An unprecedented trend of flat or below-inflation support for biomedical studies is squeezing scientists at every point along the research pipeline

BY COLLEEN STEELQUIST

Dr. Dusty Miller has spent decades studying the biology of certain viruses so he can better understand how to use them to fight human diseases. His viral delivery methods were used in the first human gene transfer studies and in gene-therapy trials in the United States and around the world.

Now, Miller wants to apply his gene-therapy tactics to better understand lung cancer, the leading cause of cancer deaths. His approach holds the potential for development of new therapies for this dreaded disease. A respected researcher, Miller has a long track record of successful science, with findings published in prominent scientific journals. There's just one problem.

He can't get funding.

It's not that Miller's ideas aren't solid. His problem — shared by a growing list of scientists around the country — is that innovative, ambitious science is having a hard time attracting federal funding.

Because federal budgets are much tighter, science is becoming more conservative, many observers say, putting this country's scientific discovery and competitiveness in all areas at risk. The biosciences in particular, including critical cancer research, provide a rich example of what happens when money begins to disappear.

The annual budget for the National Institutes of Health has remained flat for the past five years when adjusted for inflation, falling short of what's needed to adequately support biomedical research. Since 2003, inflation has eroded the purchasing power of NIH by more than 13 percent.

"I've been at the Hutchinson Center for 24 years, and the past four years are probably the worst funding I've seen," Miller said. "In the past, I've had multiple grants, run the research and have been pretty self-sufficient, but lately I've been struggling to get grant support."

If someone of Miller's stature is having problems, then one must consider what's happening with many young and promising investigators throughout the United Sates who are having greater difficulty getting their research done — research that could advance science and save lives.

"You can lose a generation of researchers pretty fast — in five or 10 years. You create such a discouraging atmosphere they just go somewhere else instead of academic research," said Dr. Joshua Boger, chair of the Washington D.C. Biotechnology Industry Organization, in response to the proposed 2009 NIH budget.

"We don't have to lose 50,000 researchers, just 50 really good ones. Once it happens, we won't get those people back," he warned.

NIH supports most medical scientific research in the United States, with more than 80 percent of its budget allocated to research at about 3,100 institutions. Since the 1930s, its grants have been considered critical to the long-term research that has led to medical breakthroughs and improved health and health care.

However, the federal budget is subject to competing priorities, including defense and homeland security needs, trade deficits and natural disaster relief. These pressures have put a damper on NIH funding, and help explain why its 2008 budget of $29 billion was a meager 1.5 percent increase over the previous year. The $29 billion may seem substantial, but it represents only 5.5 percent of the $2.1 trillion total United States health care annual spending, according to Research!America.

The NIH's Research Projects Grants (R01), which are multi-year awards to scientists and have long been recognized as the lifeblood of research, have been flat since 2004, but the cost of research has increased. The flattening of the budget has meant fewer projects are being funded, with R01 grants declining from 29,061 in 2004 to 27,850 in 2007.

The overall success rate for NIH research project grants dropped from 32 percent in 1999 to 24 percent in 2007. That means that three out of four proposals are not funded. For young researchers, the budget situation is even more perilous. Their success rate in applying for their first independent research grants has dropped from 29 percent in 1999 to 12 percent today — a one in eight chance.

Budgetary constraints have also prevented NIH from reaching its goals for postdoctoral stipends, and compensation for this highly skilled and extremely productive group of scientists has remained flat for several years.

The Hutchinson Center has long ranked first or second among independent research institutes in total NIH funding. The Center received more than $219 million in NIH funding in 2007, 88 percent of its grant and contract revenue. Its 38 percent success rate for project grants reflects the high quality and diversification of its science.

But like other institutions around the country, which benefited from a doubling of the NIH budget between 1998 and 2003, some Center scientists are feeling the pain from NIH budgets that have barely kept up with inflation.

The proposed 2009 federal budget, still in flux at press time, again shows flat NIH funding. The Association of American Medical Colleges has calculated that the purchasing power of the 2009 administration proposal is $3.6 billion less than in 2003.

