by The NIH Catalyst Editorial Advisory Board

NIH scientists are no exception to the recent trend toward increased collaboration in biomedical research. Yet, intramural researchers may not be taking full advantage of the wealth of collaborative opportunities in their own back yard. Frequently mentioned obstacles to interlab or interinstitute collaborations include lack of information about other researchers' interests and expertise, reluctance to approach other NIH researchers, and a dearth of informal outlets for scientists from a wide range of disciplines to mingle and exchange ideas.

 Ira Pastan, left, and David Davies , whose competition on the tennis court led to collaboration in the lab.

The NIH Catalyst recently turned to its Editorial Advisory Board to get a reading on the current collaborative atmosphere within NIH, as well as suggestions on how it could be improved. The board members who responded said they had collaborated other NIH researchers outside their own immediate labs, and that with their collaborations were roughly divided between inter- and intrainstitute projects.

"I have been at NIH for 20 years and have always collaborated as much as possible with intramural scientists. The benefits are enormous because the people are local and generally more supportive than university people--possibly because of the availability of resources," says Hynda Kleinman of NIDR.

Hynda Kleinman

David Lim, who came to NIDCD 3 1/2 years ago from Ohio State University in Columbus and will be leaving Sept. 1 to become executive vice president for research of the House Ear Institute, which is affiliated with the University of Southern California in Los Angeles, says intramural, indeed interagency, collaboration is vital to his lab's efforts to develop a conjugate vaccine against nontypeable Haemo-philus influenzae, a major pathogen causing otitis media. The vaccine project involves researchers from NIDCD, NICHD, and FDA's Center for Biologics Evaluation and Research. "Without this collaboration and pulling the resources together, this project could not have been possible for a small institute like ours," says Lim, who currently has four collaborative projects within NIDCD, five within NIH, and five outside NIH.

David Lim

NINDS's Michael Rogawski says most of his collaborations have been with labs in other institutes, drawing on their expertise in medicinal chemistry, analytical chemistry, mathematical modeling, behavioral pharmacology, and neurochemistry.

Michael Rogawski

"No one lab can do everything and, in times of constricting budgets, sharing of resources is a necessity," Rogawski says. "In the heyday of NIH, when resources were virtually limitless, the argument could be made that duplication of effort was an effective, if inefficient, path toward research excellence. We can't afford this anymore."

Elise Kohn, who was recently tenured in NCI's Laboratory of Pathology, agrees, noting that many of the interinstitute collaborations in which she has been involved were initiated because an outside colleague possessed a technique, a model, or expertise she did not have or would take a long time to acquire. "In most cases, it has expanded my horizons and knowledge and, in some cases, I think, also that of my collaborator."

The scientific achievements of NIDDK's David Davies over the past 40 years stand as an impressive testament to the benefits of cultivating intramural collaborations. "Very few of my collaborations have been outside of NIH. It's been such a rich resource," says Davies, whose relatively rare expertise as an protein crystallographer at NIH has become increasingly in demand as intramural molecular biologists scramble to learn more about the proteins encoded by the genes they have isolated. When he was a young scientist, Davies says, he usually had to be the one to make the first move to seek out collaborators. Now, as a senior researcher with a well-established reputation, he finds that most collaborations arise from other people approaching him for help in characterizing their proteins of interest.

Davies' list of successful intramural collaborations includes several projects involving other NIDDK researchers: the discovery of the guanine, or G, tetraplex that is characteristic of telomeric DNA, with Marie Lipsett and Martin Gellert; the determination of the structure of human immunodeficiency virus (HIV) integrase, with Robert Craigie and Kiyoshi Mizuuchi; and work on the high-resolution structure of the bifunctional enzyme complex tryptophan synthase, with Edith Miles. However, over the decades, Davies has also ventured beyond his home institute to explore the structures of antibody Fab fragments with Michael Potter of NCI, antibody-antigen complexes with Sandra Smith-Gill of NCI, the ribonuclease H domain of the HIV reverse transcriptase with Paul Wingfield and Stephen Stahl of the Protein Expression Lab, and domain III of the Pseudomonas aeruginosa exotoxin with Ira Pastan of NCI.

As the Davies-Pastan work illustrates, personal interactions can sometimes serve as a springboard for professional associations rather than vice versa. For years before they launched their collaborative investigation, which shed light on the Pseudomonas toxin's mechanism of action by locating the nicotinamide adenine dinucleotide (NAD) binding site, Davies and Pastan had been engaged in quite a different sort of collaboration: playing early bird tennis at the Linden Hill Club. Their informal banter while waiting for courts led to more serious discussions and, eventually, Pastan's suggestion that they launch a collaborative research project. "An enormous amount of NIH business was conducted at those courts between 7 a.m. and 8 a.m.," says Davies, lamenting the club's closure in the late 1980s to make way for a condominium complex.

The nuts and bolts of setting up interinstitute collaborations may be simpler than many scientists think. One editorial board member, who asked not to be named, remarks that, lately, collaborations within the researcher's own institute "seem to have required upfront negotiations (requested by the other parties) more than my outside collaborations do, but that is probably just personalities."

As for the downside of in-house collaborations, the editorial advisers said the kinds of problems they encounter in working with NIH colleagues are not substantively different from those posed by outside collaborations, where authorship, commitment, and speed-of-work issues, for example, also come up. So, what barriers are standing in the way of NIH maximizing its collaborative potential?

"Knowing how to find people with the needed knowledge, or resources, or assays," says NINDS's Joan Schwartz, who is collaborating within her institute on a transgenic mouse line and is currently working with researchers at NEI on ongoing research related to the effects of a novel neurotrophic factor, called PEDF, that affects three different types of neural cells.

