by Seema Kumar

In the extramural world of soft-money science -- a place where getting a grant may mean the difference between a bright scientific future and no future at all -- knowing how to get grants is an important part of being a well-rounded scientist, says Jerome Green, Director of the Division of Research Grants (DRG). Measured by this criterion, say Green and other extramural scientists, intramural scientists are still a bit rough around the edges.

"Intramural scientists are very good at what they do, but most of them, even senior people, do not know how the grants process in the extramural program works," says Green. What's more, says Judith Greenberg, Program Director of the NIGMS Genetics Program, "many senior intramural scientists are ... not in a good position to advise their outgoing fellows or postdocs, either."

Intramural scientists' lack of grant-writing savvy is understandable -- they are, by design, freed of this burden so that they can devote their time and energies to conducting innovative, high-risk research -- but it is not excusable. Greenberg says that when they finally leave NIH, intramural researchers and their students may find themselves at a disadvantage if they don't know the workings of the primary source of support for biomedical research in the outside world.

Some intramural scientists acknowledge their ignorance about NIH grant mechanisms and the ins and outs of grant writing. "We are terrified of going into research on the outside," says one anonymous intramural researcher in a FAX-BACK response to part I of this article. "If our grants get rejected as frequently as our papers, we will be in big trouble, especially now."

Typically, this realization hits intramural scientists only when it's time to leave NIH, say extramural NIHers. "Departing intramural scientists often discover us at the last hour," says Fann Harding of NHLBI in her FAX-BACK response to part I of this story. And it comes as no surprise to her and other extramural NIHers that when NIGMS holds its annual course on "How to Apply for a Grant," the course is filled to capacity.

The course, which NIGMS started in 1978 to prepare its departing pharmacology research associate training fellows for grant writing, "was so popular that NIGMS opened it up to the entire intramural community," says Greenberg, who coordinated the course in the 1980s.

The course now serves an important function at NIH, say Green and Greenberg: It provides a training similar to that offered by universities and private companies to train postdocs and others in grant writing. This year, to accommodate more participants, the seminar will be held in Masur Auditorium, and the date has been shifted from spring to Oct. 27, when the information will be more timely for scientists hoping to leave NIH with a grant in hand come next spring.

The important message, says Joan McGowan, Chief of the NIAMS Bone Biology and Bone Research Branch, is that "grant writing is not some arcane field that is difficult to learn. Intramural scientists can easily master the mechanics of grant writing, and this course provides them that opportunity." Intramural scientists may not become experts on grant-writing overnight, but "they will know who to call, where to go and what to do, after this course," says Paul Wolfe, a Program Administrator at the NIGMS Genetics Program and coordinator of this year's course.

In part II of our story on extramural NIH, The NIH Catalyst describes key elements of this popular course on NIH grant-writing and peer-review mechanisms. We interviewed, among others, the dean of grant writing, DRG's Green, and Greenberg, intramural-investigator-turned-extramural-administrator.

How to Apply for an NIH Grant

First the basics: to apply for an NIH grant, you must use the PHS 398 kit, which you can get from your institution's grant office or from DRG (Grant Information Office, phone: 594-7248). Applications for new grants are due at DRG on Feb. 1, June 1, or Oct. 1, depending on which of the three annual funding cycles you apply in. If your application has not been funded, you can revise and resubmit the application in the next cycle. "About a third of the 40,000 applications DRG receives each year are revisions of previous applications," says Green. Each revision is reevaluated for scientific and technical merit and for responsiveness to the previous review.

The NIH Peer-Review Process

The heart of the process for selecting among the almost 40,000 applications for NIH funding is the peer-review system, which has evolved over 40 years and is one of the most rigorous and systematic in the world. "Peer review ensures that the applications receive an objective evaluation and helps decide which among the many excellent proposals are the most meritorious and promising," says Green. Extramural peer review is entirely different from the intramural review conducted retrospectively by a Board of Scientific Counselors (BSC), says Green.

Peer review, extramural style, is prospective, says Green. That is, a project is reviewed on the merit of what is proposed for future work. "When we review a grant application, we look at what a scientist plans to do, what his or her objectives, hypotheses, and methods are, what the investigator's experience with an area of research is, and how much money and time the investigator proposes to spend," says Green.

"The extramural peer review system may seem like a bunch of hoops that administrative people have put up for scientists to jump through, but it is in fact a very science-driven process," says McGowan. She stresses that for any project, "good science comes first, and intramural scientists need no lessons in that respect. What they need to learn are the procedural aspects of grant writing."

