre-clinical trials and at least 10 – 15 years before any could reach the clinic. Should the detoxification of Tunicamycin be successful it is likely to be rapidly taken up by industry given the growth of antibiotic resistance and the fact that there is no known clinical resistance to Tunicamycin. According to the Department of Health, antibiotic resistance is one of the greatest threats to modern health and ‘Antibiotics are losing their effectiveness at a rate that is both alarming and 29 irreversible – similar to global warming’. Professor Dame Sally Davies, Chief Medical Officer The Department of Health plans to publish an Antimicrobial Resistance Strategy and Action plan in 2013, which aims to encourage responsible use of antibiotics and to encourage development of new antibiotics among a range of measures. JIC’s research therefore has a close fit with Government policy in this area and can make a major contribution to tackling resistance. The European Centre for Disease Prevention and Control estimates 25,000 people die in Europe every year due to antibiotic resistance, with resistance to the five main drugs costing €1.5bn based on €927.8m extra hospital costs, €10m outpatient costs, €150.4m productivity 30 losses due to work absence and €445.9m productivity losses from patients who died . This is seen as a very conservative estimate as it is based on resistance to only five drugs. According to the Guardian, ‘The pipeline of future antibiotics has been described by the World Health Organisation as "virtually dry"’. Across Europe, there is increasing reliance on last line antibiotics, such as carbapenems, which are now showing some resistance in Southern Europe for the first time. There are market failures in delivery of new antibiotics as the cost and uncertainty over regulatory approval combined with perceived low returns hinder private investment. A recent £180m collaboration jointly funded by the Innovative Medicines Initiative (IMI) and the pharmaceutical industry highlights the priority being given to this area with GSK and 31 AstraZeneca contributing experimental drugs . In the USA, the Government is considering extending patent length to improve antibiotic profitability and to make research more attractive 32 through the Generating Antibiotic Incentives Now Act . JIC’s work in Tunicamycin has a key role to play in de-risking antibiotic development for the pharmaceutical industry by undertaking fundamental science to support new antibiotic development. As this research is taken forward by industry, it has real potential to reduce the costs of antibiotic resistance. While new drug development is expensive, (see ‘Super Hosts’ 29 http://www.dh.gov.uk/health/2012/11/eaad-cmo European Centre for Disease Prevention and Control and EMA (2009) The bacterial challenge: time to react. Technical Report 31 Kollewe (2012) Drug makers join forces in £180m research in battle against threat from bugs' th resistance to antibiotics The Guardian, 24 May 32 http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm320643.htm 30 Page 15 for costs) every 10% reduction in the costs of antibiotic resistance at the EU level will conservatively deliver £125m. 3.4.1.2 Super Hosts JIC has just developed a series of Streptomyces strains that can be used as ‘Super Hosts’ for efficient production of natural or engineered antibiotics or as a means of discovering new compounds. The ‘Super Hosts’ have been developed for their stability, lack of any antibiotic activity (facilitating their use in screening), much simplified metabolic profile (facilitating compound discovery and analysis) high levels of production and ease of manipulation. Their development is a form of synthetic biology, a growing research area. The ‘Super Hosts’ are used in the following way. DNA is taken from the strain of interest and inserted into E. Coli, which is used to identify gene clusters of interest. These are then transferred to the ‘Super Hosts’ for expression and compound production. The strains belong to JIC but academics and members of JIC’s Streptomyces Industrial Club have access to them (the latter after payment of a fee that is used to fund JIC’s fundamental Streptomyces research). Several pharmaceutical companies have acquired the Super Hosts, as have prominent academics, including the world-leading laboratory of Professor Chris Walsh at Harvard University. As highlighted previously, the ‘Super Host’ has potential to reduce further the costs of antibiotic production for academic and commercial users. Drug R&D is expensive, risky, and time-consuming with estimates of at least 10-15 years and total investment of £500m to 33 £1.1bn to bring a drug to market . There is also a set of Streptomyces expression vectors developed by JIC (‘Strep-X Toolkit’) under evaluation by several commercial companies via Plant Bioscience Ltd (PBL). JIC’s Super Hosts are playing a key role in speeding up antibiotic development and reducing R&D costs for academia and the pharmaceutical industry. This will potentially reduce drug development costs where every 1% saving is worth £5-£10m. They may also contribute to production of high value compounds (see next section). 3.4.2 High Value Chemicals from Plants Plants produce a rich and diverse array of natural products. These compounds have important ecological functions, providing protection against pests, diseases, ultraviolet-B damage and other environmental stresses. They are also exploited by humans as pharmaceutical drugs, agrochemicals, within the food and drink industry, and for a wide variety of other industrial biotechnology applications. Research is being undertaken at JIC using genomics to understand pathways to sourcing high value chemicals from plants and to discover new natural product pathways and chemistries. This research is also investigating strategies for production of ‘new to nature’ compounds and developing techniques to scale up production. 33 Infectious Diseases Society of America (2004) BAD BUGS, NO DRUGS As Antibiotic Discovery Stagnates A Public Health Crisis Brews Page 16 Terpenes are the largest class of plant-derived natural products. They have important ecological functions and numerous applications in the agriculture, food and health industries. Examples include the anti-cancer drugs vinblastine and vincristine, produced by Madagascar periwinkle (Catharanthus roseus), the anti-malarial compound artemisinin from sweet wormwood (Artemisia annua), and traditional medicines from plants such as liquorice and ginseng. Although over 40,000 different terpenes have been reported, the biosynthetic pathways for most of these compounds are unknown. Terpenes are a major focus of research at JIC with several high-potential programmes examining terpenes across a wide range of applications. The current and potential impact of work in this area is presented in one example below. 3.4.3 Vinca alkaloids Typically, in order to extract a natural product from a plant, it has to be isolated then purified. Often these natural products can only be extracted in very low quantities, with the plant 34 material yielding much less that 1% of the natural product by weight . For many plants, the natural product cannot be extracted economically for a number of reasons. For example, some plants are difficult to grow and others are rare or endangered. This leads to the price of natural products being extremely high, in some cases at more than £1m per kg. This is particularly the case for the anti-cancer drugs vinblastine and vincristine, which are among the 35 most expensive drugs in the world, with prices ranging from $2m to $15m per kg . These compounds, known as ‘vinca alkaloids’, cannot yet be synthesised and are directly isolated from the leaves of the plant Catharanthus roseus (the Madagascan periwinkle). The benefits of these drugs in treating a number of cancers have been known since the 1950s; however very low yields (less than 0.5% compound for weight of plant) make extracting them costly. Although the plant can be cultivated at large scale, the low yields limit commercial 36 applications . 37 JIC has received funding of around £1.75m through several grants to undertake research into vinca alkaloids aimed at improving understanding of how Madagascan periwinkle produces these compounds, identifying ways of improving synthesis and extraction, and developing techniques to manipulate the pathways to make novel or improved natural products. 38 Vinca alkaloids are the second most used class of cancer drugs . Vinblastine and vincristine are used to treat a variety of cancers including Hodgkin's lymphoma, lymphoblastic leukaemias and nephroblastomas. For example, vincristine is particularly effective in the treatment of childhood leukaemia, the most common form of cancer among children. In 2010, 8,257 people in the UK were diagnosed with leukaemia, with 500 cases of childhood leukaemia. The five-year survival rate for childhood leukaemia has increased from just 9% in 1966-70 to around 85% in 2001-05, with most of the improvements attributed to improved treatment. 34 Catharanthus roseus (L.) G. Don. An Important Drug: Its Application and Production, IJCP, 2010 http://www.northeastern.edu/lee-parsons/research/ and http://www.redbook.com/redbook/online/ 36 Catharanthus roseus (L.) G. Don. An Important Drug: Its Application and Production, IJCP, 2010 37 ERC grant - €1.5m over 5 years; BBSRC grant £400k over 3 years; EPSRC grant of £350k over 3 years 38 http://chemoth.com/types/vinca-alkaloids 35 Page 17 Although market information on the drugs is limited, estimates indicate that in the early 1990s the world market consumed 5-10kg of vinblastine and vincristine with a total market value of 39 $25 - $50m. In 2005, the market for vinblastine was estimated at between $150m - $300m . A report on chemotherapy drugs estimates that demand for alkaloid drugs will continue to 40 grow while doctors report that there is a current shortage of chemotherapy drugs . Improving yields will have a significant impact on the industry, reducing the cost of producing vinca alkaloids and increasing their availability. A 10% increase in yield through JIC’s research could be worth between $15m - $30m (£9.4-£18.8m) annually in cost savings for the pharmaceutical sector. 