By Rich McManus

On the Front Page...

It might not be quite as detailed, yet, as the Rand McNally version, but the "NIH Roadmap" — an elucidation of the need for speed in making discoveries and applying them to patient care — was unveiled at length at the 86th advisory committee to the NIH director meeting June 30 on campus. NIH director Dr. Elias Zerhouni introduced the initiative then let three institute directors carve turns around its major features: new pathways for discovery, the shape of future research teams and revitalized clinical research.

Continued...

Before embarking on the tour, Zerhouni gave his customary wrap-up of major campus issues of the past 6 months since the ACD last convened. The President's FY 2004 budget request for NIH stands at $27.9 billion, or $549 million more than in FY 2003, he reported. This represents an overall increase of around 2.0 percent. The House's FY04 markup is the same as the President's and the Senate figure is $319 million more than the President's, offering a $1 billion, or 3.7 percent, increase. "Obviously there needs to be reconciliation between the two budgets," Zerhouni said, "and we'll be watching the issue closely."

Scrutiny from Inside and Out

Also on Capitol Hill, House and Senate committees are reviewing NIH programs and management, Zerhouni noted. NIH is in the midst of a series of reauthorization hearings; the agency was last authorized in 1993.

The director said a blue-ribbon panel has been named to maximize the effectiveness of the new Mark O. Hatfield Clinical Research Center, which is set to open next summer. Also, the Institute of Medicine is nearing completion of a report on how NIH is organized, Zerhouni related. Meanwhile, he has appointed an "NIH steering committee" composed of select institute and center directors who serve 3-year terms and will "focus more extensively on issues that affect NIH." The committee's goal is to expedite decision-making, Zerhouni explained. "We need more coordinated and coherent decisions because with growth has come complexity, and that has had a tendency to slow us down. So we want to streamline that."

Zerhouni paused to give a brief primer on A-76 activities at NIH, reemphasizing that the agency "needs to absolutely do the best we can to win competitions [with private contractors]...It is very hard for me to see how any outside entity could compete with us, if we do our jobs properly."

He also mentioned restructuring efforts mandated by the Department of Health and Human Services, but said NIH has been able "to define its own level of interaction to the greatest extent possible."

Reporting on home-grown restructuring was NIH deputy director Dr. Raynard Kington, who is also head of ARAC, a new administrative restructuring advisory committee that, since April, has formed 8 working groups — each chaired by an institute or center director — focusing on such areas as budget, EEO, information technology and human resources. Kington conceded, "In an ideal world, this [effort] wouldn't co-occur with A-76." He said the working groups issued their reports to him in June and that NIH is currently in discussions with the Office of the Secretary and would have "a solid picture of where we want to go" within a few weeks.

The director's advisors — several of whom are new to the ACD, and six of whom were absent for various reasons (the meeting had been rescheduled from June 5) — had comments during Zerhouni's update. New member Dr. Linda Waite, a professor at the National Opinion Research Center at the University of Chicago, asked whether A-76 would affect the NIH intramural program. NIH deputy director for intramural research Dr. Michael Gottesman said it would, but not at the leadership level. Dr. Donald Wilson, dean of the School of Medicine at the University of Maryland, Baltimore, who was attending his final ACD meeting, wanted to know the fiscal impact of A-76. Charles "Chick" Leasure, Jr., NIH deputy director for management, said there are costs in the short-term — he said it costs from $2,000 to $5,000 per position studied — but said that "over the long-term, we hope to get that money back." Dr. Thomas Cech, president of the Howard Hughes Medical Institute, asked if Zerhouni had any new thoughts about how to protect the number of new and competing extramural grants in the post-doubling era. The director replied, "We have tried to engineer somewhat of a softer landing...Our goal is to maintain the number of new grants."

The morning portion of the meeting concluded with reports from Dr. Ruth Kirschstein, senior advisor to the NIH director, on postdoctoral training and career development, and from Dr. James Battey, Jr., who gave an update on NIH actions in stem cell biology. Kirschstein said a working group of the ACD would meet Sept. 11-12 at the Cloister (Bldg. 60) to address the problem of an ever-lengthening postdoctoral training period that has left some young scientists in a kind of limbo. She said NIH would host a summit next spring on this issue, with input from IOM and the National Academy of Sciences, as well as from a new group, the National Postdoctoral Association. Many around the table hinted that a new system of training should be developed, but there were questions about just how strong a role NIH could play. Cech stated bluntly that many mentors may need "behavior modification" to more honestly and successfully train postdocs, so that training stints don't drag on interminably.

