Christoph Lengauer

I joined Andreas Weith’s lab (IMP) in November 1992 with the goal to find a Neuroblastoma tumour suppressor gene on the short arm of human chromosome 1. Andreas’ lab had just described a consensus deletion, and I thought that combining the newly established YAC technology with the multicolour FISH approach that I had helped develop, should allow us to map and clone the gene. As it turned out, the more detailed we molecularly characterized this region, the bigger (rather than smaller) it got, and finding the tumour suppressor appeared impossible soon after my arrival.  I was very frustrated.

I had such high expectations when moving from Heidelberg to Vienna. But my time at the IMP turned out to be difficult. I wanted to leave Vienna, and was thinking of getting out of science as a whole.  Then I thought, before quitting science, maybe I should first apply to the best molecular cancer lab in the world. If I would not like it there, I can stop science with good conscience. I applied to Bert Vogelstein’s lab at Johns Hopkins in spring of 1994 and moved to Baltimore on July 24th, 1994.  This was the most impactful decision of my professional career.

I discovered that all cancers are genetically unstable. We identified somatic mutations in several cancer driver genes including PIK3CA, CDC4 and MSH6. I loved the creative environment and enjoyed working with the greatest minds in molecular cancer genetics.

After 12 incredible years with Bert at Hopkins, I joined the Novartis Institutes of Biomedical Research. Some close friends had died of cancer, and I wanted to contribute to the making of cancer drugs. I built the Oncology Target Identification and Validation group in Cambridge, MA and learned the difficult art of discovering cancer drugs. The SMO and CDK4 inhibitors that came out of this work, are now in late stage clinical development.

Later, I got the opportunity to become the Global Head of Oncology Drug Discovery and Preclinical Development for Sanofi. Our family moved to Paris, France. With the help of a great team of 200 scientists, I transformed sanofi-aventis from a classical cytotoxics company to a modern oncology drug discovery organization. We formed the first fully integrated oncology business unit in big pharma and started a new and different drug discovery group in Cambridge, MA for which I hired 125 new scientists within the first year. During my time in big pharma, I was honoured to contribute to the making of some novel and effective cancer drugs that change patients’ lives, incl. Afinitor, Tasigna, and Jevtana.

At the beginning of this year, I joined a young start-up biotech called Blueprint Medicines as CSO. Using the “molecular blueprint of cancer” to guide its efforts, Blueprint Medicines is committed to improving the lives of cancer patients by transforming genomically defined subsets of cancer from a life-threatening diagnosis to a manageable condition. We are back in Cambridge, MA. The small team and creative but focused culture of Blueprint remind me of the Vogelstein lab. Though cancer drug discovery is only one step away from being impossible, I am optimistic that we will help patients with enormous medical need.

Twenty years later, the IMP is still a great place. Its mission to elucidate the mechanisms and principles that underlie complex biological processes, is noble and very important. Unfortunately, most of academic science is not translatable into drug discovery and development. I hope that the IMP will continue to strive for the exception.

By Christoph Lengauer, first published in 2012