3.4.4 Molecular Pharming Plants naturally produce a wide range of complex molecules. Some of these substances are of direct use to mankind but it is also now possible to manipulate the biochemistry of plants such that they produce novel substances of value for medicinal and biotechnology purposes. JIC has developed a plant molecular production system that can be used to produce a wide 41 variety of novel substances. Known as the CPMV-HT technology it is a highly efficient and flexible technology that is finding application in a wide variety of fields. The CPMV-HT technology is based on JIC research in the 1980s and 1990s on cowpea 42 mosaic virus and is an example of Synthetic Biology in practice. The breakthrough came in 2005-8 when the technology finally enabled plants to express a wide variety of proteins of 43 potential value . The technology could revolutionise vaccine screening, production and yield novel metabolites. It does not require high containment facilities or a license to handle viral pathogens. It can radically reduce the costs and time required for vaccine development and production allowing vaccines to be rapidly and accurately tailored to specific threats. Plant systems can also express complex products that simpler organisms such as bacteria cannot. The technology was patented in 2008 by PBL. An open-IP approach has allowed the CVMV-HT system to be supplied to c. 120 labs worldwide for experimental use, greatly contributing to academic understanding of the opportunities and the opening up of routes to create value from the work. Total funding for the work has included £4.42m from BBSRC and €1.5m from the EU. Potential applications, some of which are already being trialled for commercial use include: • Vaccine production • Anti-cancer drug delivery • HIV drugs 39 Medicinal Plants 1, Prota, 2008 http://chemoth.com/economics 41 Cow Pea Mosaic Virus – HyperTrans 42 Lomonossoff et al (1993) Insertion of Foreign Antigenic Sites into the Plant Virus Cowpea Mosaic Virus. In: Proceedings of the Second AFRC Protein Engineering Conference. 43 Sainsbury and Lomonossoff (2008) Extremely High-Level and Rapid Transient Protein Production in Plants without the Use of Viral Replication, American Society of Plant Biologists. 40 Page 18 Influenza vaccine production: Medicago, a Canadian biotechnology company has a licence to use the technology to produce vaccines for influenza virus, including the potentially pandemic H5N1 avian strain. In tests in 2012 for DARPA, Medicago went from initial gene 44 sequence to delivery of 10m effective doses in 30 days , while the traditional route using egg culture would have taken 9 – 12 months. Medicago has completed construction of a VirusLike-Particle (VLP) vaccine facility to produce 10m doses of influenza vaccine per month. On an annual basis, the facility could have production capacity of 30m doses of quadrivalent seasonal influenza vaccine or 120m doses of pandemic influenza vaccine. Medicago is now attracting substantial investments to enable further product development and production with international partners and customers. 45 Every winter there are around 8,000 flu-related deaths in England and Wales . Seasonal flu mutates making it necessary to develop quickly a different vaccine, as the time from identification of the strain to start of the outbreak is short. Pandemic flu can be devastating; 46 Spanish flu killed at least 25m globally in 1918 . The time between identification of a pandemic strain and the first wave of the pandemic is only three to four months. Rapid vaccination programmes before the pandemic has time to become established will save lives and ill health and minimise the economic impact of the disease. Economic modelling suggests that pandemic flu could reduce UK gross domestic product (GDP) by between 0.5% (£8.4bn) and 4.3% (£73.2bn) or more, depending on severity and other factors. Adequate vaccination could reduce the maximum impact to about 1% of GDP 47 i.e. c. £16bn . One UK business calculated that flu cost the UK economy £1.35bn in 2010, 48 with 7.5m working days lost . If this technology results in more effective rapid vaccines that reduce the incidence of annual flu by just 1%, then it would save the UK economy £13.5m per year. Anti-cancer drug delivery: A £360k BBSRC Industrial Partnership Award for 3 years from Feb 2011 has enabled the development of patented technology to produce empty nanoparticles or Virus-like-particles (VLPs). JIC’s partner, US Company Aura Biosciences is investigating using these adapted CPMV particles as a targeted drug delivery system, initially based on delivering an anti-cancer drug to cancerous cells. JIC will receive royalties from drug sales. This has potential to be a disruptive technology if commercialised. Antibody production: As of 2011, the global market for therapeutic antibodies was worth $23bn. 90% of global bioreactor capacity provides just 10 products out of the 80 or so in this marketplace. Just about all of these rely on mammalian cell culture, which is comparatively slow and expensive. Plant based HT technology could provide additional global capacity. Once the specific molecular requirement is established, the optimal product can be rapidly developed and scaled up for production of the final product at much lower capital cost. There 49 are currently only three plant based production units in the world, all in the USA . 44 Medicago successfully completes the production of more than ten million doses of H1N1 VLP influenza vaccine in one month, Medicago press release, July 2012. 45 DoH press release 30 Sept 2010 ‘Don’t underestimate seasonal flu’. 46 Medicago website 47 BMJ 2009; 339: b4571 48 Co-operative Group press release; 7.6 million working days lost due to flu, October 18, 2010 49 Medicago, Icon Genetics, USA Fraunhoffer. Page 19 50 Animal diseases: In 2009, a JIC-led EU funded research consortium of 11 labs in 7 countries demonstrated production of plant-based proteins as veterinary vaccines, including a potential vaccine against bluetongue virus. A licence has been granted to a South African company where this disease is endemic but its real value to the UK economy lies in 51 enhancing preparedness lest this disease be detected in the UK. A capacity within AHVLA to diagnose the strain causing an outbreak and very rapidly provide a treatment could contain 52 an outbreak which otherwise could cost the UK up to £500m and 10,000 jobs . Other impacts: The technology has also been used by other research groups at JIC and elsewhere to help understand many aspects of fundamental plant biology and to rapidly evaluate new vaccines and therapeutics for application in humans and animals, for example, to produce biologically 53 active pharmaceuticals for HIV neutralisation . The annual cost of providing HIV treatment 54 and care in the UK could be as high as £758m by 2013, or over £1bn including social care . A 1% reduction in these costs as a result of JIC developed technology would save the UK £10m per year. Molecular Pharming facility at Norwich Research Park (NRP): A consortium of academic and commercial partners is considering the option of establishing a bespoke, modular commercial pharming facility on the NRP to capitalise on applications not yet licenced or commercialised and would operate in specialised glasshouse facilities using the HT system and other non-genetically modified organism technologies. The niche for Norwich would be to produce materials for clinical trials, vaccines and antibodies for smaller disease areas where the plant-based technology is competitive in cost and scalability. A larger scale vaccine production facility could enable the UK to swiftly develop and produce vaccines against emerging pandemics, increasing national preparedness and economic resilience. There is competition, with a variety of protein expression providers in the UK, mainland Europe, the USA and Israel. The five immediate UK competitors are small and are using non55 plant based systems, though they each have viable market niches . In the medium-term this facility could catalyse an indigenous fast-response vaccine production capacity, strengthening national preparedness against natural and terrorist disease threats. It would also cement the UK’s position in a leading-edge technology with potential to grow a new UK industry sector with high value jobs. 50 PLAPROVA - Plant Production of Vaccines develop a rapid plant-based system to produce and assess the capacity of different proteins to act as vaccines against important diseases of livestock such as avian influenza and blue tongue; EU Framework 7 programme (Research area: Cooperation; Theme: Food, agriculture and fisheries, and biotechnology) 51 AHVLA is required to provide an emergency response capability for exotic notifiable diseases of animals, including Bluetongue 52 http://www.pirbright.ac.uk/ecosoc/docs/Blue-Tongue-case-study.pdf 53 Rapid Transient Production in Plants by Replicating and Non-Replicating Vectors Yields High Quality Functional Anti-HIV Antibody, PLOS ONE, Sainsbury et al 54 Mandilia S et al. Rising population cost of treating people living with HIV in the UK, 1997-2013. PLoS One, 5, 12: e15677, 2010 55 For example, the University of Southampton hosting the Cancer Research UK non-GMP protein production labs and the translational GMP lab for the production of vaccines of Phase 1 & 2 trials Page 20 3.5 