Leisurely pace

Hormone research

Perseverance

Culture as a talent magnet

New Ciba buildings from 1937 at the edge of the Klybeck site, with the adjacent Dreirosenbruecke on the left.

Milestones of medicine

Medical history is unimaginable without the inclusion of Klybeck. Here, not only important medicines were produced. Scientists also developed and synthesized new molecules which have enabled millions of people with cancer, inflammatory diseases and heart problems to lead longer and healthier lives.

Text by Goran Mijuk, photos from the Novartis Company Archive, illustration by Capucine Matti

The early days of biological research at Ciba’s Building 133. The photo dates to around 1917.

Table of contents

Leisurely pace

Hormone research

Perseverance

Culture as a talent magnet

Published on 13/09/2021

When Martin Missbach joined Ciba-Geigy in 1990, the company had grown to one of the world’s largest pharmaceutical organizations and was considered a dream destination for young chemists. This was because, unlike at university, scientists from different fields had the opportunity to collaborate and engage in cross-disciplinary projects.

“My career at the university was quite special because I not only studied chemistry, but also biochemistry and molecular biology,” Missbach recalls when we meet him for an interview in Research Building K-136, where he worked for many years. “For me, the interplay between chemistry, which is the only discipline that can produce new molecules from small building blocks, and biology, which deals with living material, has always been fascinating.”

But Missbach wanted one thing above all: to work on drug development: “I was particularly interested in the interplay between chemistry and biology, an interdisciplinary field that was not well established in universities at that time. Thus, I resolved to pursue a career in the industry, where I could test compounds synthesized in the lab on biological systems and maybe even develop new drugs.”

Early expansion of research

Research at Klybeck was something to behold. In the early 1880s, the predecessor company Bindschedler & Busch became the first Swiss company to set up a chemical research department here, in the beginning focusing on dyes and later, after the founding of Ciba, also on pharmaceuticals. Initially, research focused on the extraction of natural substances, then on their artificial production.

The establishment of a separate chemical research department occurred primarily at the instigation of the company’s founder Robert Bindschedler, who was a chemist himself. Furthermore, with Alfred Kern and Robert Gnehm, both graduates of the Polytechnic in Zurich, he also brought two specialists into the company who forged close links between academia and industry and helped establish Basel as a center of research and production.

Around three decades later, a biological-pharmacological research department was established. Although its size remained modest at first, this start-up-like department laid the groundwork for many medical breakthroughs and would later attract Missbach and many other researchers to work for Ciba-Geigy.

One of the first scientific employees of the new unit, R. L. Baumgartner, described the early days in Ciba’s in-house magazine in 1948 as follows: “On October 1, 1908, the first employee, Dr. Berthold Schreiber, joined the biological-pharmacological department that had been founded on the initiative of Director Dr. Jacob Schmid. On the second floor of Building 27, three small rooms had been prepared for this new unit.”

The technical equipment was sparse, Baumgartner noted. “A Zimmermann’s kymograph with ink-writing, an improvised apparatus for isolated organs consisting of a tripod frame, an enamel basin, an intestinal vessel and a suspension lever, and some rabbit and rat cages, together with some mouse jars, made up the inventory.”

Leisurely pace

Compared to today’s hectic pace, things were unhurried then, and it took until 1912 for more scientists to join the small biological-pharmacological department in Klybeck. In 1916, more researchers were hired, and the number of staff reached about a dozen.

The relatively leisurely progress wasn’t surprising, given that the pharmaceutical industry was still in its infancy. Medical science, which only really gained momentum during the Age of Enlightenment, focused on natural ingredients and was primarily driven by the search for active substances in plants under the influence of chemists such as Antoine Laurent de Lavoisier and Sigismund Friedrich Hermbstaedt.

In this process, many active substances such as morphine, colchicine, nicotine, codeine and salicylic acid were discovered. At the beginning of the 19th century, a myriad new companies sprang up following the extraction of the active ingredients quinine, caffeine, chlorophyll and strychnine by French chemists Joseph Bienaimé Caventou and Pierre-Joseph Pelletier, who also launched a drug for malaria.

