Development of Artemisia annua L. as a crop for production of the antimalarial drug artemisinin

Artemisinin is the parent compound for the latest generation of anti-malarial drugs. In many cases of severe or drug-resistant malaria, the artemisinins are the only effective means of treatment for this common and life-threatening parasitic infection. However, the current supply of artemisinin is unstable, and is predicted to fall far short of demand in the coming years. As artemisinin can currently not be economically synthesised, the only source of the compound is the Chinese herb Artemisia annua L. With the ultimate objective of stabilising the global supply of artemisinin, a Consortium of academics, agronomics and business partners was established. The Consortium, with funding from Defra and the Horticultural Development Company under the name of Project LINK 0822, was to examine the feasibility of establishing an “artemisinin supply chain” – from crop in the field to pure, active pharmaceutical ingredient – based entirely within the UK. The work presented in this thesis formed part of this Consortium’s research – namely, the establishment and validation of rapid, accurate and economical means of quality control of both raw herbal material and purified ingredient. To that end, methods were developed allowing both field-based, triaging quantification and more accurate, high-throughput laboratory-based quantification of sample material. Improved means of artemisinin purification – in particular the removal of the inactive metabolite deoxyartemisinin, which co-elutes and co-crystallises with artemisinin - were also developed. In addition, the potential pharmacological value of other compounds besides artemisinin was explored – namely, chrysosplenetin. This latter is a methoxylated flavonoid that accumulates with artemisinin in the plant, and has been shown, in this study, to have potential in the treatment of cancer. Finally, the feasibility of self-medication with Artemisia annua L. - in the form of herbal teas and over-the-counter preparations of the plant – was examined, and the amount of artemisinin, deoxyartemisinin and chrysosplenetin in such preparations was examined. 22 During the four years in which the LINK project ran, the Consortium members worked together to ultimately develop new lines of Artemisia annua L, that not only flourished in the UK climate, but also consistently yielded high (> 2.2 % w/DW) levels of artemisinin – almost a twofold increase from that at the beginning of the project. These new lines, together with the improved analytical techniques and means of artemisinin purification, demonstrate clearly that an artemisinin supply chain can indeed be based within the UK, thus contributing to a stable, year-on-year supply of artemisinin.