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Manfred Eigen (1927–2019)

Eigen made his name measuring chemical reactions too fast for anyone to follow, and then turned the same physical chemistry on the origin of life. In “Selforganization of Matter and the Evolution of Biological Macromolecules” (1971) he argued that Darwinian selection is not something that begins with living things: it follows, as a law of physical chemistry, whenever molecules copy themselves with occasional errors and compete for a limited supply of building blocks. From that starting point he derived a limit on how much information a copying system can hold, the error threshold, described the population of variants that replicating molecules actually form, the quasispecies, and proposed a cycle of mutually supporting replicators, the hypercycle, as the way molecular evolution could climb past the limit.

Manfred Eigen was born on 9 May 1927 in Bochum. He took his doctorate at the University of Göttingen in 1951 under Arnold Eucken, joined the Max Planck Institute for Physical Chemistry in Göttingen in 1953, and became its director in 1964; in 1971 it merged with the Max Planck Institute for Spectroscopy to form the Max Planck Institute for Biophysical Chemistry, where he spent the rest of his career. He shared the Nobel Prize in Chemistry in 1967 with Ronald Norrish and George Porter for the study of extremely fast chemical reactions. He was president of the Studienstiftung des deutschen Volkes, the German National Academic Foundation, from 1982 to 1993, helped found the biotechnology companies Evotec and Direvo, and was an accomplished pianist. He died in Göttingen on 6 February 2019.

Key concepts

Relaxation methods. Reactions that finish in a millionth of a second or less could not be followed by mixing the reactants and watching. Eigen’s approach was to disturb a system already at equilibrium, by a sudden jump in temperature, pressure or electric field, and to measure how quickly it relaxed to its new equilibrium. The methods opened the time scale of nanoseconds to measurement and are what the Nobel Prize recognised.

Selection as physical chemistry. The 1971 paper, drawing on Sol Spiegelman’s experiments on replicating RNA and on Prigogine’s thermodynamics of systems far from equilibrium, treated populations of self-replicating molecules mathematically. Where replication is autocatalytic, its products copy themselves, errors introduce variants, and resources are limited, the variants with the best combination of copying speed, accuracy and stability take over. Selection, on this account, is a consequence of the kinetics.

The error threshold. Copying is never perfect, and the longer a sequence, the more errors each copy carries. Eigen showed that for a given error rate there is a maximum length beyond which the information in the population cannot be maintained and dissolves into random sequences. Without accurate copying enzymes, early replicators would be limited to short sequences; but to code for such enzymes a sequence must be long. The difficulty became known as Eigen’s paradox: no large genome without enzymes, and no enzymes without a large genome.

The quasispecies. A population of replicators under mutation is not a set of copies of one best sequence but a cloud of related variants around it, and selection acts on the cloud as a whole. The quasispecies model, developed with Peter Schuster and later John McCaskill, has been applied since to RNA viruses, whose high mutation rates keep them near the error threshold.

The hypercycle. With Schuster, in a series of papers of 1977–78 and the book The Hypercycle (1979), Eigen proposed a way past the paradox: several short replicators, each of which helps the next to replicate, closed in a cycle, so that the cycle as a whole can carry more information than any single member while each stays below the threshold.

Evolution in the laboratory. Eigen and his colleagues built machines that ran selection on molecules continuously, and he argued for evolutionary biotechnology, using variation and selection to produce molecules with desired functions, an approach that the companies he helped found put to commercial use.

Where Eigen stops

The hypercycle was pressed at once on its stability. John Maynard Smith’s “Hypercycles and the Origin of Life” (Nature, 1979) pointed out that a cycle of cooperating replicators is open to parasites: a mutant that receives help from the cycle without giving any in return would spread at the cycle’s expense, and a mutant that short-circuits the cycle would shrink it. Later work showed that spatial structure or compartments can protect hypercycles against such parasites, and the question of what first held cooperating replicators together passed to models of protocells and spatial self-organisation.

Key works

See also: Evolution · Chemical evolution · Prigogine · Maynard Smith · Kauffman