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Institute of Medicine (US) Forum on Microbial Threats. Microbial Evolution and Co-Adaptation: A Tribute to the Life and Scientific Legacies of Joshua Lederberg: Workshop Summary. Washington (DC): National Academies Press (US); 2009.

Cover of Microbial Evolution and Co-Adaptation

Microbial Evolution and Co-Adaptation: A Tribute to the Life and Scientific Legacies of Joshua Lederberg: Workshop Summary.

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Preface

The Forum on Emerging Infections was created by the Institute of Medicine (IOM) in 1996 in response to a request from the Centers for Disease Control and Prevention (CDC) and the National Institutes of Health (NIH). The purpose of the Forum is to provide opportunities for leaders from government, academia, and industry to meet and examine issues of shared concern regarding research, prevention, detection, and management of emerging or reemerging infectious diseases. In pursuing this task, the Forum provides a venue to foster the exchange of information and ideas, identify areas in need of greater attention, clarify policy issues by enhancing knowledge and identifying points of agreement, and inform decision makers about science and policy issues. The Forum seeks to illuminate issues rather than resolve them; for this reason, it does not provide advice or recommendations on any specific policy initiative pending before any agency or organization. Its value derives instead from the diversity of its membership and from the contributions that individual members make throughout the activities of the Forum. In September 2003, the Forum changed its name to the Forum on Microbial Threats.

ABOUT THE WORKSHOP

To a great extent, the Forum on Microbial Threats (hereinafter, the Forum) owes its very existence to the life and legacies of the late Dr. Joshua Lederberg. Along with the late Robert Shope and Stanley C. Oaks, Jr., Lederberg organized and co-chaired the 1992 Institute of Medicine study, Emerging Infections: Microbial Threats to Health in the United States. The Emerging Infections report helped to define the factors and dynamic relationships that lead to the emergence of infectious diseases. Its recommendations addressed both the recognition of and interventions against emerging infections as well as identified major unmet challenges in responding to infectious disease outbreaks and monitoring the prevalence of endemic diseases. This report ultimately led to the Forum’s creation in 1996. As the first chair of the Forum, 1996–2001, Lederberg was instrumental in establishing it as a venue for the discussion and scrutiny of critical—and sometimes contentious—scientific and policy issues of shared concern related to research on and the prevention, detection, and management of infectious diseases and dangerous pathogens.

Lederberg’s long shadow may readily be appreciated in the Forum’s 2005 workshop, Ending the War Metaphor: The Changing Agenda for Unraveling the Host-Microbe Relationship. Its central theme was derived from a comprehensive essay that he published several years earlier in Science entitled “Infectious History.” Under the heading, “Evolving Metaphors of Infection: Teach War No More,” Lederberg argued that “[w]e should think of each host and its parasites as a superorganism with the respective genomes yoked into a chimera of sorts.” Thus began a discussion that developed the concept of the microbiome—a term Lederberg coined to denote the collective genome of an indigenous microbial community—as a forefront of scientific inquiry.

Having reviewed the shortcomings and consequences of the war metaphor of infection Lederberg suggested, in the same essay, a “paradigm shift” in the way we collectively identify and think about the microbial world around us, replacing notions of aggression and conflict with a more ecologically—and evolutionarily—informed view of the dynamic relationships among and between microbes, hosts, and their environments. This perspective recognized the participation of every eukaryotic organism—moreover, every eukaryotic cell—in partnerships with microbes and microbial communities, and acknowledged that microbes and their hosts are ultimately dependent upon one another for survival. It also encouraged the exploration and exploitation of these ecological relationships in order to increase agricultural productivity and to improve animal, human, and environmental health.

More than a century of research, sparked by the germ theory of disease, underlies our current appreciation of microbe-host-environment interactions. Our “war” on infectious microbes has restricted the spread of several pathogens and drastically reduced the burden of human disease, but the tide of the human conquest shows many signs of turning. Over the past 30 years, 37 new human pathogens have been identified as disease threats, and an estimated 12 percent of known human pathogens have been recognized as either emerging or reemerging.1 Due in large part to the HIV/AIDS pandemic, the number of deaths in the United States attributable to infection, having fallen steadily since the turn of the century, began to increase in the early 1980s. Infectious diseases continue to cause high morbidity and mortality throughout the world, particularly in developing countries. In 2001, infectious diseases accounted for an estimated 26 percent of deaths worldwide.

Clearly, a reconsideration of our interactions with pathogenic microbes is warranted, and it must be based on a better understanding of host-microbe relationships in general. Estimates indicate that 90 to 99 percent of the approximately 1014 cells that comprise a healthy human body belong to the complex microbiota that share our space. Only a small fraction of the roughly several thousand bacterial species that inhabit our bodies cause illness; very little is known about the other nonpathogenic bacteria, or even about microbes that in most cases cause chronic, subclinical disease in humans, and that only occasionally produce illness and death. Research into our own microbial ecology and that of our fellow eukaryotes, including plants, appears certain to reveal new strategies for preventing and treating a broad spectrum of infectious disease.

Dr. Lederberg’s death on February 2, 2008, marked the departure of a central figure of modern science. It is in his honor that the Forum convened this public workshop on May 20 and 21, 2008, to examine Dr. Lederberg’s scientific and policy contributions to the marketplace of ideas in the life sciences, medicine, and public policy. The agenda for this workshop demonstrates the extent to which conceptual and technological developments have, within a few short years, advanced our collective understanding of microbial genetics, microbial communities, and microbe-host-environment interactions. Through invited presentations and discussions, participants explored a range of topics related to microbial evolution and co-adaptation, including methods for characterizing microbial diversity; model systems for investigating the ecology of host-microbe interactions and microbial communities at the molecular level; microbial evolution and the emergence of virulence; the phenomenon of antibiotic resistance and opportunities for mitigating its public health impact; and an exploration of current trends in infectious disease emergence as a means to anticipate the appearance of future novel pathogens.

As Adel Mahmoud, first co-chair of the Forum observed, “Joshua believed very strongly in the work of this Forum. He had great confidence in the ability of scientists and researchers to continue to solve some of the riddles that still confront science in the fight against infectious diseases. By remembering him with this tribute, we are also remembering the many things that his life and career can teach all of us. I hope that every time we meet at this Forum, Joshua Lederberg will be an inspiration and a reminder that our work can truly change the world, just as his life and career certainly did.”

It is to Josh’s life and living legacies that we dedicate this volume.

Footnotes

1

Merell, D. S., and S. Falkow. 2004. Frontal and stealth attack strategies in microbial pathogenesis. Nature 430(6996):250–256.

Copyright © 2009, National Academy of Sciences.
Bookshelf ID: NBK45706

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