It’s a pity that Salvador Luria lectured only once in Lindau. He must have been a brilliant teacher with a talent to inspire young researchers. His first graduate student at Indiana University where he taught between 1943 and 1950 was James Watson, and the Center of Cancer Research at MIT, which he was asked to set up in 1972 and directed until his retirement in 1985, generated four Nobel laureates, namely David Baltimore, Susuma Tonegawa, Philipp Sharp and Robert Horvitz. “Salva was a visionary who protected his young faculty from unnecessary interruptions, thus allowing their research programs to flourish in an ideal scientific environment. He was also a role model for how a scientist could shape and lead a community“, his early MIT recruit Philipp Sharp later recalled Luria’s excellence.[1] In cooperation with Max Delbrück and Alfred D. Hershey with whom he shared the Nobel Prize in Physiology or Medicine 1969, Luria “set the solid foundations on which modern molecular biology rests“, according to the Karolinska Institute[2]. Working with bacteriophages - viruses that infect bacteria – Delbrück and Luria had demonstrated in a famous experiment that “resistant bacteria arise by mutations of sensitive cells independently of the action of virus“[3], i.e. that bacteria are affected by natural selection. This knowledge laid the foundation for both explaining the development of antibiotic resistance and for discovering restriction enzymes, the major tools of genetic engineering. When molecular biology began to flourish at the end of the 1950s, genetic analyses bored Luria however. Rather than being involved “in putting together little pieces of a large puzzle whose overall features were already evident", he wanted to dig in “unplowed fields“. He decided to work on cell membranes.[4] He investigated the effect of certain bacteriocins and discovered that these colicins exert their lethal effect by opening ion channels in the cell membranes of bacteria. These findings took already center stage in his Nobel lecture and still are in the focus of his interest in this lecture in Lindau. Luria distinguishes between intelligent, neurotic, less intelligent and stupid membrane channels, and complains that they all share one unpleasant feature: “The proteins of these channels have to insert themselves into the membranes, and the biochemist who works with them finds them more or less distasteful, because they generally are poorly soluble in water”. In this regard, colicins are a remarkable class of proteins, he says: “They attach themselves to certain bacteria and kill them – by exactly what a biochemist would like to do, by inserting themselves in the phospholipid bilayer and creating a hole whose conductance is relatively non-specific and allows substances to pass with a molecular weight of up to 800 or 900”. Amazingly, one single molecule of colicin can trigger in one bacterium a whole series of physiological effects from arresting the synthesis of macromolecules to blocking active transport mechanisms and decreasing ATP levels. Referring to Peter Mitchell’s (Nobel Prize in Chemistry 1978) chemiosmotic theory, Luria suggests that colicin influences the proton motive force across the bacterial membrane. But can one measure how one molecule of colicin affects the proton motive force? What does colicin do to abolish the membrane potential? And what are the best experimental systems to explore that? These are the questions Luria discusses in the second half of his talk, which he concludes with an advice from his personal experience: “If you can do something in a simple way without any instruments, do it that way and you are likely to be more right than people who have a big powerful apparatus.” Joachim Pietzsch [1] Cf. The Salvador Luria Papers (National Library of Medicine: Profiles in Science. http://profiles.nlm.nih.gov/ps/retrieve/Narrative/QL/p-nid/164 [2] http://www.nobelprize.org/nobel_prizes/medicine/laureates/1969/press.html [3] Luria, SE and Delbruck M. Mutations of Bacteria from Virus Sensitivity to Virus Resistance. Genetics 28, (November 1943): 491-511, 510. [4] Cf. The Salvador Luria Papers