When original and interesting research is distorted to garner additional attention, both the work in question and previous studies can be shortchanged. Here, I will describe a recent and notable case from the journal Science in which the perceived novelty and importance of a study were significantly enhanced. In the 20 March, 2009, issue of Science, researchers from Genentech (Bostrom et al.) show that it is possible to select a new specificity for a therapeutic antibody with an established specificity while maintaining the original specificity.1 The authors started with an antibody (Herceptin) specific for the tumor antigen, HER2, in clinical use for patients suffering from breast cancer. After mutagenizing the gene encoding the light chain variable domain of the antibody, they were able to select a variant antibody that had gained the ability to bind another clinically-relevant target protein, vascular endothelial growth factor (VEGF). The new antibody...
et al2Science3 -- The formation of a stable complex does not require a perfect fit between two complementary configurations. The heterogeneity of the antibodies com binding with a single haptene and the re actions of the same antibody with different haptenes provide experimental evidence for this premise. -- A single globulin molecule may combine with a large number of different substances in the same sense that a master key may open a large number of different locks. There should be many different antigenic configurations structurally suited to combine with the same globulin if a lack of perfection in the fit in one area may be compensated by an increased binding energy elsewhere.(pp. 1645-1646, format edited for clarity)456-7811Science12-1516et aNature17et alet alScienceNatureScienceNeil Greenspan is an immunologist and professor of pathology at the Case Western Reserve University School of Medicine.References:ScienceImmunol RevScienceJ ImmunolProc. Natl. Acad. SciProc. Natl. Acad. Sci. USAJ. Mol. Biol.J Immunol.Cell.CellNat Biotechnol.Nature.Science.Science.Proc Natl Acad Sci U S A.Science.Nature.
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