Stretching the boundaries of science is a leap in the dark, augmented by high tolerance for risk and a big dollop of committed
cash. Napoleone Ferrara's career in medicine is an illustration of this maxim, which, through his own dogged persistence and
an ideal environment at Genentech, led to the commercialization of an entirely new field of molecular biology linked to the
process of angiogenesis—the formation of blood vessels. Application of this discovery has produced a new class of cancer medicines
that can enhance or extend the lives of some patients by choking off the blood supply that helps feed tumor growth. The potential
of angiogenesis is now being investigated by researchers in a range of other therapeutic areas.
In 1988, Ferrara began work as a young researcher for Genentech, where he was encouraged to pursue his interest in the protein
VEGF (vascular endothelial cell growth factor). Ferrara's early work isolating sequencing and cloning VEGF ultimately led
to the first clinical proof of concept that an anti-angiogenic antibody could help slow the deadly proliferation of tumor
cells. As with most breakthrough medical discoveries, the trajectory from bench to bedside was painfully slow: although the
initial scientific premise around angiogenesis dates back to the 1930s and 1940s and became public knowledge in the 1970s
through the work of Dr. Judah Folkmann, it took Ferrara's identification of the VEGF gene in 1989 and publication of the results
in a 1993 peer reviewed paper in Nature before Genentech considered formal clinical trials, which began in 1997. It took another seven years to obtain FDA approval
of the first therapy to inhibit VEGF, Avastin (bevacizumab), for first-line metastatic colon cancer, in February 2004.
"At the time, there was little interest in the wider research community in VEGF and its role in nourishing cancerous cell
growth. Genentech still gave me the freedom and resources to pursue my ideas, although it was unclear that this research could
lead to a drug, much less a drug that would help hundreds of thousands of patients worldwide like Avastin," Ferrara says.
The company helped bridge a crucial step in the analysis of the VEGF protein by funding a new, targeted process technology
on gene sequencing that shortened the investigation time frame and made it easier for other researchers to corroborate his
results. "I cannot imagine anywhere else but Genentech where I would have overcome the skeptics and delivered a series of
papers that led to a breakthrough in our understanding of molecular biologics and the treatment of disease."
Looking forward, Ferrara contends the most important factor in ensuring medical progress is maintaining an inclusive R&D management
culture that offers space for experimentation, in open collaboration with others, especially around ideas neglected by the
scientific establishment. "The lesson from my career to date is that progress in science is a social, cooperative exercise,
not an escape to the ivory tower. It can't be done alone."
Unfortunately, budget constraints and politics around the public research enterprise are making it harder to finance riskier
projects, so the role of the private sector in taking a long view is more important than ever. "The research potential around
angiogenesis is vast and capable of addressing innumerable areas of unmet medical need, particularly if we are able to build
into this the predictive biomarkers that can target patients most likely to benefit from a new drug," says Ferrara.
– William Looney