Non-Food Crop Projects: Phyto-pharmaceuticals: nature’s medicines People have used plants for medication since pre-historic times. In the 21st century we can exploit plants as whole extracts - often referred to as phyto-therapies, extract the single molecule pharmaceutical compounds favoured by Western medicine or use them as factories to produce therapeutic proteins and secondary metabolites. building the supply chain The Traditional Herbal Phytotherapies Single compound pharmaceuticals Medicinal Products Directive There is increasing interest in the use of herbal extracts as medicines: surveys in Some 30% of our prescription drugs are based on plant-derived metabolites. Non-Food uses of crops supply chain European Commission published the US suggest that some 40% of Americans consume medicinal botanicals. Although many of these, aspirin for instance, are now synthesised chemically, a Barriers to crop-based the Traditional Herbal Medicinal Importantly there is an increasing body of scientific evidence for efficacy of some significant proportion are too difficult or expensive to make in vitro. Examples include assessment & development R&D programme Products Directive (2004/24/EC) of these extracts. For instance phase III clinical trials of selective extracts from painkillers based on opioids from poppies, anti-cancer compounds found in in April this year. All EU states are The NNFCC has been supporting Defra in running a Cannabis have shown they are effective treatments for multiple sclerosis and mayapple, yew and Madagascar periwinkle. Foxgloves are cultivated to produce the building materials now required to comply with this programme of R&D on “Non-Food Uses of Crops: Supply neuropathic pain. The herbal supplement market has been growing at 8.7% heart drug digoxin and Artemisia annua for the anti-malarial, artemisinin. Crop-based materials for buildings are beginning to Directive by 30th October 2005. Chain Assessment and Development”. The first competitive annually and many of the plants to satisfy this demand can be grown in the UK. find niche opportunities within the building industry The Medicines and Healthcare call for proposals under this programme provoked thirty where sustainable construction technologies are products Regulatory Agency Echinacea three applications by the closing date in May 2004. Taxol attracting attention amongst the general public as well (MHRA) is already involved in an Echinacea, or purple coneflower, has been used to treat Following advice from the Programme Advisory Committee as building professionals. For an instance insulation informal consultation with colds and coughs for centuries and has attracted Extracts from the bark of Taxus brevifolia were shown to which met for the first time in June, Defra has issued one attention for HIV therapies. The German Commission E materials manufactured from wool, and flax are interested parties on the possess anti-cancer properties in the early 1960s. Ten years contract and is negotiating four others. Two projects which has approved the oral use of Echinacea purpurea herb, commercially available, linseed oil and starch are transposition of the directive into later the active compound, named taxol after the genus of the have been recommended for funding are described below. i.e. the above-ground parts, for colds, respiratory tract exploited in surface coatings and plant fibres are used UK law. species, was isolated and its structure determined. Interestingly, infections, and urinary tract infections and its topical use to reinforce composite boards, blocks and plaster. no patent was filed on the compound because investigators What does the legislation seek to for poorly healing wounds. As for many herbal New resins derived from crops for the achieve? The formal recognition thought the amounts of taxol obtained were too small to justify preparations, there is a need for standardised, chemically its development - the bark of a whole tree was required for a manufacture of composite materials However that medicinal plants can have defined preparations. Formulations of Echinacea extracts single dose of taxol. As the mode of action of taxol was Some 85% of the composites used in the EU still use exploitation of powerful effects on the body has represent around 10% of the herbals market. unravelled and its utility in cancer therapy demonstrated, richer formaldehyde based resins. Formaldehyde has recently crop-derived necessitated that they be treated sources of the compound were required: Bristol Myers Squibb been classified as a class A carcinogen. It presents a resources for in much the same way as St John’s Wort synthetic medicines, with respect Extracts of Hypericum perforatum are widely found that a related species, Taxus baccata, produces a