Max L. Birnstiel (1933–2014)

Max L. Birnstiel When I first met Max in Zurich in the fall of 1974, ‘‘Switzerland’’ seemed to be written all over him. I had just arrived from the United States, and his reserved politeness, his aversion to jokes, and his habit of neither wasting nor mincing his words all fitted the cliché of the Swiss German. My impression was reinforced when he told me that his paternal ancestors had been gunpowder manufacturers and he himself had served as an artillery officer in the Swiss Army. It was only later that I learned that about half of his genes— and all of his mitochondrial ones—came from sea-faring Portuguese who had settled in Brazil sometime in the past. The two genomes entered this world united in Bahia on July 12, 1933when little Max was born to the Swiss merchant Max Birnstiel and his Brazilian wife Dalila Varella. When Max was five, his parents decided to move to Switzerland in order to allow Max and his brother Fritz to get a solid education. Max attended primary school and gymnasium in Zurich and then enrolled at the Swiss Federal Institute of Technology with the goal of studying biology, a subject that had fascinated him since childhood. On the advice of the botanist Albert Frey-Wyssling, he majored in physical chemistry—at that time an unorthodox gradus ad Parnassum for an aspiring biologist. As Max tells it, he never regretted this choice, as it taught him to look at complex biological systems with a quantitative eye. After his doctoral thesis with Frey-Wyssling, he spent 3 1/2 years at the California Institute of Technology at Pasadena, working as a postdoctoral fellow with the botanist James Bonner. This stay at one of the world’s premier scientific institutions brought him face to face with scientific giants such as Linus Pauling, George Beadle, Max Delbrück, and Renato Dulbecco and the first stirrings of the biological revolution. His postdoctoral work led to the discovery that the ribosomal RNA genes of the plant Pisum sativum were highly repetitive, existing in hundreds of copies. Max was never quite satisfied with his postdoctoral harvest even though it furnished the basis of some of his breakthrough discoveries soon to come. His collaboration at Caltech with the British biologist Margaret Chipchase on ribosomal RNA genes was also fruitful in other ways: the two married in 1961. In 1963, Conrad H. Waddington recruited the promising young Swiss to the Epigenetics Research Group at the Genetics Department of the University of Edinburgh, where Max rapidly rose through the ranks from Lecturer all the way to Professor. Inspired by his postdoctoral work on plant ribosomal RNAs, Max, his PhD students Adrian Bird and Michael Grunstein, together with team members started investigating the repetitive ribosomal RNA genes of the South African toad Xenopus laevis. By hybridizing total Xenopus DNA to the two major Xenopus ribosomal RNAs and subjecting the hybrids to isopycnic centrifugation in cesium chloride gradients, they purified the reiterated RNA genes as complexes with their cognate RNAs—the first gene purification ever, well before the advent of gene cloning. The ribosomal RNA genes could also be purified directly by repeated gradient centrifugation because they had an unusually high G+C content and, hence, a higher buoyant density than the bulk DNA. By today’s standards,