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In memoriam : Piotr Slonimski (9 November 1922–25 April 2009)

2009; Wiley; Volume: 26; Issue: 10 Linguagem: Inglês

10.1002/yea.1704

1097-0061

C.J. Herbert,

Mitochondrial Function and Pathology

After the war Piotr wanted to pursue a career in research and moved to France to work with Boris Ephrussi. Ephrussi was not always an easy person to work with, but Piotr worked closely with him for many years, which earned him the title of 'Le mutant résistant' from the molecular biologists of the Institute Pasteur. After a brief and unsuccessful period working on development in sea urchin eggs, Piotr began his work with yeast, studying 'petite' mutants. This was the beginning of Piotr's studies on mitochondria that would occupy the major part of his career. Initially, Piotr worked on the biochemical properties of petite mutants and he was able to show that they had an altered respiratory physiology. Ephrussi had started working on yeast to study genetics, but for this purpose the petite mutants were something of a dead end, as they had a non-Mendelian inheritance. During this period, Paris was one of the leading centres for what came to be known as molecular genetics, and the discovery of non-Mendelian inheritance led to many impassioned discussions between the members of the 'Club de Physiologie Cellulaire', which, along with Piotr and Ephrussi, included André Lwoff, Elie Wollmann, Jacques Monod and François Jacob, amongst others. In the 1960s, after the discovery of mitochondrial DNA, Piotr's group was able to show that the petite mutants had large deletions in their mitochondrial DNA with a concomitant amplification of the remaining segments, and that these deletions were preferentially induced by the mutagen acriflavin that Ephrussi had used. In the 1970s Piotr and his co-workers isolated mitochondrial antibiotic-resistant mutants and mitochondrial point mutations that were respiratory-deficient. Using these mutants, they laid the foundations of mitochondrial genetics, demonstrated the mosaic (intron/exon) structure of some mitochondrial genes and identified RNA maturases; intron-encoded proteins that are necessary for the excision of the introns by which they are encoded. Already in the mid-1960s, Piotr had isolated a mutation that affected respiratory physiology and showed a Mendelian segregation pattern. In the late 1970s and early 1980s, this was followed up by a series of studies of nuclear genes and suppressors affecting mitochondrial physiology that put Piotr and his group in the vanguard of the work on mitochondrial biogenesis. During his life, Piotr received many honours and prizes; he was a member of the French National Academy of Sciences and in 1985 he was awarded the Gold Medal of the CNRS, one of the highest awards in French science. The Minister for Research presented the medal and in his acceptance speech, Piotr thanked the CNRS (National Centre for Scientific Research) '… for its sustained support that had permitted the development of mitochondrial genetics, a subject that grew outside the main currents of modern biology'. Then, in a way that was typical of Piotr, he disingenuously added 'Minister, from a purely administrative point of view, this medal has rewarded a remarkable thematic immobility, and gratuitous research on a subject of minor importance'. Political pressure to focus research in 'useful' directions had already begun, this was anathema to Piotr and he knew that the 'gratuitous research' he had initiated over two decades previously was currently being used as a paradigm for understanding many degenerative diseases. In 1987, at the age of 65, a time when most people are thinking of retiring, a new phase of Piotr's career began. André Goffeau had the responsibility of organizing a genomic project for the European Community, he contacted Piotr and together they decided to promote the sequencing of the yeast genome. In 2009 it is difficult to imagine how controversial this project was; opposition came in many forms and from both inside and outside the yeast community. Inside the community, many people thought that sequencing the genome was a waste of time and some even thought that traditional genetic methods had already found all the 'interesting' genes. Outside the community, Jim Watson was responsible for the American human genome project and argued that all the effort should be focused on sequencing the human genome. Piotr was convinced that the analysis of the human genome would be too complicated without the information that could be assimilated from simpler model systems. In 1988, he used the XIV International Conference on Yeast Genetics and Molecular Biology in Finland to launch the project and, in his own inimitable style, managed to get the majority of yeast community behind the project. The organization of the project was original; many different European laboratories were responsible for sequencing short overlapping fragments and the project began with chromosome III, which was coordinated by Steve Oliver. To many people's surprise it worked and, as the project advanced, Japanese, Canadian and American laboratories joined the sequencing consortium and the sequence of the yeast genome was completed in 1997. The European approach was often described as a 'cottage industry' and it is true that it was not the most efficient way to sequence a genome. But it worked, and it was the results of this cottage industry that clearly demonstrated the wealth of information that could be obtained from genome sequencing and stimulated and justified the formation of the sequencing factories that took over the sequencing projects. With hindsight, it is easy to see the foundational role that the European yeast genome project played in modern '-omic' biology and Piotr's personality and scientific reputation provided the activation energy needed to launch the project. Piotr's curiosity and passion for research never diminished. He was the Director of the Centre de Génétique Moléculaire of the CNRS from 1971 until 1991 and, even after he had officially retired, the first question he would ask when he walked into the laboratory would be 'Quoi de neuf?' (What's new?). During the last part of his career he was able to spend more time in his native Poland, often teaching biology to mathematicians, which he found very stimulating as he said, 'They ask all the simple questions, which are so hard to answer'. This period was dedicated to the bioinformatic analysis and comparison of whole genome sequences, but this was not a new interest for Piotr. In the mid-1960s he had published two articles on long-distance correlations in the amino acid sequences of proteins, but in the post-genomic era he had more data to work with and better tools for the analysis. His last article was published in 2009 and at the time of his death he was working on other manuscripts. It is not possible to summarize Piotr's career without talking about his teaching. He was an inspirational teacher and, with his colleagues, he revolutionized the teaching of genetics in France. Through his university courses and in the laboratory, he was responsible for the training of generations of students, many of whom went on to occupy key positions in the French academic community, extending his influence far beyond the students with whom he had personal contact. With his ever-present pipe and his charming smile, he will be much missed by all his friends and colleagues, as well as the wider yeast community.