in this issue
Chemical innovation: The modern research lab––made in Germany
11:54 AM MDT | June 2, 2014 | —Michael Ravenscroft
The German chemical industry is fourth-largest in the world, with sales of €188.7 billion ($258 billion) in 2013. Germany is world champion in the export of chemicals: Chemical exports, including pharmaceuticals, were worth €113.7 billion in 2013, or 60% of total production, generating a trade surplus of €47 billion. The industry directly employs about 436,000 people, according to chemical industry association VCI (Frankfurt). As recently as the late 1990s, three of the world’s five-largest chemical companies were German. The chemical industry occupies a close third spot in Germany behind the automobile industry and mechanical engineering. In the first 30 or so years of the 20th century, Germans won 14 Nobel Prizes in chemistry.
Research spending in the German chemical industry climbed to a record €9.6 billion in 2012, an increase of 6.0% compared with that in 2011, according to VCI. The chemical-pharmaceutical industry wants to increase R&D spending in 2014 to €10 billion, according to VCI.
Nobody who studies chemistry can overlook Germany’s contribution. One of the first pieces of equipment encountered in the laboratory is the Bunsen burner. Common glassware familiar to all chemists include the Erlenmeyer, or conical, flask; the Liebig condenser; the Claisen flask; the Büchner funnel and flask, and the Soxhlet extractor. Liebig’s Kaliapparat is one of the elements of the logo of the American Chemical Society.
The modern plastics industry would be unthinkable without Ziegler-Natta catalysts, polystyrene, synthetic rubber, polyurethanes, or polycarbonates. Reactions such as the Diels-Alder reaction and the Wittig reaction are formidable tools in the repertoire of the synthetic organic chemist.
Chemists at Hoechst developed Tuberculocidin in 1892, a tuberculosis diagnostic based on work by Robert Koch. This work was followed in 1894 by production of the first serum against diphtheria.
Felix Hofmann synthesized acetyl salicylic acid—aspirin, “drug of the century”—at Bayer in 1899. “Within a period of two weeks, Hofmann discovered one of the most useful substances known to man—aspirin—and one of the most deadly, heroin,” says Peter Watson in The German Genius. Aspirin continues to generate significant revenues for Bayer, which continues to find new applications and ways to market the substance. Total aspirin sales for the company were €916 million in 2013, split almost evenly between the pharma and the consumer health segments.
Acetophenatedine, a more powerful antipyretic than acetanilide, with fewer side effects, was derived from p-nitrophenol, a waste product of the dye industry. Nobel Prize–winner Paul Ehrlich developed Salvarsan in 1910, the first drug effective against syphilis.
Sulfonamides, discovered by Gerhard Domagk at Bayer, were a key breakthrough in the treatment of infectious diseases, and Prontosil was launched in 1935. Dormagk was awarded the Nobel Prize for his work in 1939.
To cite all the chemistry-related inventions, discoveries, reactions, equipment, and processes made by Germans would require far more space than is available here—and would be tediously long.
German chemists have also been responsible for producing chemical journals and handbooks, through which the scientists could both share their inventions and progress with as well provide access to reliable scientific information and data. Examples of journals include Justus Liebig’s Annalen der Chemie (founded 1832) and Chemische Berichte (1868). Beilstein’s Handbook of Organic Chemistry first appeared in 1881 and contained information on 15,000 organic compounds. Other reference works include Gmelin’s Handbook of Inorganic Chemistry (1817), Houben-Weyl’s Methods of Organic Chemistry, and Ullmann’s Encyclopedia of Industrial Chemistry (1914).
Factors for success
A number of factors were responsible for the success of the chemical industry in Germany. One was the large workforce, well educated and well trained in chemistry and engineering. Another was the creation of polytechnic institutes, which supported the German chemical industry’s ever-increasing need for trained scientists and engineers. German-trained chemists often moved to other countries to work. August Wilhelm von Hofmann was persuaded by Prince Albert, a compatriot and husband of Queen Victoria, to become the first professor at the Royal College of Chemistry in England. As new products were developed, companies worked on improving the processes to make these products efficiently and cost-effectively on a large scale. German companies were also willing to tackle difficult, longer-term problems. Even at an early stage, a network of close collaboration existed among disciplines and among industry, academia, and government. But, one innovation was groundbreaking: the industrial R&D laboratory.
