Walter Fischli: “It could have gone horribly wrong.”

We are meeting with ETH alumnus Walter Fischli at Actelion’s research building in Allschwil. He moves through the rooms with so much joy and verve, it’s as if Actelion had moved into the building just yesterday, rather than nine years ago. The first thing you notice about Fischli is that he speaks not just as a manager, but as a founder; every corner of the building tells a piece of Fischli’s story. He is particularly proud of the spacious lobby on the first floor. Concerts are held here regularly and sometimes he comes in on his own on Saturday afternoons to practice his violin – “this room has fabulous acoustics,” he says in a lovely Swiss Glarus dialect. In the research building, you can’t help but notice the two huge murals stretching upwards across several floors and depicting a complex molecule: it is the chemical structure of bosentan, a drug to treat pulmonary arterial hypertension and the company’s centrepiece. “This drug has given independence back to people who were once too weak to leave their houses,” explains the now retired biochemist. “That’s exactly what we’d hoped for at the time. That was our drive in introducing bosentan to the market.”

A biochemist from a musical family

For a large part of his success as a biochemist enthusiastic biology teacher at the Lucerne High School to thank. “He really got me excited about the sciences. Moreover, since then, I’ve known how important a positive stimulus is.” Prior to that, Fischli’s attention was focused on his music. He grew up in a musical family in the canton of Glarus. Like his three siblings, he began playing music at a very young age and has always done so with passion. At 16, he played the violin in a chamber music ensemble and appeared on stage regularly. Today, he is convinced that music and science have much in common: “Albert Einstein, the biochemist Gottfried Schatz and many other excellent scientists and researchers were also outstanding musicians.” The intuition and creativity that flow when playing, the networked thinking among the ensemble members, all of that benefited him later on as a head of research.

Networking research and medicine

When Fischli began his studies at ETH Zurich in 1969, biochemistry was still in its infancy. It took time for spectroscopy, nuclear magnetic resonance and computer-aided methods to find their way into biological research. While working on his doctoral thesis, Fischli developed model systems for the first photo markings of proteins. That was fundamental research and very exciting, but nevertheless unsatisfactory for the young researcher. “I was never one to perform science in a vacuum,” he recalls. “How to apply it was what truly interested me.” The move into medical application came about for him during post-doc work at the Addiction Research Foundation at Stanford University, a famous medical research centre in California. Fischli had recently done research at ETH on enkephalins, which are endogenous opioids. He found a job straightaway in the lab of Avram Goldstein, whohad already achieved world fame in this research field. “Here, the networking of research and medicine was already far more advanced than at ETH,” remembers Fischli, adding: “At the same time, research was much more competitive. When colleagues were working on their papers, they covered their written work with their hands for fear that someone could steal their ideas.” After three years, Fischli decided to return to Switzerland. He and his wife had had their first child and the second one was on the way. “It was important to us to be near family and in a familiar setting,” he explains. Whether this might have a negative impact on his career was secondary. Later, during his performance review meetings, he was always miffed about questions concerning his “career planning”: “I simply wanted to do good research.”

From trial and error to design

After his return to Switzerland in 1982, Fischli was offered a job by the pharmaceutical giant Roche in Basel. “That was a stroke of luck, because it was a time when many outstanding scientists began working in the pharmaceutical industry.” Simultaneously, it was the dawn of the age of rational drug design, driven by new technologies and new findings in medicine and biochemistry.  Drug molecules were being very purposely “designed”, not only just selected from a huge pool of molecules based on trial and error as they had been in the past. Fischli worked for 15 years on cardio-vascular diseases in the research department, heading up a 10-person research group, among other responsibilities. It was there that he also met the three later co-founders of Actelion: cardiologist Jean-Paul Clozel, pharmacologist Martine Clozel and physician and computer scientist Thomas Widmann. Starting in 1986, Fischli’s and Clozel’s group were researching a new control mechanism, the endothelin system. They discovered bosentan, a receptor antagonist and very promising candidate to fight congestive heart failure. Yet in phase 3 of clinical development, there were signs of side effects. Roche dropped the project in favour of a different drug. But the idea of jumping ship had begun to take shape among the biochemist and his colleagues. “It wasn’t that we were frustrated,” emphasises Fischli, “but we were confident in our research and the potential of endothelin receptor antagonists.” To get these drugs out of the lab and into hospitals, they founded Actelion.

From trial and error to design

After his return to Switzerland in 1982, Fischli was offered a job by the pharmaceutical giant Roche in Basel. “That was a stroke of luck, because it was a time when many outstanding scientists began working in the pharmaceutical industry.” Simultaneously, it was the dawn of the age of rational drug design, driven by new technologies and new findings in medicine and biochemistry.  Drug molecules were being very purposely “designed”, not only just selected from a huge pool of molecules based on trial and error as they had been in the past. Fischli worked for 15 years on cardio-vascular diseases in the research department, heading up a 10-person research group, among other responsibilities. It was there that he also met the three later co-founders of Actelion: cardiologist Jean-Paul Clozel, pharmacologist Martine Clozel and physician and computer scientist Thomas Widmann. Starting in 1986, Fischli’s and Clozel’s group were researching a new control mechanism, the endothelin system. They discovered bosentan, a receptor antagonist and very promising candidate to fight congestive heart failure. Yet in phase 3 of clinical development, there were signs of side effects. Roche dropped the project in favour of a different drug. But the idea of jumping ship had begun to take shape among the biochemist and his colleagues. “It wasn’t that we were frustrated,” emphasises Fischli, “but we were confident in our research and the potential of endothelin receptor antagonists.” To get these drugs out of the lab and into hospitals, they founded Actelion.

Apharmaceutical blockbuster

In December 1997, the four new entrepreneurs moved from the Roche headquarters in Basel into an empty building on the outskirts of town, furnished it with furniture from the Clozel family and drew up their first business plan. They were aware of the risk they were taking by leaving secure and well-paying jobs despite having children in school. The startup capital came out of their own pockets, and there were no wages in the beginning. “Everything could have gone horribly wrong,” Fischli remembers, “but we simply had to give it a shot!” Five months after founding Actelion, the company received 18 million Swiss francs from a conglomerate made up of European investors. That was more than enough for them to build their own research lab, to license from Roche the drug that they themselves discovered, and to pay for initial clinical development. Two years later Actelion went public, raising 1.2 billion Swiss francs of capital. Then came the shock: bosentan was useless in fighting congestive heart failure – even though, up until that point, all models and clinical results had pointed to the opposite conclusion. Luckily, it was extremely effective against pulmonary arterial hypertension, a rare disease with 80,000 patients worldwide that mainly affects young women and children. If left untreated, 50 percent of sufferers die within two to three years. In 2001, bosentan was approved for use in the United States, then came Europe, Japan and many other countries. The bosentan drug called Tracleer became a blockbuster and was soon earning revenues of over one billion Swiss francs annually. “We were never a company that was founded with the sole purpose of earning a lot of money,” explains Fischli, “we were researchers who primarily wanted to cover a medical need.” Today, Fischli is convinced that the company’s financial success is a bit like his career: “You can only plan up to a certain point.”