When the BioRegion Rhein-Neckar-Dreieck (BioRegion Rhine-Neckar-Triangle) Initiative was started in 1996, only a few small biotech companies existed in the area. Five years later the region at the intersection of the German “Länder” (States) Baden-Württemberg, Rheinland-Pfalz and Hessen with the principal cities of Heidelberg, Mannheim and Ludwigshafen, has become one of the most dynamic centres of the biotechnology industry in Europe. Presently there are about 45 research-driven biotech companies and a similar number of service companies with 1.900 employees altogether. A workforce of approximately 8.000 in industry and another 6.000 in public research institutions of the Rhine-Neckar-Triangle are dependent on biotechnology which has become the fastest growing industry sector and a motor for the regional development.

What distinguishes BioRegion Rhein-Neckar-Dreieck from other biotech regions is the high concentration of innovative companies in direct neighbourhood to university institutes and hospitals as well as international research institutions. The Technology Park Heidelberg located on the campus of the university is completing another five buildings by the end of 2002 to house more than 50 tenant companies. With a total of 50.000 sqm lab and office space this will be the largest life science park in Germany.

BioRegion Rhein-Neckar-Dreieck was initiated when the region became a winner in the so-called BioRegion Competition of the Federal Ministry of Education and Research. The prize for the best concepts to develop a biotech industry in the region was a special funding of roughly 25 Million Euro over the period 1997 to 2001 for research projects with prospects of commercialisation. Together with a seed capital fund of about 12 Million Euro raised by local investors and saving banks, this money sparked the foundation of innovative biotech companies. “BioRegion funding gave rise to fourteen companies in our area which today have on average 60 employees each”, says Stefan Meuer, chairman of the non-profit association BioRegion Rhein-Neckar-Dreieck e.V. which was implemented to foster the emerging biotech industry in the region. “Our advisory board which consists of renowned representatives from science and industry, selected the projects by world standard criteria of scientific quality and novelty, a focus on the regional strength in science, particularly genomics, proteomics and bioinformatics for medical applications, the creation of jobs, and the potential for commercial success on the global marketplace. The success of this strategy is shown by the remarkable growth of the enterprises we had supported.”

Even though funding has been an important catalyst for the start of the biotech industry in and around Heidelberg, the main driving force for the growth of the bioregion was the formation of a network and the commitment of its members. Decision makers of big pharmaceutical and small biotech companies, public research institutions, city councils and venture capitalists joined the BioRegion Rhein-Neckar-Dreieck e.V. association to combine their efforts for providing and improving the infrastructure in which biotech start-ups can flourish, for cutting through red tape, when necessary, and for encouraging the risky steps towards entrepreneurship. For a region which is divided by administrative boundaries of three Bundesländer, it is significant that from each Land big players with global interests have thrown in their weight in favour of the bioregion - in Baden-Württemberg: Roche Diagnostics (formerly Boehringer Mannheim); in Rheinland Pfalz: BASF and Abbott (formerly Knoll); and in Hessen: Merck Darmstadt. They have given substantial support to build and sustain the network, and their co-operations in long-term projects with the academic institutions led to the formation of new biotech companies.

The region's outstanding research is the substrate which nourishes the growth of biotech start-ups. It is the blending of basic science with medical application which proved the most fertile breeding ground. This approach seems to be commonplace today, but the oldest university of Germany in the romantic town of Heidelberg was one of the first places in the world where this idea was realized.

In 1929 the Director of the University's Medical Clinic, Ludolf von Krehl, established the Kaiser-Wilhelm-Institute for Medical Research - today the Max-Planck-Institute for Medical Research - and appointed the physiologist Otto Meyerhof, the chemist Richard Kuhn and the physicist Karl Hausser as directors to integrate disciplines of natural sciences with medicine toward the understanding of metabolic processes and their pathologic disorders.

Major breakthroughs in biochemistry and the study of living cells are the result of this multidisciplinary approach, for example the elucidation of glycolysis, the bioenergetic role of ATP, the development of synchrotron radiation for biological experimentation, the chemistry of biological resistance and the discovery of the calcium pump.

Following this tradition the German Cancer Research Centre (Deutsches Krebsforschungszentrum, DKFZ) was founded in Heidelberg in 1964 combining fundamental research in the areas of cell and molecular biology, genetics, immunology, virology, radiation biology and informatics under one roof for progress in the understanding, prevention and therapy of cancer. Clinical cooperation units have been created jointly within the University Hospitals of Heidelberg/Mannheim and research opportunities are provided by the DKFZ for university clinical groups. The German Cancer Research Centre is leading in the exploration of tumour viruses which are thought to be involved in 10 % of all cancer cases worldwide, and on apoptosis, or programmed cell death, and its significance in tumour research and in the immune system. Diagnostic markers for a whole range of cancers using re-expressed fetal antigens, or through the detection of soluble keratins and other components of the cytoskeleton were discovered here and are now applied on a routine basis throughout the world. Important contributions to the sequence analysis of the human genome have been made at the DKFZ, and one of two operating units of the Resource Centre within the German Human Genome Project, which provides the international scientific community with cDNA and genomic libraries and databases, is located here.

