Model Organisms in Drug Discovery

paradoxical phenomenon that, on the one hand, Drosophila is widely
recognized for its predictive power for human gene function, including
genes involved in safeguarding DNA and chromosomes, yet, on the other
hand, it lacks broad use in testing the genotoxicity of pharmaceutical
compounds. The likely explanations are: the classical SLRL assay is complex,
requires special training and facilities not available in most toxicology
laboratories in industry and has some weaknesses; a genotoxicity test requires
extensive evaluation before it becomes a standard test and only recently has
such a level of validation been achieved for the SMART assays; and, most
importantly, Drosophila assays are not yet included in recommendations or
guidelines issued by international regulatory agencies, such as the International
Conference on Harmonization of Technical Requirements for
Registration of Pharmaceuticals for Human Use (ICH). For example, in the
ICH topic S2B, Genotoxicity: a Standard Battery for Genotoxicity Testing of
Pharmaceuticals, three tests are recommended: a test for gene mutation in
bacteria (such as the Salmonella Ames test); an in vitro test with cytogenetic
evaluation of chromosomal damage with mammalian cells or an in vitro
mouse lymphoma tk assay; and an in vivo test for chromosomal damage using
rodent hematopoietic cells.
Even though it will take some time before Drosophila assays are included in
the regulatory tests, they can be applied immediately in some toxicology
studies in drug discovery. For example, for lead compound prioritization,
rapid and inexpensive assays are preferred after in silico evaluation of the
mutagenic potential of the compounds based on their chemical structures and
prior experience. The SMART assays are perfectly fitted for this application,
especially if higher throughput assay formats and fly handling methods are
developed. Drosophila assays also may be used as complementary or
confirmatory tests when ambiguous results are obtained by the standard
guideline tests. In addition, as an excellent genetic, biochemical and molecular
biological experiment system, Drosophila is well suited for studying the
mechanisms of genotoxicity of an important compound.
4.2 Research tools in Drosophila studies
Information resources
RESEARCH TOOLS IN DROSOPHILA STUDIES 101
A century of innovative research and community effort has given Drosophila
biologists a wide array of research tools. One of the most important research
tools is the extensive information resource. Currently, the compiled
information is primarily made available through the Internet and books.
We list some of the major ones here.