{"id":6123,"date":"2009-06-29T11:11:38","date_gmt":"2009-06-29T18:11:38","guid":{"rendered":"http:\/\/oralcancernews.org\/wp\/?p=6123"},"modified":"2009-06-30T04:29:16","modified_gmt":"2009-06-30T11:29:16","slug":"grant-system-leads-cancer-researchers-to-play-it-safe","status":"publish","type":"post","link":"https:\/\/oralcancernews.org\/wp\/grant-system-leads-cancer-researchers-to-play-it-safe\/","title":{"rendered":"Cancer researchers “play it safe” due to grant system"},"content":{"rendered":"

Source: NYTimes<\/strong>
\nAuthor: Gina Kolata<\/strong><\/p>\n

Among the recent research grants awarded by the\u00a0National Cancer Institute<\/a> is one for a study asking whether people who are especially responsive to good-tasting food have the most difficulty staying on adiet<\/a>. Another study will assess a Web-based program that encourages families to choose more healthful foods.<\/p>\n

Many other grants involve biological research unlikely to break new ground. For example, one project asks whether a laboratory discovery involving\u00a0colon cancer<\/a> also applies to\u00a0breast cancer<\/a>. But even if it does apply, there is no treatment yet that exploits it.<\/p>\n

The\u00a0cancer<\/a> institute has spent $105 billion since PresidentRichard M. Nixon<\/a> declared war on the disease in 1971. TheAmerican Cancer Society<\/a>, the largest private financer of cancer research, has spent about $3.4 billion on research grants since 1946.<\/p>\n

Yet the fight against cancer is going slower than most had hoped, with only small changes in the death rate in the almost 40 years since it began.<\/p>\n

One major impediment, scientists agree, is the grant system itself. It has become a sort of jobs program, a way to keep research laboratories going year after year with the understanding that the focus will be on small projects unlikely to take significant steps toward curing cancer.<\/p>\n

\u201cThese grants are not silly, but they are only likely to produce incremental progress,\u201d said Dr. Robert C. Young, chancellor at Fox Chase Cancer Center in Philadelphia and chairman of the Board of Scientific Advisors, an independent group that makes recommendations to the cancer institute.<\/p>\n

The institute\u2019s reviewers choose such projects because, with too little money to finance most proposals, they are timid about taking chances on ones that might not succeed. The problem, Dr. Young and others say, is that projects that could make a major difference in cancer prevention and treatment are all too often crowded out because they are too uncertain. In fact, it has become lore among cancer researchers that some game-changing discoveries involved projects deemed too unlikely to succeed and were therefore denied federal grants, forcing researchers to struggle mightily to continue.<\/p>\n

Take one transformative drug, for breast cancer. It was based on a discovery by Dr. Dennis Slamon of the\u00a0University of California<\/a>, Los Angeles, that very aggressive breast cancers often have multiple copies of a particular protein, HER-2. That led to the development of herceptin, which blocks HER-2.<\/p>\n

Now women with excess HER-2 proteins, who once had the worst breast cancer prognoses, have prognoses that are among the best. But when Dr. Slamon wanted to start this research, his grant was turned down. He succeeded only after the grateful wife of a patient helped him get money from Revlon, the cosmetics company.<\/p>\n

Yet studies like the one on tasty food are financed. That study, which received a grant of $100,000 over two years, is based on the idea that since\u00a0obesity<\/a> is associated with an increased risk of cancer, understanding why people have trouble losing weight could lead to better weight control methods, which could lead to less obesity, which could lead to less cancer.<\/p>\n

\u201cIt was the first grant I ever submitted, and it was funded on the first try,\u201d said the principal investigator, Bradley M. Appelhans, an assistant professor of basic medical sciences and\u00a0psychology<\/a> at the\u00a0University of Arizona<\/a>. Dr. Appelhans said he realized it would hardly cure cancer, but hoped that \u201cit will provide knowledge that will incrementally contribute to more effective cancer prevention strategies.\u201d<\/p>\n