Nitrogen Fixation instead of Fertilisers Cereal production is highly dependent on inputs of nitrogen based fertiliser, produced using fossil fuels as the energy source, and responsible for the major source of pollution from agriculture. UN World population prospects suggest the world population will increase from 7bn in 2012 to 9bn by 2048. Around half of these people will be in sub-Saharan Africa. Feeding the world’s growing population will be a major challenge. In developing countries cereal production is limited to 20-40% of its potential yield due to 56 nutrient limitations for plant growth , while in developed economies, yields of crops may be maintained using unsustainable levels of inorganic fertilisers. If productivity could be improved in developing countries by improving crop nutrition, there is potential to contribute to solving the world’s food security problem. Legumes form symbiotic interactions with rhizobial bacteria through formation of root nodules that provide the plant with a source of nitrogen and with mycorrhizal fungi to facilitate phosphate and other nutrient uptake. JIC is researching the potential for cereal plants to benefit from these symbiotic interactions in the way legumes do. By understanding the symbiosis signalling components in legumes, JIC is investigating how these can be transferred to initiate nodulation in cereals. JIC has also identified the genes within bacteria that enable them to convert nitrogen in the atmosphere to ammonia. Introducing these genes directly into plants is an alternative way of creating selffertilising crops. This £8.6m research project is the first step towards nitrogen-fixing cereals with the ultimate aim of improving productivity for smallholder farmers in sub-Saharan Africa without using synthetic fertilisers. 57 A recent study of the economics of maize production in one region of Nigeria showed that at a yield of 3.19 tonnes per hectare (higher than the overall average in sub-Saharan Africa) fertiliser costs accounted for £37 per hectare with profit of £282 per hectare (based on maize selling at £158 per tonne). It was noted that availability of money to buy fertiliser and agrochemicals was the main constraint on production. Assuming N fixing maize was adopted, it is expected that increased yields would be obtained for either the same or a reduced fertiliser cost, thus removing a key constraint on increasing production. This is a high-risk research area, but if successful, new cereal varieties could be in the field within 20-30 years requiring further research effort and investment. 58 The total area of maize production across sub-Saharan Africa was 31m hectares producing 49.2m tonnes in 2011 suggesting average yield of 1.6 tonnes per hectare. Yields in other 59 tropical nations in 2011 were 4.2t/ha (Brazil), 2.9t/ha (Mexico) and 4.3 t/ha (Thailand) . 56 Foley et al Nature 478:337 Oladejo and Adetunji (2012) Economic analysis of maize (zea mays l.) production in Oyo state of Nigeria. Agricultural Science Research Journals Vol. 2(2) pp. 77-83 58 Defined as Central, Eastern and Southern Africa excluding South Africa. 59 FAOstat 57 Page 21 Adoption of improved maize seed in the area is around 60% the area could be reached with a new N fixing maize variety. 60 suggesting 18.6m hectares 61 of Based on the assumptions above, if part of the nutrient limitation identified by Foley et al in Nature could be removed and yields were able to reach the lowest of the tropical country benchmarks (Mexico at 2.9 t/ha), N fixing maize could deliver an additional 24m tonnes of maize in sub-Saharan Africa, an increase of 50% on 2011 production. Maize accounts for around a quarter of starch consumption in Africa with per capita consumption ranging from around 26 kg per head per year in Central and Eastern Africa to 85 62 kg in Southern Africa (excluding South Africa) . Taking a mid-range of these figures as 55 kg per head per year, the additional maize delivered through a N fixing variety could meet the starch needs and improve food security for 0.436 billion people. The project is also likely to reduce greenhouse gas emissions, as less synthetic fertiliser will be needed versus alternative scenarios. This project may not have a direct economic impact in the UK if GM restrictions remain the same, but reducing greenhouse gas emissions will contribute to decreasing the speed of climate change with indirect benefits to the UK and the rest of the world. Were N fixing cereals to become a reality they would significantly influence the GM debate in Europe. JIC’s research is high risk, but if successful, could offer an alternative more sustainable route to global food security away from dependence on synthetic fertilisers. 60 World Bank (2011) Maize Revolutions in Sub-Saharan Africa 60% of the 31m ha in sub-Saharan Africa 62 World Bank (2011) Maize Revolutions in Sub-Saharan Africa 61 Page 22 4. Operating Impact of JIC The operating impact of JIC relates to the on-site running of the Institute, such as expenditure incurred and staff employed, plus the knock-on effects as these expenditures ripple through the UK economy and support further activities. The total economic impact of operating JIC therefore encompasses three distinct elements: 4.1 1. Direct impact: output generated and persons employed in the day-to-day operation of the Institute in Norwich; 2. Indirect impact: output and employment created in the businesses which supply the inputs or materials used by the Institute; and 3. Induced impact: output and employment created when workers employed directly or indirectly spend their income in the local economy. Direct Impact JIC’s income in 2011/12 was £35.2m. Figure 4.1 illustrates JIC income by source over the last 4 years. Income has been similar to over the last 3 years, but is significantly above the level in 2008/09. Between 2008/09 and 2011/12, total revenue income has increased by £1.7m and capital funding has increased by £3.8m. The main source of the increase in revenue finding has been BBSRC competitive funding and EU funding Figure 4.1: Sources of JIC Income (£000’s) 40,000 35,256 35,388 35,191 35,000 29,681 30,000 Capital BBSRC - Maintenance Capital BBSRC - Capital 25,000 JIC Other 20,000 JIC Other public e.g. TSB 15,000 JIC Private 10,000 JIC EU funding 5,000 JIC BBSRC competitive funding 0 08/09 09/10 10/11 11/12 JIC BBSRC core funding Source: JIC Management Accounts 63 JIC directly employs 346 staff comprising 255 in research and 91.2 FTEs central services . In addition, in 2011/12, JIC had 86 students and 128 visiting scientists. The students receive a stipend that varies according to the sponsor. Visiting scientists are supported by their host institutions, or by EU funding for training purposes – see Figure 4.2. 63 In total, there are 152 staff in Central Services. JIC pays 60% of these staff costs, so 91.2 FTEs have been allocated to JIC. Page 23 Figure 4.2: Staffing at JIC (2011/12) Visiting Workers Students Central Services Management KEC Scientific Support Research Staff 0.0 50.0 BIO MET 100.0 150.0 GRO WISP 200.0 NCG Source: JIC HR database 4.2 Indirect Impact JIC spent £12.3m with suppliers in 2011/12, of which £11.4m was with UK based suppliers. This supplier expenditure forms the inputs for calculating the indirect operating impact of JIC. Figure 4.3 illustrates the supplier expenditure by type. Figure 4.3: JIC Expenditure by Type Sub contracting 2% Equipment Other 2% 4% Professional services 5% Transportation 4% Consumables 19% Utilities 23% Computer services 2% Construction 38% Education 1% Source: JIC Management Accounts In 2011/12 construction was a major element of the expenditure, comprising buildings, repairs and maintenance and ‘other capital’. Page 24 This profile of supplier expenditure supports output and employment amongst supplier industries, and their suppliers in turn. The extent of this impact can be estimated using the UK National Accounts published by ONS, estimating the level of expenditure required to support a FTE job in each supplier, and their knock-on expenditure. In total for 2011/12, JIC’s supplier expenditure is estimated to generate a total of £24.9m output for UK industries, supporting 193 jobs. This comprises 92 FTEs in those UK companies directly supplying JIC, and a further 101 employed through further supply chain effects (i.e. as JIC’s suppliers purchase inputs in-turn from their suppliers, which is still attributable to JIC’s initial demand). 4.3 Induced Impact Total salaries paid to JIC staff amount to £13.1m for 2011/12. Other salary costs paid by JIC include support services of £4.7m and a further £1.3m of student costs. In addition, the salaries paid to staff working within the JIC supply chain are estimated at £4.4m. In total, this £23.6m of direct and indirect salaries accrues to households to be spent on a profile of consumer goods and services, generating further economic activity in the UK. This forms the basis for JIC’s induced impact. Modelling this household income using an average consumer profile, indicates that the direct and indirect salaries will lead to increased spending of £10.8m and will support a further 97 jobs across the UK economy. While these induced impacts can be attributed to JIC, they will largely occur in sectors out-with the profile of direct and indirect industries, occurring instead in consumer industries such as retail and recreational services. 