NIDCD director Battey, fresh from a series of June symposia on stem cells, reported on that topic for ACD members, noting that, of the 78 human embryonic stem cell lines listed on the federal registry, 12 are now available for use. NIH spent $370 million in FY02 on all forms of stem cell research, he said, $10 million of which was devoted to human embryonic stem cells (hESC). Former Sen. Connie Mack of Florida, a new ACD member, asked whether funding for hESC research might fall victim to political concerns, but Battey assured him, "There is no indication that funding will become less permissive in the future." Battey did warn that intellectual property and cost issues — a vial of stem cells can cost up to $5,000, he said — could also be potentially discouraging to investigators, in addition to the widely discussed moral and ethical concerns about hESC work. The recent stem cell workshops, he added, only "reinforced my impression that we're still very much in the basic phase" of hESC research.

On The Road Again

When ACD members returned from a quiet and collegial lunch at Stone House, Zerhouni led off an afternoon session devoted entirely to his roadmap initiative.

The stakes in the initiative, both financial and human, are high, he said. "Fourteen percent of the GDP (gross domestic product) is related to health care," he said. A potential 20 percent reduction in health care costs is foreseen if the roadmap objectives are met, he added. The roadmap effort, now just a year old, aims to accelerate the pace of discovery in the life sciences, urges quicker translation of therapies from bench to bedside, and expresses an urgent need for novel approaches that are "orders of magnitude more effective than current approaches."

Distinguishing a map from a strategic plan, Zerhouni said, "Strategic plans tend to look great from 50,000 feet — and they make great public relations — but they are seldom realistic." He offers instead a matrix approach that defines challenges, identifies roadblocks, poses solutions to obstacles, and responds to NIH's mission to do what only it can do. He envisions a series of sequential actions leading eventually to the ultimate goal — doing the readily doable first, then scaling higher.

Some 16 working groups, chaired mostly by IC directors, have been laboring for almost a year now, chipping away at three themes that emerged during colloquies with authorities from around the country: new pathways to discovery, research teams of the future, and re-engineering the clinical research enterprise. Congress, too, is aboard for the roadmap journey, Zerhouni reported: the FY04 budget provides $45 million to the Director's Discretionary Fund, up from $25 million in FY03, to pursue roadmap goals.

NIDDK director Dr. Allen Spiegel gave an overview of the types of "building blocks" needed to forge new pathways of discovery. These include all functional elements in genomic DNA, all RNA species, all proteins, all carbohydrates, lipids and metabolites, and involve multiple organisms. "This project vastly dwarfs the Human Genome Project, in terms of cataloging," he said.

He also described a "molecular libraries" initiative that would take advantage of genome project data and new expertise in combinatorial chemistry, compound availability and robotic technology. Combined with advances in molecular imaging, the libraries initiative could result in an era of pre-clinical disease detection, personalized and targeted therapeutics and, eventually, a sort of "systems biology" understanding of how organisms function in both health and disease, said Spiegel.

And who is going to usher in this brave new world of ambitious medicine? NIDCR director Dr. Lawrence Tabak made the case for a new kind of science dependent on multidisciplinary teams, which is a radical departure from the culture of the independent investigator, around whom an entire system of rewards and goads has been constructed over decades.

Rounding out the roadmap tour was NIAMS director Dr. Stephen Katz, whose discussion of revamping and revitalizing clinical research concluded with his vision of "nirvana: a translational research infrastructure which facilitates the integrated, smooth, safe and efficient transition from bench to bedside and back." Each one of those adjectives came with its own sub-agenda, including establishment of some 20-30 Regional Translation Research Centers, with an associated trove of research core services, as well as improved assessment of clinical outcomes. Katz said there would be great value in establishing a National Clinical Research Corps, backed up by something called NECTAR, the National Electronic Clinical Trials and Research Network, which would tie far-flung sites and programs together.

The three roadmap presentations were so data-heavy and comprehensive that the advisors were momentarily speechless. Zerhouni rallied them with a series of provocative questions and observations, such as that "fewer than 3 percent of those eligible for enrollment in clinical trials now participate, with few exceptions."

Perhaps summing up the group's response was Dr. Steven Paul, who used to be scientific director at NIMH but who now heads research and development at Lilly Research Laboratories. "This is a very impressive set of goals, but the challenge now is how to see it through," he said. "It seems to me that the real heavy lifting starts now."