Unchaining a champion

Biotechnology in North Rhine-Westphalia already has a colorful history and a number of achievements. But the success story is only just beginning.

By Joachim Pietzsch

The view from BioCampus on the outskirts of Cologne, Germany.

On a clear day the panorama from the BioCampus on the outskirts of Cologne, Germany, is impressive. From the conference room atop its eleven-story main building, the view stretches from the Seven Mountains (Siebengebirge) above Bonn in the south to the branches of the Ruhr area in the northeast, passing along the flat land towards Aachen and the Belgian border in the west. Downstream along the Rhine River, the view almost extends to the state's capital, Düsseldorf, before it finally reaches the trees, walls, and bridges of the timeless city of Cologne itself. Steeped in Roman history, and constantly reinventing itself since that era, Cologne's magnificent cathedral rises up as a testament...

Amaxa, a spin-off from Cologne University and pioneer in transfection technologies, was so successful that it was acquired last year by Lonza, the Swiss company that is a market leader in providing primary cell cultures. Memorec—an acronym for Medical Molecular Research Cologne—had its labs here, and was the first company in North Rhine-Westphalia (NRW) to receive grants from the federal Bioregio competition in 1997. Later, Memorec was acquired by Miltenyi Biotec, another Cologne University spin-off that was founded in 1989 by physicist Stephan Miltenyi. His invention of magnetic cell separation technology met the need for a simple method to purify cell populations. It uses magnetic microbeads conjugated to one or more specific antibodies which bind to unique antigens on the cells' surface. These days Miltenyi Biotec is a global company with 1,100 employees in 18 countries.

Enabled by education

Like Qiagen, which spun off from Düsseldorf University in 1984 and is now among the world's top biotech companies, Miltenyi and Amaxa became successful by bridging gaps in the market for lab solutions and making the professional life of scientists a lot easier. This business focus on enabling technologies rather than on medicines characterizes NRW's red biotechnology sector even today. The Jülich-based company Dasgip, for example, is an international provider of parallel bioreactor systems. Dasgip CEO Thomas Drescher confirms that "14 of the 15 worldwide leading pharmaceutical companies are among our customers—and we are working on covering the top 20."

Success stories like these would not have been possible without the exceptional educational standards in North Rhine-Westphalia. Of the 16 German federal states, it boasts the broadest and densest network of universities, technical schools, Max Planck institutes and research centers. While post-war NRW possessed only three classical universities in Bonn, Cologne, and Münster, plus the renowned technical university in Aachen, the state government began to overcome this handicap in the 1960s, coinciding with the decline of its coal mining regions. Driven by the desire to develop the state's economic structures and include students from all social classes in higher education, new universities in Bochum, Dortmund, Düsseldorf, and Bielefeld were founded, followed by more than a dozen others over the next decade. The research center in Jülich, which would become the biggest of its kind in Germany, had already been established in 1958. Soon, genetics and biotechnology were taught at the new universities, too, and even a relatively remote place like Bielefeld in eastern Westphalia became a hotspot of genetic research in Germany.

Gene center grants

A marriage of two minds

North Rhine-Westphalia is a British invention. Without it, the reconstruction of postwar Germany would not have succeeded.

In 1946, both the Soviet Union and France insisted on placing the economically important Ruhr area under international control. London responded by launching "Operation Marriage." The Ruhr area lay within the British occupational zone, and the far-sighted merger between the northern part of the Rhineland and Westphalia preserved Germany's economic powerhouse undivided and laid the foundation for the German Wirtschaftswunder (economic miracle) in the 1950's and 1960's. Today the region is just one of 16 federal states of Germany, but is home to almost one quarter of its inhabitants. The Rhine axis and the Ruhr area—the latter is often referred to as Germany's biggest city as so many towns and cities are contiguous—are the state's most populous regions with 3.7 and 5.4 million inhabitants, respectively. NRW, the only German state that is almost always addressed by its acronym, contributes 21.7 percent to Germany's Gross Domestic Product. As an independent country, it would rank 17th at the international level in terms of economic strength. For almost fifty years, between 1949 and 1998, the Federal Republic of Germany had its provisional capital in NRW's small, established university town of Bonn.

