The Impact of the NIH Roadmap in Shaping Dental Research in the 21st Century

In May 2002, new NIH director Elias A. Zerhouni, M.D. launched a series of meetings to chart a "roadmap" for medical research in the 21st century. At these meetings, over 300 leaders from various fields of science helped to identify the major opportunities and existing gaps in biomedical research that no single NIH institute could pursue alone but that the agency as a whole must address to make the biggest impact on the progress of medical research. Although a great deal of background material is available about the NIH Roadmap [see, for example, Science 302, 28-29 (2003) or visit http://nihroadmap.nih.gov, little has been written about the potential impact of the NIH Roadmap in shaping dental research during the 21st century. Recently, the Inside Scoop spoke to NIDCR director Lawrence Tabak, D.D.S., Ph.D. to hear his thoughts on the initiative and what it means for the oral health research community.

I think we all recognize the tremendous progress that has taken place in science over the past several years. Biological problems that were seemingly intractable just five years ago are now much better defined and potentially understandable. With this progress, the scale and stakes of our research have now grown so much more complicated, and I think it became apparent to the NIH leadership that the future required a scale of science that was so broad that no one institute or center could possibly hope to meet the challenge. So, a truly trans-NIH strategy became necessary to meet scientific needs of the new century.

Certainly. The accelerator analogy is one that Dr. Zerhouni has used frequently, and it is quite apropos. When all is said and done, I think the fundamental question here is: Now that we have the opportunity to make great progress in understanding disease, do we want to reach our goal of targeted, molecular based treatments in 2050? Or, do we want to reach it in 2010? Obviously, the latter is where everybody wants to aim.

First a little background. For the past half century, NIDCR has funded the overwhelming majority of oral, craniofacial, and dental research in this country. But, as a smaller institute, we have been unable to deliver to our community some of the infrastructure needs that are so essential to move the research enterprise forward. These include a variety of computational tools, large-scale screening of small molecules, clinical trials network, and so on.

With the NIH Roadmap, everything changes. Our traditional community gains the unique opportunity to integrate with the whole NIH community in the areas that I just mentioned and more. That's why I see virtually every Roadmap initiative as a tremendous opportunity for oral health researchers to be able to participate on a much larger scale than ever before. At NIDCR, we are excited about this opportunity for the community. The Roadmap is timely, and it's exactly what we need.

What's also interesting, the Roadmap has catalyzed the institute's need to get our community in place so that we can play in the larger field. Let me give you an example. One of the Roadmap initiatives relates to integrating existing practice-based clinical research networks under one organizational umbrella. These networks have existed in some areas of medical science for years. Although oral health researchers have had an interest in establishing a comparable network, they have not yet moved in this direction. That's why NIDCR rapidly issued an initiative to establish practice-based networks in oral health. By the time the integration and link up of existing medical-based networks has coalesced via the NIH Roadmap, we will have a viable network of our own that would be allowed to participate in this arena. The Roadmap catalyzed us to do something that probably was a bit overdue, and that is a good thing.

Absolutely. Heretofore, I think many members of our traditional research community have somehow thought that, unless the "DE" designation for NIDCR was present, they need not apply. What we're trying, through a variety of means, is to encourage our investigators to apply actively for the Roadmap initiatives. We feel that our traditional members will bring a rather unique perspective on anything that is submitted and will compete favorably. The Roadmap opens the door to communities, such as ours, that have tended to focus predominantly on one NIH institute. Roadmap RFAs or RFPs will be designated as "RM" and will be managed by a consortium of institutes, including NIDCR.

Some scientists have assumed the biomedical research community as a whole isn't interested in oral health. So, unless it is an NIDCR-sponsored initiative, they won't receive funding. I think the Roadmap is just a wonderful conduit to break down these artificial cultural barriers. Having in my former life in academia reviewed grants for NIDCR and other NIH institutes, I can tell you that they very much were artificial. With the Roadmap, all disciplines will get into the mix and participate on a level playing field.

That's absolutely right. It's also another reason why the members of our community should respond to these initiatives. Their investigative approach in many cases will be dramatically different than their medical colleagues, and I think will only serve to strengthen the overall science that can be accomplished.

For example, it's become very fashionable in the study of infectious disease to talk about biofilms. Well, dentists have known about biofilms since the time of Lowenhoek. Back then, we called it "dental plaque." But, because the oral cavity is so readily accessible, there are certain types of real time observations that can be made using the mouth as a model that would be extremely difficult to do on other mucosal surfaces, for example. We think oral health researchers have an enormous set of new and novel approaches to give to the medical sciences. So, we really are anxiously looking forward to their participation.

This is really an attempt to expand our molecular parts list. The Human Genome Project succeeded in decoding the so-called "blueprint of life." Now that we know where all of the genes are, the next set of challenges - and they are formidable - will be to understand how all of the genes interact with one another. Moreover, we'll need to know how the protein products of these genes interact with one another. There also are non-proteinaceous biologicals, such as carbohydrates and lipids, which are sort of the third and fourth level of the molecular parts list. We'll need to understand them, too.

The Roadmap aims to complete the molecular catalogue. But, much more importantly, it will allow scientists to begin to piece together how these things interact and influence one another as an integrated system. Within this system, we'll need to understand the temporal and spatial qualities of these interactions. So, that's very formidable - but certainly very exciting.

