Research Grants 2000-2001

Experiments Using a Computer Model of the Immune System

Franco Celada, MD, PhD
Hospital for Joint Diseases, New York City, New York

Milestones for the Year 2000
1. Modelling of vaccination strategies. We will consider and evaluate the effect on vaccine effectiveness of a wide range of immunogenicity gaps between vaccine and wild-type antigen, pertaining to epitope and MHC-peptide differences. We will also study the effect of vaccination on humoral versus cellular parameters.
2. Performing vaccination when the wild-type antigen is mutable. Evaluation of parameters: affinity maturation of the immune response versus epitope and T-peptide mutations in the foreign invader.
Description of the Project in Lay Language
Experimentation is the key feature of modern science; it consists of reproducing natural phenomena under controlled conditions and measuring its effects against those expected by the scientists' projections, which will thus be confirmed or refuted. In biology, experiments must be done in organisms similar to those under study. In human biology, since ethics forbids experiments in man, mammals -- from primates to mice -- are the choice organisms that support the advancement of knowledge. It is part of a scientist's mission to try to reduce experimentation in living animals to a minimum. The result, of course, should not be jeopardized; in certain cases it may be substantially enhanced. A giant step in this direction has been the introduction of the culture of tissues and cells, allowing tests and experiments to be conducted in vitro instead of in vivo. In basic immunology, experiments unthinkable in the animal can be realized in the test tube, where cell hybridization has yielded monoclonal antibodies, and such phenomena as presentation of antigen and T-B cell cooperation have been elucidated. These cell cultures are not substitutes for boring/necessary safety tests; they are the new avenues of fundamental research, the kind that twenty years ago required hundreds of mice and rats for each experiment.

Our activity, a tight collaboration between the P.I. and Dr. Philip Seiden, a physicist and Research Staff Member Emeritus with IBM's T.J. Watson Research Center, has been focused toward a further extrapolation, the experimentation in machina, that is, constructing a model immune system in the computer and conducting experiments with it. We believe that by showing that our model can be applied to real research problems -- such as the present project, a systematic study of vaccination -- we will foster its use by more and more immunologists (and, eventually, biologists), thereby catalyzing a cultural transition among bench scientists.