Axel Ullrich: Cancer pioneer and entrepreneur

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Axel Ullrich is the Director of the Department of Molecular Biology at the Max Planck Institute for Biochemistry in Martinsried. Quelle: MPI Martinsried

02.08.2011  - 

When Axel Ullrich moved to the US after his graduation in 1975, only a few highly specialised academics working in biotechnology could have imagined what lay ahead for the field. Today, Ullrich is Director of the Max Planck Institute for Biochemistry in Martinsried, and biotechnology is a growing area of industry and science all around the world. In recent decades, the work of the biochemist has led to a number of medical breakthroughs in cancer ­treatment. Almost incidentally to his other work, a total of four biotechnology companies have been established under his aegis.

Ullrich has been active in the field of cancer research for decades, and much of his current research continues to focus on this area. Tumours occur whenever cell growth gets out of control. Even today, many of the details are not properly understood; the basics, on the other hand – also thanks to Ullrich's efforts  – are now more or less known: For example, how the cell genome changes over time as a result of mutations. “Depending on the section of DNA that is affected, it can be totally harmless, or can actually influence the activity of a gene,” says Ullrich. In some cases, for example, the gene for cell growth can be too strongly activated, meaning that the cell would then divide much more frequently than usual. In other cases, a gene that regulates natural cell death can be affected by a mutation, thereby losing its function. Such cells would no longer die as usual after a specific period of time, but would live indefinitely. Two different mechanisms, but with the same outcome: a tumour.

Novel approaches to cancer therapy

Many modern cancer drugs aim to block the mode of action of specific cancer-causing genes by inhibiting the associated protein. These have only been limitedly successful. Ullrich is convinced that “the targeted approaches bring partial success against cancer, at best. At this time, they extend the lives of patients often only by a few months.  That's disappointing.” The cancer expert has an explanation at hand as to why this is so. The genetic makeup of cancer cells is changing constantly – there is simply no single dominant factor in cancer. Instead, his view is more that there is a mosaic of different factors: “If only a single oncogene is attacked, then a different one becomes active in the tumor, nullifying the previous success.”

Rather than directly attacking the tumor, Ullrich is thus focusing on alternative targets. One of these is a receptor going by the name of FGFR4 (fibroblast growth factor receptor 4), to which growth factors can bind. Normally, fibroblast growth factors are responsible for the formation of new blood vessels, and are involved in wound healing.  In combination with an existing and developing malignancy, an abnormal form of FGFR4 can have a disastrous effect. The mutation is found mainly in Europeans, Asians and Americans originating from Europe, and does not normally affect the lives of those carrying it. “If an individual with the abnormal variant of the receptor falls ill with cancer, tumor growth proceeds approximately five times faster than those with the normal gene,” says Ullrich. No one yet ­knows why this ­is the case. Nevertheless, the first attempts are already underway to put the brakes on the growth of such cancers, specifically with anti-FGFR4 antibodies.

U3 Pharma – one of the four companies founded by Ullrich, now owned Japanese pharmaceutical outfit Daiichi Sankkyo – is also involved in this work. “For me, the companies have been a means to an end. I want to convert my ideas and projects into medical applications,” says the passionate basic researcher. His work involves taking close care of the company, as well as paying detailed attention to the scientific side, and working on new concepts and innovative approaches to development. “I don’t see my main role as being in management per se; I gladly leave that to others,” says Ullrich.

Axel Ullrich is hoping to pass on his experiences as a serial founder to other young entrepreneurs, such as here at the Charité Entrepreneurs chip Summit 2011. Quelle: BIOCOM AG

Passionate basic researcher

In his heart he is still a basic researcher –something that the cancer expert is keen to point out. After gaining his post-doctorate in 1975 in Heidelberg, he went to the USA, “to find out if all the visions of the early era of genetic engineering could really ­be true.” In 1979, after a stopover at the University of California at San Francisco, he ended up working at the then unknown start-up Genentech. Three decades later it was the second largest biotechnology company in the world, and was acquired for many billions of dollars by the Swiss pharmaceutical group Roche. In the Seventies, Genentech was focused on the production of human proteins in genetically modified microorganisms. The assignment for Ullrich's team: describe the molecular arrangement and structure of a variety of receptors. One result of this work is the antibody drug Herceptin (Trastuzumab), which blocks the HER2/neu receptor, vital for the development of cancer. The drug was approved in 1998 for the treatment of breast cancer. By this time, Axel Ullrich was no longer employed at Genentech. Ten years before, in 1988, Axel Ullrich had been appointed Director of the Department of Molecular Biology at the Max Planck Institute for Biochemistry in Martinsried. “As companies get bigger, they develop corporate structures.  This makes work very complicated,” remembers Ullrich.

For Ullrich and the Max Planck Society, his coming on board proved a godsend. The research has provided a swathe of good ideas and important discoveries in cancer research. And to convert his concepts into application, Ullrich has established one biotechnology start-up after the other. Firstly, the company Sugen in the US in 1991. The San Francisco-based company concentrates on cancer research. The idea: a specific class of molecules known as kinase inhibitors could possibly be used to block important signalling pathways in tumours, and thus inhibit tumour growth. It took years to demonstrate that this mechanism actually works. After numerous acquisitions, Sugen was finally snapped up by US pharmaceutical giant Pfizer in 2003. Since 2006, the company has produced Sutent (Sunitinib), which is used among other purposes to treat kidney cancer, and which employs the mechanism developed by Ullrich and his colleagues.

After the successful launch of Sugen, there continued an almost five-year cycle of company foundings. Axxima Pharmaceuticals in 1998; in 2001 the previously mentioned U3 Pharma, then finally Kinaxo Biotechnologies GmbH in 2005. All firms are now in the hands of larger companies. “A small company like Sugen could never have achieved the marketing authorisation for Sutent alone,” says Ullrich.  And yet, the 67 year-old is still not quite satisfied. Just when he is beginning to be honoured for his work, he remains inwardly unsure: “I am aware that the fight against cancer is not yet won – and is unlikely to be won many years ahead.”

Author: Bernd Kaltwaßer