Erwin Neher and Bert Sakmann

Erwin Neher (born March 20, 1944) and Bert Sakmann (born June 12, 1942) are German cell physiologists who developed the patch clamp at the Max Planck Institute for Biophysical Chemistry in Göttingen and used it to record the electric current through a single ion channel. They published the first such recordings in 1976 and shared the 1991 Nobel Prize in Physiology or Medicine "for their discoveries concerning the function of single ion channels in cells".^[1][2]

The Nobel Assembly's press release said that the two had "conclusively established with their technique that ion channels do exist and how they function". The current through one channel is about a picoampere, and the technique followed a channel's changes of shape over a few millionths of a second.^[3]

Neher was born in Landsberg and grew up in Buchloe, a town in Bavaria 70 km west of Munich, where his father worked in the administration of a dairy company. As a schoolboy he read about cybernetics and "studied everything in my reach on the 'Hodgkin-Huxley theory'", the Hodgkin-Huxley model of nerve excitation, and by his final examinations he had decided to be a biophysicist.^[4] He studied physics at the Technische Hochschule in Munich from 1963. A Fulbright scholarship took him in 1966 to the University of Wisconsin at Madison, where in a little over a year he earned a master's degree with a project on molecular beams of macromolecules for mass spectrometry. Back in Munich he did his doctoral work at the Max Planck Institute for Psychiatry in the laboratory of H. D. Lux, voltage-clamping snail neurons through suction pipettes.^[4]

Sakmann was born in Stuttgart, the son of a theater director, and grew up in Lindau on Lake Constance. As a boy he built model motor ships, sailing ships and radio-controlled aircraft, and it was generally assumed he would become an engineer.^[5] In his last year at school he learned about cybernetics, and being unable to choose between physics and biology he enrolled at the medical faculty in Tübingen. For his doctoral thesis he chose electrophysiology, which "seemed to be closest to engineering". Common practice let him study at several medical schools, and he attended Freiburg, Berlin and Paris as well. His decision to finish in Munich, he wrote, "was largely dictated by a beautiful young lady whose attention I was desperate to catch in Tübingen, though without initial success". She is now his wife.^[5]

In Munich Sakmann worked on the visual system of the cat with Otto Creutzfeldt, then joined Lux's laboratory to learn the voltage clamp, and learned it from Neher. They talked often and became friends.^[4][5]

Sakmann went on to London, to Bernard Katz's department at University College, to study the neuromuscular synapse. Katz and Ricardo Miledi had inferred "elementary events" from the noise in the response of muscle to acetylcholine, and Sakmann wanted to record them directly.^[5] The two friends met again in 1973 in Göttingen. Neher had joined a physical chemistry laboratory to learn single-channel recording in artificial membranes, and Sakmann brought experience of the neuromuscular junction. In Neher's account, "it required only little discussion to agree on a collaboration, aiming at the measurement of single channel currents."^[4]

Their paper of 1976 described currents recorded from patches of frog muscle fibers that had been cut off from their nerves. In the 1780s Luigi Galvani had made the muscles of frog legs twitch in the experiments that began the study of animal electricity; frog muscle was again the tissue in which individual channels were first seen. While the paper appeared, Neher was spending a year in Charles Stevens's laboratory at Yale.^[4] The seals between glass and membrane were still weak, 50 to 100 MΩ, and the recordings were noisy. The giga-seal that cured this, and the recording configurations built on it, are described in the Patch clamp article.^[6]

Their department heads, Hans Kuhn and Otto Creutzfeldt, gave each of them an independent "Young Investigator Laboratory", which let them attract postdoctoral fellows including Joseph Patlak, Fred Sigworth, Alain Marty and Owen Hamill. "Together we perfected the technique, and developed the different recording configurations," Neher wrote.^[4] The methods paper by Hamill, Marty, Neher, Sakmann and Sigworth appeared in Pflügers Archiv in August 1981.^[7] A practical course in Göttingen led to a book, Single-Channel Recording, which they edited together.^[8]

After 1983 Neher's interest moved from the channels to the processes they start inside cells, such as the secretion of hormones and neurotransmitters. Sakmann applied the patch clamp to neurons in brain slices and, with others, to receptors expressed from injected genes, and then moved his laboratory to Heidelberg, after sixteen years of working beside Neher in Göttingen.^[4][5]

The Nobel Prize followed more than a dozen other awards between 1977 and 1991, most of them shared, among them the Leibniz Prize of the German Research Foundation and the Louisa Gross Horwitz Prize of Columbia University in 1986 and the Gairdner Award in 1989.^[4] The Nobel Assembly credited the work with helping to explain the cellular mechanisms of several diseases, among them diabetes and cystic fibrosis.^[3]

Nanopore recording uses the patch clamp's amplifier and much of its vocabulary. In the game of Molecular Reality Corporation, the founder's essay "How to Play Epic Quest Bio" says that the Sparky character class commands "the logic of lightning trapped in arcane patterns by the spellbooks of" a list of electrical engineers and physicists, and the list includes "Neher & Sakmann".^[9]

• Patch clamp
• Ion channel
• Single-molecule biophysics
• Picoampere
• History of nanopore sequencing