“The Germans made an invention in the 1870s that was an organizational innovation, the development of the modern research laboratory in the industry, within companies,” says Carsten Reinhardt, president and CEO of the Chemical Heritage Foundation (Philadelphia). “Several of the companies founded in the 1860s, such as BASF, Bayer, Hoechst, Agfa, Kalle, which were fledgling companies but already quite successful, went into the invention business, setting up their own laboratories, using their own workforce[s], and hiring chemists,” Reinhardt says. “These R&D laboratories had their roots partly in the manufacturing process, partly in analysis, but also because the need for innovation was so strong. Innovation was a German invention,” Reinhardt says. William Perkin in England also had an R&D laboratory attached to his factory, but the lab was more of a personal toy, according to Reinhardt.
The creation of the factory laboratory was an historic event that changed the techniques of scientific research, Watson says in The German Genius. The cooperation of several specialists working in a research team led by a research director produced results faster than individuals working alone, Watson says. “Places [in the research team] could be found for impractical but gifted theorizers, gadget-minded but skillful experimenters, and for those who were poor observers but who could make links between newly discovered and old facts,” he says.
Carl Duisberg created a separate pharmaceutical division at Bayer with a dedicated laboratory, organized into two parts: a pharmaceuticals group, charged with inventing new drugs, and a pharmacology group, to test them. This successful model has been much copied, Watson says.
The chemical industry in Germany has its origins in the development and production of synthetic dyes derived from coal tar. The target for companies making synthetic dyes was the textile market, which was growing rapidly in Germany at the time, in the wake of industrialization. Bayer was founded in 1863 with the “objective of manufacturing and selling synthetic dyes.” Hoechst was founded in the same year for the “production of coal tar dyes.” Hoechst’s first product was fuchsin, a red-violet dye, which earned the company the name “red factory.” BASF was founded in 1865, establishing the first company R&D laboratory in 1867 for the synthesis of new dyes. One of the fruits of BASF’s research was a process for the industrial production of alizarin, followed by the production of echtrot, auramin, and eosin. The first German Reichspatent was granted to BASF in 1877 for coal-tar dyes derived from methylene blue. This dye later helped Robert Koch make bacteria visible under the microscope. BASF achieved the industrial synthesis of indigo only in 1897, after 17 years of development work. The “king of dyes” was then available in large amounts at a reasonable price.
“Innovations based on chemistry have improved people’s lives in the past and have spurred economic growth,” says Kurt Bock, chairman at BASF. “It all began with dyes. There was enormous demand, but few could afford expensive natural dyes. The challenge [to develop synthetic dyes] pushed researchers to the limit and nearly spelled the end of BASF,” Bock says. The company invested 18 million deutsche marks in research at a time when BASF’s share capital was only 21 million deutsche marks. BASF’s board of executive directors intensely debated whether so much research would actually help the company grow. Ultimately, the supporters won the argument, according to Bock.
“Research is the key to BASF’s success,” Bock says. “Finding solutions to difficult problems is only possible through cooperation. The synthesis of ammonia was achieved only after 6,500 attempts with 2,500 catalysts. The Haber-Bosch process established the foundation for modern industrial catalysis. Almost everything in modern chemistry relies on catalysts, which play a role in the production of more than 80% of all chemicals,” Bock says.
Evonik Industries recently developed a new oxidation catalyst that makes synthesizing acrolein—used to make methionine—more efficient, although the company has been making acrolein for more than 50 years. “Process technology and engineering are very important, with over 800 engineers working on process innovation. We see this as one of Evonik’s strengths,” says Patrik Wohlhauser, executive board member at Evonik.
Germans are willing to wait for research to produce breakthroughs. Developing the industrial synthesis of indigo at BASF took 17 years. The scale-up of Haber’s laboratory-scale synthesis of ammonia in 1908 was successfully developed on an industrial scale by Bosch in 1913. “Eight to 10 years would be nothing for development of new products for Creavis [the innovation division of Evonik],” says Peter Nagler, chief innovation officer at Evonik.
The network of collaboration among industry, universities, and government is an important part of chemical R&D in Germany. Evonik collaborates with about 250 universities globally, “to nurture contacts and develop new knowledge and competences,” Wohlhauser says. “Developing external networks—getting knowledge from outside—is essential for Evonik,” Wohlhauser says.