At first, it was mainly pharmacists such as Emanuel Merck who profited from the discovery of new active ingredients. By venturing into this new field, they could scale up their small, usually family-owned businesses considerably.

Only later did companies from the dye sector jump on the bandwagon, applying their know-how in synthetic chemistry to boost pharmaceutical production. They also made use of the screening method developed by Paul Ehrlich, which involved the testing of active ingredients in biological tissues.

From aniline dyes to medicine

However, the entry of dye companies into pharmaceuticals was partly due to chance. Aniline dyes were used in medicine to stain tissue samples and showed antibacterial effects in some tests, which, in turn, spurred the research and development of medical products.

Scientists from Klybeck were among the first to take up this trend. Initially, their strategy was to imitate existing products, including the anti-inflammatory drug antipyrine, which had been discovered in Germany. This was soon to be followed by original products based on natural substances, which were developed and synthesized in-house – such as Dial, a sleeping pill launched in 1913.

Modern tissue analysis.

Hormone research

Although chemistry remained the supreme discipline for a long time, the importance of biology grew steadily, especially when Ciba started to focus on hormones, which were first harvested from animal gonads and later synthesized in the lab.

The synthesis of the complex molecules was achieved not least through collaboration with academic researchers such as Leopold Ruzicka and Tadeus Reichstein, who had made great strides in hormone and steroid research for which both won the Nobel Prize.

Between 1918 and 1939, based on this vast accumulated knowledge, numerous hormone products were launched on the market, including Percoten, which was isolated from the adrenal cortex and later artificially synthesized; this was to be followed by the analgesic and antiinflammatory cortisone in the 1950s, about which the author Lea Haller wrote an informative book, Cortisone – History of a Hormone, 1900–1955.

As commercial success grew, so did confidence in the biological-pharmacological business. For instance, R. L. Baumgartner reported that in 1935, there were already 23 researchers on the team, while the figure reached over a hundred in 1948. “Under Prof. Dr. R. Meier, the large construction project for Building 122 was realized in 1935 and 1936 (and) on June 1, 1936, the first laboratories could be occupied.”

Building 122, next to which the Ciba logo hung for a long time, became the hub of a global research operation, which ranked among the most important in the world well into the post-war period, contributing to the company’s economic success. This was also made possible by close collaboration with the Swiss Federal Institute of Technology.

Basel marriage

Although pharmaceutical sales increased steadily from 1945 until the late 1960s, and America became an important export market, Swiss companies came to face tougher international competition and higher research costs.

This was also the case at Geigy, which was headquartered in the neighboring Rosental area. According to Geigy Chairman Louis von Planta, if the company were to remain among the leaders in the field and generate growth, closer cooperation with Ciba or Sandoz was necessary. While Sandoz rejected a merger, Ciba reached out to join forces, resulting in the so-called Basel marriage at the end of 1970.

With the merger, the newly formed Ciba-Geigy not only strengthened its sales force. The merger also brought talented researchers to Klybeck, among them Alfred Sallmann, later to be known as Mr. Voltaren.

Even before the merger, the Geigy scientist had been working on the antiinflammatory drug Voltaren, which initially launched in Switzerland and Japan, and later in the USA and worldwide, and was set to become a key driver of growth. Its research took place in Kleinbasel at the Rosental site, the former headquarters of Geigy.

Handwritten documentation of synthesis experiments in a researcher’s laboratory notebook.

Perseverance

However, the road to the drug was long and challenging, and it took a lot of patience and courage to bring the project to completion.

Sallmann had the idea for the substance early on, his widow, Ursula Sallmann, whom we met in Bottmingen, told us: “I remember it was 1963, when men were still coming home for lunch. He was all excited and scribbled something on the napkin, the structural formula of Voltaren. He held out the napkin to me and said, ‘Isn’t this beautiful; look at this harmony!’ I didn’t understand it myself.”

But it took more than 10 years until the product was ready for launch. Innovation, as Sallmann pointed out in an interview with the Ciba-Geigy newspaper upon his retirement, requires not only perseverance, but also a bit of luck: “The tension in our daily work lies in whether a new compound produced in the laboratory – often at great expense – will prove successful in subsequent clinical trials. There are often setbacks. Although we had great success with Voltaren, I am no stranger to failures. Equally exciting, however, is something else: Even during the first trial, a substance can have a surprising effect in a way that was not intended at all.”

