From dyes to breakthrough therapies

Over more than a century, molecules developed here changed medicine. Researchers created therapies for inflammatory and cardiovascular diseases as well as cancer. They pioneered hormone research, contributed to the development of psychotherapeutic drugs and turned targeted cancer therapies into a scientific reality. What began in the late nineteenth century with synthetic dyes gradually evolved into one of the world’s most important pharmaceutical ecosystems. It is a story of scientific perseverance, interdisciplinary collaboration, and the quiet conviction that even the most difficult medical problems can eventually be solved – values that still drive Novartis today. The chemical roots of pharmaceutical research Like so many things in Basel, this story began with color. In the late nineteenth century, synthetic dye chemistry was among Europe’s most advanced scientific disciplines. The discovery of aniline dyes triggered an industrial boom that transformed Basel into a center of chemical production. Companies such as Ciba, Geigy, and Sandoz initially focused on textile dyes derived from coal tar and developed extraordinary expertise in organic chemistry and industrial synthesis.

What first appeared to be a purely industrial business soon laid the foundation for pharmaceutical research. Scientists realized that the same synthetic methods used to produce dyes could also be applied to biologically active molecules. Some dyes even showed antibacterial effects in biological tissues – an early indication that chemistry could directly influence disease processes. The transition from dye chemistry to medicine was gradual. Early drugs were derived from natural substances extracted from plants or fungi. Soon, however, chemists began synthesizing molecules directly in the laboratory. By the beginning of the twentieth century, Basel’s chemical companies were already moving beyond industrial manufacturing toward pharmaceutical research.

A. Hoffmann and W. Bischoff in the hydrogenation laboratory, 1945.

In St. Johann, Sandoz established its own research department during the First World War. Arthur Stoll, who studied at ETH Zurich, developed the drug Gynergen from ergot alkaloids, one of the company’s first successful medicines. Shortly afterward came Calcium-Sandoz, which became a commercial breakthrough and demonstrated that pharmaceutical research could become an independent core business. At the same time, Ciba expanded its biological and pharmacological research activities in Klybeck. What began in 1908 with only a handful of scientists and improvised laboratory equipment would later grow into one of the world’s most important pharmaceutical research centers.

Sandoz 1929: first calcium production plant at Building 64.

Building a culture of research Partnerships with academia were early on a hallmark of Sandoz, Ciba and Geigy. Scientists moved easily between universities and industry. ETH Zurich, the University of Basel, and the pharmaceutical companies formed a tightly interconnected scientific ecosystem with researchers collaborating across disciplines at a time when such interdisciplinary work was still far from common. This became particularly visible in hormone research during the interwar years. Ciba worked closely with Nobel Prize winners Leopold Ruzicka and Tadeus Reichstein in steroid and hormone research, which led to important therapies such as Percorten and cortisone and established Basel as a center of endocrinology and pharmaceutical chemistry.

At the same time, research infrastructure expanded rapidly. In Klybeck, Building 122 became a central hub for pharmaceutical research. Chemists, biologists, and pharmacologists increasingly worked side by side. This culture of collaboration later became one of the great strengths of Novartis. Likewise, daily interactions were characterized by a culture driven less by hierarchy than by scientific curiosity. Young scientists were encouraged to pursue difficult questions and experienced researchers closely supported younger colleagues. Failure was seen as part of the scientific process – which helped attract up-and-coming talents from academia. Martin Missbach, who joined Ciba-Geigy in 1990 and is leading Global Discovery Chemistry Basel today, described how attractive this environment was for scientists interested in the intersection of chemistry and biology. “I was particularly fascinated by the interplay between chemistry and biology,” he recalled. The age of modern therapeutics In the decades following the Second World War, pharmaceutical research increasingly became the strategic center of Sandoz, Ciba and Geigy. One of the most important breakthroughs of this era was an anti-inflammatory drug developed by Geigy scientist Alfred Sallmann, who had the idea for the drug after lunch at home in 1963, scribbling the molecule’s structure on a napkin. But transforming that idea into a safe and effective medicine required enormous patience and more than 10 years of hard work and self-experimentation. At one point, the project nearly collapsed because management became concerned about side effects and considered terminating development. Sallmann’s supervisor, Ruedi Pfister, however, tested the drug on himself to demonstrate its tolerability. It eventually saved the project, leading to one of the industry's first blockbusters.

