The patients' entrance at the National Institutes of Health. (Gary Cameron/Reuters)

This story ha been updated.

Nearly two decades ago, a pair of Boston scientists worked on an idea that had failed so many times it had been pushed to the fringes of cancer medicine: the idea that the body's immune system could be unleashed against tumors.

Immunotherapy had been proposed as an idea for 100 years, but nothing had worked. We cured a lot of mice, but no people,” said Gordon Freeman, a researcher at Dana-Farber Cancer Institute. “Not only was it not trendy, it was in low esteem. No company was aggressively funding immunotherapy — it just didn't have much appeal.”

As a seemingly fringe endeavor, the initial work wouldn't have been possible without federal support — much of which came, as it happens, from a research institute that is devoted not to cancer but to allergies.  

“It was really the NIH grants, from the National Institute for Allergy and Infectious Diseases, that really supported this work at that point in time. The funding was absolutely critical,” Sharpe, a professor of comparative pathology at Harvard Medical School, said. “The hope was, if we got a basic understanding of the molecules involved, that could then translate to different types of therapy.”

Science is, by its nature, about unraveling things we don't yet understand, and Freeman and Sharpe's work — along with others — laid the intellectual foundation for what has rapidly become the hottest area of cancer medicine. Multiple pharmaceutical companies licensed the patents that emerged from their research, and they helped spur development of a new type of cancer drug that unleashes the immune system on cancer cells, also releasing what Freeman calls “a tsunami of scientific enthusiasm — and pharmaceutical enthusiasm.” Today, there are more than 800 clinical trials targeted at the immune pathway that Freeman, Sharpe and others helped elucidate.

Anecdotes abound about how federal biomedical research funding has real-world effects, but a new study in the journal Science systematically adds up that impact, tracing the ripple effects of 365,000 grants over almost three decades. It found that 8 percent of grants directly led to patents, and that patents by the private sector depended on nearly a third of the grants they studied.

“If your view was that the research done by academics in teaching hospitals, in universities in the biomedical area [is] just a parlor game between academics with no ramifications for the real world and the development of new medicines — well, that view is not correct,” said Pierre Azoulay, a professor at the Massachusetts Institute of Technology's Sloan School of Management, one of the authors of the study, which was led by Danielle Li at Harvard Business School.

The study was in the works well before the election, but it comes at a timely moment, after President Trump's administration has proposed to slash the National Institutes of Health's $31.7 billion discretionary budget by nearly a fifth next year. A budget memo outlining proposed cuts for the remainder of 2017 includes an additional $1.2 billion cut to the agency.

Health and Human Services Secretary Tom Price testified at a Congressional hearing Wednesday that he valued the NIH's contributions and wanted to cut out waste, such as grant money that is used for indirect costs such as facilities or equipment.

"Our goal is to fashion a budget that focuses on the things that work, that tries to decrease the areas where there are duplications or redundancies or waste or whether we can get a larger return for the investment the American taxpayer in his area which is vitally important," Price said.

NIH is an agency with broad bipartisan support. It spreads the vast majority of its budget across the nation, meaning every politician has constituents interested in preserving and increasing the funding. That makes many scientists hopeful that the proposed cuts will never become a reality. Even so, the specter of funding cuts send a powerful signal, said Stephen Hauser, chair of neurology at the University of California at San Francisco. Hauser's work began decades ago — bolstered by federal funding and philanthropy — and resulted in the approval this week of the first drug for severe multiple sclerosis.

The proposed cuts “send a chilling message to physicians, to scientists, because these even if they are rescinded — as I expect — a flat budget will likely mean that the special considerations for new investigators will not happen at the same level, and it will be very destructive to young physicians and scientists,” Hauser said. He said that even if the budget is not cut, competition for limited federal funding is intense and he doubts that the work he began four decades ago would have been possible if he were proposing it as a young scientist today.

The research also may help settle a debate about what kind of grant is most useful: curiosity-driven basic research that is sometimes lampooned for seeming to have no practical point vs. pragmatic science aimed at turning existing knowledge into useful technology. Advocates of basic research argue that it's impossible to predict where the next big breakthrough will come from, while those in favor of applied research argue that more effort needs to be spent turning insight into useful drugs. The study found no major difference in the likelihood that basic or applied grants led to patents.

“The findings illustrate a key principle of science — scientists build their findings on the previous work of others,” Mike Lauer, deputy director of extramural research at the National Institutes of Health said in an email. “Whether we focus on scientific or technological advancement, these findings underscore the value of investing in a diverse portfolio of work.”

Finally, the paper also found that the lag between the research and the patent was considerable, and that patents often came seven to 15 years after the work was first published.

“It will probably take a really long time, 10 years, until the missing research” has an impact on medicine, Azoulay said. “When people say, a little bit glibly, the wall is going to be paid with the health of cancer patients, what they're not saying is it's the health of cancer patients 20 years from now.”

Correction: The post has been updated to reflect that Danielle Li of Harvard Business School led the study.