The British "Operation Marriage" brought together two totally different German tribes: the merry, more easy-going, sometimes high-spirited Rhinelanders, and the solid, sometimes stolid, hardworking Westphalians. Although no love match, both partners have learned to complement, and occasionally compliment, one another. They now value their differences, as well as the diversity introduced by many immigrants who are integrated here more easily than in any other area of Germany. There's some truth in the saying that Westphalians often feel obliged to keep the promises that Rhinelanders have made—and this kind of job sharing is one reason for NRW's ongoing success.

For entrepreneurial minded German graduates, placing emphasis on biotechnological methodologies rather than on developing recombinant proteins was the best way to escape the heated and somewhat irrational public debate on biotech during the 1980s. During that time, US companies like Genentech had long since come of age while Hoechst of Frankfurt, then the biggest chemical company in the world, had to fight for more than a decade to get its recombinant insulin plant up and running. Given the situation, Bayer, the company whose scientists discovered Aspirin, preferred to pursue its biotech activities in California. Hoechst had caused an uproar in the German media, when it entered into long-term research collaboration with Massachusetts General Hospital in Boston in 1980. Would German biotechnology go into exile? The federal government decided that it should not, and set up four dedicated gene centers in Cologne, Heidelberg, Munich, and Berlin.

Of the 16 german federal states, NRW boasts the broadest and densest network of universities and research centers.

These gene centers nucleated rapid progress. By the time federal funding ended in 1995, Germany's biotech research was competitive again. In the same year, federal research minister Jürgen Rüttgers, now minister-president of North Rhine-Westphalia, launched the Bioregio competition to forge synergies between science and business, Germany's biotech scene quickly grew and NRW was again at the forefront with its Cologne-based state initiative BioGenTec. Founded in 1994, this association of 45 personalities from economics, science, labor unions, leagues, chambers, politics, media, and the government was unique in Germany at the time.

BioGenTec relentlessly promoted NRW's lively biotech scene and organized the award winning application of the Rhineland in the Bioregio contest. Social Democrat Wolfgang Clement, then the state Minister for Economy, was a powerful supporter: "Emulating the highly successful US model in the major biotechnology centers of California, Massachusetts, and New York, NRW has in place the infrastructure needed to grow a business," he said, courting potential US investors.

The Hohenzollern Bridge into Cologne.

One year later, however, the state's Social Democrats lost their absolute majority. To stay in power they had to form a coalition with the Greens, a party reluctant to involve itself in biotechnology. Nevertheless, entrepreneurial enthusiasm persisted: In 1998, Peter Stadler, resigned his position as head of Bayer's pharmaceutical biotechnology arm, to continue drug hunting at his start-up company Artemis. He was supported by distinguished partners, Nobel laureate Christiane Nüsslein-Vollhard, and leading immunologist Klaus Rajewski. Both federal and state politicians heartily applauded Artemis' start in an official ceremony.

At the end of the 1990's came the dot-com crash and a worsening climate for biotech innovations. BioGenTec became a mere distribution agency for funds from the Bioregio contest, giving every applicant a slice of the pie, rather than focusing on candidates with the highest potential. Also, NRW politicians seemed to lose their interest in biotechnology altogether. "We've been through a vale of tears since then," recalls Detlev Riesner, NRW's eminent liaison between science and business. "BioGenTec was literally stalled, and our best talents felt frustrated."

Bioriver revival

In 2004, an initiative called BioRiver, which was relatively free of political influence, revived the Rhineland's huge biotech potential—and the repercussions have been felt throughout the state. "It was a business movement which strove to liberate private creativity from dependence on public funds," says Martin Kretschmer, managing director of BioRiver. "We wanted to say goodbye to the watering-can principle and focus on competitive quality again." BioRiver set out to provide a new biotech platform for the Rhineland region and to promote technology transfer between science and industry.

