Grant system undercuts major cancer advances

Studies With a Different Goal
Researchers like Dr. Appelhans, who is studying weight control and tasty foods, do not expect to change the outlook for cancer patients anytime soon. But, they say, that does not mean their work is unimportant.

Dr. Appelhans will study 85 overweight or obese women, measuring how much the tastes and textures of food drive their eating. Then they will be given a weight loss diet and nutritional counseling. Dr. Appelhans will ask whether those who are most tempted by the tastes and textures also have the most trouble following the diet.

As for the grant to assess a Web-based program to improve food choices, it is predicated on studies indicating that what people eat in childhood and adolescence may have an impact on cancer risk in middle and old age, said the grant recipient, Karen Weber Cullen, associate professor of pediatrics at Baylor College of Medicine. Some studies have found that people who reported having eaten fruits and vegetables when they were younger and maintaining a healthy weight were less likely to have cancer.

Of course, it would not be feasible to follow participants for 30 or 40 years to see if their cancer risk was altered, Dr. Cullen noted. But, she added, “we try to achieve improvements in diet and physical activity behaviors that become permanent and will make a difference in later years.”

In the study asking whether a molecular pathway that spurs the growth of colon cancer cells also encourages the growth of breast cancer cells, the principal investigator ultimately wants to find a safe drug to prevent breast cancer. She received a typical-size grant of a little more than $1 million for the five-year study.

The plan, said the investigator, Louise R. Howe, an associate research professor at Weill Cornell Medical College, is first to confirm her hypothesis about the pathway in breast cancer cells. But even if it is correct, the much harder research would lie ahead because no drugs exist to block the pathway, and even if they did, there are no assurances that they would be safe.

Dr. Howe said she hoped that she would find such drugs, or that companies would. Then she wants to develop a way to selectively deliver the drugs to precancerous breast cells. If it all works and the treatment is safe, women with precancerous conditions could avoid developing cancer.

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Dr. Howe has reviewed grants for the cancer institute herself, she said, and realizes that, among other things, those that get financed must have “a novel hypothesis that is credible based on what we know already.”

Trying to Change the System
The National Institutes of Health has started “pilot experiments” to see if there is a better way of getting financing for innovative projects, its acting director, Dr. Kington, said.

They include “pioneer awards,” begun in 2004 for “ideas that have the potential for high impact but may be too novel, span too diverse a range of disciplines or be at a stage too early to fare well in the traditional peer review process.” But only 3 percent to 5 percent of the applicants get funded. Now the institutes have decided to set aside up to $25 million for “transformative R01 grants,” described as “proposing exceptionally innovative, high risk, original and/or unconventional research with the potential to create or overturn fundamental paradigms.”

About 700 proposals have come in, but only a small number are expected to be financed, according to Dr. Keith R. Yamamoto, a molecular biologist and executive vice dean of the school of medicine at the University of California, San Francisco, and co-chairman of the committee that reviewed the proposals last week.

“From reading the applications so far, there are really some fantastic things,” Dr. Yamamoto said.

There also is new money from the federal economic stimulus package passed by Congress, which gives the National Institutes of Health $200 million for “challenge grants” lasting two years or less.

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But the N.I.H. has received about 21,000 applications for 200 challenge grants, and researchers who have applied concede there is not much hope.

“I did submit one of these challenge grants recently, like the rest of the lemmings,” said Dr. Chi Dang, professor of medicine, cell biology, oncology and pathology at the Johns Hopkins University School of Medicine. But, he added, “there are many, many more applications than slots.”

Some experienced scientists have found a way to offset the problem somewhat. They do chancy experiments by siphoning money from their grants.

“In a way, the system is encrypted,” Dr. Yamamoto said, allowing those in the know to wink and do their own thing on the side.

Great discoveries have been made with N.I.H. financing without manipulating the system, Dr. Klausner said.

“But,” he added, “I actually believe that by and large it is despite, rather than because of, the review system.”

This article, “Grant System Leads Cancer Researchers to Play It Safe ” first appeared in The New York Times. The article is part of the ongoing series "Forty Years War."

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