Kleinman agrees. "The biggest obstacle to collaboration is the problem of not knowing who is doing what. We use the annual bibliography when we want a cell type or antibody ... to see first, if anyone on campus has the desired reagent or information. The problem is that there are not enough copies of the bibliography, and it is somewhat outdated by the time it reaches our labs."

Some of the lack of awareness about collaborative opportunities may lie in the very nature of NIH. "There is less contact among the `faculty' at NIH than at universities, medical schools, and private research institutes. Faculty members in these environments interact on departmental and university-wide committees, in the organization and teaching of courses, and in the development of initiatives to seek funding," Rogawski says. "We often feel fortunate as NIH scientists in not being burdened with these distractions. The downside is that we don't get to know our colleagues."

Attitude can be another roadblock. "It often appears that despite the fabulous opportunities within NIH as a whole, and individual institutes separately, many investigators see themselves in competition with their colleagues here, not as potential collaborators," an editorial board member wrote in an anonymous comment. "During visits to the outside, I see core facilities and collaborations of necessity due to personnel or funding restrictions, and sometimes more of an atmosphere of teamwork. Some of that may be necessary due to funding restrictions and the extremely tight grant situation. Some may be caused by the educational atmosphere, with graduate and undergraduate students requiring mentors and role models. We have a remarkably open environment, yet I am occasionally disappointed by what I see."

Young researchers, Davies says, must also learn to accept the risks of collaboration--that even within NIH, some joint research projects will not pan out the way the researcher had originally hoped. "Even though throughout my career I have had many successful collaborations, not all my collaborations have been successful," he says.

Lim notes that shifts in the focus of the NIH intramural program may also erect barriers to collaboration. "As more pressure is put on the intramural scientists to `publish or perish,' collaboration may be viewed as a sidetrack and as unfocused. If this environment continues in the intramural program, some important aspects of the tradition of collaboration among NIH scientists may suffer."

Although one scientist observes that "it's hard to change people," The NIH Catalyst editorial advisers remain optimistic, offering the following suggestions on how to create an intramural atmosphere that is more conducive to collaboration--and on how NIH researchers can better exploit the opportunities that already exist.

Computer Resources--Researchers should be encouraged to take advantage of existing electronic databases on NIH scientists and their research projects, such as the Computer Retrieval of Information on Scientific Projects (CRISP) system [see box]. It may also be helpful to set up a "research matchmaker" electronic bulletin board for intramural scientists in search of collaborators who have particular interests, skills, or reagents.

Lectures and Seminars--Scientists should regard the time before and after lectures and seminars as opportunities for exchanging ideas with colleagues, as well as for discussing the speaker's presentation. Editorial board members are divided about whether the larger, more generalized seminars, such as the NIH Director's Lectures and Wednesday Afternoon Lectures, or the smaller branch/lab seminars are the best places to establish such contacts. Special events, such as the NIH Research Festival, also promote collaborative exchanges. "At research day--usually at the poster sessions--we have made a lot of connections for collaborations," Kleinman says.

Interinstitute Interest Groups--These relatively informal groups, which meet occasionally to discuss topics related to a specific interest, such as the cell cycle or hard-tissue disorders, would seem by their very design to encourage interinstitute collaborations. However, Kleinman says she personally has not found the interest groups useful, observing that some of them may be too big to allow for detailed exchanges. Davies cautions that "one needs to avoid becoming embedded in one's group," and Rogwaski adds that although the Research Festival and interest groups are steps in the right direction, he thinks they are not enough.

Social Interactions--Pausing to munch a cookie after a lecture, checking out a different cafeteria, or joining an NIH-affiliated recreational group are activities that seem to have little to do with the business of science. But, as Davies notes, some of the most innovative collaborations arise when two researchers from disparate fields meet in a social setting and discover that, much to their surprise, their scientific ideas or techniques actually complement each other. "If you don't make such efforts, it's not very easy to meet people from other institutes," says Davies, who, in addition to his many scientific activities, is a member of the NIH Sailing Club.

Administrative Leadership--The NIH administration should institute "faculty" meetings where researchers could become more familiar with the interests and concerns of their colleagues, according to Rogawski. In addition, Rogawski suggests that senior research administrators use their "broad view" to identify potential interplays between disparate research areas and then bring together scientists in those areas to promote cross-fertilization of ideas. NIH scientists with good collaborative skills, especially when it comes to working with their intramural colleagues, should be recognized. Board members say efforts to encourage collaboration are crucial to NIH's intramural productivity. As Lim says, "We should maintain this wonderful tradition that makes this place a hotbed of cutting-edge science and a training ground for young researchers."


CRISP and More

Many intramural scientists just think of the Public Health Services' Computer Retrieval of Information on Scientific Projects (CRISP) system as the place where they are obliged to file annual descriptions of their research. In fact, scientists should be able to get as much out of CRISP as they put in and can readily use the biomedical database as a tool for identifying promising scientific contacts and collaborators inside and outside of NIH.

To access CRISP through your desktop computer, use Gopher or a World Wide Web browser, such as Mosaic or Netscape, to go to the NIH home page. Then, enter the Grants section, click on CRISP, and follow the instructions to do a search by name, institution, or research topic. The database, which is updated weekly, includes NIH-, CDC-, SAMSA-, and FDA-funded grants, contracts, and cooperative agreements, as well as intramural projects at these institutions.

In addition to CRISP, the Grants section contains links to other computer databases that may help facilitate scientific collaboration. The "Searching for Biologists" area, a pilot project coordinated by Welchlab at Johns Hopkins University in Baltimore, has listings of e-mail addresses for researchers in a wide variety of biomedical disciplines, including yeast and crystallography. The database also allows you to search for biologists by name, location, and research interests and can connect you to the phone books of research institutions around the world.

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