The intramural research program of he National Institute on Drug Abuse originated before NIDA was born - as the research unit of a prison-affiliated PHS hospital in Lexington, Kentucky, where addicted prisoners were treated and studied. It was renamed the Addiction Research Center and attached to NIMH before it relocated to NIDA and its current Baltimore location on the Johns Hopkins Bayview Research Campus about 40 miles from Bethesda. In June, NIDA's IRP became the third (after NCI and NIMH) to complete a detailed appraisal by outside reviewers. A panel chaired by Stanley Watson, professor of psychiatry and codirector of the University of Michigan Mental Health Research Institute, studied the program for six months. A summary of its findings follows.

Though criticisms of the program's recent lack of leadership, mentoring, spirit, and scientific vision were pointed, they were offered within the context of two fundamental conclusions, neither of which had been foregone: that the program remain in existence and that it remain in Baltimore. Both issues were on the table in the panel's deliberations, and these two conclusions reflected the belief that the IRP could and would set the country's pace for drug-abuse research once certain recommended changes were implemented.

"The pivotal issue in the decision to keep the intramural research division open was the opportunity . . . to produce an integrated view of drug use and substance-abuse biology across species, including humans," the panel stated. Not least among the panel's reasons for optimism was the recent recruitment of Barry Hoffer, "a superb scientist, admirable mentor . . . and a person of vision and administrative experience" to fill the long-vacant scientific director slot. "His strong reputation in neuroscience will bring much-needed stature and scientific credibility to the IRP," the panel said.

Conversely, the more than four-year absence of a permanent clinical directorand the resulting deterioration in the quality of clinical research, characterized by "mediocre protocols . . . and poor integration of clinical and basic studies"remains to be corrected, the panel said.

Also to improve the clinical research climate, the panel recommended involving clinical investigators in study-participant recruitment, and recruiting more African-American clinical scientists to enhance the "ethnic match" between the researchers and a large proportion of study volunteers.

THE BLESSINGS OF BALTIMORE

In the matter of facilitating connections between basic and clinical research, the reviewers viewed the Baltimore facility in an especially favorable light, calling one of its "most valuable features" the "housing of its entire scientific operation [including] basic, translational, and clinical research and researchers . . . within that one site." They considered this arrangement a strong argument against moving any part of the IRP to Bethesda, despite the fact that their review had revealed "virtually no significant information flow between basic and clinical programs" and an "almost universal lack of communication between groups," especially between branches, whose interactions they found to be marked by secrecy and fierce competition for resources.
Consequently, they recommended incentives for collaboration, such as:

• Allocating budget and space resources contingent on active collaborations.

• Tying funding for new basic science models to plans for shared use, either with other intramural labs or the extramural community.

• Establishing team projects in such areas as translational research and drug development.

The panelists counted among other advantages of the Baltimore site its spaciousness, its "potential linkages" with Johns Hopkins and other academic institutions, and its shared location and increasing collaboration with components of the National Institute on Aging (NIA) and the National Human Genome Research Institute (NHGRI). They lauded NIDA's collaborative project with NHGRI's Center for Complex Heritable Diseases on the human genetics of substance abuse and its plans to share core facilities with NIA, including DNA sequencing and space for nonhuman-primate studies. The panel encouraged NIDA-NIA collaboration in "constructing a new shared facility."

ON MONEY AND MORALE

The panel noted that NIDA's intramural research budget in proportion to its total budget is only half that of other institute allocations, accounting for 5.6% (of NIDA's $489 million), compared with the 11.3% slice accorded NIH intramural research programs overall. It did not, however, suggest any change.in the amount but instead recommended changes in the way the money is divvied up within the IRP.

Each independent investigator's lab should have its own budget, the panelists advised, with the scientific director - not the branch chiefs - making budgetary decisions based on each lab's past productivity and future plans and NIDA's research priorities. This change, the panel reasoned, would minimize competition at the branch level, raise investigator morale from its current low level, and foster investigator independence from the branch chief.

Currently vacant branch chief slots should be filled promptly, the panelists said, with fine scientists who are also accomplished mentors.