more hazard during composite manufacture, where workers may building is still abundant relative that can be converted to taxol in vitro. be exposed to high levels, and during use, due to release embryonic and to safety and quality. However, prescribed in Germany and clinical trials have from the composites themselves. Defra therefore the safe traditional use and suggested that, in the medically supervised Although this has been good news for victims of cancer - the accepted efficacy of many herbal treatment of mild to moderate depression, Picture commissioned the Courtesy drug is widely used to treat breast cancer, Kaposi's sarcoma and A contract has been issued to a consortium led by Keele Building Research medicines has allowed for a preparations of St. John’s Wort are of comparable of some forms of lung cancer - there have been problems in North efficacy to synthetic antidepressants. JavaJane.co.uk University which aims to commercialise resins derived from Establishment simplified regulatory framework East India where the high value of extracts has led to an illegal plant sources to replace formaldehyde-based resins in (BRE) to conduct a review of regulatory, commercial or to be applied, which accepts trade which is devastating the sacred groves of Himalayan Yew. that, for many herbs, there is a manufacture of composite materials. It builds on a LINK technical barriers to adoption of crop-based materials. reduced need for pre-clinical and Modern biotechnology may resolve the shortage, and hence the project which developed This found that regulatory barriers were not of Molecular pharming: crops as drug bio-factories Etoposides clinical studies. price, of taxol-derived drugs. Phyton Catalytic, a division of DFB improved methods for use of themselves insurmountable, but that the cost of Podophyllotoxin, from mayapple (Podophyllum peltatum) pharmaceuticals, have developed a plant cell culture method for By applying common, vegetable oils in co-polymers. producing technical data required to satisfy building Plants have enormous potential for economic, large scale is a precursor for a class of anti-cancer drugs known as its production. A number of the genes encoding enzymes appropriate regulations regulations can be prohibitively large for new products. production of therapeutic proteins. Compared with current etoposides. It is extracted from roots and rhizomes of involved in biosynthesis of this complex molecule have now throughout the European The main objectives of the project production platforms in genetically modified bacteria or the plant. As these plant species can not yet be been characterised, opening the possibility of biotech Community, the desired goal of involve scale up of the resin Fire hazard is often misquoted as a potential risk in use mammalian cells, capital costs are around ten fold lower and cultivated, one source of the molecule, P. hexandrum production routes. producing and prescribing safe, manufacture to the metric tonne of straw bales as a construction material. However production capacity is easily scaled up. Plants do not harbour became an endangered species in India. effective, high-quality medicines level, identification of market human pathogens and natural storage organs such as seeds can Artemisinin BRE found good fire resistance when they tested should be achieved. Registered Because the yield of podophyllotoxin in mayapple is opportunities and potential eliminate the necessity for cold-storage. rendered straw bales. products will be able to move very low, scientists are looking for alternative sources Extracts of Sweet Annie, industrial partners and trial testing Scientists have freely throughout the EU, and Although the potential of plants as factories for production of and trying to understand the biosynthesis of the Artemisia annua, have been of the resin on full scale plant manufacturing facilities. The successfully expressed The full report will be published shortly on the NNFCC patients in all member states will pharmaceutical proteins has been recognised for some two molecule. There is some interest in podophyllotoxin used for over three thousand project encompasses a partnership between Keele proteins in tomatoes website and it will be used to develop strategic plans have access to the same range decades no plant-produced therapeutics are yet on the market. derivatives for treatment of HIV so discovery of years in China for treatment of University, Advance Enterprises Limited, Cargill Industrial which could be used as to exploit crops in construction. of treatments and medicines. edible vaccines. alternative sources of the molecule is increasingly malaria. The active molecule, Oils and Lubricants and Boustead Consulting Limited. Pharma-Planta urgent. artemisinin, was isolated