The merger that changed cancer research When Ciba and Geigy merged in 1970 – the so-called “Basel marriage” did not just strengthen the two firms’ commercial operations and market presence, but also its scientific research. New talent arrived in Klybeck and investments in biology and molecular medicine increased. Cancer research grew in importance even as the field hardly made any progress during the 1970s and the early 1980s. At the time, most cancer therapies were toxic and poorly targeted. For many patients, a diagnosis still amounted to a death sentence.

Alex Matter.

It was in this context that Alex Matter began pursuing a radically different approach. Matter, a physician and biochemist at Ciba-Geigy, believed that certain cancers could be treated through targeted intervention in molecular signaling pathways. Many colleagues considered the idea unrealistic. Protein kinases – the “switches” of cells – were thought too complex to be influenced pharmacologically. But Matter remained convinced. His research focused on leukemia, a disease caused by an abnormal fusion protein. The challenge was to identify a molecule capable of blocking precisely this disease-causing kinase without interfering with other cellular processes. To solve this problem, Matter turned to a young chemist named Jürg Zimmermann. Jürg Zimmermann and the creation of the first personalized cancer therapy Zimmermann’s life story is almost archetypal for Basel’s scientific culture. Raised on a farm in Adelboden, he originally wanted to become a football player. Because his family lacked the financial means to send him to college, he first completed an apprenticeship as a laboratory technician before later studying chemistry at ETH Zurich under Albert Eschenmoser and Dieter Seebach. From an early stage, he was drawn to difficult scientific questions. His diploma thesis tackled one of the biggest questions imaginable: How does life emerge from simple molecules? Scientifically, the project failed, but it deeply shaped his way of thinking. “The time I spent trying to solve the problem was tremendously fascinating,” he later recalled.

When Alex Matter asked whether he wanted to work on kinase inhibitors, Zimmermann immediately understood the scale of the challenge. “The problem was finding a chemical key capable of switching off the disease-causing kinase without affecting the other switches,” Zimmermann told live magazine. The work became an obsession. Zimmermann spent years synthesizing and testing molecules, often working weekends. Eventually, he developed a compound, which later reached the market as the first personalized cancer treatment. The significance of this discovery can hardly be overstated. Unlike conventional chemotherapy, the therapy targeted the molecular cause of leukemia directly. The drug blocked a defective kinase while largely sparing healthy cells.

The clinical results were spectacular. Patients who previously had almost no chance of survival suddenly experienced dramatic remissions. Around 95 percent responded positively to treatment. For many, leukemia changed from a fatal disease into a manageable chronic condition. But the importance of the therapy extended far beyond leukemia itself. For the first time, the drug demonstrated that cancer could be treated through highly precise molecular therapies. Decades of research into signaling pathways, genetics, and kinase biology were validated. Modern precision oncology was born. “For me, the development of the therapy was almost a miracle,” Zimmermann later said, “because it showed that an idea I had developed could actually change people’s lives.” A new era of innovation The development of this cancer breakthrough coincided with a period of profound transformation. In 1996, Ciba-Geigy and Sandoz merged to form Novartis. Annual investments in research and development increased dramatically, rising from around 2 billion US dollars to some nine billion US dollars. At the same time, scientific work itself changed fundamentally. High-throughput screening, a deeper understanding of human biology and DNA technology as well as the fast advance of digitalization greatly facilitated collaboration. Data could be shared between teams in real time with chemists, biologists, and clinicians working together more closely than ever before. Missbach later described how dramatically research culture had evolved. “In the past, chemists guarded their lab notebooks almost jealously,” he said. “Today, everything is much more open.” The research buildings themselves also changed. Facilities such as Research Building K-136 in Klybeck were specifically designed to encourage spontaneous encounters. Offices, laboratories, and cafeterias were arranged to facilitate communication among scientists. With the creation of the Novartis Campus in St. Johann this concept was developed even further and extended to sites in Cambridge and Shanghai and will be driving scientists in San Diego too.

New therapeutic horizons Over time, Novartis expanded its research far beyond traditional small-molecule medicines, which included blockbusters such as Diovan, which was developed in Klybeck, where operations and research have since been reduced. This was followed by advances in immunology, oncology and neuroscience, among others. More recently, Novartis has invested heavily in gene therapies, radioligand therapies and RNA-based medicines and is among the industry leaders when it comes to embedding artificial intelligence deeply into its R&D structure. The scientific complexity of these technologies exceeds anything the early dye chemists of the nineteenth century could ever have imagined. But something remained constant. The determination to tackle difficult problems, the interplay between chemistry and biology as well as the conviction that scientific progress is only possible through collaboration and the personal drive of scientists. What was true a century ago, remains true today. Driving top-notch innovation only goes together.