C. Kumar N. Patel

Both the pace and the scale of research are increasing in all sciences, especially the biological and medical disciplines. There are two forces at work. First, humans around the world face “grand challenges ” from infectious diseases that involve large populations of people and/or significant numbers of genetic variations. Because of their sheer size and risk, such problems justify focused efforts to create and analyze enormous quantities of laboratory-based data. Second, the very nature of many of these diseases requires capabilities for rapid response from the research and clinical communities. The long-term societal costs for not being able to respond to these challenges are likely to be high. As a response to the perceived needs, relatively small efforts (composed of a few technicians working at the bench) are giving way to much larger automated laboratory efforts that analyze and generate quantities of information often amounting to petabytes (10¹⁵). Leading universities around the country, having seen what lies ahead, are struggling to respond by initiating high-throughput research and development programs for competing in the “post-genomics” era. The start-up costs for such programs can easily exceed $25 million over two to three years. The problem is that few, if any, government grants are available for intermediate-cost (e.g., user-centric as opposed to facilities-centric) research efforts. On the other hand, we have done well in the areas of small “single private-investigator” grants (PI-centric) and very large grants, which are directed toward construction, and in the operation of “one-of-a-kind” national efforts (facility-centric national efforts as characterized by synchrotron and neutron facilities, which are key for many biological studies).

Small-cost grants are plentiful and typified by RO1 awards from the National Institutes of Health (NIH). Generally speaking, such PI-centric awards provide less than $2 million dollars, span two to four years, and support one to three investigators. Large grants are not plentiful, but nonetheless allocate substantial amounts of national research expenditures and provide facilities support to a large number of PIs on a visiting basis. In contrast, intermediate-cost grants are relatively few and far between, sometimes approved in exceptional circumstances but never really sustained as a mechanism that meets a national need. Such user-centric awards would provide $25 million dollars, span four to five years, and support 10 to 15 investigators. The key difference between the traditionally large facilities-centric programs and the proposed user-centric programs is that the latter can be cloned and adapted to similar types of problems at many locations throughout the country. In this model the first-generation facility serves as a prototype or shakedown, with second-generation facilities costing far less. A cutting-edge program at one institution can thereby seed innovative programs at others.

Large-cost grants are represented by line-item expenditures in congressional budgets and are targeted to specific government agencies. Such funding arises from efforts drawn out over extended periods of time and involving scientific consensus, congressional testimony, and commissioned studies. Such facility-centric awards often provide over $50 million, have buildup times of three to five years before becoming operational, support teams of many simultaneous users, and are national in scope. Because of its size and operational complexity, the one-of-a-kind facility cannot be physically moved or easily cloned. Various Department of Energy (DOE) -based synchrotron and neutron sources have such features; so does the NIH-based National Human Genome Research Institute.

It is clear that many of the problems discussed during the colloquium “Automation in Threat Reduction and Infectious Disease Research: Needs and New Directions” fall into the category of intermediate-cost grants. It also is clear that building new automated high-throughput laboratories is scientifically and technically feasible. Such intermediate-scale resources would take advantage of existing know-how, would be operational within one to two years, and would enable new solutions to grand challenges. There is a clear and present national need to address the policy vacuum for providing such intermediate-scale grants. That such a hole exists in the national granting process is clearly evidenced from data gathered from NIH, DOE, and the Department of Defense (DOD).

I believe the topics covered in this volume will give elected representatives and high-level federal officials sufficient ammunition to move forward. Most of the infectious disease, food safety, and bioterrorismrelated

FIGURE 1.3 Distribution of DOE funds by grant size (average duration three years).

related applications discussed are for the public good and therefore not in direct competition with the private sector. With the current wave of economic prosperity and sharp reductions in the federal deficit, the time is doubly right to facilitate intermediate-cost grants.

I would choose compelling new directions that serve as test cases and within the next one to two years would allocate up to 10 intermediate-cost grants at $25 million each. Appropriate national committees such as those supported by the National Research Council should evaluate the outcome and effectiveness of such grants, since this funding mode is a departure from the business-as-usual mode. If a thorough review confirms that such grants have catalyzed tangible benefits, a strong case can be made for continuation of intermediate-cost grants. The $125 million to $250 million expenditure would then be a wise investment and a sound experiment in scientific policy.