Center for Biological Transformation

[Front row, seated from left to right: Dr. Paul Turner (Director), Dr. Margaret Riley , Dr. Debra Bessen, Caroline Obert, Carla Goldstone;

Middle row, from left to right: Jeffrey Huckaby, Dr. Milind Chavan, Siobain Duffy, Dr. Susanna Remold, Lisa Nigro, Alicia Bennett, Cynthia Winkworth;

Back Row, from left to right: Ben Kirkup, Dr. Remy Froissart, Dr. Kara O’Keefe, Dr. John Wertz, Hamid Rafi, Chijioke Okeke, David Kysela.]

YIBS Center for Microbial Diversity

The Yale Institute for Biospheric Studies Center for Microbial Diversity’s mission is to apply our understanding of microbial ecology, evolution and diversity to address human health and ecological concerns. To this end the Center for Microbial Diversity (CMD) is coordinating the efforts of the wealth of existing Yale microbial-minded faculty to address such concerns in a synthetic and cross-disciplinary way. The first concern the Center will tackle poses a truly a life-threatening challenge. Can we apply microbial evolutionary and ecological information to address one of the primary and increasing threats to human health; the emergence of multiply-resistant pathogenic bacteria?

Within the next 15 years, the death toll due to bacterial infection will skyrocket and no new ‘magic bullet’ is on the horizon. Every new antimicrobial we find, design or develop will encourage the emergence of already existing resistant microbes. The spread of this resistance to human pathogens is then simply a matter of time and intensity of human-mediated selection (by over-use and misuse of antibiotics). To address this concern will require more than simply developing a larger arsenal of antibiotics. It will take more than reinforcing to the medical community (and the public) the importance of following rationale guidelines for proper antibiotic use. Long-term solutions demand the coordinated efforts of epidemiologists, population geneticists, microbial physiologists and ecologists as well as engineers, physicians and clinicians. Proposed solutions must gain acceptance from the pharmaceutical and agricultural companies and politicians. Physicians and other health workers must be convinced to employ these novel solutions and society at large must be willing to accommodate and accept the changes in current health practices required. There are no existing programs at NIH or NSF, no national centers or even university departments that have attempted to coordinate such a multidisciplinary effort to tackle this challenging and critical concern.

The Center for Microbial Diversity will take a first step towards addressing this challenge by bringing together Yale researchers as well as representatives from Connecticut-based pharmaceutical companies and physicians and clinicians from the Yale-New Haven hospital to define the existing problem, to view the problem from a variety of perspectives and to generate research strategies aimed at novel, long-term solutions. What we require are truly novel approaches to solving this critical national and worldwide need. One such solution involves the development and use of narrow spectrum, rather than the traditional broad spectrum, antibiotics. Such a switch would ensure a longer shelf life per drug, reduce the intensity of selection for any particular resistance mechanism and allow the patient to retain her healthy microbial communities and therefore reduce the rate of nosocomial infections. This solution makes perfect sense from an ecological and evolutionary perspective. However, implementing such a solution creates an extraordinary challenge. First, narrow spectrum drugs must be discovered or developed (which Yale researchers are actively pursuing). Second, appropriate diagnostics are required for rapid and specific pathogen diagnosis in the hospital (a procedure currently avoided with the use of broad spectrum antibiotics). Third, application of evolutionary and ecological theory is required to design the most effective strategy of administration to avoid or delay the emergence of resistance. Fourth, the pharmaceutical companies must be convinced that production of such drugs is in their long-term financial interests. I will stop short of including the steps involved in the regulation and enforcement of such an approach.

In this example, the role of the CMD is to focus its resources on enabling and coordinating these disparate stages of development. It will provide resources to aid in discovery and/or development of narrow spectrum antimicrobials and will initiate partnerships with pharmaceutical companies to explore the potential of such drugs in the market and the requirements for mass production. The Center will enable discussions between University and pharmaceutical researchers and clinicians to determine methods for rapid diagnosis to identify specific pathogens in real time in a hospital setting. This series of steps represents just the tip of the iceberg in achieving the desired long-term solutions, but clearly represent the cross-disciplinary nature and new pathways of communication required.

The CMD has an integrated educational mission. First, there is the traditional approach of developing courses to train our undergraduates, medical students and physicians about the seriousness of this health concern and the absolute requirement for a change in our current practices to achieve a long-term solution. One such graduate course already exists: Ecology and Evolution of Infectious Disease. However, it is critical that we target a broader audience. The center is currently developing a course for non-science majors that will address more generally the role of microorganisms in our modern world, from human health and bioterrorism to the health of the biosphere. A second, novel educational approach involves the development of a series of workshops to serve in the education of researchers and clinicians in pharmaceutical companies, hospitals and governmental agencies, such as the CDC or NIH, as well as the general public. These workshops will not only educate the participants about the problem and our proposed solution, but will also continuously supply the center with new perspectives from the field about alternative solutions to consider.

The newly created Center for Microbial Diversity has set for itself an extraordinary challenge. There are no existing solutions to the antibiotic resistance emergency. No magic bullets are in the pipeline. With the breadth of microbial-minded researchers at Yale and with the development of strong ties between Yale faculty and Connecticut-based pharmaceutical companies, health workers and legislatures we are poised to meet this critical challenge.