The bottom line, says Green, is that intramural and extramural review differ considerably and, therefore, "it behooves intramural scientists who are planning careers outside to get to know about the NIH extramural review system and to know what their prospects are."

Green says that the potential for making mistakes on grant applications is high, especially if you don't know how the review system works: "You may think, 'My budget may be cut next year, so I'll ask for much more than I need,' and that is bad," says Green. "A panel will look at it and say that this investigator has no realistic idea of how much research costs and that this is a ridiculous request and, so, reject it." On the other hand, says Green, "if you request an amount of money that is grossly insufficient, the panel is likely to reach the same conclusion." Greenberg says the importance of the grant seminar is that it teaches people these subtleties. "It teaches you not only how to apply for a grant, but also the process by which they are referred to institutes and study sections, how applications are reviewed, what reviewers look for in an application, and how funding decisions are made," says Greenberg.

What Happens After You Apply:

The NIH peer-review process begins at DRG, the central receipt point for all grant applications. DRG processes the applications and assigns each one to a study section and to the most relevant of NIH's 21 funding institutes. Each application is given a unique number, and most are handed over for two levels of review.

"The first round of review is for scientific merit, and 80% of these reviews are done by one of DRG's 100 study sections, each comprising an average of 18 experts from around the country who are appointed for 4 years," says Green. These experts are identified and nominated based on their experience and expertise in a certain area by the Scientific Review Administrator (SRA), an NIH employee who coordinates the study section.

The study sections meet typically for 2 to 3 days, three times a year -- once during each funding cycle -- and review 75 to 100 applications at each meeting. At these meetings, members discuss each application individually and judge it by the following criteria:

* scientific significance and originality,

* adequacy of methodology,

* qualifications and experience of the principal investigator and staff,

* reasonable availability of resources, and

* reasonableness of the proposed budget and time schedule.

In addition, other criteria, such as provisions for adequate protection of human and animal subjects, and of the environment, come into play. At the end of the discussion on each application, study section members give a priority score for the application if they think it is worth further consideration. Approximately 85% of applications are scored or graded at the study section level, whereas about 15% are not recommended for further consideration.

Every application that is recommended receives a rating, ranging from 1.0 for the most enthusiastic to 5.0 for the least enthusiastic response from the members of the panel. The average of the members' individual ratings is multiplied by 100 to obtain a three-digit priority score, and these scores are ranked on a percentile basis within each study section. "These scores are important guides to Councils and Institutes to make funding decisions on the grants," says Green.

The SRA then prepares a summary statement for each application, giving a short description of the project, a critique of its strengths and weaknesses, and, for each application that is recommended, the priority score it received, its percentile ranking, and a recommended budget and duration for the project. The grant applications that are recommended for further consideration and their summary statements are forwarded to the appropriate Institute, where they undergo a second level of review by Institute-wide National Advisory Councils (called Councils) or Boards.

"Council reviews not only the scientific merit of the project but also how it meets other criteria, such as programmatic needs, portfolio balance, and availability of funds," says Green. On the basis of the study section's scores, the reviewers' comments, the summary statement, Council's recommendations, and the Institute's programmatic considerations and availability of funds, decisions are made regarding the funding. Each Institute has a team of Health Scientist Administrators who help the Institute Director make final decisions about which applications will get funded. "In making these decisions, we don't have to take reviews in perfect numerical-priority-score order," says Greenberg. "We take into account various things such as whether an area is underrepresented."

At the end of this process, "only 20 to 25% of all applications get funded, and the competition is very keen," says Green.

The Recipe for a Successful Grant Application

Now comes the important part: What distinguishes the 20 to 25% of the applications that get funded from those that don't? The answers to this question, says Green, are the ingredients that make for successful grant writing.

"First, start with a good scientific idea," says McGowan. "A good project is, first and foremost, about creative, innovative, and sophisticated science; it is the most important ingredient." That said, "There is more to applying for a grant than being a brilliant scientist," says Green. "You have to know how to present yourself in a written application within certain constraints: you can't have 90 pages describing your proposed work; you are limited to 25 pages."

Reviewers are also interested in investigators' past productivity, says Green. "They want to know: Are you publishing? Are you publishing in good journals? Are you publishing in closely related areas of science?" But the majority of the reviewers' verdict is going to depend on the project, says Green, "which is why we will sometimes get an application from a Nobel Prize winner and it will not do well. The individual may have a fantastic track record, but the project description may be poor."