4.4 Summary of Operating Impacts Figure 4.4 summarises the direct, indirect and induced impacts of JIC highlighting the 636 jobs and £30.4m of Gross Value Added (GVA) across the UK economy. Figure 4.4 Summary of JIC Operating Impacts Output (£m) Direct 35.2 Indirect 24.9 Induced 10.9 Total 71 Employment (jobs) 346 193 97 636 GVA (£m) 19.1 9.1 2.2 30.4 Page 25 5. Wider JIC Impact In addition to the operational impacts and those associated with specific research areas, JIC has many wider academic, economic and social impacts. These wider impacts are discussed here and broadly follow the RCUK pathways to impact 64 framework . There are three primary areas where the wider impacts of JIC are seen: • • • 5.1 Knowledge Exchange and Commercialisation Learning, Teaching and Training; and Networks, Collaborations, Public Engagement and Influence. Knowledge Exchange and Commercialisation 5.1.1 High Impact Journal Articles JIC publishes extensively in the scientific literature as one means of disseminating its scientific knowledge for impact. JIC, along with The Sainsbury Laboratory (TSL) has been 65 independently ranked first in the world plant and animal science citations 1999-2009 . 66 JIC publishes around 15 papers per year in the highest impact scientific journals including Cell, Nature, Science, PLOS Biology, Current Biology and PNAS. This top performance in publications underlines JIC’s focus on long-term fundamental science to address key challenges of food security, sustainability, industrial biotechnology and healthy ageing. 67 In 2009, the US magazine ‘Science’ produced a special issue on plant- microbe interactions; JIC and the Sainsbury Laboratory authored 3 of the 7 articles, demonstrating the global recognition of JIC’s work in this area. A list of articles published in journals with impact factor of 5 or more is set out in Appendix 3. 5.1.2 Collaborative Research, Consultancy and Company Engagement Since 2008, JIC has engaged in industrial collaborations worth nearly £5m in research 68 funding . These have varied from providing direct funding (e.g. Bayer BioScience, Monsanto, Syngenta, BASF), co-funding (e.g. AHDB, BASF, KWS UK Ltd, Elsoms seeds, RAGT Seeds), and in-kind contributions (e.g. HGCA, BASF PLC, CPB Twyford, Monsanto, Nickersons). JIC has three innovation clusters, which aim to develop practical application from JIC’s science. The cluster leaders focus on Crop Flowering Time, Crop Pathogen Interactions and Anti-Infectives Technologies. Three examples of industry engagement projects are set out below. 64 http://www.rcuk.ac.uk/kei/impacts/Pages/meanbyimpact.aspx http://www.timeshighereducation.co.uk/story.asp?sectioncode=26&storycode=411170&c=1 66 Journals such as Nature, Cell and Science have Impact Factors of 30 and above. 67 ‘Science’ 2009 Vol 324, issue 5928, pages 677-840 68 JIC Director’s Statement 65 Page 26 Vernalization in brassicas - funded through Defra LINK, BBSRC and industry is a JIC collaboration with Elsoms Seeds, Bejo Zaden and Weatherquest. This joint project has focused on better understanding vernalization requirements of different varieties of broccoli and cauliflower to improve certainty in crop scheduling and yield: Trait Tag - JIC developed a new genomic methodology for identifying molecular markers in 69 gene expressions called Trait Tag . Trait Tag enables plant breeders to identify these markers quickly and robustly by identifying and scoring variation across very large sets of plants. It allows plant breeders to improve the quality of plants in a shorter timescale and at lower cost than previously possible. JIC collaborated with Eagle Genomics Ltd, a bioinformatics software company in Cambridge, who fine-tuned the software. JIC receives 5% royalty from Eagle Genomics. 70 CASE PhD studentships - JIC hosts a number of students, jointly supervised by academic and industrial partners. One recent example is Chris Burt who was funded by BBSRC and HGCA to work with plant breeder RAGT on ‘eyespot’, a fungal disease that causes large yield losses in cereals in North West Europe and North West USA. 5.1.3 Intellectual Property JIC makes use of two approaches to intellectual property (IP). Firstly IP protection and secondly Open-IP or open innovation. Both are exploited for commercial, economic and societal benefit as appropriate. IP protection and exploitation - JIC has an IP management and technology transfer company - PBL. Since its inception, PBL has invested £2.3m in the costs of patent protection for JIC IP and has generated revenues of £2.8m from licensing JIC’s innovations. As a result, JIC and JIC inventors have received over £0.85m from PBL. JIC currently has 24 active patented technologies, of which over 60% have already started to generate revenue and four 71 have generated in excess of £100,000. Several of these technologies could be at the point of significant breakthrough in terms of income generation and UK job creation. Examples include: • DA1 – by identifying and removing genes that are negative regulators of growth, there is potential to deliver a 5% increase in wheat yield that would deliver £110m at the UK level and £1.16bn at the EU level. The technology has been licensed to industry and is being refined further. • Crop root hairs – JIC has identified the genes that cause plant root hairs to grow longer thus improving moisture and nutrient uptake. This technology is licensed to industry with worldwide patent cover. The original JIC inventor is now a named Professor at Oxford University, demonstrating the academic impact of JIC alumni. If successful, it is likely to be adopted into maize, soya beans, wheat, rice and other major crops around the world. • Temperature Sensing - JIC has discovered genes responsible for temperature sensing and controlling growth such that plants can continue to grow at lower or higher temperatures. This is licensed to a grower in the covered vegetable sector where it is saving energy used to heat greenhouses. A 10% reduction in energy costs 69 For which JIC scientists Martin Trick and Ian Bancroft were nominated Innovators of the Year, 2010. Collaborative Awards in Science and Engineering (CASE) are 4-year doctoral training studentship grants that give students high quality research training in collaboration with an industrial partner. 71 JIC IP Summary November 2012. 70 Page 27 could save the UK sector £17m-£26m per year and reduce CO2 emissions. The research could also help plants adapt to climate change and improve food security. The original inventor at JIC has now moved to the Sainsbury Laboratory in Cambridge demonstrating again the academic impact of JIC. Open-IP – in parallel with protected IP, much of JIC research is made available widely to industry and academia with little or no-IP restrictions. This method ensures that benefits of public good research are quickly and widely distributed and adopted. Examples include the Wheat Improvement Strategic Programme (WISP), which shares the benefits with plant breeders, aspects of Streptomyces research that are shared with academics and industry through the Streptomyces Industrial Club and molecular pharming where the CPMV-HT plant production technology has been widely shared amongst academics for research use. 5.1.4 Spin-Out Companies JIC has formed a number of spin-out companies that continue to develop strongly. Examples include: Inspiralis - supplies topoisomerase enzymes, tools and resources to large pharmaceutical companies, biotech companies and academics worldwide. Its products and services are used for drug discovery, saving time and costs for clients. The company has grown to employ 5 FTE employees and is profit making. Sales for the financial year 2011/12 were £330K, 85% of which were exports worldwide including to Japan, USA, India and Europe. Sales have been rising since the company started in 2008 while exports have formed a similar proportion of sales each year. There are no UK competitors, the main direct competitor being in the USA while there are other international competitors offering some of what the company provides. Inspiralis therefore brings additional economic benefits to the UK. Inspiralis received investment by the Iceni Seed corn Fund. Procarta Biosystems - has developed a new type of DNA-based antibiotics based on JIC research. Procarta’s technology blocks the metabolism of the bacteria (the transcription factor binding site) making it almost impossible for bacterial resistance to develop. The approach has proven to be successful against MRSA and is now in pre-clinical development. Procarta has just received further investment of £500,000 from Morningside Venture Investments and an EU patent that it expects to take worldwide. Dr Michael McArthur, CSO of Procarta Biosystems said ‘It is becoming recognised among investors and grant funders that something must be done about the challenge of antibacterial resistance. What we can offer is a genuinely novel and potent approach that can be rapidly developed to treat numerous bacterial infections, for which the number of effective treatments is dwindling’. As already highlighted in the report, antibiotic resistance costs at least €1.5bn per year across the EU. As well as new antibiotic discoveries at JIC, Procarta’s technology could present a new way of countering resistance in bacterial infections. Page 28 Novacta - is working on discovering new anti-infectives that target Clostridium difficile and the superbug MRSA. It already has compounds in clinical trials. Deaths involving C. difficile are now falling in England and Wales from a peak of 8,324 in 2007 to 72 2,053 in 2011 . A review by the National Institute of Clinical Excellence estimated the economic cost to the 73 NHS at the peak to be £194m . The company completed a Phase I study of NVB302 against C. difficile infection in healthy volunteers in August 2012. 5.2 Learning, Teaching and Training JIC runs an extensive programme of training and engagement across the entire school and university spectrum aimed at inspiring the next generation of scientists. This continuum of training has impacts in terms of changing perception of science as a career and attracting young people into bioscience. 