The Center for Biotechnology
204A Mugar Hall
(617) 373-8766
Please mouse over the pictures for an explanation.
Plants are an important source of small molecule drugs or
pharmaceuticals (pictured is the Madagascar rosy periwinkle
plant). The biodiversity found in unique environments such as
the rain forests contain a wealth of potentially powerful
drugs for the treatment of critical diseases such as
infections, cancer, and AIDs. The availability of the plant
may limit the supply of important plant-derived
pharmaceuticals.
Cell cultures of plants can provide an alternative source of
plant-derived drugs. Our vision is to meet and supply the
need of these plant-derived drugs by producing the medicinal
compounds in cell cultures rather than extracting them from
the whole plant. Plant cell cultures can be grown in 125 or
250 mL Erlenmeyer flasks as shown here. These small-scale
systems allow the study of a variety of parameters affecting
growth and production (i.e. nutrient composition, inducer
compounds, temperature, pH, dissolved gas composition).
Once growth and production of the plant-derived drug has been
optimized in the flasks, cells are cultured in a larger scale
system such as this bench-top bioreactor (2 L bioreactor
pictured) for further process development. Large-scale
bioreactors (10 - 10,000 L) are necessary for producing large
quantities of these plant-derived drugs. The bioreactor system
also allows for the control of parameters affecting growth and
production such as pH, temperature, dissolved gas composition,
and nutrient concentrations. Once made by the cells, the
product is harvested or recovered from the cells, isolated and
separated from other compounds made by the cells, and finally
purified.
Cells are micro-bioreactors housing enzymes (biological
catalysts) that catalyze a network of reactions leading to the
desired products. Single plant cells are approximately 20
µm in diameter but generally plant cells grow as
aggregates ranging in size from 100 - 1000 µm. The plant cells shown
here have been treated with a viability stain (fluorescein
diacetate); living or viable cells will fluoresce green under
UV light.
The chemical structure of vincristine and vinblastine,
produced by the Madagascar periwinkle, is shown here. These
two small molecule drugs are used in the treatment of cancers
and are currently marketed by Eli Lilly and other companies.
Vinblastine sulfate (tradename Velbane and Velsar) costs
~$2/mg or $2 million/kg and is used in the treatment of
testicular cancer, various lymphomas particularly Hodgkin's
disease, and Kaposi's sarcoma. Vincristine sulfate (tradename
Oncovin and Vincasar PFS) costs ~$15/mg or $15 million/kg and
is presently the treatment of choice in childhood leukemia.
Both of these drugs prevent the multiplication of cancer cells
by binding to tubulin and blocking the polymerization to form
microtubules required for cell division. (Drug prices from
Redbook 2002)