As part of this area, a program will be established to screen small molecules. Some have mistakenly assumed this is really a drug-discovery program. In point of fact, it's not. It will provide a new set of small molecules as tools for basic and translational scientists, who have come to realize that they need additional tools to perturb biological systems to get a better understanding of their function. Some people have called this "chemical genomics." Old-time pharmacologists would just call it "pharmacology." The point is it is really designed to provide a new toolkit, and I think that is in part why people from Big Pharma have been so encouraging. It's the research that they would never be able to do on such a large scale. But clearly the fundamental insights that would be gained can greatly enhance drug discovery, which is what they do best. So, I think this is a particularly synergistic and exciting model.

In our community, think of the complicated events that are required to build a head. Small molecule perturbants will be necessary to dissect the regulatory circuitry of this process. Understanding pain circuitry could be greatly influenced by small molecules. Signal transduction in salivary gland secretion could also be helped in a great way. There are many, many reasons why this would be a particularly good opportunity for the members of our traditional community.

During the planning of the NIH Roadmap, I was very fortunate to co-chair a subsection on interdisciplinary research. We recognized that NIH has been extremely good at supporting multidisciplinary research. That's when people from one or more disciplines come together, tackle a common problem, then sort of go off and remain biochemists or physiologists or psychologists or whatever may be their primary field of interest. What this is trying to do is catalyze the formation of interdisciplinary teams. Interdisciplinary science, like the multidisciplinary approach, brings together people from various disciplines. The difference is: What emerges from interdisciplinary research is not problem solving, in the sense that everybody leaves unchanged by the experience. Rather, interdisciplinary science provides the genesis of a new discipline. That is when you get a quantum leap forward in science. For example, think about the world 25 years ago before neuroscience was a discipline. Now, it's one of the largest biomedical disciplines.

Again, as oral health researchers, we have the opportunity to contribute to the formation of some new interdisciplinary disciplines. Part of it relates to the unique tools that we bring to the table, and the fact oral health researchers have been working in teams for decades. Truly, this is a unique opportunity for our traditional community to step up and be well represented in the new research teams of the future. Most of the diseases that we deal with are complex in nature. Therefore, by their very nature, they require interdisciplinary approaches. So, I think there are some really great opportunities.

Yes. That culture exists both within the NIH and at universities. In my former life at a university, I can tell you as a member of tenure and promotion committees, great stock is given to peer review. The individual grant, the RO1, is sort of seen as the seal of approval that one needed to get before one could be considered for a promotion or a tenural decision. Universities struggle with what to do with all of the co-investigators, and that is, in part, exacerbated by some of the ways that NIH has historically gone about classifying everybody but the principal investigator of the grant.

So, I think working together with universities, we can come up with logical ways of apportioning appropriate credit to the other members of the research team. Because as teams get larger and each member will make his or her own unique contribution, we've got to recognize and, at some level, quantify how these different accomplishments will be made.

Now, other forms of science have somehow done this. Take high energy physics, for example. There will be literally hundreds of people listed on a publication. Somehow they all thrive and do well. So, we need to look to other types of science for ways to overcome some of these issues. At NIH, we are working very hard on some of the mechanical issues that are, in part, responsible for some of these issues. And I think we are coming up with some reasonable solutions, which will be thoroughly vetted through the extramural community before changes are initiated.

Well, of course, this is the area where the rubber meets the road. Everybody understands that NIH's mission is to improve health, and it is so dependent upon our clinical research efforts. Clinical research, as is true of most things, has gotten so much more complex in recent years. We now can propose studying novel, extremely complex interventions that could have been only dreamed of five or ten years ago. As a result, we need to become much more sophisticated in how we do clinical research in general and clinical trials in particular. This has led to a bit of discordance amongst agencies and their respective interpretations of some guidelines and rules, such as the requirements for reporting adverse clinical events, human subjects protections, and privacy and conflict of interest policies for electronic data submission.

What this set of initiatives will do is, first, provide a basis to harmonize these guidelines across agencies. It also will provide a more coherent and expanded way to foster collaboration, which I now see as a real must at universities. As part of the initial Roadmap analyses, I can share with you that this need for harmonization of clinical rules and regulations was number one on virtually everybody's list, including basic scientists. So, everybody understands that this is a good one.

The other elements are things that I think will dramatically benefit our traditional community. NIH wants to provide a permanent infrastructure for clinical trials. That is, these individual sites will NOT assemble and disassemble every time a clinical trial ends. NIH plans to create individual nodes around the country, much like the cooperative groups that are in place for cancer researchers.

Correct. I imagine that eventually a public-private partnership will have to occur to enhance those nodes, allowing either pharmaceutical or biotechnology companies to become engaged at some levels. The reason this is so important, particularly for our community, is the expense of clinical trials is largely driven by the infrastructure needs. You depend on a particular application to recreate the infrastructure each and every time that a new clinical trial is conceived. You quickly run out of resources. Even the mid-sized institutes have these problems. So, I think there will be a wonderful value added to assure the inter-operability of the different nodes and their continued maintenance over time, which, in the long run, will be less expensive.

I think, ultimately, that's the way it is going to play out. But I think the initial intent of the initiative will be to establish and sustain the nodes. Then, subsequently, I think that's how the initiative will play out.

So, the initiative is still evolving?

That's right.

In summary, then, you see the NIH Roadmap as a great opportunity for the dental research community?

I think this is a unique opportunity for the traditional NIDCR community. I encourage all of our colleagues to become active "roadies," as we call them here, and, to contact program staff, if they have any questions about how their idea might best fit in. Certainly, we look forward to seeing some wonderful applications from those interested in oral health. Now's the time to get on the train before it leaves the station.

February 2004