NIH Director Dr. Elias Zerhouni predicts the number of new grants, the average size of a grant, and the expected success rate for NIH grant competitions will all fall in 2009.

Many strong research proposals that would have been approved for funding by NIH reviewers in years past now have to seek funding from other sources.

That means the Hutchinson Center, Dana-Farber Cancer Institute and M.D. Anderson Cancer Center, three of the biggest players in cancer research, have increasingly relied on non-federal dollars to round out their budgets.

Funding comes from donors, investment income and royalty income. At the Hutchinson Center, nearly all of this money is invested back into research support, either to cover ongoing financial commitments to faculty members, or to fund new initiatives and recruit new faculty members.

The current funding climate offers opportunities to educate people about the cost of doing science, as well as make them aware of the leveraging power of private dollars, said Nancy Wells, the Center's vice president of Development.

"The economy may be slowing down, but the war on cancer cannot," she said. There are many ways for donors to partner with the Center to fund the innovative research that often leads to federal funding, Wells said. The Hutchinson Center's science has an excellent reputation — with three Nobel Prizes to back it up — and it retains a solid edge when it comes to competitive funding.

However, it still means going out and explaining to people why the science is important and why every dollar helps. The Center often holds educational events and invites the public to visit the campus and meet researchers during special events.

"We're hoping these events will educate people on the expenses of science and inspire them to support our science at the same time," Wells said.

Every bit helps, because with their grants, investigators must cover salaries, as well as equipment and laboratory supplies. Today's technology is especially expensive. A mass spectrometer, equipment that can be used to discover early warning signs of cancer in the blood, can cost more than $1 million.

"The cost of research has escalated like everything else," Miller said. "Some of the cutting-edge technology that's now accessible to us costs $10,000 to run an experiment. Those are out of bounds for me. I'm limited in what sort of research approaches I can use."

Recruiting and setting up a lab for a scientist can cost more than $2 million depending on equipment needs and how long it takes the researcher to secure grant funding.

And because NIH funding is so tight, research institutions sometimes have to walk a tightrope between needs.

"It may take new faculty recruits longer than expected to secure funding to support their own labs, and existing faculty may have trouble renewing grants, resulting in funding gaps that are generally covered with discretionary institutional funds," said Randy Main, the Hutchinson Center's chief financial officer.

"Since the Center's first priority is to take care of existing faculty, tight NIH funding means scarce institutional resources may not be available to fund new initiatives, and planned faculty recruitments may be delayed," he said.

The United States has long been considered the best scientific training ground in the world. Past investments in biomedical research have returned exceptional benefits to the American people and the rest of the world, but there are troubling indicators that the country's scientific edge is slipping.

Globalization is now increasing worldwide competition in scientific discovery, technological innovation and scientific talent. The United States has declined to near parity with the European Union in recent years in biology publications.

"Other countries see the connection between basic science and societal benefit with more vigor and conviction than exists in the United States," Boger said.

Miller's five-person lab team — once more than twice that size — used to include many foreign students. "But given visa problems and our economic situation in science, those people aren't coming to us anymore," he said. "If Italy and France are doing better gene therapy, they'll attract the best candidates. There's a huge brain drain because people find better situations elsewhere."

Basic research funded by the NIH fuels technological innovations and fosters the vitality of the American scientific enterprise. It helps create new industries and jobs, improves quality of life for people and provides technology that contributes to national security. Biomedical research is an essential foundation for future U.S. scientific competitiveness, knowledge-based industries, and highly skilled jobs.

Over the past 30 years, investment in medical research through the NIH has amounted to about $44 per American per year.

Yet the return on this investment has been truly spectacular, reaching far beyond the nation's borders. Life expectancy has increased, deaths from cancer, heart disease and stroke are declining, and new treatments have virtually eliminated transmission of the HIV virus from mother to child.

"I know people are struggling to pay their mortgages and put food on the table. It's a hard sell to care about research given our economic condition right now," Miller said. "But science requires a long-term view. Unless we focus on some of the long-term issues, we're going to really lose."