in the Detailed information on the The Pharma-Planta consortium brings together 1970s. Scientists at John Sustainable & renewable reactive vegetable oil based resin systems for timber preservation Traditional Herbal Medicines Hopkins University have Registration Scheme, and of laboratories from eleven European countries to build a Funding has been recommended to support a consortium resistance and a vegetable oil based resin provides the plant-based production system for pharmaceuticals in recently announced that they other proposed regulations, is have synthesised drugs based led by the Biocomposites Centre to develop a bio-derived, preservative function within the timber. It is envisaged that available from the MHRA web- Europe and enter the first candidate pharmaceuticals into vegetable oil-based resin / heat treatment to improve the the resin will form a surface layer sealing the oil within the clinical trials. on the structure of artemisinin site (www.mhra.gov.uk ). which are claimed to be even more effective than quality, appearance and durability of UK-grown softwoods timber. Pharma-Planta's first targets are diseases that affect the such as spruce and fir. The scope of the Directive is the natural molecule. limited to manufactured, over- developing world - HIV, TB and rabies - as well as diabetes, a The BioComposites Centre is working with BSW Timber The World Health Organisation has now recommended that the-counter (OTC) herbal growing problem of the West. Professor Ma, scientific co-ordinator at Wood preservation chemicals are an important market PLC, Cambridge Biopolymers Ltd and Clifford Jones Timber Artemisinin Combination Therapies (ACTs) are the drugs of products, but the Department of St George’s Hospital Medical School, points out that current sector with nearly two million cubic metres of softwood Ltd. They have chosen choice for combating drug-resistant malaria - a disease that Health has issued proposals for fermentation capacity simply can not produce enough proteins for treated each year in the UK. It now faces a significant two product kills 3 million people each year. the statutory regulation of herbal new therapies such as antibodies for use in contraceptive creams to challenge as preservation systems based on heavy metals, applications to practitioners. In additon the block HIV infection during intercourse. Artemisinin is synthesised in specialised organs, glandular CCA, and creosote systems are phased out because of demonstrate the new MHRA will soon publish the trichomes, on the surfaces of leaves and flowers. Biologists environmental concerns. Wood is a sustainable building treatment – wood Regulation and biosafety are a major focus of the consortium: their biosafety co- response to their consultation ordinator, Professor Philip Dale, an expert on GM safety issues, points out “The ability are investigating development and metabolism of these material and new preservation systems are needed now. decking and playground letter (MLX 299) on proposals to specialised chemical factories with a view to enhancing equipment – as high to isolate these from other crops is the crucial ”. A major consultation exercise reform the regulation of individual will be undertaken to determine critical issues such as the species to be used for yield or profile of important secondary metabolites such as The project involves technical development of a treatment profile markets that are unlicensed herbal remedies. production (probably maize or tobacco), the site (EU and/or South Africa) and the artemisinin system where heat reduces the shrinking and swelling easily understood by method (contained or in open field). characteristic of softwood as well as increasing fungal the public. Non-food crop news and views Events• Publications• Funding Pharmaceutical Crops

News from Europe Straw for paper Funding for Non-food uses of crop in the 21st Century BioRegional MiniMills is finalising funding to build a £1.3m Two sources of funding specifically for development of ministers support research into pilot plant to turn straw into pulp, for papermaking. non-food uses of crops have recently been Man has produced “medicines” from natural products since time immemorial but it is renewables announced: The National Although straw is in perhaps surprising that with the vast amount of scientific knowledge available today Eight EU Agriculture ministers supported a proposal to short supply this Non-Food Uses of Crops - supply chain extracts from over 1,000 different plants are still being used in prescription medicines. promote research into renewable raw materials for the Non-Food year, it has been assessment and development. production of energy or as a substitute for fossil fuel products, estimated that especially within the