NEWS & VIEWS NATURE|Vol 444|7 December 2006 OBITUARY Reinhart Heinrich (1946–2006) Pioneer in systems biology. In biology, mathematical systems analysis where he showed that the flux of was until recently nearly invisible in the reaction was shared by several the dazzling light of twentieth-century enzymes. Much later, he extended discoveries. But it has emerged from the his ideas to signal-transduction shadows in the field of systems biology, pathways, introducing control a subject buoyed by immense data sets, coefficients to dynamic processes. conveyed by heavy computing power, and Sticking to real examples, such as addressing seemingly incomprehensible the Wnt signalling and MAP kinase forms of complexity. If systems biology has pathways, he again demonstrated heroes, one of them is Reinhart Heinrich, a that new properties and constraints former professor at the Humboldt University emerge when the individual steps in Berlin, who died on 23 October, aged are combined into a complete 60. His most famous accomplishment was pathway. metabolic control theory, published in Heinrich also pointed the way to 1974 with Tom Rapoport and formulated considerations of optimality theory independently by Henrik Kacser and James and evolution that will confront A. Burns in Edinburgh, UK. systems biology for the next From the 1930s to the 1960s, biochemists century. The question of evolution were busy describing metabolic pathways, lies just beneath any effort to just as molecular biologists today are understand biology. Yet in most feverishly trying to inventory the cell’s cases, physiological function and gene-transcription and signalling circuits. evolutionary change are considered The basic kinetic features of the enzymes in distinct and are investigated by the major pathways were studied in great different people. Heinrich’s work detail and with exceeding care. It seemed illustrated how systems biology self-evident that, knowing the properties might develop, where the central of each element, the behaviour of a pathway question will be not only how a system works, worked with the son, Tom. Rapoport senior in vivo could simply be understood as the but why it has the specific design it has. was a biochemist who himself was a refugee sum of its enzymes. In examining optimization for metabolic (in this case from anti-communist hysteria One assertion, drilled into the head of pathways, he found that there is no unique in the United States). In East Berlin, travel every biochemist, was the concept of the solution for the individual rate constants and and outside communication were severely rate-limiting step. In this view, the flux affinities, but many solutions that are each restricted, but Heinrich partly coped with through a pathway was determined by optimized with respect to certain conditions. the isolation by organizing meetings in East the slowest reaction, in the way a bucket By considering the criteria for optimization, Germany. When the Berlin Wall fell, his fame brigade fighting a fire would be limited by such as pathway flux or minimization of began to spread more rapidly, increasing as the speed of the slowest member. Yet this enzyme concentration, he nevertheless systems biology has taken off as an organized concept, as shown by the metabolic control found general tendencies, such as a match discipline over the past few years. theory, was theoretically flawed, practically between the Michaelis constant and substrate Reinhart Heinrich’s character is incomplete and often wrong, as many efforts concentration. Evolutionary optimization revealed both in his originality in seeking to genetically engineer enzymes by changing is becoming a central feature in systems rational explanations in biology and in his ‘rate-limiting steps’ would ultimately show. biology. approach to life in general. He published a Metabolic control theory introduced Some of the wrenching political prizewinning philosophical novel (Jenseits the concept of control coefficients developments of the twentieth century von Babel [Beyond Babel]) and a book of — dimensionless quantities indicating how framed Heinrich’s life, and it is a tribute to poems. He played the violin and was well the flux of a pathway depended on a given the collegiality of science that his reputation versed in history and literature; he also had step. Only a pathway where every control and influence were able to transcend such an amazing ability to remember what he had coefficient except one was zero would have considerations. He was born in Dresden, but done on every day of his life. His humour and a rate-limiting step, since the flux of that spent his early years in Kuibishev, Russia. His charm were contagious. He trained a whole pathway would depend only on that step. father, a professor of applied mathematics, generation of students, becoming the father Several pathways in fact had rate-limiting belonged to the group of scientists in East of the Berlin school of theoretical biophysics, steps, but that often reflected the structure Germany who, after the Second World War, and led us to the edge of a new domain of of the pathway, and could not simply be were rounded up by the Russians to help knowledge. Reinhart died too young. But deduced from the maximum rates of the build their aviation industry. he was fortunate enough to have glimpsed individual enzymes, their Michaelis constants The family returned to East Germany in the future outlines and promise of systems or their displacement from equilibrium. the early 1950s, and Heinrich studied solid- biology, a field he himself was instrumental Many pathways were instead networks, with state physics in Dresden. But after his PhD in founding. ■ the fluxes distributed in a self-governing way he became interested in applying physics Marc W. Kirschner among its various branches. to biology, and moved to East Berlin to join Marc W. Kirschner is at Harvard Medical School, Heinrich went on to apply this theory to the group of Samuel Rapoport — a family Boston, Massachusetts 02115, USA. the real case of glycolysis in red blood cells, connection that later continued when he e-mail: [email protected] 700 ©2006 Nature PublishingGroup.