It has been roughly fifty years since the humoral immune response was first conceived of as a compelling example of evolution via selection of individual cells on a time scale that is short relative to standard organismal evolution (Talmage, 1957, Burnet, 1957; reviewed by Forsdyke, 1995).  Multiple lines of evidence supportive of this concept were forthcoming over the next fifteen years (briefly reviewed in Talmage, 1986).   Instead of individual organisms competing for multiple resources that facilitate reproduction through mating, B lymphocytes compete, through cell surface versions of the immunoglobulin molecules they will ultimately secrete, for binding to antigen molecules that with other inputs stimulate cellular proliferation.  The descendants of the B cells expressing the receptors best able to complex noncovalently with the antigens introduced into the body will tend to dominate the B lymphocyte population at subsequent times.  Thus, the B cell population evolves in a neo-Darwinian fashion, i.e. the clonal composition of the population changes over time.

Numerous methods have been developed to exploit similar processes in vitro for the purposes of research.  A previous post ( provided one example of such in vitro selection which was used for the purpose of producing an antibody able to bind to the hemaggluitinin molecules of multiple type A influenza virus subtypes.  An article that appeared in March of this year by Bostrom et al.(2009), at Genentech, describes a novel application of selection techniques to producing a an antibody capable of potential use as a therapeutic agent in cancer.  Elsewhere (Greenspan, 2009), I have explained why some of the claims made for the broader significance of this paper were over-stated, but my dissatisfaction with the paper on that score does not diminish my appreciation for the originality of the question addressed or for the impressive manner in which an array of sophisticated methods were deployed.

Herceptin® (trastuzumab) is an antibody with specificity for the human epidermal growth factor receptor 2 (HER2) that is used to treat patients whose tumor cells overexpress HER2. (more…)