Alex Matter, Director, Novartis Institute for Tropical Diseases, Singapore

When Alex Matter went into industry 28 years ago, academic colleagues warned that the move would mark “the end of my scientific career”, he says. Since then he has managed to usher a successful cancer drug through the development pipeline and has now moved back into a more academic environment.

That's not to say his career path was easy when it veered off into industry (see CV). He found the shift initially “pretty horrible”, because many of the people who had recruited him were gone by the time he arrived, making it hard for him to get his bearings. “I had to find my way through this labyrinth,” Matter says. After a year of negotiating the maze, he assembled his research team — only to learn that the project they wanted to take on was to be killed. “I discovered this sort of thing is very routine,” Matter says.

His advice to anyone considering a similar path in drug discovery? Get used to adversity. Having projects shelved, stalled or killed “should not deter you”, he says. It taught him to find bosses who were on the same page. That strategy led him to Ciba-Geigy, where a friend said, “Let's do something in cancer”.

That friend left not long after Matter joined, too. But Matter spent the next three months in the library, inspired by a string of oncogene discoveries. He was convinced that there must be a better way to target cancer: chemotherapy, he felt, had “plateaued” and immunotherapy seemed ineffective. So he became captivated by kinases and hit the books.

The gap between inspiration and results proved long and tedious. He wrote down the general concept underlying Glivec/Gleevec (imatinib mesylate) in 1983, formed a team that had a molecule ready in 1992, and after many ups and downs in preclinical studies, it finally entered clinical trials in 1998. The drug was approved in 2001.

That slog also taught him something else about surviving in the high-stakes world of drug discovery. “You have to have bread-and-butter projects in order to pursue the high-risk stuff,” he says.

Now, he thinks his goal at the Novartis Institute of finding drug leads for tuberculosis and dengue fever within three years is “immensely do-able, as we have much more information than when we started on Glivec”. He has also learned that tenacity reaps rewards.