context of the 7th Framework Programme. This programme, funded by Defra, supports highly Crops Centre Many drugs which were previously extracted from plants are of course now being usually there is four Their submission also recommended changes to the regulatory applied industrial R&D to develop and/or assess million tonnes produced synthetically although the synthetic versions are not always as good as framework and promotion of products based on renewable raw supply chains based on the non-food use of crops. excess. If the the natural one. An example of this is the materials in order to encourage Technologies used throughout the supply chain from technology works on production of Galanthamine, which for some the development of non-food novel crop agronomy through product development to a commercial scale, a totally new £27m/year market for up applications. economic and environmental analyses of production years was extracted from daffodil bulbs until a to 900,000t of straw could develop, generating pulp with a systems and product and process life cycle synthetic version was produced. However this value of £144 million. assessment are solicited. Although the proposal backs bio- synthetic product has proved to be less fuel applications, it is worth Vegetable oils for the HGCA is contributing £49,100 to the project to support Deadline: 15 November 2004 effective in a number of specific areas and the noting that the European work on energy and chemical recovery and re-use in the For further information tel 01904 435341 natural extract is once again being used. Environment Bureau opposes hydrogen economy pulp mill . "If the project takes off straw could be used to http://www.nnfcc.uk/funding/index/cfm them, arguing that their benefits subsitute 20% of imported wood pulp, creating a local in terms of reduced carbon In other cases despite exhaustive research it Researchers at the University of Leeds together with Dupont renewable source." commented HGCA's market HGCA Enterprise Awards emissions must be balanced have produced an experimental generator which turns development chairman, Julian Gibbons. A new round of Enterprise Awards has just been has proved impossible to produce a suitable against pollution caused by their vegetable oil into hydrogen. The MiniMill technology allows plants to be cost launched which offers all types of businesses funding synthetic replacement and morphine is a typical use of fertiliser and pesticides. for developing, producing and marketing products The generator can yield hydrogen at a purity of 90%, which is competitive at around a tenth of the size of conventional example of this. made from cereals such as oats, barley and wheat: more efficient than current models which achieve a purity of wood pulp mills. A meeting of the council in ranging from £5,000 to £50,000. 70%. August welcomed the Deadline: 31 December 2004 In the there are currently a Commission’s intention to develop a action plan to Hydrogen is thought to be the fuel of the future with most car FORTHCOMING EVENTS Contact: 020 7520 3927 considerable range of crops being grown for the address issues like biomass definition, administrative barriers, manufacturers working on development of fuel cell technology. http://www.hgca.co.uk/enterprise/windows.htm Issue 3 - Autumn 2004 pharmaceutical industry and whilst it is unlikely availability of biomass and transparency of biomass markets. THE GREEN SUPPLY CHAIN One of the barriers to its adoption isdevelopment of a Further information on sources of funding relevant to that any of these crops will reach broad acre distribution network. The technology developed in the UK from crop to consumer non-food uses of crops can be found at the NNFCC proportions they represent interesting and Biolubricants could be refined to allow filling stations to manufacture NNFCC first annual conference - 4/5 Nov 2004 website. Central Science Laboratory, York profitable break crops for the UK farmer and a Biolubricants have been the subject of a fast- hydrogen on-site using renewable resources. www..co.uk Tel: 01904 435182 track procedure to develop an eco-label. The useful source of income for the contracting draft proposal includes criteria for merchant. 