5.2.1 Inspiring the Next Generation JIC’s mission statement puts the development of human capital at the heart of what it does. A key objective is “to train scientists for the future”. Schools activities range from working with primary schools, informing them about scientists and their work, to school lectures at JIC and non-residential camps and placements. The SAW Trust – The SAW (Science, Arts and Writing) Trust, established in 2006, is a registered charity that encourages science education in schools through engagement between science and the arts. Since its inception, it has delivered over 70 projects with around 3,500 school children in the UK, around 50 projects in the US and was launched in China in December 2012. Teacher Science Network (TSN) - JIC hosts, and is an active member of, the Teacher Science Network, which puts members of the Norwich Research Park in contact with local science teachers to support delivery of up to date science; to counteract ‘boffin’ stereotypes; and encourage interaction. As part of this wider role, JIC has made inputs to current school scientific textbooks. 5.2.2 Scientists of the Future JIC has a wide range of activities to train young scientists including the following: Linkages to the University of East Anglia (UEA) - JIC is part of the Graduate School at UEA. JIC Project Leaders are honorary Professors at UEA schools of Biology, Chemistry, Pharmacology and Computer Science and contribute to undergraduate and postgraduate courses. In particular, JIC scientists teach a Masters degree at UEA in Crop Improvement. 72 73 Office for National Statistics Economic Impact of John Innes Centre 2008 Page 29 Summer research training programme - JIC hosts an undergraduate summer research training programme, which last year received 500 applications for 16 places. It offers insight into careers in bioscience research, access to world-class scientists and facilities, and the opportunity to gain new skills and laboratory experience. Placements with JIC - Through affiliation with three universities, JIC offers two students annually a ‘year in industry’, enabling them to spend up to 12 months working alongside a JIC scientist. Post Graduates, Post Doctorate and Visiting Workers - around 60% of JIC researchers are post graduates, post doctorate or visiting masters. JIC’s global reputation means strong competition for training places and a very high standard of candidates. At any time, JIC will have around 100 PhD students. This continual flow of training researchers means that JIC benefits from considerable scientific research output, adding value to its research and reputation. 5.2.3 Career Development and Continuing Professional Development JIC has a structured career development path for staff, to help realise the potential of their scientific research, to support lifelong learning and CPD. 5.3 Influence, Networks and Public Engagement JIC plays a key role in informing policy, in influencing debate, in sharing its knowledge and expertise and in public engagement. These areas are considered below at local, national and international levels. 5.3.1 Local 5.3.1.1 Norwich Research Park (NRP) The NRP is centred around six research institutes/organisations, employing around 2,700 scientists and 12,000 staff (plus UEA students). All six organisations have their primary facilities on-site, providing a critical mass of multidisciplinary activity and expertise at the NRP. This mix is very appealing to potential inward investors. The large number of multidisciplinary research staff onsite is also likely to lead to a growing number of spin-outs and start-ups. In 2011, the NRP was awarded £26m UK Government funding to enable the development of a research and innovation campus. The first phase of this new development is already well underway. The strength of JIC’s science has supported development of the NRP. For example, JIC enabled NRP partners to secure a BBSRC Doctoral Training Partnership award for PhD funding by demonstrating high levels of revenue from research. JIC’s proposed molecular pharming facility could have a major impact on direct jobs and inward investment (see molecular pharming case study). Number of jobs and GVA attributable to JIC Assuming equal attribution amongst the partners, the NRP will lead to 1,300 net additional jobs and £70m GVA per year as shown in Table 5.1. Page 30 Table 5.1 Jobs and GVA supported by both current and future potential commercial space at NRP Net additional Net additional 10 yr. NPV @ 3.5% jobs GVA 220 £12,094,353 £104,104,396 Current commercial space Future potential commercial space Total 7,502 £412,629,707 £3,295,871,730 7,722 £424,724,060 £3,399,976,126 Attributable to JIC 1,287 £70,787,343 £566,662,688 Source: Brookdale Consulting based on consultations with NRP Earth and Life Systems Alliance (ELSA) - a major strategic collaboration between JIC and the University of East Anglia to integrate world-class expertise in biological, earth and social sciences to tackle the challenges posed by a changing climate. Industrial Biotechnology and Bioenergy Alliance – JIC is also contributing to this growing research area along with partners on the NRP and elsewhere to harness the potential of new production methods for high value compounds and renewable energy. 5.3.2 National House of Commons - JIC annually hosts House of Commons dinners, which enable NGOs, ministers and MPs to talk openly with scientists about key scientific developments such as synthetic biology, food security, the value of knowledge generation, working with industry and the economic and societal impact of science. This enables useful science based discussions to take place before topics become over politicised. JIC has also used this forum to inform the science curriculum on the importance of plant biology which tends to have less profile than human biology. Government Briefings - JIC often prepares Briefing Documents for Ministers. Issues include topics such as GM, Marker Assisted Breeding and the implications of the EU Directive banning the future use of pesticides. JIC’s inputs help ensure any debate is based on robust scientific evidence. Government Consultations - JIC actively helps inform government policy by formally responding to consultations, either in its own capacity, or jointly with partners or BBRSC. On average, two formal consultation responses are issued by JIC annually. Leadership positions - JIC staff sit on various influential committees and partnerships. For example, JIC’s Director sits on the Synthetic Biology Leadership Council, responsible for implementing the Synthetic Biology Road map, and the Food Research Partnership, chaired by Sir John Beddington. Policy Response - In response to the recent UK Ash Dieback outbreak, JIC led a research bid to BBRSC to examine both the tree and pathogen genetics in order to find potential solutions to the disease. This is a joint bid with The Sainsbury Laboratory (TSL), the Page 31 Universities of Exeter and Edinburgh and a Norwegian tree pathologist. This demonstrates JIC’s ability to respond to major biological challenges facing the UK. 5.3.3 International JIC Alumni - A high proportion of JIC PhD and post-doctoral researchers are international and over half leave the UK following their time at JIC. Therefore, JIC attracts a high inflow of talent and exports a high outflow of talent overseas. JIC and its alumni form a truly global network of highly skilled researchers that often network or collaborate on projects. International collaborations - JIC scientists have around 330 active international collaborations across the globe. JIC has strong collaborations with China and emerging research partnerships with Vietnam, Thailand and Malaysia creating a strong basis for further developing scientific programmes in Asia. Through a NRP led initiative, JIC is developing collaborations with research organisations in Brazil. Partnership between JIC and subSaharan Africa will encourage engagement and knowledge transfer to support the agriculture of developing nations. JIC-China Centre of Excellence - JIC has had links with the Chinese Academy of Science (CAS) for over thirty years. More than 100 JIC alumni have academic positions in China, including three within CAS itself. In June 2011, JIC and CAS signed a Memorandum of Understanding to collaborate in areas of public good research such as food security, sustainable agriculture and healthy living. The research will focus on sustainable production of wheat and rice. A joint CAS-JIC Centre of Excellence will be established in China and there will be regular staff exchanges and alignment of research to drive development of new crops and production of valuable raw materials and complex chemicals to underpin industries as diverse as plastics and pharmaceuticals. Alongside the impacts of successful research, benefits to JIC will include an expanded research base, enhanced reputation and attraction of the best scientists. 74 CGIAR - JIC staff serve on many international science advisory boards including CGIAR whose institutes may take up JIC research and apply it globally including: • • • • International Crops Research Institute for the Semi-Arid Tropics (ICRISAT) International Maize and Wheat Improvement Centre (CIMMYT) International Potato Centre (CIP) International Rice Research Institute (IRRI) Together with these bodies, JIC provides important contributions to the Global Food Security programme. 