Wishful Thinking and Semantic Specificity

Image: Anthony Canamucio In a recent commentary in Science, on the semantics of cloning,1 three eminent members of the scientific community asserted, "Scientists who are fluent in the language of any specific discipline can speak to one another using shorthand expressions from this dialect and can convey an exact understanding of their intended meanings." It is a comforting thought, but the preponderance of evidence does not support this grand claim, if by "can convey" the authors mean to suggest that, within a discipline, scientists always communicate "exact understanding." A term can certainly have different meanings within a technical field and outside of it, and scientists put considerable effort into precisely defining terms. Perhaps scientists do sometimes convey exact understanding to their colleagues. Nevertheless, the ideal of absolute lexical specificity is as unreachable as the molecular equivalent. As one of the authors of the commentary in question notes in (my old edition of) his textbook of molecular and cellular biology,2 absolute molecular specificity is not possible. Ironically, on the page following the Science commentary, a review of a new book on the species concept3 suggests that evolutionary biologists do not have a uniform understanding of the precise meaning of the term species. And a former editor of Science recently expressed his view that there is no simple, consensus definition of life.4 In the absence of a definition accepted by all, it would be remarkable in the extreme if all biologists knew precisely what every other biologist meant by the term. This conclusion is certainly consistent with the failure of a group of the scientific elite to agree on whether a virus or an enzyme should be regarded as alive.4 But the existence of imprecision in meaning is not limited to cases where there is no agreed-upon definition. One interesting example, from immunology, is epitope, an alternative to the older term, antigenic determinant. These terms are conventionally taken to refer to the structural subunits, such as the amino acids of a protein antigen, that are physically contacted by an antibody (or a T cell receptor). In spite of the fact that almost all immunology textbooks feature a definition along this line5-7 and that the vast majority of immunologists nominally accept it, this definition obscures some important realities that result in implicit use of a different definition. The cryptic assumption in the standard definition, that a structural subunit involved in contact with antibody is contributing, energetically, to complex formation, is not necessarily justified. Contact residues can be energetically neutral or even inhibitory with respect to the formation of a complex, and noncontact residues can contribute significantly to the stabilization of a complex.8 Furthermore, immunologists often use methods that cannot actually reveal so-called contact residues, but can reveal which residues are energetically important to the molecular interaction of interest.9 As revealed by their use of these nonstructural methods, immunologists are, in most cases, not really all that interested in characterizing contact residues per se--they are interested in knowing to which residues one can attribute affinity (or specificity) with respect to a particular immunological receptor. This situation has led to the absurd result that immunologists identify energetically important residues and then feel compelled to rationalize their results in terms of which residues are in contact with the antibody. Thus, immunologists sometimes appear to accept the standard definition and then proceed to use a different, never-articulated definition, based on which subunits actually favor binding. It is not always clear which definition is in force. So, why is it so difficult to create terms with absolute semantic precision? There may be no single, simple answer, but I would draw attention to two factors. The first is the existence of metonymy, the process by which a single attribute is permitted to stand for a whole constellation of associated attributes. The ability of a single epitope to represent a much larger antigen for the purposes of a particular antibody or B lymphocyte is an instance of metonymy at the molecular level. A second factor is the process of generalization or abstraction. Once a term is defined for a particular setting, it may be used to label entities or processes that share some essential logical relationship with their counterparts in the original setting despite significant differences of detail. Two conclusions are clearly in order. First, if scientists do convey exact understanding within a field, it is cause for celebration because frequently it does not happen. Second, guarding against the polysemy-associated peril of muddled thought10 will require continuous vigilance, as new meanings for old words are forever arising. References 1. B. Vogelstein et al., "Please don't call it cloning," Science, 295:1237, Feb. 15, 2002. 2. B. Alberts et al., Molecular Biology of the Cell, 2nd ed., New York: Garland Publishing, 1989, p. 94. 3. K.L. Shaw, "Evolution: Do we need a species concept," Science, 295:1238-9, Feb. 15, 2002. 4. D.E. Koshland Jr., "Special essay. The seven pillars of life," Science, 295:2215-6, March 22, 2002. 5. C.A. Janeway Jr. et al., Immunobiology 5: The Immune System in Health and Disease, New York: Garland Publishing, 2001, pp. 102, 691. 6. R.A. Goldsby et al., Kuby Immunology, 4th ed., New York: W.H. Freeman and Co., 2000, pp. 67, 613. 7. P. Parham, The Immune System, New York: Garland Publishing, 2000, pp. 36, G:7. 8. N.S. Greenspan, "Epitopes, paratopes, and other topes: Do immunologists know what they are talking about?" Bulletin of the Institute Pasteur, 90:267-79, 1992. 9. N.S. Greenspan, E. Di Cera, "Defining epitopes: It's not as easy at it seems," Nature Biotechnology, 17:936-7, 1999. 10. J. Lederberg, "The meaning of epigenetics," The Scientist, 15[18]:6, Sept. 17, 2001. Neil S. Greenspan, MD-PhD, is professor of pathology at the Institute of Pathology, Case Western Reserve University, Euclid Avenue, Cleveland, Ohio 44106-4943.

Wishful Thinking and Semantic Specificity

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