13 - 15 October 2004 European Panel Products inclusion of a significant proportion of Symposium 2004 Llandudno, UK. Contact: Sue Griffiths, Interesting publications renewable oil, further securing the place of Growing EU market for The BioComposites Centre 01248 370588. New medicines from an old plant crop-based oils in lubricants. The Eco-label The opportunities for use of esters of rapeseed oil as bio- board discussed the proposal at their meeting 18 October 2004 BRE: Wood Plastics Composites renewable solvents. D B Turley, F J Areal and J E Copeland 28th September 2004 and will vote on it at their Biopolymers seminar: Opportunities in the construction industry. BRE, http://www.hgca.com/publications/documents/cropresearch/ December meeting. Watford. Contact: BRE Events 01923 664800. RR52_Final_Review.pdf The opium poppy, Papaver somniferum, has Although biopolymers still hold a very small share of the been used as a source of analgesics for over 40 million tonnes of plastic that is used in the EU, that 21 October 2004 Crystal Faraday Seminar Selective Buying Green: a handbook on environmental public 5000 years and is currently the source for Pembrokeshire farmers launch share is growing. Oxidation for Greener Processes. The Samsung Centre, procurement.European Commission codeine, morphine and other important co-operative Wynyard, Billingham, Cleveland. Contact: Crystal Faraday http://europa.eu.int/comm/internal_market/publicprocurement Opium Poppy head Farmers in Pembrokeshire have launched a co-operative to The International Biodegradable Polymers Association Partnership 01788 534487. /docs/keydocs/gpphandbook_en.pdf pharmaceuticals of Western medicine. Around and Working Groups (IBAW), the industrial platform of 40% of the legally traded opiates are produced in Tasmania, but the UK is now produce, market and supply biofuels. Pembrokeshire 21 - 22 October 2004 FaraPack Briefing 2004. New Life cycle environmental performance of renewable building will focus on public buildings such as hotels, swimming pools the biopolymer industries, estimate that total Technologies for Innovative Packaging. Ebor Stand, York materials. Bruce Lippke et al competing with poppies cultivated in the South of England. and large detached properties. biopolymer consumption in the EU15 has nearly Racecourse. Contact: Pauline King 0113 284 0213. http://www.corrim.org/reports/ doubled between 2001 and 2003, from 20,000 to

NEWSLETTER Since 1997, farmers have been growing a mutant, known as Norman, which does not The chair of the groups’ 40,000 tonnes. 1 November 2004 2nd Green Chemistry and the Consumer Business as usual projections of agricultural outputs steering committee, Paul Symposium, , UK. Contact: Mrs Louise Summerton Centre for rural economics research, University of Cambridge produce morphine or codeine but accumulates precursors that can be converted into Ratcliffe, points out “The Importantly new markets have been developed: 01904 434546. http://www.environmentagency.gov.uk/commondata/103599/ even more effective pain killers or treatments for heroine addiction. Scientists in new Welsh Assembly biopolymer packaging consumed 5-10,000 tonnes in busiasusualwfd_854912.doc Australia are studying this mutant to understand the complex metabolic network 2 - 3 November 2004 4th Annual Bioscience Forum York, Biocentre building is heated with 2003, a ten fold increase over 2001. Mulch film and film UK. Contact: Shahla Siddiqui. White Rose University Biomass and agriculture: , markets and policies. York Science Park associated with the morphine pathway. Here in the UK molecular biologists have woodchips, which have packaging show particularly strong growth rates, OECD http://oecd.org/agr/env isolated enzymes from micro-organisms found in the soil near poppy plants and are the environmental benefits especially in markets where biodegradability/ Consortium 01904 435337. Innovation Way 2 using them as a clean and cost-effective way to transform morphine into more of being CO neutral and compostability are important features. 19 November 2004 Annual Cranfield Conference: The Rural Strategy 2004 Heslington Defra effective drugs. providing habitats for Curry Report - From Theory to Practice, from Planning to York wildlife” Growth in the biopolymer market could be significant Delivery. Cranfield School of Management, Cranfield, http://www.defra.gov.uk/rural/pdfs/strategy/rural_strategy_20 04.pdf YO10 5DG ps to cashflow: b for non-food uses of crops: most of the biodegradable Bedford. Contact: Helen Knight 01234 754362. cro uildin s The NNFCC recently polymers are manufactured from inputs that are 40- rom g su ain Green Plants as Biofactories for Drugs. James Flinn and F stai ly ch published a practical 95% renewable. 08 - 10 Dec 2004 Bioplastics 2004 and Natural Fibres 2004. Juliet Zavon Tel: (01904) 435182 nable supp guide to wood fuel heating Sheraton Hotel, Frankfurt, Germany. Contact: http://www.biopharmmag.com/biopharm/article/articleDetail.j Fax: (01904) 435345 for public buildings, which For further information on the EU market for sp?id=115117 tel. 0207 505 6044 email [email protected] [email protected] is available at biopolymers visit http://www.ibaw.org www.nnfcc.co.uk www.nnfcc.co.uk

This newsletter is printed on paper which is 50% recycled pulp and 50% from sustainable rain forest.