74 Formerly known as the Consultative Group on International Agricultural Research Page 32 European Plant Science Organisation (EPSO) – JIC is a member of EPSO, which brings together more than 204 research institutes, departments and universities from 29 countries in Europe and beyond. It aims to improve the impact and visibility of plant science in Europe. Streptomyces networks – over decades, JIC has pioneered Streptomyces research to support antibiotic development. As well as the Streptomyces Industrial Club, there are global networks of researchers who share information on Streptomyces to support their research. Coordination of International Collaborative Projects - JIC takes a leading role in the coordination of collaborative research programmes. Within the EU Framework 7 programme JIC was a partner in eleven programmes, coordinating five and interacting with 152 research organisations from 30 countries. Additional international collaborations led by JIC include the Japanese funded Human Frontiers Science programme and UK Government funded initiatives with foreign partners through international aid (Department of International development, DFID) and with charitable trusts (Bill and Melinda Gates Foundation). Examples include: MM4TB EU consortium - JIC is one of 25 laboratories across Europe collaborating to find 75 new drugs to combat TB, which kills 1.8m people per year . Current TB treatments are old and require to be taken for a long time. A previous EU FP6 consortium NM4TB delivered a new drug for clinical trials ahead of schedule. The current project involves academics and industry and aims to screen widely for compounds that would not be commercially viable for industry to take forward. The Grain Legumes Integrated Project (GLIP) was a €14.75m multinational project, cofunded by the EU FP6 Framework Programme, to develop new strategies to enhance the use of grain legumes crops in food for human consumption and animal feed throughout the world. JIC coordinated this ultimately successful project, with another 67 contractors at 80 locations participating. At evaluation, the project was given the highest rating and considered to have fully met its objectives. ATHENA is an FP7 collaborative project, involving 11 European institutions, coordinated by JIC. The project is assessing anthocyanins in protecting against cardiovascular disease, cancer and obesity in preclinical studies with animals. 75 http://www.mm4tb.org/ Page 33 Fellowships – JIC is successful in securing EU grants and prestigious fellowships as shown in the Table below for the period 2007-12 International Grants 2007-2012 FP7 Marie Curie European Research Council (ERC) FP7 Programme Intra-European Fellowships International Incoming Fellowships International and European Reintegration Training Networks (consortia) Advanced Investigator Grants Starting Grants Collaborative Grants Cost Action (consortium) Coordination and Support (consortium) Action Number Awarded 16 4 3 4 2 Number Coordinated 4 9 1 1 2 3 5.3.4 Public Engagement The final area of JIC’s engagement is with the general public including the following: Science in Society Programme - JIC operates an active programme of engagement with the general public ranging from providing speakers in public debates, engaging with interest groups, exhibiting at shows, through to hosting events and discussions. Events attended by JIC include the Edinburgh Science Festival, Cereals, the International Fascination of Plants Day, Big Bang Fair, British Science Association Science Festival, the Royal Norfolk Show and the Royal Society Summer Exhibition. Social media – JIC has active social media accounts as a means of engaging the public. It has over 2,300 followers on Twitter, more than 800 ‘likes’ on Facebook and 443 followers on LinkedIn. These figures do not include the numerous Twitter and social media accounts of individual scientists and departments which are used extensively to converse with peers and the public. Friends of JIC - has 4,000 members made up of general public, alumni, industry and partnership organisations, who receive the ‘Advances’ newsletter and are invited to around 89 events annually, discussing key topics with the scientific lead. Media partners - JIC works with media partners, aiming to be the trusted first port of call for information relating to plant and microbial science. Interest groups - As with genetic modification, there are interest groups with concerns about the use of synthetic biology. JIC has aimed to make the debate more accessible to the interested public by hosting presentations and discussion on YouTube – one example being 76 seed store . Hosted visits and open days – JIC scientists regularly host visits and take part in open days for members of the public and for schools. These include site open days, visits to Church Farm and visits by local and wider interest groups. 76 http://www.youtube.com/watch?v=C6PSNMFV20k Page 34 6. Summary and Overview JIC’s focus is on long-term fundamental high quality research with a longer-term horizon than universities and aspirations to address global challenges. Within the context of fundamental research, it is a relatively short period since the last impact report, nevertheless: • JIC’s KEC strategy is supporting a wide number of industrial collaborations, research projects and Intellectual Property with significant potential. • Areas in which JIC previously had substantial impact are continuing to have great potential e.g. wheat, brassicas and antibiotics. • A number of promising new areas of research have emerged, in particular, industrial biotechnology and synthetic biology. • Royalty income may be at a turning point - following years of relatively small returns, a number of technologies are coming to fruition at the same time that could deliver very substantial income for JIC. • There is strong evidence to support JIC’s contribution to grand challenges such as global food security with a time horizon beyond many funders and researchers. • Synergies from the Norwich Research Park are increasing and joint research between JIC, TGAC and UEA is increasing. TGACs capabilities are important in underpinning JIC research that would not have been possible even 5-10 years ago. • In wheat, JIC is demonstrating that the gap between what plant breeders can deliver (13%) and what forecasts suggest is required (50%) could be bridged by innovative new technologies exploiting JIC’s fundamental science over many years. Very large yield increases are still possible through step changes in genetic improvement, though time horizons are 10-20 years. • N-fixation has a potential role in global food security – it is high risk but potentially very high reward over the next 20-30 years. • There is a balance between actual and potential impacts. Some very long-term research projects are now coming to fruition, e.g. Beneforte Broccoli, which is now on sale. Other areas such as molecular pharming could soon deliver very substantial impacts and represent a completely new opportunity for the UK economy. Some of these areas will require substantial investment that may not be forthcoming from the private sector given the risks. 6.1.1 On-going impacts JIC has a substantial impact on the regional economy around Norwich. This includes 636 jobs, plus annual Gross Value Added (GVA) impacts of £30.4m at the UK level per year. JIC’s work has been key in supporting plant breeders in delivering £373m-£445m of gross wheat yield benefits per year at the UK level compared to 1982 yields. This includes the benefits of reduced cereal diseases. At the global level, gross productivity increases supported by JIC’s research could be worth £8.7bn in 2012. JIC’s work in antibiotics has supported additional global sales revenue potential of £247m per year for actinomycete-derived antibiotics, forecast to be £306m by 2017 through market growth. Page 35 6.1.2 Gross Research impacts A summary of the main gross impacts arising is set out below across the case studies. Crop Improvement Improving wheat yields – In addition to the on-going impacts above, for every 1% increase in yield achieved by WISP and QTLs, the JIC share of impact will be £3.67m at the UK level and £38.7m at the EU level per year. Reducing cereal diseases – JIC’s long-term work in cereal diseases supports the UK and global industry as set out above. By enabling breeders to produce varieties with half the current level of septoria disease losses (3%) it is estimated that the future impact attributable to JIC could be £3.3m at the UK level and £70m at the EU level per year while work in take-all could ultimately lead to reduced costs for UK wheat farmers of £60-340m per year. Oilseed rape – JICs work to reduce pod shatter in OSR could increase yields by 15% worth £165m at the UK farm gate or £1.7bn if implemented across the EU. Enriched Broccoli – Beneforte is now on sale in UK and US supermarkets. It has the potential to reduce cardiovascular disease and prostate cancer and work to support a health claim is on-going. Potential benefits of £38m per 1% reduction in disease can be anticipated at the UK level. 50% of these are attributed to JIC. Nitrogen fixing cereals – If JIC’s work on N-fixing in maize is successful, it could improve food security for 0.436 billion people in sub-Saharan Africa and provide an alternative to synthetic fertilisers. Industrial Biotechnology and Synthetic Biology Tunicamycin – JIC is working to reduce toxicity of Tunicamycin such that it can be taken up by the pharmaceutical industry as a completely new class of antibiotics. Antibiotic resistance is a major policy priority in the UK and EU. Every 10% reduction in the costs of antibiotic resistance at the EU level will conservatively deliver £125m. Super Hosts - JIC has just developed a series of Streptomyces strains that can be used as ‘Super Hosts’ to reduce drug development costs where every 1% saving is worth £5-£10m. High Value Chemicals from Plants – one example of improving yields of vinca alkaloids will have a significant impact on the industry, reducing costs and increasing availability. A 10% increase in yield through JIC’s research could be worth between £9.4-£18.8m annually in cost savings for the pharmaceutical sector. 