Reservations on Project K

RESERVATIONS ON PROJECT K PETER R. SMITH* Of course, the final answers to biological problems must, ultimately , 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 "Project K: 'The Complete Solution ofE. coli' " [2]. First, he suggests that an intellectually satisfying "complete" solution ofa 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 Günther 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 Delbr ück 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 molecular 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 components . 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. Perspectives in Biology and Medicine · Autumn 1974 | 21 necessary if we wish to investigate, for example, an enzyme reaction within it, does not correspond with reality. There are no closed systems in nature. The cell is an artificial abstraction from the total cellenvironment interreactive field. From this position, Project K is not feasible and must by its very nature fail. It is possible to argue that, if a paradox does exist between the laws of atomic physics and the phenomena of life, it will be uncovered if we continue to analyse life in terms of atomic physics, and it matters little whether you join Delbrück in actively seeking it or with Crick in not expecting it. This view could allow one to support Project K even ifit was seen as a fundamentally impossible task. Such an argument would not, however, be supported by Thomas Kuhn's [5] analysis of the relationship among theory, fact, and experimental design in science. These he considers to be intimately related. We see the real world only through the distortions introduced by our theoretical paradigm, and we design experiments in terms of that paradigm to investigate our distorted reality. I am not trying to suggest that Crick and his fellow practitioners of the molecular deterministreductionist closed-system paradigm will not find much within living systems that they can investigate and explain to their satisfaction. Rather, I feel that they will concentrate their efforts on these fertile areas to the exclusion of areas where their paradigm is less capable of forming testable hypotheses. Yet it is in these complex areas that the putative paradox is most likely to be met in its sharpest focus. Thus, it is possible that Crick's proposal for a large research laboratory to provide the solution to E. coli Kl2 may either positively inhibit our understanding of living systems or become an intellectual white elephant. Scientists...