Use of Model Organisms in Drug Discovery

Organizers: Marla Weetall, PTC Therapeutics; Ellen Welch, PTC Therapeutics; John Hambor, Pfizer

1:00 PM Welcome and Introduction, Marla Weetall, PTC Therapeutics (South Plainfield, NJ)

1:05 PM "What Mice Can Tell Us About the Human Future." Lee Silver, Princeton University (Princeton, NJ)

1:45 PM "Comprehensive Phenotyping of Genetically Modified Mice to Identify New Target Disease Indications." Sandra Engle, Pfizer Global R&D (Groton, CT)

2:25 PM Coffee Break

2:50 PM "Drosophila in Drug Discovery: Genes, Pathways and Compounds." Dan Garza, Novartis Institutes for Biomedical Research (Cambridge, MA)

3:30 PM "The Zebrafish as Disruptive Technology for Drug Discovery and Development." Randall Peterson, Harvard Medical School (Boston, MA)

4:10 PM "C. elegans in Drug Discovery: High-throughput Chemical Genetics." Ann Sluder, Cambria Biosciences (Woburn, MA)

4:50 PM "Model Systems to Study Small Molecule Suppression of Premature Stop Mutations." David Bedwell, University of Alabama (Birmingham, AL)

5:30 PM Thank you and Concluding Remarks

Lee M. Silver Princeton University. "What mice can tell us about the human future."

The origin of mice, men, and all other organisms from a common ancestor has been clear since Darwin, but the extraordinary conservation of both genetic elements and differentiation processes among mammals has only been revealed during the last two decades. The similarity is most obvious during the initial steps of development between fertilization and implantation. Indeed, preimplantation mouse and human embryos are essentially equivalent in size and appearance, they are guided by the same program of genes turning on and off, and they produce the same distribution of cell types. Preimplantation conservation suggests that if a genetic or cellular manipulation technology can be applied successfully to mouse embryos, it could be optimized, as well, for human application. This guiding assumption provided the impetus for the decade-long pursuit of in vitro fertilization, and the establishment of methods to culture human embryonic stem cells.
The same reasoning makes it all but certain that technology for engineering the human embryonic genome could be perfected with sufficient research funding and support. It is unlikely that this path will be followed anytime soon both because our current, still-primitive, molecular knowledge limits the potential market for applications and, more importantly, because of strong societal opposition. However, at some point in the future, advances in science and technology will lead to the development of a suite of genomic enhancements related to physiology and disease suppression that ordinary people would eagerly desire for their children. For health improvements alone, parents and societies need not go beyond what already exists elsewhere in the human gene pool. However, once allele-replacement technology becomes feasible, it is a short step to add novel genetic elements to the human genome. The unanswerable question -- more philosophical than scientific during our lifetimes -- is whether and when human descendants will evolve into one or more post-human species.

Sandra Engle, Pfizer Global R&D."Comprehensive Phenotyping of Genetically Modified Mice to Identify New Target Disease Indications."

The use of genetically modified mice to establish gene function has been well documented in the literature and their role in drug discovery has proven to be extremely valuable. This presentat