77 Molecular Pharming - JIC has developed a plant molecular production system CPMV-HT that can be used to produce efficiently a wide variety of novel substances. It could revolutionise vaccine-screening production, yield novel metabolites and is licensed to industry. If the technology results in more effective rapid vaccines that reduce the incidence of annual 77 Cow Pea Mosaic Virus – HyperTrans Page 36 flu by just 1%, then it would save the UK economy £13.5m per year. A 1% reduction in costs of HIV treatment and care because of the technology would save the UK £10m per year. Wider impacts Wider impacts of JIC include: • independent ranking with the Sainsbury Laboratory as number one in the world for 78 academic citations in 2009 • engagement in £5m of current industrial collaborations • growing spin-out companies with increased investment, turnover and employment • training scientists from school age children and students through to JIC staff • JIC is active in the public debate around science, food security and GM, informing government and society about the direction of scientific research. • Important contributions to the Global Food Security programme and around 330 active JIC global collaborations. • The JIC-China Centre of Excellence represents a substantial research collaboration that will have global impact. For example, over 100 JIC alumni have academic positions in China. • Norwich Research Park impacts of 1,300 net additional jobs and £566m GVA over 10 years estimated by Brookdale Consulting as attributable to JIC. 6.1.3 Net impacts UK In addition to the operating impacts highlighted in 6.1.1, a summary of the net impacts across the case study areas is set out below (Table 6.1). It takes the gross impacts calculated for each case study and assesses research costs, implementation costs, timescales of adoption, and additionality at the level of the UK economy. These figures are summed together to derive the net cumulative impact expected over the next 10 years. Finally, Value for Money (VFM) ratios are also presented for each area. Overall, the VFM of the JIC research areas considered is £11.99 of GVA at the UK level. See Appendix 4 for further details. 78 Plant and animal science see: http://www.timeshighereducation.co.uk/story.asp?storyCode=411170§ioncode=26 Page 37 Table 6.1 Summary of 10-year net impacts of JIC Research at the UK level Summary of Net Impacts of JIC Research TOTAL Total research funding assessed £ Funding Gross Impacts JIC share of research funding assessed Gross annual benefits identified (£) Implementation timescale Gross Benefits over 10 years (£PV) Gross Implementation Costs over 10 yrs (£PV) Net Benefits (£PV) 42,660,000 £ £ 18,657,500 506,000,000 Over 10 years £ 858,102,298 £ 25,461,429 £ 789,980,869 100% £ 789,980,869 44% £ 347,065,370 £ 223,781,154 408 Net Additional Benefits Additionality of the impacts Value of benefits to the economy (£PV) for the UK Economy JIC attribution based on share of work Impacts Attributable to Additional Output over 10 years (£PV) Additional GVA over 10 years (£PV) JIC Additional Jobs Supported (FTE) VFM - JIC research funding only (GVA Value for money leverage per £1 JIC research funding (10yr GVA NPV)) 11.99 6.1.4 Net impacts globally and long term UK Given JIC’s global leadership in many science areas and the long-term nature of its research, we have also considered impacts that are not captured within the UK 10-year figures above. These include non-UK, EU and global potential impacts of technologies such as N-fixation and longer-term UK potential impacts such as those related to antibiotic resistance. Table 6.2 summarises these impacts. It can be seen that over a thirty-year period, there could be a further £24bn of cumulative impacts attributable to JIC if its research is successful. See Appendix 5 for further details. Table 6.2 Summary of net impacts of JIC Research (long term UK and international) Summary of Net Impacts of JIC Research TOTAL Total research funding assessed £ 21,118,000 JIC share of research funding assessed Gross annual benefits identified (£) Implementation timescale £ £ 21,118,000 8,517,400,000 Gross Benefits over 30 years (£PV) Gross Implementation Costs over 30 yrs (£PV) £ 48,819,178,749 £ 403,226,394 Net Benefits (£PV) Additionality of the impacts Value of benefits to the economy (£PV) JIC attribution based on share of work Additional Output over 30 years (£PV) £ 48,386,164,355 100% 48,386,164,355 49% 23,877,630,812 Funding Gross Impacts Net Additional Benefits globally Impacts Attributable to JIC Over 10 years or more £ £ Page 38 Appendix 1: Market Failure Table A1.1 sets out how JIC’s activities relate to different market failures. Table A1.1: Market Failure – Why public funding of JIC is justified Market failure Public good Rationale for JIC Role Public goods are those where individuals cannot be excluded from using them and that when one person using the goods does not reduce the amount available for anyone else. Scientific research where the results are widely disseminated enhances the knowledge within the sector and benefits industry as a whole Knowledge is an important public good. In many instances, there is little incentive for any individual company to bear the cost of developing the knowledge (i.e. through research) which will subsequently become widely available to the whole industry. It is often not in the interests of any one commercial business to pay for the science that will also benefit the other businesses in the industry. JIC performs an essential role in undertaking the research that can then be used and accessed right across industry for example, wheat and brassica genomes. Market power Access to knowledge can be restricted through patents. However, if a company was given the funding to do work and protected the resulting intellectual property, it will have a monopoly or sufficient market power to influence prices to its own advantage and the benefits of the research will not be widely shared. Imperfect, asymmetric or lack of information Many within industry may not be aware of the potential benefits to be gained from undertaking research. Excess market power disadvantages consumers either through price or because access to the findings of the research, and therefore the improved product, is restricted JIC operates independently of industry and frequently makes freely and widely available those findings funded by the public purse e.g. CPMV-HT molecular pharming technology shared amongst academics and Streptomyces ‘Super Hosts’. Businesses may lack the information to know that a problem exists within a particular plant or that there is a possible solution to a known problem. JIC knowledge and expertise in this area enables the organisation to undertake research to address relevant issues e.g. LINK projects, JIC cluster programmes Risk Aversion Business may lack the information to assess the likely returns on investing in research, or they may be unwilling to invest in something where it is uncertain whether the benefits will outweigh the costs. Research is time consuming and uncertain in its outcomes. Businesses may not invest in undertaking research in areas where the returns on investment may be a long way off, or the science is not sufficiently advanced to provide confidence that it is worth investing in. JIC is able to undertake research where the commercial returns to the research may not be realised within a typical business planning cycle of industry. N fixation research is one example. Externalities Externalities are the costs or benefits that are not borne by the people that buy or sell the product. The spillover benefits of much of the scientific research undertaken at JIC enable other researchers in different fields to build on the findings and make progress in other areas of scientific research that is not the direct focus of the funding. Page 39 Appendix 2: Methodology In order to measure impact, each area of JIC science was reviewed and routes to impact assessed. Thirteen areas were chosen as case studies in consultation with JIC science leaders. The areas were chosen to give the best representation of current research effort, taking into account the 2008 impact report and giving a mix of existing and new research areas. Nine of these are reported in detail in this report, though impacts are modelled for all thirteen areas. In each case, the impacts were assessed by modelling socio-economic outcomes of the research such as improved health, improved productivity, and reduced costs. Where relevant, such outcomes are quantified at the UK level, though much of JIC research has global application. Softer impacts such as academic, collaboration and human capital are also highlighted along with international impacts. The report contains a mixture of actual and potential impacts, as some research has not yet fed through to final impacts. In all cases, best estimates have been used of actual and potential impacts based on available evidence with conservative estimates. The impacts reported in the case studies are gross. They are then reduced to net impacts by taking account of implementation costs required to achieve impact (by researchers and industry), what would have happened in the absence of the work (deadweight) and any activity which may be displaced. Displacement at the UK level is important to note. Where JIC has assisted an individual company leading to increased sales, it may simply displace other economic activity at the UK level. The company will have benefited but the UK will only benefit if imports can be displaced or there is some other value added. Attribution of the results to JIC is calculated based on either its share of total project costs or its share of the research undertaken. This varies for each area. Estimates of the rate of adoption of the research/technologies are also included so that net impacts are measured over a 