New hybrid varieties of Artemisia annua
from the University of York
The CNAP Artemisia Research Project
Tackling malaria with fast track plant breeding
The CNAP Artemisia Research Project
CNAP
Department of Biology (Area 7)
The University of York
Heslington
York
YO10 5DD
UK
Tel: +44 (0) 1904 328834
Fax: +44 (0) 1904 328830
[email protected]
www.cnap.org.uk
The CNAP Artemisia Research Project
This project is using the latest genetic and
We are using molecular plant breeding and
analytical technologies to rapidly improve
not GM to create these new varieties.
supplies of a vital malaria drug. With the
help of molecular plant breeding, we are
developing higher yielding, more robust
varieties of the world’s most important
medicinal herb: Artemisia annua. Artemisia
is the source of the most effective cure for
malaria and the new varieties are urgently
“Their results are innovative
in terms of the scale of the
research and sophistication of
the technologies involved.”*
needed to help meet increasing demand for
affordable malaria medicines.
*”The botanical solution for malaria,” W.K. Milhous and O.J. Weina, Science
327. no. 5963, pp. 279 - 280 (2010).
The research is based in the Centre
for Novel Agricultural Products (CNAP)
at the University of York, UK where
Professor Dianna Bowles and Professor
Ian Graham lead a project team of around
30 molecular biologists, geneticists,
biochemists, plant breeders and
horticulturalists. The scientists have
state-of-the-art facilities for chemical
analyses, molecular genetics and
bioinformatics. The project is funded by
the Bill & Melinda Gates Foundation.
Context
Malaria control
Malaria is one of the world’s most serious
public health problems, claiming almost a
million lives a year every year and undermining
development in some of the world’s poorest
countries. However, with new tools and
increased malaria funding, there is now real
hope of making progress against this disease
and possibly even eradicating it. A massive
scaling up of control efforts is underway, and
this includes increased use of artemisinin
combination therapies (ACTs) to cure malaria.
Artemisinin Combination Therapies (ACTs)
ACTs are currently the most effective
cure for malaria. Their active ingredient is
artemisinin, which is extracted from the
plant Artemisia annua. Demand for ACTs
is predicted to increase dramatically, from
around 100 million treatments in 2008 to
250 million by 2015. However, the low yield
of Artemisia creates problems for production
and there are concerns that artemisinin
supplies will not reliably keep pace with
increasing demand for ACTs.
Agricultural production of Artemisia
Artemisia is farmed in Asia and Africa, where it is an
important income source for tens of thousands of smallscale growers. Production in these regions creates a yearround supply and enables malarial countries to contribute
to their own national health.
However, relatively little has been done to develop the
Artemisia plant from a weed into an agricultural crop. Yields
are extremely low, and this makes agricultural production
of artemisinin expensive and often uneconomic. Artemisia
farmers badly need robust higher-yielding varieties.
Although synthetic methods of production are being
developed, plant production is expected to remain an
essential source of supply.
©MMV
Benefits from the new varieties
High-yielding Artemisia varieties from this project will
bring a range of benefits, helping to;
Stabilise artemisinin supplies
farmers will be encouraged to grow more Artemisia,
which will prevent shortage-driven price hikes.
Lower production costs
increasing the artemisinin content of the plant substantially
reduces the costs of both cultivation and extraction.
Support small-scale farmers in less developed regions
by providing them with a more robust and profitable crop.
Reduce environmental impacts
by lowering the requirements for transport and the amount
of solvent needed for extraction.
Support production of high quality ACTs
seed for the new varieties will be available for Artemisia growers
supplying high quality ACTs.
Contribute to increased efforts to tackle malaria
the first high yielding seeds will be available in time to supply
increasing demand for ACTs.
