Lifesaving dollars

It would be fair to say that Patient 5 owes his life to medical research. Also known as David Aponte, he was the headlining success story from a recent clinical trial at Memorial Sloan-Kettering Cancer Center. The trial tested a new approach — in which a portion of the immune system is genetically altered and then reintroduced to the body — for treating an otherwise fatal leukemia.

But when we celebrate the remarkable achievement made possible by the doctors behind the experimental treatment and the patients who volunteered themselves for research, there are two other guests of honor to include at the party: years and years of basic science, and the public dollars that funded them. Sadly, those guests are finding it increasingly tough to get invitations.

For the last several years, the federal budget for the National Institutes of Health, the world’s largest source of basic research funding, has remained at about $30 billion a year. If inflation is factored into the numbers, funding has decreased since 2002. The 2012 NIH budget was $30.7 billion, a $299million increase over 2011 levels, but accounting for only about 1.25% of all tax revenue collected in 2012. The sequestration enacted March 1 cut the NIH budget 5.1%, a loss of $1.6 billion annually.

The NIH funds scientific research through a variety of research grants. Ranging from about $100,000 to millions of dollars, these awards support research into cancer, Alzheimer’s disease, depression, obesity, stem cells, genomics, hepatitis, nutri- tion — every facet of human health and illness.

The oldest type of NIH grant, known as R01, covers the largest number of researchers. These grants provide years of coverage for salary, supplies, publication fees, administrative support and other costs essential to laboratory research. In 2002, 24.5% of R01 applications were funded. By 2012, the approval rate had dropped to 14.9%. Such decreases exist across the range of NIH grants and are exacerbated by the sequestration

Health research and medical progress are in peril amid NIH budget cuts.

measures, which will result in about 700 fewer research grants in 2013 than in 2012, according to an analysis by Sen. Tom Harkin (DIowa) a sponsor of the Budget Control Act.

Already, young investigators find it harder to get funded than older academics deep into a specific pursuit. With funds increasingly difficult to come by, young investigators are more likely to leave academia, leave the U.S. or leave science entirely. And with 70% of NIH grant money going toward salaries, less funding means fewer young researchers will be hired to work at the large, well-equipped laboratories of more senior grantees.

In its purest form, basic research is about asking questions and using the scientific method to answer them, one at a time. CD19, the B-cell protein present on the leukemia cells that were targeted by the genetically altered T cells of Aponte’s immune system, was first identified through laboratory research during the 1980s. It took more than 20 years for that work to lead to a major medical advance with the potential to save thousands of lives. The progress made over those decades relied almost entirely on federal grant money.

The cell therapy that saved Aponte’s life is hardly the first example of basic research leading to an unexpected leap in medical care. It took 30 years for the causative connection to be made between the genetic mutation known as the Philadelphia chromosome and chronic myeloid leukemia. But establishing that link led to the creation of Gleevec, the first drug that targets cancer at its root cause, a breakthrough that transformed the future of cancer research and drug development.

Examples abound of breakthroughs that grew out of long, costly scientific inquiry. Studies of the microscopic structure inside corals eventually led to the creation of an implant that promotes tissue growth after bone grafts. The Human Genome Project was funded by about $2.7 billion in taxpayer dollars. Even the skinsmoothing bacterial toxin known as Botox is the result of taxpayersupported science — the compound was originally used to treat rare muscular disorders affecting the neck and eyes, a discovery derived from laboratory research.

Grants from the NIH fund curiosity. They fund the means to the end. Basic research is as inherent to medical care as the doctor who writes a prescription.

NIH funding isn’t perfect, and it needs some course correction. The average age of NIH grantees is 45, skewing toward established professors rather than newly minted doctorates with fresh ideas. About 50 institutions across the U.S. receive 70% of NIH funds. About 20% of investigators who apply for grants receive about 50% of the money, often because prominent researchers are awarded multiple grants, leading to bloated salaries and a potential lack of innovation. Because R01 grants last three to five years, an increase in the NIH budget wouldn’t necessarily lead to an increase in the number of grants being funded. And the “publish or perish” situation — grant awards often depend on how many significant papers a researcher has published — can eliminate the spirit of curiosity and inquiry from the equation of deciding what experiments to pursue.

But whatever the problems with current funding structures, the fact remains that public support for basic science is inherent to medical progress. “If you do good basic research, then who knows what’s going to happen down the way?” Herb Abelson once told me. A pediatric oncologist, he made laboratory investigations of a leukemia-causing virus in the 1960s that were unexpectedly vital to the eventual creation of Gleevec. Without adequate support, good research becomes increasingly impossible.