Even top federal cancer officials say the system needs to be changed.<\/p>\n

\u201cWe have a system that works over all pretty well, and is very good at ruling out bad things \u2014 we don\u2019t fund bad research,\u201d said Dr. Raynard S. Kington, acting director of theNational Institutes of Health<\/a>, which includes the cancer institute. \u201cBut given that, we also recognize that the system probably provides disincentives to funding really transformative research.\u201d<\/p>\n

The private American Cancer Society follows a similarly cautious path. Last year, it awarded $124 million in new research grants, with some money coming from large donors but most from events like walkathons and memorial donations.<\/p>\n

Dr. Otis W. Brawley, chief medical officer at the cancer society, said the whole cancer research effort remained too cautious.<\/p>\n

\u201cThe problem in science is that the way you get ahead is by staying within narrow parameters and doing what other people are doing,\u201d Dr. Brawley said. \u201cNo one wants to fund wild new ideas.\u201d<\/p>\n

He added that the problem of getting money for imaginative but chancy proposals had worsened in recent years. There are more scientists seeking grants \u2014 they surged into the field in the 1990s when the National Institutes of Health budget doubled before plunging again.<\/p>\n

That makes many researchers, who need grants not just to run their labs but also sometimes to keep their faculty positions, even more cautious in the grant proposals they submit. And grant review committees become more wary about giving scarce money to speculative proposals.<\/p>\n

Philanthropies, which helped some researchers try outside-the-box ideas, are now having financial problems. And advances in technology have made research more expensive.<\/p>\n

\u201cScientists don\u2019t like talking about it publicly,\u201d because they worry that their remarks will be viewed as lashing out at the health institutes, which supports them, said Dr. Richard D. Klausner, a former director of the National Cancer Institute.<\/p>\n

But, Dr. Klausner added: \u201cThere is no conversation that I have ever had about the grant system that doesn\u2019t have an incredible sense of consensus that it is not working. That is a terrible wasted opportunity for the scientists, patients, the nation and the world.\u201d<\/p>\n

A Big Idea Without a Backer<\/span><\/p>\n

For 25 years, Eileen K. Jaffe received federal grants to run her lab. As a senior scientist at the Fox Chase Cancer Center, with a long list of published papers in prestigious journals, she is a respected, established researcher.<\/p>\n

Then Dr. Jaffe stumbled upon results that went against textbook explanations, suggesting that it might be possible to find an entirely new class of drugs that could disable proteins that fuel cancer cells. Now she wants to find chemicals that might be developed into such drugs.<\/p>\n

But her grant proposal was rejected out of hand by the institutes of health, not even discussed by a review panel. She had no preliminary data showing that the idea was likely to work, something reviewers always want to see, and the idea was just too unprecedented.<\/p>\n

Dr. Jaffe epitomizes the scientist who realizes that if she were to single-mindedly pursue her unorthodox idea, her \u201ccareer may be ruined in the process,\u201d in the words of Dr. Brawley of the American Cancer Society.<\/p>\n

Dr. Jaffe is just conceiving her project; it is much to soon to know whether it will result in a revolutionary drug. And even if she does find potential new drugs, it is not clear that they will be effective. Most new ideas are difficult to prove, and most potential new drugs fail.<\/p>\n

So Dr. Jaffe was not entirely surprised when her grant application to look for such cancer drugs was summarily rejected.<\/p>\n

\u201cThey said I don\u2019t have preliminary results,\u201d she said. \u201cOf course I don\u2019t. I need the grant money to get them.\u201d<\/p>\n

Dr. Young, chancellor at Fox Chase, said Dr. Jaffe\u2019s situation showed why people with bold new ideas often just give up.<\/p>\n

\u201cYou can\u2019t prove it will work in advance,\u201d he said. \u201cIf you could, it wouldn\u2019t be a high-risk idea.\u201d<\/p>\n

It is a long haul, Dr. Jaffe knows. And she has already had to downsize her lab. But, she said, she will persist.<\/p>\n

Angels Outside Government<\/span><\/p>\n

At the Dana-Farber Cancer Institute in Boston, Dr. Ewa T. Sicinska knew she would have a similar problem with her research. She wanted to grow human cancers in mice. Unlike Dr. Jaffe, though, Dr. Sicinska did not even apply for government money.<\/p>\n

