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Artemisia annua

Developing Artemisia annua, for the extraction of Artemisinin to treat multi-drug resistant malaria

Contact: Steven Bentley

This project started in 2006 following previous studies funded by Defra and the partners. We have tackled agronomic, genetic, biochemical and plant physiological issues relating to the cultivation of Artemisia annua.

A. annua contains a natural chemical called artemisinin, which kills the principal malarial parasite, Plasmodium falciparum. Artemisinin is a complex secondary plant metabolite which cannot be economically synthesised de novo. The unique configuration of the oxygen atoms in this molecule make it difficult to synthesise and this is key to its potent anti-malarial activity. Artemisinin is thought to work though generation of a carbon-centered free radical, which interferes with more than one biochemical pathway important in the growth and infection process of P. falciparum parasites. This complex mode of action, which could be said to ‘starve’ the parasite, may also help to limit the build up of resistance. The WHO has recommended artemisinin-based therapies in combination with another effective blood schizontocide (such as mefloquine) to reduce recrudescences and to slow the development of resistance. See also http://www.who.int/malaria/. More than fifty countries have now adopted A. annua-based anti-malarials as the front line treatment for multi-drug resistant malaria. Malaria still kills over a million people every year, mainly in the under-five age group.

We have put in place the necessary steps for developing this crop; addressing each step in the value chain. Using a new germplasm collection, the consortium have evaulated and improved the plant genetic resources, aided by development of improved tools for rapid, accurate testing artemisinin. The partnership have developed a system for provision of good quality seed, developed a field production system, harvest, stabilisation, extraction and finally, purification for delivery to the pharmaceutical company.

Seed was obtained from a range of sources, and this collection formed the basis of a programme of improvement using classic plant breeding approaches. So far, the artemisinin concentration has been improved by 100% over commercial lines, but this is only part of the process for real improvements in the supply of this valuable pharmaceutical. The high percentage level of artemisinin in the leaf tissue needs to be matched with healthy robust plants that produce high levels of biomass, so that the harvest of artemisinin per hectare is economically feasible. Furthermore, agronomy and agrochemical inputs in the field can have an impact on artemisinin concentration and yield per plant; the levels in our trials are now approaching 2% w/w dry material. The consortium has been tackling issues relating to seed quality and germination and establishment of the crop in the field, which can be initially slow due to the tiny seed size and subsequent problems associated with weed competition. The harvest regime and the timing and method of preliminary fixing of the material are being addressed to ensure that both measured concentrations of artemisinin and total yields per hectare are maintained.

Funding: Project sponsored by Defra through Renewable Materials LINK programme; Horticultural Development Council and industrial support

Collaborating Organisations: De Montfort University; East Malling Research, Botanical Developments Ltd, Frontier Agriculture and Humber VHB