New Scientific Director On the Move - and Here to Stay Barry Hoffer "Addiction is a brain disease." "I was sufficiently new to have had no opportunity to do anything wrong" is how Barry Hoffer, NIDA's new scientific director explains the praise accorded him by the independent panel that reviewed NIDA's intramural research program. Not only did the reviewers deem him a "superb scientist" and an "admirable mentor," they also predicted his leadership would position NIDA to be the "premier substance-abuse research center in the world, in both the basic and clinical arenas." But they also put forth an extensive "to-do list" to overcome the deficiencies that have kept that potential from being realized. It's a list that Hoffer embraces. "Virtually all the recommendations are being implemented, or will be," Hoffer said in an interview with The NIH Catalyst. The most crucial of the panel's directives, he said, are to inspire NIDA intramural research groups to communicate with one another, to strengthen the clinical research program, and to "protect and develop younger investigators and staff scientists." Hoffer came to NIDA last September from the University of Colorado School of Medicine in Denver, where he was a professor of psychiatry and pharmacology. The reviewers began their work in December and issued their report and recommendations in June, but the new SD began fixing things as soon as he unpacked. "Many of the needs [the panel addressed] were obvious" at the start, he said, citing especially a "clear need for mentoring." ACTIONS Hoffer selected Roy Pickens to be associate director for training and education. "I have a short institutional memory, but to my knowledge, no one previously was charged with mentoring fellows and postdocs," he said, noting that there is now a written document to guide the mentoring process. A weekly seminar series is also in full swing. In the realm of improved communication among the branches, Hoffer has "called in people from different branches to talk and also to let it be known that I have a modest director's reserve fund, a little extra to prime the pump for projects, particularly those with collaborative components. They're writing proposals to me," he said, crediting NIDA director Alan Leshner with having provided him with the discretionary funds. A direct funding line from the SD to independent investigators, another panel suggestion to which Hoffer subscribes, is actually also in line with "new winds blowing through all of NIH that independent investigators ought indeed be independent, free to work on projects of their choosing." Scrutiny by the Board of Scientific Counselors, he added, is the quality-control mechanism for their research. "We formed an implementation committee, to which the branch chiefs will have input, that will report to Dr. Leshner and Dr. Michael Gottesman [deputy director for intramural research] by October 1." Hoffer also responded with alacrity to the panel's exhortation that a permanent clinical director be found to replace the nearly five-year rotating directorship that had left the clinical research arm of the intramural program dangling. "Jean-Luc Cadet, a clinician-scientist and intramural section chief, is our new clinical director," he said, adding that filling the two branch chief vacancies awaits "overall restructuring" of the IRP that targets more collaborative and translational research. "We don't know yet how those two branches will fall out," he said. He estimated that the reorganization would take six months to a year. He and Cadet, Hoffer said, are working to draw together another extramural panel to evaluate exclusion and inclusion criteria for clinical trials. He expressed uncertainty regarding the wisdom of the review panel's suggestion that clinical investigators be involved in recruiting for their own trials. Regarding the panel's observations on the ethnic mismatch of NIDA clinical investigators and the 80% African-American study population, Hoffer noted that the study population reflects the demographics of the Baltimore area, where NIDA's Addiction Research Center is located, as well as the demographics of that segment of the population willing to participate in research - not the demographics of addiction in this country. "I am committed to diversity in the patient and investigator pool," he added, noting, however, that there is currently only one other African-American clinical investigator in the IRP in addition to Cadet. PROJECTIONS Staying in Baltimore seems not only inevitable - "Bethesda is very crowded" - but also desirable. "We have good space here, and we're planning research on the genetics of drug abuse with NHGRI's Center for Complex Heritable Diseases, which is right here." The recommendation that NIDA and its other Baltimore neighbor, NIA, share resources is especially appealing to Hoffer. "My background is in aging research, and NIA's scientific director, Dan Longo, and I have started a series of discussions with the directors of our institutes and with Dr. Varmus. I'm not sure where it will all go, but I'm certainly enthusiastic. NIDA and NIA have common interests in molecular biology and gene sequencing, in animal research - and a common vivarium makes sense - and collaboration with NIA scientists only 50 paces away would be even better than the short walk we now have." He hesitated to stipulate scientific objectives for NIDA's IRP, explaining that he's a "firm believer in investigator-initiated research." He sees a general need for more translational research in treatment and prevention - especially in cocaine-addiction therapies and methamphetamine-addiction prevention - and more collaborative research with other neuroscience institutes. "Addiction is a brain disease, like schizophrenia and Parkinson's disease," he said. He pointed to the need for more research in fundamental neuroscience - a field with which he has more than passing familiarity. Hoffer's Catalyst interview was by phone at the end of one of the days of the Gordon research conference on catecholamines, where he presented a talk on his research on dopamine neuronal plasticity and development and was a discussant at another session on neuroimaging applications in addiction research. He fully intends to continue his research. "I would not have taken this job otherwise," he said, adding that he's "hoping to stay at NIH indefinitely, as long as the Board of Scientific Counselors is happy with me." - Fran Pollner

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