Cloning and expression of human interferon-beta: from bc to ac.

Abstract

In 1963 I started the Laboratory of Molecular Biology (LMB) at the University of Ghent. Molecular Biology was then a new scientific discipline. Nucleic acids (NA) could be sequenced, manipulated, and recombined to form genetic information which never before had existed. Cloning of DNA-segments allowed multiplying a single molecule a billion-fold. By 1975 recombinant DNA-technology had sufficiently progressed that one could start the pursuit of a medically important goal. Our choice was to go for Interferon, a mysterious substance which could protect against viral infection, and might possibly be used as an anti-cancer agent if available in unlimited quantities. Fortunately, Piet De Somer, then Rector of the KUL, was one of the pioneers in interferon research. He encouraged his young colleague Erik De Clercq to collaborate with us. Erik brought extensive interferon expertise and reagents to the collaboration. But molecular biologists work with NA and interferon is a protein. There was a missing link which was provided by Jean Content of the Brussels Pasteur Institute. Jean had developed a system to convert interferon mRNA into protein, which was send to Leuven for quantification. This close collaboration between 3 laboratories led in January 1980 to the cloning of the human fibroblast, now interferon-beta, gene, and to the primary structure of the protein. However, 2 months earlier, Tadatsugu Taniguchi had succeeded already to obtain such a clone. But we were the first to express the clone in E. coli, and this was the definite proof that the cloned gene coded for human interferon-beta.