It is not that the project was unimportant.<\/p>\n

\u201cRather than have to start a human clinical trial to test new drugs, we want to test them first in mice with real human\u00a0tumors<\/a>,\u201d said Dr. George D. Demetri, who leads the research group supporting Dr. Sicinska.<\/p>\n

Researchers have studied mouse cancers but, they acknowledge, they are just not the same as human cancers \u2014 they are much easier to treat, and drugs that cure mice often do nothing in people. So, over the years, scientists have tried to implant human cancer cells in mice, but with little success.<\/p>\n

\u201cEveryone told us that if you take tumors out of patients and put them in mice, they don\u2019t grow,\u201d Dr. Demetri said. The\u00a0tumor<\/a> cells usually were put in a plastic dish before being implanted in mice. \u201cWe said \u2014 wait a minute. The cells are not growing in the plastic dish. They probably are dying. What if we bypass the dish?\u2019\u201d<\/p>\n

With that idea in mind, Dr. Demetri, convinced it was too speculative to get federal money, tapped an unusual source, the Ludwig Fund. Endowed by Daniel K. Ludwig, one of the world\u2019s richest men in the 1960s and 1970s, the fund supports unfettered cancer research at six medical centers in the United States, including Dana-Farber, to be used at the institutes\u2019 discretion. That put Dr. Sicinska in a very different position from that of Dr. Jaffe. She could try something chancy without a grant.<\/p>\n

Dr. Sicinska used a quarter of a million dollars of Ludwig money for this project, buying mice without immune systems, which meant they could not reject human tumors, and housing them in a germ-free basement lab. She spent months learning to implant tumors in the mice and enlisted geneticists to study the implanted tumors, making sure they did not mutate beyond recognition.<\/p>\n

She spends her days in the lab, using a miniature\u00a0ultrasound<\/a> machine to scan the mice, hairless creatures with prominent ears. Four types of sarcomas \u2014 cancers of fat, muscle or bone \u2014 are growing in them and look genetically identical to the tumors removed from patients.<\/p>\n

Dr.\u00a0Elias A. Zerhouni<\/a>, former director of the National Institutes of Health, said he was not sure that a grant for the project would have been turned down. The N.I.H., he said, does finance research on mouse models for human cancer.<\/p>\n

But Dr. Demetri said he did not apply \u201cbecause we have lots of experience in what\u2019s fundable.\u201d His mouse work, he said, is exploratory, and he cannot predict what he will find or when. He certainly could not lay out a road map of what he would do and promise results in a few years.<\/p>\n

Studies With a Different Goal<\/span><\/p>\n

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.<\/p>\n

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.<\/p>\n

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\u00a0adolescence<\/a> may have an impact on cancer risk in middle and old age, said the grant recipient, Karen Weber Cullen, associate professor ofpediatrics<\/a> 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.<\/p>\n

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, \u201cwe try to achieve improvements in diet and\u00a0physical activity<\/a> behaviors that become permanent and will make a difference in later years.\u201d<\/p>\n

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.<\/p>\n

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.<\/p>\n

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.<\/p>\n

Dr. Howe has reviewed grants for the cancer institute herself, she said, and realizes that, among other things, those that get financed must have \u201ca novel hypothesis that is credible based on what we know already.\u201d<\/p>\n

Trying to Change the System<\/span><\/p>\n

The National Institutes of Health has started \u201cpilot experiments\u201d to see if there is a better way of getting financing for innovative projects, its acting director, Dr. Kington, said.<\/p>\n

They include \u201cpioneer awards,\u201d begun in 2004 for \u201cideas 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.\u201d 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 \u201ctransformative R01 grants,\u201d described as \u201cproposing exceptionally innovative, high risk, original and\/or unconventional research with the potential to create or overturn fundamental paradigms.\u201d<\/p>\n

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\u00a0University of California, San Francisco<\/a>, and co-chairman of the committee that reviewed the proposals last week.<\/p>\n