German companies regard investment for research as an important activity. “R&D has always been a high-priority subject at Wacker,” says Florian Degenhart, manager/media relations at Wacker Chemie. “We spend around 4% of our sales every year for developing new products and technologies, [which] makes us one of the most research-intensive companies in the chemical industry,” he says. “Another objective of our R&D activities is continuously optimizing manufacturing processes in order to be the technology leader and to be sustainably profitable,” Degenhart adds.
Germany’s preeminence in chemistry is also partly related to its mining industry, according to Watson. The mining of silver grew rapidly, especially in Saxony, in southeastern Germany, since silver was becoming the basis of the money supply. Towns such as Freiberg and Chemnitz were founded on the mining industry. The addition of certain fluxes to kaolin, China clay, made it fusible. This discovery enabled the Germans to producte high-quality porcelain at places like Meissen. In this way, mining and chemistry became intimately related, Watson says.
The further development of existing processes and the development of new processes are important parts of the research conducted by companies in Germany. Wacker—like IHS Chemical Week, celebrating its 100-year anniversary this year—developed the direct oxidation of acetylene to acetaldehyde in 1913. The process, known as Wacker process number one, was licensed worldwide and was one of the company’s most important processes for six decades.
Acetylene chemistry formed the basis of polyvinyl acetate, polyvinyl alcohol, and polyvinyl chloride (PVC), which, for 60 years, was one of Wacker’s major “cash cows” following the introduction of suspension polymerization in 1935, according to Christian Finger, senior manager/information management at Wacker.
Wacker patented a process—the second Wacker process—for the production of acetaldehyde by the direct oxidation of ethylene in 1957. This discovery was also groundbreaking, signaling the start of the petrochemical age at Wacker, and the more economic production of ethylene, itself obtained from petrochemical sources. The process was scientifically important but also very successful commercially, being licensed in about 20 countries.
“Germans were not just innovators but also rapid adopters,” Reinhardt says. “The contraceptive pill, although it was an American invention, was quickly introduced in Germany by Schering (Berlin), a company with rich experience in endocrinology and hormone chemistry,” he says.
The important contribution being made to maintaining and further developing the German language in chemical research and teaching, particularly with a view to fostering the rising generation of scientists, has been emphasized by Francois Diderich, professor of chemistry at the Swiss Federal Institute of Technology (ETH Zürich) and a supervisory board member at BASF. The continuing appearance of chemistry articles, particularly reviews, in German helps make it possible to teach modern chemistry in German at high schools and other educational establishments, he says.
Over the years, the German chemical industry has continued to evolve. Hoechst broke itself up in 1999, becoming Sanofi, Celanese, and Clariant. “Bayer is [now] a life sciences company. It is not a chemical company,” a Bayer spokesperson tells CW. Degussa and Hüls have become Evonik Industries. BASF—self-styled “The chemical company”—is still the world’s largest chemical company, both by annual sales and by market capitalization.
“Production of PVC and halogenated organics is being replaced at Wacker by new product fields, predominantly biotechnology,” Finger says. A biotech research center was started up at Burghausen in 1990. The acquisition of ProThera in Jena and the establishment of Wacker’s biotech business in 2005 expanded the company’s existing pharmaceutical operations to include the contract development of pharmaceutical proteins, or biologics.
“With the possible exceptions of pharmaceuticals and agricultural chemicals, single molecular entities are no longer the target of company research,” says Andreas Kreimeyer, board member responsible for research at BASF. “Companies are looking increasingly to provide solutions rather than molecules,” Kreimeyer says.
“The focus of innovation in the chemical industry—and also in science as a whole—has shifted increasingly over the last few decades from molecules to materials, effects, and systems,” Kreimeyer says. “Today more than ever, the emphasis is on intelligent chemistry in the form of holistic systems designed to find solutions along the value chain for securing water and energy supply as well as maintaining quality of life,” Kreimeyer says. “In the 1970s, research was still centered on the development of single molecules. The focus of value creation has now shifted increasingly toward functional materials from raw materials, basic products, and intermediates towards systems solutions. These types of more-and-more sustainability-driven innovations require an interdisciplinary approach and new ways of linking together different areas of expertise—both in industry and academic research,” he adds.