Green's advice to potential grant applicants is to think the project through well, follow instructions, observe the rules of good writing, and check and double-check for any errors. He also recommends that applicants call DRG or ask to see a videotape or check out brochures from the DRG Grants Information Office. "We have lots of good material available for the asking," says Samuel Joseloff, who heads this office. Published below are some additional tips that come straight from DRG and their reviewers.

Filling Out the PHS 398 Form.

* Plan your project carefully. Use the same care developing an idea as you would for a research publication.

* Think about your audience: the busy, overworked people reading the application. Clarity, brevity, and economy, getting to the heart of what you want to express, are the key. "Most of the study section members are on the faculty of a university or an institute, and they have their own jobs. They read grant applications at home and in the evenings or on weekends. You want to make it very easy and clear for them. You want to make it very clear," says Green.

* Don't assume reviewers know what you mean. Spell it out. Competition has never been stiffer, and you may have to pay a heavy price for any doubt that you leave in the reviewer's mind.

* Don't leave out potential pitfalls and alternate approaches. The reviewers will think you never even considered them.

* Set up informal pre-reviews of your own: ask some unbiased colleagues, preferably successful grantees, for feedback at every step of the process. Get an editor and allow yourself enough time to incorporate suggestions.

Doing Your Homework

* Adhere strictly to the rules on the number of pages, citations, type size, appendices, reference letters, and overlapping support. Be sure to make provisions for the protection of human and animal subjects.

* Check and double-check everything. Proofread and let someone else do it, too. Check figures on the budget page. If you have any questions about filling out your application, call the Grants Information Office at 594-7248.

* Take extra care preparing a realistic and adequate budget. A poorly conceived budget makes people wonder whether you can manage a project.

Most Common Reasons for Applications not Being Funded

DRG experts also pinpoint the most common reasons for applications not being funded.

* Not original or significant; it must be good science. "The whole application has to be imaginative, good science and realistic, sophisticated, and mature," says Green.

* Too diffuse, superficial, or unfocused: "Give reviewers enough information to conclude that you are knowledgeable and experienced, and that you are not going after new information with a butterfly net," says Green. "State a well-formulated hypothesis."

* Vagueness on where the project is going in the future.

* Questionable reasoning in experimental approach.

* No acceptable scientific rationale.

* Not enough preliminary data to justify the project.

* Proposes an unrealistically large amount of work.

* Too uncritical in approach.

What Happens Next

Let's say you have followed all this advice and have sent a grant application to NIH. What happens next and how soon do you know how you have fared? Six to eight weeks after you apply for a grant at NIH, DRG sends you an acknowledgment and tells you to which institute and study section your application has been assigned. Your contact point, if you have any questions, then becomes the SRA of the study section. During this period, your application is going through the first level of review. A few months later, you will receive a so-called pink sheet -- a summary statement with a description of your project, a critique of the project's strengths and weaknesses, and, if it has been recommended, its priority score, percentile ranking, and the recommended budget and time limit. At this point, your application, if it has been recommended, has been forwarded to the appropriate institute, where it undergoes a second level of review at Council.

Once the funding decision has been made, you receive word about whether your grant was funded. Program staff members notify grantees about the dollar amounts, which are often different (and usually lower) than the requested amount, and work with the Grants Management Office to send out official notices -- memos that initiate payments on grants -- to successful applicants.

Throughout this process, NIH administrators try to remain available. "We work with investigators before, during, and after the application process and answer their questions on what NIH or our institute is looking for in the application and discuss the merits of their ideas and the type of grant they should apply for," says McGowan. Program directors also help scientists focus on their scientific areas and guide them through the application process. "For some investigators, the grant-writing process is a scary, nebulous process. What we are here to do, as part of our jobs, is to help them through that process as best as we can, given the resources we have and the time we have," says Dennis Mangan, Director of the Periodontal Diseases Program at NIDR.

But, says Green, "there are no special breaks for an intramural investigator" applying for a grant to work extramurally. Greenberg observes that it wouldn't hurt intramural scientists to get to know some their extramural colleagues before leaving NIH to establish a contact point.

"We have great respect for what intramual scientists do and would love to work with young and senior investigators and help them with any questions they may have about the process of grant writing," says McGowan.

For more information on any aspect of NIH grant writing and review, call the DRG Grants Information Office at 594-7248...and Good luck!

(Look for part III of this story, featuring a discussion on mentoring and career development for young scientists, in the next issue of The Catalyst.)