Molecular tools for faster plant breeding
We have developed DNA-based techniques for the early stage
recognition of promising Artemisia plants. To do this, we
identified variations in the plant’s DNA that are consistently
linked to certain plant features. These DNA sequences may
represent genes for a given plant feature, or they may be
molecular markers: sequences that lie close to the gene and are
usually inherited with it. Molecular markers are reliable DNA
indicators that a plant has inherited the associated feature. G5
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A13
In 2010, we published the first genetic map of Artemisia annua
in Science*. The map plots the relative position along the plant’s
DNA of around 700 molecular markers and 50 genes, as well
as QTLs for key traits. This work represents a major advance in
our understanding of Artemisia genetics. It means that valuable
Artemisia plants can now be recognised from their DNA at an
early stage and makes it possible to breed improved varieties in
a fraction of the time it would otherwise take.
* The genetic map of Artemisia annua L. identifies multiple trait
loci affecting yield of the antimalarial drug artemisinin.” Ian A.
Graham, Katrin Besser, Susan Blumer, Caroline A. Branigan, Tomasz
Czechowski, Luisa Elias, Inna Guterman, David Harvey, Peter G.
Isaac, Awais M. Khan, Tony R. Larson, Yi Li, Tanya Pawson, Teresa
Penfield, Anne M. Rae, Deborah A. Rathbone, Sonja Reid, Joe
Ross, Margaret F. Smallwood, Vincent Segura, Theresa Townsend,
Darshna Vyas, Thilo Winzer, Dianna Bowles. Science 327, no. 5963,
pp. 328 - 331 (2010).
G6
C4-L
A pipeline of potential
We select the most promising individuals for our
plant breeding with a series of specially-developed
tests. Plants are chosen on the basis of features
such as metabolite profile and, plant biomass. They
are also selected according to their genetics, using
our new genetic map. For example, we choose
plants with positive genetic scores for key traits
such as leaf area and artemisinin concentration.
Over 32,000 plants have been assessed in this
way, generating a collection of potential high
performers. These plants are crossed, using
a variety of breeding strategies, to produce
experimental hybrid plants. Each stage of this
process is guided by further trait and DNA
assessments. As the project progresses, more
data becomes available to inform each choice.
Thus, a pipeline of increasingly high-performing
new plant lines is in operation.
Field testing
The best plant lines are selected for further development
on the basis of extensive field trials in the commercial
production centres of Africa and Asia. These tests ensure that
the varieties we develop will perform well when grown under
regional agricultural practises. Plants are assessed for their
yield, for their robustness and for their resistance to pests
and diseases.
Our partners for this work are local artemisinin-producing
companies, chosen for their extensive grower networks and
their links to the ACT supply chain. The Swiss not-for-profit
organisation, Mediplant is also field- testing our plants. Early
results have demonstrated that our best plant lines yield
significantly more than the current market leader.
Southwest China
Kitale KenyaEast Africa
India
Madagascar
field trial sites
User tests
We are producing several new varieties of Artemisia.
All will be significantly higher yielding than the current
market leader (Artemis) and non GM. In order for our new
varieties to make an immediate contribution to malaria
control efforts, they must be readily adopted
by industry.
To this end, we subject high-performing plant lines to user
tests by Artemisia processors and ACT manufacturers.
These tests are designed to ensure that our new varieties
are compatible with current manufacturing processes. For
example, leaf material from large-scale field experiments is
sent for commercial pilot extraction to test the artemisinin
yield and purity of extracts from our plant lines.
A long-term legacy from the project
In 2011, we are planning to supply seed of our first stage new
hybrids for demonstration purposes. Large-scale distribution
of hybrid seed will be ready for the 2012 growing seasons.
This timing will enable us to supply the predicted peak in
demand generated by the scaling up of malaria control
measures. Conservation of the project’s germplasm will be
maintained over the long term in tissue culture at Mediplant.
The artemisinin from the new varieties will contribute to
supply chains for the manufacture of high quality ACTs.
In this way, the project will make a lasting contribution to
improved artemisinin supplies and help to secure better
access to effective malaria medicines. We are also working
to maximise the benefits to Artemisia growers in developing
countries. The Syngenta Foundation for Sustainable
Agriculture and Mediplant are working with us to ensure
such growers have the knowledge they need to get the best
out of the new varieties.