The agony column

tion is the importance of random events in generating cell behavior. All biological processes, at the cellular as well as the organismal and evolutionary levels, rely on the energy-dependent reinforcement and perpetuation of random accidents to maintain and transmit information. We appreciate the overwhelming importance of random events in evolution, but randomness rules biology at the microscopic level as well. To give one example, the first event in frog development is a random collision between sperm and egg. The arbitrary choice of sperm entry point then determines the direction of the first cortical rotation and, in direct consequence, the primary body axis of the tadpole. If the direction of the cortical rotation is experimentally altered, a normal tadpole still develops but with its body axis defined by the artificial rotation [3]. No level of detail in understanding the chemistry of the egg could enable us to calculate exactly how it will develop without this absolutely critical random input. How can frog eggs accept random initial axial determinants but all generate tadpoles that look more or less alike? This property of living systems — the capacity for plucking order and reproducibility out of random chaos — is not unique to the egg. In many developing tissues, if a particular cell is destroyed, one of its neighbors will assume its fate. The differing fates of individual cells within an 'equiva-lence group' of cells with the same set of potential fates may be determined by signals arising either from outside the group (induction) or from other cells within the group (lateral specification or lateral inhibition) [4]. In vertebrates, invertebrates, and even cooperative colonies of free-living amoebae, lateral specification often occurs when one cell in the equivalence group, apparently at random, gains a slight lead on its fellows in the race towards a chosen fate. The winning cell then sends signals to the other members of the equivalence group to prevent them from assuming the same fate, or to direct them to assume an alternative fate. In most cases, it cannot be predicted and does not seem to matter which cell in an equivalence group wins the race. Each embryo becomes a functional adult, regardless of the precise origin and history of any given cell. We can predict that the explanations for these amazing feats must lie in the spectacularly wasteful expense of energy by living cells. Living systems are always in a state …