enzymes (See Metabolic Control Analysis). They showed that the expectation that a metabolic pathway will be controlled by a single pacemaker reaction is a fallacy, and most of the experimental criteria used in the supposed identification of such steps are misleading. Instead, varying amounts of control can be distributed over the enzymes of the pathway, but this is a property of the metabolic system as a whole and cannot be predicted from the characteristics of the enzymes in isolation. The molecular basis of dominance The molecular basis of dominance (Kacser & Burns, 1981) is the companion paper to The control of flux and reveals the full meaning of its footnote "the implication of this for the problem of dominance and its evolution will be dealt with in a separate publication". The connection was that if the flux–enzyme relationship is quasi-hyperbolic, and if, for most enzymes, the wild-type diploid level of enzyme activity occurs where the curve is levelling out, then a heterozygote of the wild-type with a null mutant will have half the enzyme activity but will not exhibit a noticeably reduced flux. Therefore, the wild type appears dominant and the mutant recessive because of the system characteristics of a metabolic pathway. Influential publications By the mid-1980s the central ideas of metabolic control analysis laid out in this paper were becoming far more widely accepted. Further experimental methods based on the theories laid out in the paper were used to help in the understanding of metabolic regulation and molecular evolution, and to show how metabolic control analysis could be applied to problems in medicine and biotechnology. The paper with Richard Beeby 1984 showed how the idea of evolution by natural selection could be applied in a constructive way to provide models for the evolution of enzyme catalysis. Other papers include: Responses of metabolic systems to large changes in enzyme activities and effectors: 1. The linear treatment of unbranched chains (Small & Kacser, 1993a) Responses of metabolic systems to large changes in enzyme activities and effectors: 2. The linear treatment of branched chains (Small & Kacser, 1993b) A universal method for achieving increases in metabolite production (Kacser & Acerenza, 1993) Control analysis of time-dependent metabolic systems (Acerenza, Sauro & Kacser, 1989) These papers, in collaboration with Rankin Small and Luis Acerenza, have shown that the prospects for achieving large increases in flux by changing the activity of a single enzyme are