A Life of Tireless Scientific Energy

24 December 1979 marked a day of great joy in both the life and career of Charles Weissmann. While on a skiing holiday in Davos, he received a phone call from his laboratory at the University of Zurich. Two members of his research team reported that they had detected the first traces of bacterially synthesized interferon. “Fantastic!” Weissmann exclaimed over the phone, immediately setting off for Zurich to see the results for himself. And indeed, as he later recalled in an article for UZH Magazin in 2008: “When I saw the analyses, I experienced a sense of happiness that occurs only rarely in a researcher’s life.”

With this discovery, Weissmann and his team took the lead in a global scientific race to clone alpha interferon. Alpha interferon, a protein of the human immune system with antiviral properties, was at the time considered a potential miracle cure for viral infections and several forms of cancer. However, the substance could not be produced in sufficient quantities to allow for detailed analysis and clinical application. The results achieved in Weissmann’s Zurich laboratory meant that this would now be possible.

The initial hope that interferon would become a broadly applicable wonder drug was ultimately not fulfilled. Nevertheless, alpha interferon proved effective in the treatment of hepatitis, certain forms of leukemia and other cancers, including renal cell carcinoma, melanoma and Kaposi’s sarcoma.

As Charles Weissmann – who also co-founded the biotechnology company Biogen in 1978, which remains successful to this day – assigned the interferon patent to the University of Zurich, the university has since received licensing revenues amounting to several million Swiss francs. In addition, the Ernst Hadorn Foundation, established by Weissmann at UZH, enabled the creation of an endowed professorship in molecular biology, first held by Michael Hengartner and currently by Lucas Pelkmans.

Charles Weissmann was one of the great figures of his discipline. “He was intellectually brilliant, exacting and far ahead of his time”, recalls Walter Schaffner. “But he was also quick-witted and humorous. His commitment to science was uncompromising, as was his criticism of sloppy experiments and arguments. He was the first to arrive at the lab in the morning and often the last to leave in the evening. I never saw him tired – he seemed to radiate an almost electric energy.” Schaffner, emeritus professor of molecular biology at UZH, is one of many students of Charles Weissmann – alongside UZH developmental biologist Konrad Basler and UZH neuropathologist Adriano Aguzzi – who went on to have successful research careers of their own.

Charles Weissmann was born in 1931 in Budapest, Hungary. Shortly thereafter, his family moved to Zurich, and in 1940, out of fear of the Third Reich, emigrated to Brazil. After the Second World War, Weissmann returned to Switzerland with his parents. He attended upper secondary school in Zurich and then studied medicine at the University of Zurich, earning his doctorate in 1957, before going on to study organic chemistry. In this field, he completed his second doctorate in 1961 under Paul Karrer, the UZH Nobel laureate and vitamin researcher. Weissmann subsequently took up a postdoctoral position in the laboratory of another Nobel laureate, Severo Ochoa, at New York University. In 1967, he returned to UZH as an assistant professor, where he founded the Institute of Molecular Biology. In 1970, he was appointed full professor of molecular biology.

Charles Weissmann and his team gained international recognition at an early stage. Initially, the molecular biologist worked on bacteriophages – viruses that infect only bacteria – and on the Rous sarcoma virus, a retrovirus that can cause cancer in birds. Using the RNA bacteriophage Qbeta, he also developed what is known as reverse genetics, a technique that allows for the precise modification of a genome. He later turned his attention to interferon research.

The final chapter of Charles Weissmann’s scientific work was devoted to the study of prion diseases, which include fatal degenerative disorders such as Creutzfeldt-Jakob disease, as well as animal diseases such as bovine spongiform encephalopathy. These conditions are caused by misfolded prion proteins. “A breakthrough was achieved by Konrad Basler,” says Walter Schaffner, “who cloned the gene responsible for the prion protein during his Master’s thesis in Charles Weissmann’s laboratory. When this gene was eliminated in mice, the animals remained viable and fertile and were resistant to all prion diseases.”

This provided definitive proof of the central role of prion proteins in the development of these disorders. Weissmann’s work on prions continued well beyond his retirement from UZH. In 1999, the accomplished scientist left Zurich, first for London and later for the Scripps Research Institute in Florida.

Charles Weissmann passed away last Friday in Zurich at the age of 94. A remark attributed to the renowned molecular biologist holds that the half-life of his publications was significantly shorter than that of his successful collaborators. In this sense, the scientific legacy of Charles Weissmann will endure – in the work of his students, and of their students in turn.