Following the footprints of biotechnology in Munich

The datasets that our project has collected on submissions and publications of DNA sequences documented Munich as a central institution across the three species we are investigating: Homo sapiens, the pig Sus scrofa and the baker and brewer’s yeast Saccharomyces cerevisiae. The Ludwig-Maximilians University of Munich (LMUM), the main higher education provider in the city, featured consistently among the top co-authors of articles reporting new yeast, human and pig sequences for the first time in the scientific literature. This leadership position seemed to be especially strong between the late 1980s and mid-1990s, the early years of genomics research. As historians, we were incredibly curious to learn about the research projects and institutional infrastructure underlying our data, especially given that Munich does not feature prominently in the historiography of biotechnology and genomics. A workshop organised by the Historical Seminar of the LMUM to which one of us was invited provided the opportunity to reconstruct these sequencing practices through oral histories and archival research in Munich.

The workshop was organised by the project Cooperation and Competition in Science, led by Kärin Nickelsen at LMUM and which also involves the Deutsches Museum, the Institute for Contemporary History and the University of Jena. Two of the project’s strands explore the collaborative patterns and rivalries that have characterised the emergence of biotechnology and big biology. These lines of research have led to the creation of a vibrant community of PhD students who investigate the early years of the Human Genome Project. At the workshop, Dana von Suffrin and Marina Schütz presented on the history of the Human Genome Organization and the transition from the worm C. elegans to the human genome as objects of large-scale mapping and sequencing techniques. Alexander von Schwerin and Magnus Altschäfl also delivered informative talks on the creation of regional biotechnology clusters by the German Federal Government in the early-to-mid 1980s, and the decision to locate one of them in Martinsried, a small town on the outskirts of Munich and home of the Max Planck Institute of Biochemistry (MPI-B). These presentations were accompanied by keynote lectures delivered by international guests, such as Doogab Yi and Soraya de Chadarevian.

Martinsried was, accordingly, the main site of the historical research I conducted during my visit to Munich. The MPI-B holds annual reports that enabled me to follow, year by year, the design of an institutional architecture to favour the rise of the then novel recombinant DNA techniques. In 1984, the Munich Molecular Biology Research Centre, also called as the Munich Genzentrum, was created as an interdisciplinary space where promising early career researchers would hold their first independent position and scientists from different departments of the LMUM and MPI-B could use their shared facilities for the synthesis of peptides and oligonucleotides, as well as protein and DNA sequencing.

These gene centres were also established in Berlin, Cologne and Heidelberg. The Munich Genzentrum was chaired by Ernst-Ludwig Winnacker, who would later become the president of the European Research Council, and had among its research faculty Peter Hans Hofschneider, one of the founders of the pioneering biotechnology start-up Biogen. With the help of Altschäfl, I examined the early research reports of the Munich Genzentrum and realised that – from the early years – groups devoted to genetic research on yeast, human and livestock species of local interest, particularly the pig, had been established around the central technological facilities.

According to our dataset, the Munich Genzentrum was the seventh largest submitter of human DNA sequences between 1985 and 1995, and the LMUM the tenth submitter of yeast sequences between 1980 and 2000. Another institution created by the MPI-B in 1988, the Martinsried Institute for Protein Sequences (MIPS), features as the largest submitter of yeast sequences. The LMUM is also the twentieth most connected node in our network of over one thousand institutions having co-authored articles describing new pig sequences between 1990 and 2015.

While in Munich, I talked to Horst Domdey, who was part of the first breed of junior research leaders at the Genzentrum. During his tenure, he became one of the first users of an automatic DNA sequencer manufactured by the chemical multinational DuPont and participated in two large-scale genomic projects sponsored by the European Commission, the Yeast Genome Sequencing Project and the Human Genome Analysis Programme. His participation in the former, yeast project, was conducted in collaboration with another unit at LMUM, the Institute for Physiological Chemistry. In that institute, now called the Adolf-Butenandt-Institut, another researcher, Horst Feldmann, led the sequencing of chromosome II of yeast as part of his investigation of transfer RNA and gene expression in a single-celled microorganism.

Both Domdey and Feldmann would send their sequences to the MIPS for quality control. This institution had been designated by the European Commission as the bioinformatics coordinator that would receive the sequences from all the laboratories involved and channel their submission to public databases. Werner Mewes and Karl Kleine, PI and researcher at MIPS, explained to me that while their first target was protein sequences, during the 1990s they shifted to DNA as the major focus of the European genome projects. The origins of MIPS are connected to the strong protein chemistry tradition at MPI-B, where Pehr Victor Edman, the inventor of the first automatic protein sequenator, finished his career.

The final piece in the Munich biotechnology jigsaw was MediGene, a start-up company that was created in the mid-1990s. This company derived from the shared sequencing facility at the Genzentrum and provided corporate services in both DNA sequencing and medical genomics. During an oral history, the director of DNA analytics at MediGene, Brigitte Obermaier, recalled that the sequencing facility at the Genzentrum had from the onset been conceived as a seed for future commercial developments. The sequencing services became the most productive business line at MediGene, which in the late-1990s was rebranded as Medigenomix and has since served the necessities of laboratories from the pharmaceutical industry. Medigenomix was acquired by the laboratory services multinational Eurofins and is now part of its commercial offer.

In spite of their strengths, neither LMUM nor MPI-B considered the establishment of a genome centre in Munich. Other large-scale sequencing facilities adopted this institutional form during the 1990s, and actively participated in the Human Genome Project and other international sequencing initiatives. The Munich institutions, in contrast, preferred to use their sequencing skills to address existing research necessities, internal at first and then providing commercial services to the European Commission, pharmaceutical laboratories and other customers. This is why the visitor to Martinsried is welcomed by a company incubator, now called the IZB, rather than a genome centre. By studying this experience, it is possible to connect the histories of biotechnology and genomics, and show that large-scale sequencing technologies can be productively used in other objectives, apart from completing whole genomes.

The Fördergesellschaft IZB or company incubator where MediGene and other biotechnology start-ups in Munich were born. It is located in Martinsried, the biomedical campus of the Ludwig-Maximilians University of Munich, a short walking distance from the Genzentrum and Max Planck Institute for Biochemistry