10-year period (base year 2012) by way of a net present value (NPV) and a discount rate of 3.5% in line with HM Treasury Green book. The 10 year NPV presented can be considered the net contribution to the UK economy. The value for money of each research area can then be measured by dividing the net economic impacts by the research costs plus any other inputs. In some cases, given the nature of JIC research, the timescales are much longer than 10 years. In these cases, given the uncertainty, we have presented annual benefit estimates and assumptions over an appropriate period. In order to comply with the RCUK impact framework, Section 5 is devoted to wider impacts that are not necessarily captured within the monetised figures or the softer impacts highlighted within the case studies. Page 40 Appendix 3: JIC Journal Articles in Journals with impact factor of five or more, 20062012. Journal ACS Chemical Biology Analytical Chemistry Annual Review of Entomology Annual Review of Phytopathology Bioinformatics Cell* Cellular and Molecular Life Sciences Chemical Communications Current Biology* Current Opinion in Plant Biology Development Developmental Cell EMBO Journal EMBO Reports FEMS Microbiology Reviews Genes & Development Genome Biology Genome Research Journal of the American Chemical Society Journal of Biological Chemistry Journal of Cell Science Journal of Molecular Biology Molecular Biology & Evolution Molecular Microbiology Nature* Nature Biotechnology Nature Cell Biology Nature Chemical Biology Nature Genetics Nature Reviews Cancer Nature Structural & Molecular Biology New Phytologist Nucleic Acids Research Organic Letters Phil Trans Royal Society B Plant Cell Plant Journal Plant Physiology PLoS Biology* PLoS Genetics PLoS Pathogens Proc National Academy of Sciences* Proteomics Science* Impact Factor 5.149 5.646 10.68 10.237 6.019 31.253 5.511 5.141 10.992 10.333 7.293 13.523 8.295 6.907 7.963 12.075 6.626 10.176 8.58 5.581 6.144 5.229 9.872 5.361 34.48 29.495 19.527 16.058 34.284 29.538 12.273 6.033 7.479 5.42 5.117 9.293 6.946 6.235 12.916 9.532 8.978 9.432 5.479 29.747 Total Publications 1 2 1 1 5 3 1 4 8 11 2 1 1 1 3 2 3 1 6 20 4 9 1 24 8 3 1 6 2 1 1 11 10 1 1 47 25 31 6 4 3 31 3 21 Page 41 Journal Small Structure Trends in Biotechnology Trends in Cell Biology Trends in Genetics Trends in Microbiology Trends in Plant Science Impact Factor 6.171 5.904 6.909 12.115 8.869 6.894 9.883 Total Publications 3 1 2 1 1 1 3 Page 42 Appendix 4: Impact Model UK 10 years Summary of Net Impacts of JIC Research TOTAL Wheat yields Wheat Diseases Septoria Total research funding assessed £ Funding Gross Impacts JIC share of research funding assessed Gross annual benefits identified (£) Implementation timescale Gross Benefits over 10 years (£PV) Gross Implementation Costs over 10 yrs (£PV) Net Benefits (£PV) Net Additional Benefits Additionality of the impacts Value of benefits to the economy (£PV) for the UK Economy JIC attribution based on share of work Impacts Attributable to Additional Output over 10 years (£PV) Additional GVA over 10 years (£PV) JIC Additional Jobs Supported (FTE) VFM - JIC research funding only (GVA Value for money leverage per £1 JIC research funding (10yr GVA NPV)) 42,660,000 £ 15,625,000 £ £ 18,657,500 506,000,000 Over 10 years £ 858,102,298 £ 25,461,429 £ 789,980,869 100% £ 789,980,869 44% £ 347,065,370 £ 223,781,154 408 11.99 £ 2,076,000 £ 44,000,000 From yr 5 £ 100,611,556 £ £ 84,986,556 100% £ 84,986,556 17% £ 14,164,426 £ 8,463,104 15 4.08 £ 1,100,000 £ 100,000 £33,000,000 From yr 5 £75,458,667 £ £74,358,667 100% £74,358,667 10% £ 7,435,867 £ 4,870,272 7 48.70 Wheat Diseases Take all included in long-term & Non UK model OSR high oleic acid and pod N-fixation shatter included in longterm & Non UK £ 1,721,000 model £ 860,500 £ 213,000,000 From yr 5 £ 354,075,119 £ 1,867,021 £ 350,487,097 100% £ 350,487,097 50% £ 175,243,549 £ 115,368,172 157 134.07 Broccoli £ 14,805,000 £ 7,402,500 £ 38,000,000 £ £ 129,659,754 £ 1,966,184 £ 112,888,571 100% £ 112,888,571 50% £ 56,444,285 £ 34,736,378 140 4.69 Page 43 Appendix 4: Impact Model UK 10 years (cont’d) Summary of Net Impacts of JIC Research Legumes Total research funding assessed Funding JIC share of research funding assessed Gross annual benefits identified (£) Implementation timescale Gross Benefits over 10 years (£PV) Gross Impacts Gross Implementation Costs over 10 yrs (£PV) Net Benefits (£PV) Net Additional Benefits Additionality of the impacts Value of benefits to the economy (£PV) for the UK Economy JIC attribution based on share of work Impacts Attributable to Additional Output over 10 years (£PV) Additional GVA over 10 years (£PV) JIC Additional Jobs Supported (FTE) VFM - JIC research funding only (GVA Value for money leverage per £1 JIC research funding (10yr GVA NPV)) £ 1,500,000 £ 720,000 £ 13,000,000 From yr 5 £ 18,747,539 £ 1,449,275 £ 15,798,263 100% £ 15,798,263 48% £ 7,583,166 £ 4,760,090 19 6.61 £ £ £ £ £ £ £ £ £ Crop Scheduling Vinca Alkaloids included in 1,000,000 long-term & Non UK model 1,000,000 10,000,000 22,419,525 21,419,525 100% 21,419,525 25% 5,354,881 3,449,222 5 3.45 Temperature Sensing Molecular Antibiotics Pharming included in £ 821,000 £ 668,000 long-term & £ 5,420,000 Non UK model £ 410,500 £ 668,000 £ 5,420,000 £21,500,000 £ 110,000,000 £ 23,500,000 £37,429,857 £ 80,758,505 £ 38,941,777 £ 871,442 £ 1,000,000 £ 18,307,507 £35,737,415 £ 79,090,505 £ 15,214,270 100% 100% 100% £35,737,415 £ 79,090,505 £ 15,214,270 50% 70% 50% £17,868,708 £ 55,363,353 £ 7,607,135 £11,653,777 £ 36,380,829 £ 4,099,309 16 50 1 28.39 Page 44 DA1 54.46 0.76 Appendix 5: Impact model long term UK and global impacts TOTAL Total research funding assessed Gross Impacts Net Additional Benefits globally Impacts Attributable to JIC Value for money included in UK 10 year model included in UK £ 10 year model £ 21,118,000 JIC share of research funding assessed Gross annual benefits identified (£) Implementation timescale £ £ 21,118,000 8,517,400,000 £ Gross Benefits over 30 years (£PV) Gross Implementation Costs over 30 yrs (£PV) £ £ 403,226,394 included in UK 10 year model Net Benefits (£PV) Additionality of the impacts Value of benefits to the economy (£PV) JIC attribution based on share of work Additional Output over 30 years (£PV) Additional GVA over 30 years (£PV) Additional Jobs Supported (FTE) VFM - JIC research funding only (GVA leverage per £1 JIC research funding (30yr GVA NPV)) £ 48,386,164,355 100% 48,386,164,355 49% 23,877,630,812 15,752,599,536 12433 £ 2,747,177,742 100% £ 2,747,177,742 17% £ 457,862,957 £ 302,189,552 136 £ 7,179,769,565 100% £ 7,179,769,565 10% £ 717,976,957 £ 473,864,791 213 included in UK 10 year model included in UK 10 year model Funding Over 10 years or more £ £ £ Wheat Diseases Take all Wheat Diseases Wheat yields Septoria Summary of Net Impacts of JIC Research 232,000,000 From yr 5 48,819,178,749 £ 2,747,177,742 £ 696,000,000 £ 1,030,000 £200,000,000 From yr 5 £ 7,179,769,565 From yr 10 £705,630,051 included in UK £ 10 year model Page 45 1,030,000 4,209,866 £700,390,186 100% £700,390,186 50% £350,195,093 £230,953,661 313 224.23 N-fixation £ 17,460,000 £ 17,460,000 £ 3,792,000,000 From Yr 22 nonUK £ 5,284,089,566 £ 21,267,564 £ 5,245,362,001 100% £ 5,245,362,001 70% £ 3,671,753,401 £ 2,419,201,765 1,095 138.6 OSR high oleic acid and pod shatter Broccoli included in UK 10 included in UK year model 10 year model £ 2,197,000,000 From yr 5 £ 19,781,940,249 £ 38,000,000 From Yr10 £382,866,723 included in UK 10 included in UK year model 10 year model £ 19,781,940,249 100% £ 19,781,940,249 50% £ 9,890,970,124 £ 6,528,040,282 2,941 £382,866,723 100% £382,866,723 50% £191,433,362 £126,346,019 140 included in UK 10 included in UK year model 10 year model Appendix 5: Impact model long term UK and global impacts (cont’d) Summary of Net Impacts of JIC Research Legumes Total research funding assessed Funding JIC share of research funding assessed Gross annual benefits identified (£) Implementation timescale Gross Impacts Net Additional Benefits globally Impacts Attributable to JIC Value for money Gross Benefits over 30 years (£PV) Gross Implementation Costs over 30 yrs (£PV) Net Benefits (£PV) Additionality of the impacts Value of benefits to the economy (£PV) JIC attribution based on share of work Additional Output over 30 years (£PV) Additional GVA over 30 years (£PV) Additional Jobs Supported (FTE) VFM - JIC research funding only (GVA leverage per £1 JIC research funding (30yr GVA NPV)) Crop Scheduling Vinca Alkaloids included in UK included in UK £ 10 year model 10 year model 1,750,000 £ £ 1,750,000 9,400,000 £ 13,000,000 From Yr 10 £107,329,552 £ 10,000,000 £ 100,754,401 £ 99,754,401 100% £ 99,754,401 25% £ 24,938,600 £ 16,374,476 22 included in UK included in UK 10 year model 10 year model included in UK 10 year model DA1 Antibiotics included in UK 10 £ year model Molecular Pharming included in UK 10 year model 878,000 £ 878,000 £ 21,500,000 £ 1,160,000,000 £ 125,000,000 £ Post 10 yr From yr 5 From yr 7 From yr 14 benefits £ 91,163,435 £ 199,417,632 £ 11,399,732,347 £ 629,850,922 £ included in UK included in UK £ 10 year model 10 year model £105,829,552 100% £105,829,552 48% £ 50,798,185 £ 33,282,002 113 Temperature Sensing 1,307,679 £ 88,105,756 100% £ 88,105,756 100% £ 88,105,756 £ 57,554,799 79 32.89 Page 46 included in UK 10 year model included in UK 10 £ 376,441,284 year model £ 199,167,632 100% £ 199,167,632 50% £ 99,583,816 £ 65,682,819 30 £ 11,399,232,347 100% £ 11,399,232,347 70% £ 7,979,462,643 £ 5,266,326,344 7,117 included in UK 10 year model included in UK 10 year model £ 252,531,638 100% £ 252,531,638 100% £ 252,531,638 £ 166,372,361 186 189.49 23,500,000 Post 10 yr benefits 209,456,564 included in UK 10 year model £ £ £ £ 204,036,564 100% 204,036,564 50% 102,018,282 66,410,666 47 included in UK 10 year model