Wittgenstein Award Laureate
Wittgenstein Award Laureate 2001 Univ. Prof. Dr. Meinrad Busslinger
Molecular Biology, The Research Institute of Molecular Pathology IMP
Research Institute of Molecular Pathology (IMP) 
”I‘m interested in voyages of discovery not only in science but also in the big, wide world and this goes along with learning foreign languages. Here in the Amazonian region of Brazil I discovered what our Viennese research institute IMP really is, namely a paradise of new things.”
IDENTITY AT THE FLICK OF A SWITCH
Meinrad Busslinger became mixed up in the revolution of biological sciences as a ”little” PhD student in the mid- 70s. While it was going on he was able to watch the pioneering work of Swiss giants in the field, including his mentor and PhD supervisor Max Birnstiel. From that point on Busslinger surfed the revolutionary wave, even when it banked up into a ”mighty wall” of water and fi nally landed on unchartered territory, where he proceeded to revise the picture geneticists had made of the laws of their microscopic world. For the identity of cells that form organs is not, as was long believed, unambiguously assigned but plastic and readily accessible to variation. A plethora of highly regarded publications from Busslinger’s group led to this important discovery, crowned by the cover article in the leading journal Nature. For the work, Busslinger received the 2001 Wittgenstein Prize.
Busslinger was born in Switzerland. At the start of his scientific career he worked on a capricious gene in the sea - urchin, whose information is only read in the organism’s suckers. As Busslinger recalls, ”we wanted to know what was responsible for restricting the expression of the gene to this one organ”. However, Zurich was so far from the sea that the group did not have access to enough sea-urchin embryos to purify the transcription factor involved.
In 1987 Busslinger followed Birnstiel to Vienna, where the latter took up the position as Director of the newly founded Institute of Molecular Pathology (IMP). By this stage he had replaced the sea - urchin model system with something better, the blood - forming stem cells that can develop into the entire range of immune cells via diverse intermediates. From then on he focussed on the transcription factors that cause lymphoid precursor cells to mature step by step into B - cells, the highly specialized producers of antibody shields that bind things that cause disease and render them harmless. Using information from the sea - urchin, Busslinger managed to clone the Pax5 protein from B - cells – this was closely related to the sea - urchin transcription factor.
”Afterwards we used knockout mice, in which the gene for the Pax5 transcription factor is missing, to show that without Pax5 the final step in the production of full B-cells doesn’t take place.” Furthermore, Busslinger’s team was astonished to find that the Pax5-free precursor B - cells in the culture were not merely broken down but differentiated to all other types of immune cell. ”In this way we were able to gain fundamentally new insights into the process of cell determination. We showed that Pax5 switches off all genes in B - cells that permit other developmental possibilities and that at the same time it switches on the specific receptors and signal transducers of B - cell function. The turning off of genes thus plays as big a part in the determination of cellular identity as turning genes on. The principle is probably applicable to all types of organ formation.”
Instead of investing the Wittgenstein Prize in his own group, ”that would only have produced more of the same”, Busslinger decided to go for diversity and ”gave a young scientist the once - in - a - lifetime opportunity to build up a research group at the IMP”. Following an international advertisement he sought a specialist in T-cells and found one in the form of Ludger Klein. ”I wanted someone who is independent but who works in the same area. The result has been highly positive.”
