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Credit: "Project K". Source: Wellcome Collection.
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![RESERVATIONS ON PROJECT K PETER R. SMITH* Of course, the final answers to biological problems must, ulti mately, be in molecular terms. What other than molecules is there for biological systems to be constructed out of ? The important point about the answers is not whether they are in molecular terms or not, but whether they are answers to the important questions.— C. H. Waddington [1, vol. 1, p. 104] Dr. Crick appears to make two major assumptions in his paper Proj ect K: 'The Complete Solution of-E. coli' [2]. First, he suggests that an intellectually satisfying complete solution of a cell in molecular terms is a possibility and, second, that Escherichia coli would be the organism to study. The first assumption illustrates one of the fascinating changes in the theoretical thinking of molecular biologists during the last 30 years. The founders of molecular biology initiated the study of the molecular basis of life not to succeed but to fail. In the words of Gunther Stent [3, p. 3], they were waiting for a paradox, a phenomenon of living systems that could not be reduced to the laws of atomic physics. They hoped from a consideration of this paradox to establish the laws of biology or, as Del brück saw them, the other laws of physics [4]. Crick and, I feel, many of his present colleagues appear to have forsaken this aim. They appear to have become so intoxicated with their successes so far that they can see no limits, except perhaps those imposed by grant-awarding bodies, to the range of phenomena that can be explained by the essentially molecu lar determinisi viewpoint of molecular biology. How has this change come about? I suggest that it is possible we have forgotten that we are forced to introduce distortions of reality when we wish to investigate experimentally intracellular molecular events. It is clear, for example, that Crick sees E. coli as meaningfully existent as an isolated cell. Surely Project K can only be proposed if its proposer believes that the cell is really a closed system whose properties are determined by its compo nents. His description of a cell as a well-integrated chemical factory [2] is itself revealing. I would argue that such a vision of the cell, although ♦Department of Microbiology, University College, Galway, Republic of Ireland.](https://iiif.wellcomecollection.org/image/b18165023_PP_CRI_H_4_12_0006.jp2/full/800%2C/0/default.jpg)
