Reductionism and the search for structure-function relationships in antibody molecules.

One of the claims of reductionism is that it can explain all the features of living systems by an analysis of their physico-chemical constituents. Such a claim disregards the existence in biological systems of emergent properties that do not exist in their isolated components but which allow autonomous organisms to be directively organized in a self-regulated and integrated manner. It is not possible to describe biological systems adequately without using functional language that is meaningless in the physical sciences. The description of biological functions is also an essential part of immunology and functional explanations are more useful than causal explanations also in this discipline. Since causality is not a relation between a material object and an event, the structure of an antibody cannot be the cause of its binding activity. When structure-function relationships are analysed, the search should be for correlations rather than for causal relations. Methods used to find correlations between the atomic structure of antibody binding sites and their binding activity are mostly based on mutagenesis studies. Since the effect of any mutation depends on the molecular context, it is usually very difficult to predict the effects of multiple mutations on antibody function. Our knowledge of the molecular basis of antigen-antibody recognition has led to the expectation that it may be possible to develop new vaccines using molecular design principles. Such unwarranted hopes arise because of a confusion between antigenicity and immunogenicity. Although knowledge of antibody structure is of little use in vaccine design, it may help to develop therapeutic inhibitors and antibodies effective in the passive immunotherapy of viral infection. Copyright 2002 John Wiley & Sons, Ltd.