With the setting up of the headquarters laboratory of the European Molecular Biology Laboratory (EMBL) in 1974, Heidelberg became an international hotspot in molecular biology. EMBL is supported by 16 countries including nearly all of Western Europe and Israel. It was founded with a fourfold mission: (1) to conduct basic research in molecular biology with research programmes in cell biology and cell biophysics, developmental biology, gene expression, and structural and computational biology, (2) to provide essential services to scientists in its Member States, (3) to provide high-level training to its staff, students and visitors, and (4) to develop new instrumentation for biological research. In all these areas, EMBL has had a deep impact on science and its publications rank amongst the most often quoted in international journals.

The Centre of Molecular Biology Heidelberg (ZMBH), established by the University of Heidelberg in 1985, further strengthened the region's scientific reputation, particularly in the regulation of gene expression, in the study of neurodegenerative disorders such as Alzheimer's Disease, and in molecular cell biology of parasitic protozoa. The ZMBH combines basic research with excellent education and it has its own graduate programme obligatory for its diploma and doctoral students.

The ZMBH was designed as an interdisciplinary institute outside the classical faculty divisions of the university. This concept proved very successful and was subsequently adopted by creating the Interdisciplinary Centre for Scientific Computing (IWR), the Biochemistry Centre Heidelberg BZH), and most recently the Interdisciplinary Centre for Neurosciences (IZN). The IZN focuses on the fringe areas between fundamental and applied research in the neurosciences, with important contributions coming from physics, chemistry, and scientific computing. It bundles research of the region's neuroscientific groups working at Heidelberg University including the University Hospitals in Heidelberg and Mannheim, the Max-Planck-Institute for Medical Research, the DKFZ, the EMBL, and the Mannheim Central Institute for Mental Health.

The cluster of molecular biotechnology and biomedicine in Heidelberg is complemented by research in related sectors at other institutions of the region. Fachhochschule Mannheim (Mannheim University of Applied Technology) focuses on cell culture and screening technologies. University of Mannheim is strong in bioinformatics and applied mathematics and as one of Germany's leading universities in business administration it is providing students with entrepreneurial skills. The University of Kaiserslautern is renowned for its microbiology and mycology department. There is also a Centre for Green Gene Technology for transgenic crop plants in Neustadt/Weinstrasse.

Most of the biotech start-ups naturally prefer to stay close to the academic centres. Confronted with high rent and living costs in Heidelberg, however, some companies have discovered that short distances and an excellent motorway system allow them to retain their links with research institutes, even when they are located at lower costs elsewhere in the region. Outside rush hours every place in the BioRegion Rhein-Neckar-Dreieck can be easily reached within one hour's drive. In particular Mannheim, the region's largest city and its economic centre and traffic hub, has profited from this trend, and a number of biotech companies have set up business here. Biotechnology in Germany has entered a difficult period. The poor performance of the national economy and the collapse of the Neuer Market, Germany's stockmarket for new technologies, has shooed off venture capitalists and finance institutions from investing in risky new enterprises. Seed capital is hardly available for biotech start-ups whose business plans don't show profits in the near future. Consequently, some companies have to change their strategies, to postpone promising long-term drug development projects and to concentrate on products for which short-term turnover can be achieved. Since July 2001 the rate at which new biotech companies are being created is strongly declining. Empty coffers of Federal and State governments have let fundings for innovative enterprises become a trickle compared to the enthusiastic years of the late 1990s. “There is no reason for pessimism, however”, insists Ernst Jarasch, managing director of the BioRegion Rhein-Neckar-Dreieck association. “The past years have laid a sound basis for many companies to grow. The potential for innovations in a region where 3.200 scientists are working in biotechnology-related research is enormous, and an efficient network has been built between academic institutions and the industry stimulating the exchange of fertile ideas and their transfer into commercial products.” He estimates that in the forthcoming years the regional biotech industry will triple its workforce to a size which will allow the BioRegion Rhein-Neckar-Dreieck to compete with the biggest biotech clusters in the world.

Measuring scientific performance

The EMBL, the DKFZ and the ZMBH consistently hold top positions in the international ranking of publication output in molecular biology. According to a recent analysis of papers published in the decade 1989-1998 in all English-language biomedical journals (Tijssen et al.: Mapping the Scientific Performance of German Medical Science, Stuttgart 2002), Heidelberg University ranked first amongst all German universities in the citation impact score and second in the output of papers. The DKFZ has been by far the most productive institute among all non-university research institutionsin Germany, both by the number of publications and the citation impact score.