In May 2005, after almost 40 years of social democratic governance, a conservative-liberal coalition took over power in North Rhine-Westphalia and biotechnology returned to the state's political agenda. The ministry for science and research, now charged with economic responsibilities, was restructured and renamed, and its head, the Liberal Democrat, Andreas Pinkwart, became Germany's first innovation minister. An economist by training, Pinkwart aimed to create a favorable innovation climate with a balanced triad of more freedom, more money, and more competition. "Our research intensity was too low," he says. "And there were too few entrepreneurs in high tech areas which are expected to lead to sustained growth." He began by supporting selected centers of innovation, including biotechnology. One funding focus, for example, is on white or industrial biotechnology which applies biological tools to synthesize more sustainable chemicals. Here, the ministry's intentions coincided with those of BioRiver. Joined by other players from NRW, their members took part in the German Federal "BioIndustry 2021" competition in 2007—and their Cluster of Industrial Biotechnology, or CLIB2021, concept was awarded the first prize, winning €20 million for projects in research & development.

Biotech for Chemistry
North Rhine-Westphalian sites of the 32 initial partners of CLIB2021 who won the federal "BioIndustry 2021" Competition in 2007. The cluster has since grown to more than 50 members.
Map Source: Bildungsklick.de

"With this cluster, North Rhine-Westphalia will make a singular difference in shaping the future of biotechnology," claims Christian Patermann, retired research program director of the European Commission. Wisely building his innovation strategy on senior expertise, Pinkwart hired Patermann as his Knowledge-Based Bio-Economy (KBBE) advisor. KBBE represents an integral part of the EU's seventh framework program and includes European technology and research areas such as food for life, sustainable chemistry, bio-energy, and plant genomics. "North Rhine-Westphalia currently is Germany's only state with a KBBE office," Patermann says. "Bio-economy means managing biological resources from plants, animals and microorganisms to improve both industrial products and processes," he continues. "It's about the 'biologization' of chemistry, based on biotechnological application of nature's toolbox, and it will contribute significantly to sustainability." A state like North Rhine-Westphalia, says Patermann, fulfills the requirements: "With its coal, steel, chemistry, car and textile heritage, the region has many traditional industries that cry for modernization by biotechnology. And it also has lots of forestry, agriculture, a large food industry, and both the economic and intellectual resources to become a model state for a bio-based economy."

During the last few years, white biotechnology has emerged as a powerful component of NRW's innovation offensive. Yet red and green biotechnologies remain important to the state's future, too. The interplay of white, red, and green matches the colors of the state flag, an auspicious indication for the future of a forward-looking and inventive region.

From Coal to CLIB

Coal mining has been the linchpin of the Ruhr economy since the mid-19th century. Coal mines, together with iron works and steel mills, was the mainstay of the reconstruction of Western Germany. In 1956, more than half a million miners dug 125 million tons of coal. After this pinnacle, however, the decline began. Cheaper imported coal and oil began to replace domestic products. Between 1957 and 1967, the number of mines sank from 140 to 76, and hundreds of thousands of miners lost their jobs. In a concerted effort federal and state governments, unions and mine owners worked to rescue the Ruhr economy, most mines were consolidated in a new enterprise—"Ruhrkohle AG " (RAG ) which was founded in 1969. In the long term, RAG could not save the mines, even though it was subsidized by the so-called coal penny paid by all electric power consumers.

RAG negotiated stepwise cutbacks of its mining quota with the federal government. In 1998 RAG took over all remaining German coal mines and quickly diversified by acquiring chemical and energy companies. In 2006, it split into a "black" and a "white" business. While the former deals with the remnants of German coal mining, which still employs more than 30,000 people, the latter's businesses are energy, real estate, and chemistry. In 2007, it was renamed Evonik, a global company pioneering white biotechnology as a major partner of the Cluster of Industrial Biotechnology, or CLIB2021. Thus, a young, innovative offshoot is flowering from an old, time-honored industry.

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