Collegial culture

Sallmann wasn’t just lucky, he also found strong support from his supervisor Ruedi Pfister, who, when things got tight and management wanted to discontinue research due to side effects, decided to test the drug’s tolerability on himself. This step proved to be crucial in taking the project forward.

Martin Missbach, who worked with Alfred Sallmann – “my first office was next to his and as a young researcher, I looked up to him with admiration” – also speaks of a unique working culture: “On the one hand, you had the experienced colleagues who stood by you with advice and support. Then, we also had a supportive management team that was very patient with researchers and receptive to new ideas. Of course, we also had pressure, but there was an understanding that things could always go wrong.”

Peter Buehlmayer, who joined Ciba-Geigy in 1981 and played a decisive role in the development of the cardiac drug Diovan, felt the same way.

Buehlmayer still sees the fact that he synthesized the active ingredient for the first time in November 1989 – six months after the move from Rosental to Klybeck – in the new Research Building K-136 as a good omen for Klybeck as a research hub, adding that the building’s architecture was pivotal in fostering collaboration. “The way the new research building was designed – with separate offices, laboratory spaces and cafeteria – enhanced the communication between researchers. The proximity to the biology department also had a positive effect. But that alone doesn’t make it. It also takes the right people.”

Peter Buehlmeyer and Martin Missbach in the reception hall of K-136.

Culture as a talent magnet

Finding the right people is not easy, especially in research. But the atmosphere in Klybeck has always attracted talented researchers and, early on, female scientists, including Eva Altmann, who joined Ciba-Geigy in the 1990s as the first female laboratory manager after completing her postdoc in the United States.

At the time, she applied to all three major pharmaceutical companies, the chemist recalled. But she ultimately chose Ciba-Geigy because she was able to build a good rapport with her colleagues right away. “I had always wanted to work in pharmaceutical research and had always been interested in researching and developing new drugs. I chose Ciba because the environment suited me better, including my future colleagues and my boss,” Altmann explains.

The lab’s modern equipment also impressed her from the start: “K-136 was a brand-new research building with new labs and an excellent infrastructure, which, when you come from university, really impresses you.” Even though she had to fight for acceptance at the beginning, it was the collegiality and flat hierarchies that intrigued Altmann: “The atmosphere and management style also suited me. I found it less hierarchical – even during the initial interview. And it stayed that way after I started working.”

Openness and collaboration

For Missbach, who worked in Klybeck for almost 30 years and now conducts research on the St. Johann Campus, collegiality and teamwork have always been paramount – aspects that have continued to develop positively over the years, not least because research has been continually expanded and grown in importance.

Not only did the 1996 merger give research a further boost – research spending of about 2 billion US dollars annually at the time had increased to nearly 9 billion US dollars by 2020 – but new technologies have led to significant changes in the way work and research is done. “Early in my career, it was common for chemists to guard their lab journals with jealous care. But this changed over time, thanks in large part to digitization. Today,” Missbach says, “everything is more open, and chemists share their ideas for new compounds online with the project team and discuss them with colleagues.”

All of this has helped propel Novartis forward. Just a few years after the merger with Sandoz, a new class of oncology compounds was developed in Research Building K-136, which led to a therapeutic breakthrough in the treatment of blood cancer. And although a promising Alzheimer’s project recently failed in the clinic despite many years of research, new projects are now underway – projects that took off here in Klybeck.

Even though Novartis is now pulling up stakes in Klybeck after more than a hundred years of research and development, it is not only nostalgia on Missbach’s part: “From the company’s point of view, it certainly makes sense for us to leave Klybeck and work more closely with our colleagues on the Campus. But it’s not as if Klybeck and, above all, Research Building K-136 have completely had their day. A first start-up has already rented space here and others have also shown their interest. It would be nice if Klybeck’s legacy survives into the future. Maybe we can even work together with the new colleagues someday.”

As such, it cannot be ruled out that Klybeck will once again become a nucleus for new scientific developments and provide the foundation for further milestones in medical research.

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