Targeting the agents of disease

In the war on infectious disease, are we spending enough—in the right places?

Megan Murray, an epidemiologist at the Harvard School of Public Health, is very worried about where her next research dollars will come from. At times, she thinks she may have to fall back on being a practicing physician to make ends meet.

The co-leader of a large study in Peru aimed at identifying risk factors for drug-resistant tuberculosis, Murray has published important papers in the field. But she’s finding that it has become highly challenging to get money from the National Institutes of Health, especially for new projects and for young scientists starting out. Some of her postdocs “are spending more time writing grants than writing papers,” she adds.

"I would like to see funds focused on the diseases that people are actually dying from, rather than ones that someone might imagine could be a problem in the event of warfare," says Harvard epidemiologist Megan Murray. Photo: Kent Dayton

At the National Institute of Allergy and Infectious Diseases, where the interim budget for 2007 was $3.8 billion, the proportion of grant proposals that will be funded has fallen over several years to just 10 percent. “We are being crunched,” acknowledges Anthony Fauci, longtime NIAID director. “We’ve had flat funding for the last three years, and with inflation, we’ve had a 10 percent decrease in purchasing power. It’s a bad signal to send for the young people.”

A bioterror money pit?

Many areas of the world are awash in infectious diseases. Some are longstanding and endemic, such as malaria. Some are of recent origin, such as HIV/AIDS. Others represent new or re-emerging threats such as Ebola or drug-resistant TB, a scourge that’s spreading through South Africa.

Scientists are working on many fronts to unravel the basic biology of dangerous microbes.

But funding for these research efforts is a major bottleneck.

Fauci points out that existing resources are being directed at emerging and re-emerging infections in the context of global health and security. He believes that the intense concern about a possible bird-flu pandemic is an opportunity to reduce the toll of ordinary seasonal influenza with better vaccines and therapies. Spending on influenza has been ratcheted up 10-fold to $222 million, says Fauci. Other NIAID priorities include developing an effective HIV/AIDS vaccine, preventing mother-to-child HIV infections and attacking the worrisome emergence of drug-resistant TB.

Though controversial, the infusion of $1.2 billion in new federal funding for research on potential bioterrorism agents has been a “boon” to NIAID-supported investigations generally, says  Fauci. While the money is earmarked for research on a list of “select agents” including anthrax, plague, tularemia and smallpox, it will yield insights and diagnostic tools for fighting civilian infections as well.

But Hidde Ploegh, Whitehead Member and immune-system expert, expresses some leeriness about this funding direction. “To my knowledge, no realistic threat assessment exists for most of the agents on this select list, nor has there been much of a debate over it,” he says. “But because there is more money in biodefense-related projects, you will see investigators move toward these agents.”

“There’s a contrast between what infectious disease people worry about—emerging communicable diseases—and what the bioterrorism people worry about, which is someone appropriating or creating a weapon out of biological material,” remarks Nobel laureate David Baltimore, who recently retired as president of the California Institute of Technology and continues his research on HIV/AIDs.

Private progress

Unexpectedly and dramatically, the funding arena has been transformed in the past several years as wealthy philanthropists have taken up the cause of global public health.

"We are being crunched," acknowledges Anthony Fauci, longtime director of the National Institute of Allergy and Infectious Diseases. Photo: Shaun Heasley /Reuters/Corbis

Most notably, the Gates Foundation provided a huge shot in the arm by committing $450 million in 2003 to launch the Grand Challenges in Global Health Initiative. A high priority on the Gates agenda is malaria, which causes an estimated 1.5 to 2.7 million deaths and infects 300 to 500 million people each year, mostly in sub-Saharan Africa.

Patrick Duffy, a prominent malaria expert formerly at Walter Reed Army Institute of Research, was lured to the Seattle Biomedical Research Institute, which receives significant Gates funding. Duffy, whose research focuses on discovering and evaluating antigens for a malaria vaccine, says that the Gates model “is more like corporate funding, in the sense that there are targeted goals and milestones to monitor progress. The NIH model has yielded outstanding basic science, but it’s less well-suited to programmatic approaches to solving problems.”

Enormous gifts from donors such as Gates and his buddy Warren Buffett make a big splash and can make a difference. By contrast, the NIH—principally NIAID—has a record of major sustained funding that adds up over the years. “Over the last 25 years,” Fauci points out, “we’ve spent over $30 billion on HIV/AIDS.” And in that same period, he adds, NIAID has grown, budget-wise, from the eighth- to the second-largest Institute within the NIH.

Tightened belts

"Our representatives in government have a grave responsibility to choose whether they advocate a war on terror or a war on microbes or a war on cancer," says Whitehead Member Hidde Ploegh. Photo: Sam Ogden

Still, after Congress doubled the NIH budget to $26.7 billion between 1999 and 2003, the increase in scientists applying for grants combined with the abrupt end of the budget largesse has spread resources thin.

Funders also need to balance basic and applied research. In Nature Immunology in 2005, Fauci wrote, “An important challenge for the NIAID is to find a way to preserve a robust commitment to the fundamental, investigator-initiated research that is the bedrock of the research enterprise while meeting expectations for more applied research, including the advanced development of vaccines, therapeutics, and diagnostics.”

Time will tell whether the federal government will eke out enough funding, in the right places, to encourage the next generation of young scientists.

“I personally would largely allocate money on the basis of global disease burden, bearing in mind that epidemic disease can happen without warning,” says Harvard’s Murray. “There is still a need to study potentially epidemic agents. But with malaria, TB and HIV as the main contributors to infectious- disease deaths, those would seem the obvious priorities.”