Yellow Gold: Innovative systems for sustinable daffodil-derived galanthemine production in the uplands

The number of people suffering from dementia is large and growing at a considerable rate. In 2010, there were over 35.6 million dementia sufferers worldwide and 4.6 million cases are diagnosed each year. Alzheimer's Disease (AD) accounts for between 50 and 75% of these cases. Galantamine has been approved by the US Food and Drug Administration, the UK Medicines and Healthcare Products Regulatory Authority and the European Medicines Agency as an AD treatment since 1998. Galantamine is mainly produced from plants, and although chemical synthesis is possible, it is difficult and expensive. Galan/th/amine is the natural plant alkaloid used to produce the pharmaceutical product galan/t/amine. It is currently being extracted from daffodils/Narcissus (in central and western Europe), Leucojum (in eastern Europe) and Lycoris (in China). However, with the exception of daffodils the source plants are wild flowers not suitable for agricultural exploitation due to limitations in either resources or research. Thus daffodils are the only economically-viable world-wide source for galantamine. The annual global consumption of galantamine is currently constrained to 3-4 t/yr by existing production levels, but published figures predict the potential global market could be nearer 40 t/yr. Independent reports project the competitive Active Pharmaceutical Ingredient price for galantamine drugs to remain between £15,000 - £18,000/kg in the medium term.

The UK uplands are characterised by poor growing conditions brought about by a combination of factors including: low temperatures; exposure to wind; high rainfall; winter frosts; thin, stony soils; and a shortage of major nutrients. Consequently agricultural production is generally limited to grassland-based beef and sheep systems that are currently heavily reliant upon Government support payments to be economic. However, previous research ('Sustainable production of the natural product galanthamine'; Defra project NF0612) esblished that the environmental challenges associated with upland areas trigger a 50% higher yield of galanthamine in daffodils that are grown there when compared to those grown in lowland conditions. Daffodils grown for galanthamine production therefore offer a novel, potentially high value crop for UK upland farmers that could provide an important new income stream, increasing their economic resilience. However, for this to happen, underpinning research is required to evaluate and overcome any problems associated with integrating daffodil production into existing pastoral based farming systems. This project will design, test and evaluate machinery for planting bulbs under long-term grass leys and selectively harvesting the subsequent green daffodil material. Field-scale agronomy trials over a 4 year period will assess establishment rates and the extent to which these are influenced by seasonal variation. Full-scale production trials will quantify the impact of incorporating daffodil production into grazed pastures on animal performance and the stock carrying capacity of the land. The extent to which fertiliser inputs influence the competitive ability of the daffodils and the yield of galanthamine obtained will also be determined in order to develop protocols which optimise simultaneous production of galanthamine and livestock from hill and upland farms. Growing daffodils in this way will ensure that the ecosystem services associated with grazed grasslands in the uplands are maintained.