\u201cFrom reading the applications so far, there are really some fantastic things,\u201d Dr. Yamamoto said.<\/p>\n

There also is new money from the federal economic stimulus package passed by Congress, which gives the National Institutes of Health $200 million for \u201cchallenge grants\u201d lasting two years or less.<\/p>\n

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.<\/p>\n

\u201cI did submit one of these challenge grants recently, like the rest of the lemmings,\u201d said Dr. Chi Dang, professor of medicine, cell biology, oncology and pathology at the\u00a0Johns Hopkins University<\/a> School of Medicine. But, he added, \u201cthere are many, many more applications than slots.\u201d<\/p>\n

Some experienced scientists have found a way to offset the problem somewhat. They do chancy experiments by siphoning money from their grants.<\/p>\n

\u201cIn a way, the system is encrypted,\u201d Dr. Yamamoto said, allowing those in the know to wink and do their own thing on the side.<\/p>\n

Great discoveries have been made with N.I.H. financing without manipulating the system, Dr. Klausner said.<\/p>\n

\u201cBut,\u201d he added, \u201cI actually believe that by and large it is despite, rather than because of, the review system.\u201d<\/p>\n

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Source: NYTimes Author: Gina Kolata Among the recent research grants awarded by the\u00a0National Cancer Institute is one for a study asking whether people who are especially responsive to good-tasting food have the most difficulty staying on adiet. Another study will assess a Web-based program that encourages families to choose more healthful foods. Many other grants involve biological research unlikely to break new ground. For example, one project asks whether a laboratory discovery involving\u00a0colon cancer also applies to\u00a0breast cancer. But even if it does apply, there is no treatment yet that exploits it. The\u00a0cancer institute has spent $105 billion since PresidentRichard M. Nixon declared war on the disease in 1971. TheAmerican Cancer Society, the largest private financer of cancer research, has spent about $3.4 billion on research grants since 1946. Yet the fight against cancer is going slower than most had hoped, with only small changes in the death rate in the almost 40 years since it began. One major impediment, scientists agree, is the grant system itself. It has become a sort of jobs program, a way to keep research laboratories going year after year with the understanding that the focus will be on small projects unlikely to take significant steps toward curing cancer. \u201cThese grants are not silly, but they are only likely to produce incremental progress,\u201d said Dr. Robert C. Young, chancellor at Fox Chase Cancer Center in Philadelphia and chairman of the Board of Scientific Advisors, an independent group that makes recommendations to the cancer institute. The […]<\/p>\n","protected":false},"author":41,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[140,722,1122,672,1123,1119,1124,1121,619,1120,1118],"class_list":["post-6123","post","type-post","status-publish","format-standard","hentry","category-oral_cancer_news","tag-american-cancer-society","tag-breast-cancer","tag-chase-cancer-center","tag-colon-cancer","tag-daniel-ludwig","tag-her-2-protein","tag-johns-hopkins-university","tag-medical-grants","tag-national-cancer-institute","tag-obesity","tag-university-of-california"],"_links":{"self":[{"href":"https:\/\/oralcancernews.org\/wp\/wp-json\/wp\/v2\/posts\/6123","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/oralcancernews.org\/wp\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/oralcancernews.org\/wp\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/oralcancernews.org\/wp\/wp-json\/wp\/v2\/users\/41"}],"replies":[{"embeddable":true,"href":"https:\/\/oralcancernews.org\/wp\/wp-json\/wp\/v2\/comments?post=6123"}],"version-history":[{"count":4,"href":"https:\/\/oralcancernews.org\/wp\/wp-json\/wp\/v2\/posts\/6123\/revisions"}],"predecessor-version":[{"id":6127,"href":"https:\/\/oralcancernews.org\/wp\/wp-json\/wp\/v2\/posts\/6123\/revisions\/6127"}],"wp:attachment":[{"href":"https:\/\/oralcancernews.org\/wp\/wp-json\/wp\/v2\/media?parent=6123"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/oralcancernews.org\/wp\/wp-json\/wp\/v2\/categories?post=6123"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/oralcancernews.org\/wp\/wp-json\/wp\/v2\/tags?post=6123"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}