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Max Birnstiel 1933–2014: Gene Pioneer

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Max Birnstiel 1933–2014: Gene Pioneer RETROSPECTIVE Max Birnstiel 1933–2014: Gene pioneer Michael Grunsteina,1 and Adrian Birdb,1 a provided with a prefabricated hut containing Department of Biological Chemistry and the Molecular Biology Institute, David Geffen b a Spinco Model E analytical ultracentrifuge. School of Medicine at UCLA, Los Angeles, CA 90095; and Wellcome Centre for Cell Biology, With his colleague Hugh Wallace, Max went University of Edinburgh, Edinburgh EH9 3JR, United Kingdom searching for the high-density satellite and succeeded in purifying the ribosomal RNA genes to homogeneity by repeated rounds Max Birnstiel, who died in November, was revolutionary technique of RNA/DNA hybrid- of isopycnic ultracentrifugation. This was a pioneer of molecular biology and a creator ization to show that the genes encoding the first time a single gene had been purified, of European scientific institutions. Born in the RNA components of the eukaryotic ribo- predating the isolation of the bacterial lac Brazil in 1933, his family moved back to their some are multicopy. operon gene—sometimes hailed as the first native Switzerland when he was 5 years old, Conrad Waddington subsequently re- gene isolation—by 3 years. In a series of papers and he completed his education there. When cruited Max to the new Medical Research in the late 1960s both from Max’sgroupand he asked his teachers how he should best Council Epigenetics Research Group in Edin- from Don Brown’s laboratory at the Carne- train to be a biologist, the counterintuitive burgh. To Waddington, epigenetics was the gie Institution in Baltimore, it was elegantly answer was that he should study biophysical study of the way the phenotype was deter- demonstrated that the genes for 18S and chemistry. He never regretted his decision to mined by the genotype, and he felt that the 28S ribosomal RNAs are clustered in head- follow this unconventional path, which, cou- only way to get at this was to understand to-tail tandem arrays. Their conclusions pled with his deep interest in the natural how genes work at the molecular level. were beautifully verified by the electron world, guided his approach to research. After The problem was that chromosomal DNA micrographs of Xenopus ribosomal RNA obtaining his doctorate in botany with Albert in those days, before restriction enzymes, genetranscriptioninprogressproduced Frey-Wyssling at the Eidgenössische Techni- PCR, or cloning, was almost impossible to byOscarMillerin1969.Herewererows sche Hochschule in Zurich, Max moved to analyze. Despite the monotonous homoge- of ribosomal RNA genes, each carrying Caltech to train with James Bonner. Here he neity of the genome, Max realized that phys- many growing RNA polymers like a chain was impressed by the egalitarian nature of the ical methods might separate out some genes of Christmas trees. Caltech research community and was ex- if they were abundant enough and had a suf- Other repetitive genes were subsequently posed to some of the 20th century’sgreat ficiently atypical composition of bases. The purified. These included the genes coding for biologists, including Pauling, Beadle, Dul- ribosomal RNA genes of the South African 5S ribosomal RNA in Don Brown’s labora- becco, and Delbruck. Other important influ- frog/toad Xenopus laevis with their high copy tory and those encoding histone mRNAs by ences were also acquired in California. It was number and C+G molar content fitted the Max’s research group. With the advent of here that Max was amongst the first to use the bill. On his arrival in Edinburgh, Max was recombinant DNA cloning and PCR, how- ever, genome analysis was revolutionized, and physical methods for isolating genes be- came obsolete. Max moved to Zurich in 1972 where he used the new methods to study the histone genes. Here his laboratory continued to make important contributions to our un- derstanding of the concept of a eukaryotic gene and of transcriptional activation by RNA polymerase II. Amongst other discoveries, he identified a specific DNA sequence which acted as an upstream enhancer of histone gene activity and which he named the “Modulator.” As chair of one of two geographically separate Institutes for Molecular Biology set up in Zurich (the other chaired by Charles Weissmann), it was only a matter of time before Max once again became restless. This time he looked for a challenge of a different kind. Genentech and Boehringer Ingelheim approached him to create a new basic research Author contributions: M.G. and A.B. wrote the paper. 1To whom correspondence may be addressed. Email: mg@mbi. Max Birnstiel. Image courtesy of Research Institute of Molecular Pathology. ucla.edu or [email protected]. 302–303 | PNAS | January 13, 2015 | vol. 112 | no. 2 www.pnas.org/cgi/doi/10.1073/pnas.1423755112 Downloaded by guest on September 26, 2021 institute somewhere in Europe, and Max tion from that tired, industrial environment ing wine and good food. Physical activity RETROSPECTIVE threw himself into this project. From the to the present day buzzing community of appealed to him less; although he was a ded- outset, his sights were set on something more life science research institutes is a testament icated world traveler, often seeking unspoiled than a single institute. He wanted to seed to his ambition and far-sightedness. natural sites. In the end, however, Max a biocenter comprising several research entities Personally, Max was driven to succeed and Birnstiel’s abiding legacy is exciting research. that would one day rank with the best in the looked for associates who, like him, had “fire He leaves behind a rich heritage that includes world. What better place to make a difference in their belly.” Although occasionally re- not only his own ground-breaking discov- than in Vienna, where biological sciences had strained in the company of his scientific eries, but also world class life science re- been in the doldrums for many years? The site peers, to his colleagues, Max was a generous search facilities that arose out of his forhisInstituteforMolecularPathologywasa and sociable mentor. Something of a bon personal intuition, vision, and creativity. street of derelict factories in what was then a vivant, his institutes never lacked opportuni- European and world science owe him a rather run down area of town. The transforma- ties for extracurricular pursuits, often featur- huge debt of gratitude. Grunstein and Bird PNAS | January 13, 2015 | vol. 112 | no. 2 | 303 Downloaded by guest on September 26, 2021.
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