Here's the CliffsNotes version of how most drugs go from idea to reality: Basic academic research provides the foundation for a series of clinical trials, first in animals and then in humans, which eventually tell us whether a new treatment is safe and effective.
But a study published Thursday in the journal Cell details how the reality of drug development is rarely that linear or precise. Rather, the path to creating a life-saving treatment can be an extremely long, labor-intensive effort that involves thousands of scientists over many decades.
Researchers at the California-based Gladstone Institutes, a nonprofit biomedical research organization, retrospectively mapped the discovery path of two drugs approved by the Food and Drug Administration in recent years: Ivacaftor, also known as Kalydeco, which is the first drug that treats the underlying cause of cystic fibrosis; and ipilimumab, also known as Yervoy, an immune therapy that has led to remarkable survival rates in some patients with metastatic melanoma.
The researchers examined published citations and other "bibliometrics" to unearth the incremental scientific advances that led to the two drugs, and their findings underscore the vast landscape of research that often lies behind a landmark treatment. They concluded that ipilimumab resulted from research conducted by 7,000 scientists at 5,700 institutions dated back 100 years. Ivacaftor, meanwhile, involved the work of 2,900 scientists affiliated with 2,500 institutions over 60 years.
"We were surprised," said Alexander Pico, Gladstone's associate director of bioinformatics, adding that the web of connections revealed a "large and complex network" of both individuals and institutions that contributed to a drug's development. "It’s more of a collective endeavor than [we often realize] ... It really does take this network of individuals over a long time to lay the foundation."
That's not to say every link in the chain is equal. Pico said researchers noticed that certain scientists played an integral role in the path toward discovery -- they were labeled "elite performers" -- while others played a more minor role.
"We’re not claiming that every paper in this network has a direct and obvious connection to the final drug," he said. "But that’s also kind of the point -- that basic research has to explore peripheral topics in order to narrow down and lead to the final drug development. It takes exploratory research on a wide range of topics."
Pico said he hopes the project will, in this age of shrinking government budgets, remind people that the seeds of future cures are often sown through investment in basic scientific research. In addition, he said he and other researchers hope the effort will be the first step toward "predictive" metrics that could help society make smarter decisions about who and what to fund, eventually speeding up the path toward discovery of new and important drugs.