National Research Council

Division on Earth and Life Studies

Institute of Medicine

Policy and Global Affairs

Board on Global Health

Board on Life Sciences

Forum on Microbial Threats

Committee on Science, Technology, and Law

When, in late 2011, it became public knowledge that two research groups had submitted for publication manuscripts that reported on their work on mammalian transmissibility of a lethal H5N1 avian influenza strain, the information caused an international debate about the appropriateness and communication of the researchers' work, the risks associated with the work, partial or complete censorship of scientific publications, and dual-use research of concern in general. Recognizing that the H5N1 research is only the most recent scientific activity subject to widespread attention due to safety and security concerns, on May 1, 2012, the National Research Council's Committee on Science, Technology and Law, in conjunction with the Board on Life Sciences and the Institute of Medicine's Forum on Microbial Threats, convened a one-day public workshop for the purposes of 1) discussing the H5N1 controversy; 2) considering responses by the National Institute of Allergy and Infectious Diseases (NIAID), which had funded this research, the World Health Organization, the U.S. National Science Advisory Board for Biosecurity (NSABB), scientific publishers, and members of the international research community; and 3) providing a forum wherein the concerns and interests of the broader community of stakeholders, including policy makers, biosafety and biosecurity experts, non-governmental organizations, international organizations, and the general public might be articulated. Perspectives on Research with H5N1 Avian Influenza: Scientific Enquiry, Communication, Controversy summarizes the proceedings of the workshop.

Scientific Inquiry, Communication, Controversy: Summary of a Workshop

Perspectives on Research with H5N1 Avian Influenza

Early detection is essential to the control of emerging, reemerging, and novel infectious diseases, whether naturally occurring or intentionally introduced. Containing the spread of such diseases in a profoundly interconnected world requires active vigilance for signs of an outbreak, rapid recognition of its presence, and diagnosis of its microbial cause, in addition to strategies and resources for an appropriate and efficient response. Although these actions are often viewed in terms of human public health, they also challenge the plant and animal health communities. Surveillance, defined as "the continual scrutiny of all aspects of occurrence and spread of a disease that are pertinent to effective control", involves the "systematic collection, analysis, interpretation, and dissemination of health data." Disease detection and diagnosis is the act of discovering a novel, emerging, or reemerging disease or disease event and identifying its cause. Diagnosis is "the cornerstone of effective disease control and prevention efforts, including surveillance." Disease surveillance and detection relies heavily on the astute individual: the clinician, veterinarian, plant pathologist, farmer, livestock manager, or agricultural extension agent who notices something unusual, atypical, or suspicious and brings this discovery in a timely way to the attention of an appropriate representative of human public health, veterinary medicine, or agriculture. Most developed countries have the ability to detect and diagnose human, animal, and plant diseases. Global Infectious Disease Surveillance and Detection: Assessing the Challenges-Finding Solutions, Workshop Summary is part of a 10 book series and summarizes the recommendations and presentations of the workshop.

Assessing the Challengesâ¬"Finding Solutions: Workshop Summary

Global Infectious Disease Surveillance and Detection

Vector-borne infectious diseases, such as malaria, dengue fever, yellow fever, and plague, cause a significant fraction of the global infectious disease burden; indeed, nearly half of the world's population is infected with at least one type of vector-borne pathogen (CIESIN, 2007; WHO, 2004a). Vector-borne plant and animal diseases, including several newly recognized pathogens, reduce agricultural productivity and disrupt ecosystems throughout the world. These diseases profoundly restrict socioeconomic status and development in countries with the highest rates of infection, many of which are located in the tropics and subtropics. Although this workshop summary provides an account of the individual presentations, it also reflects an important aspect of the Forum philosophy. The workshop functions as a dialogue among representatives from different sectors and allows them to present their beliefs about which areas may merit further attention. These proceedings summarize only the statements of participants in the workshop and are not intended to be an exhaustive exploration of the subject matter or a representation of consensus evaluation. Vector-Borne Diseases : Understanding the Environmental, Human Health, and Ecological Connections, Workshop Summary (Forum on Microbial Threats) summarizes this workshop.

Understanding the Environmental, Human Health, and Ecological Connections: Workshop Summary

Vector-Borne Diseases

The emergence of severe acute respiratory syndrome (SARS) in late 2002 and 2003 challenged the global public health community to confront a novel epidemic that spread rapidly from its origins in southern China until it had reached more than 25 other countries within a matter of months. In addition to the number of patients infected with the SARS virus, the disease had profound economic and political repercussions in many of the affected regions. Recent reports of isolated new SARS cases and a fear that the disease could reemerge and spread have put public health officials on high alert for any indications of possible new outbreaks. This report examines the response to SARS by public health systems in individual countries, the biology of the SARS coronavirus and related coronaviruses in animals, the economic and political fallout of the SARS epidemic, quarantine law and other public health measures that apply to combating infectious diseases, and the role of international organizations and scientific cooperation in halting the spread of SARS. The report provides an illuminating survey of findings from the epidemic, along with an assessment of what might be needed in order to contain any future outbreaks of SARS or other emerging infections.

Preparing for the Next Disease Outbreak: Workshop Summary

Learning from SARS

National Academies of Sciences, Engineering, and Medicine

Board on Health Sciences Policy

Forum on Medical and Public Health Preparedness for Catastrophic Events

Forum on Drug Discovery, Development, and Translation

Emerging infectious disease threats that may not have available treatments or vaccines can directly affect the security of the world's health since these diseases also know no boundaries and will easily cross borders. Sustaining public and private investment in the development of medical countermeasures (MCMs) before an emerging infectious disease becomes a public health emergency in the United States has been extremely challenging. Interest and momentum peak during a crisis and wane between events, and there is little interest in disease threats outside the United States until they impact people stateside. On March 26 and 27, 2015, the Institute of Medicine convened a workshop in Washington, DC to discuss how to achieve rapid and nimble MCM capability for new and emerging threats. Public- and private-sector stakeholders examined recent efforts to prepare for and respond to outbreaks of Ebola Virus Disease, pandemic influenza, and coronaviruses from policy, budget, and operational standpoints. Participants discussed the need for rapid access to MCM to ensure national security and considered strategies and business models that could enhance stakeholder interest and investment in sustainable response capabilities. This report summarizes the presentations and discussions from this workshop.

Enabling Sustainable Capabilities Through Ongoing Public- and Private-Sector Partnerships: Workshop Summary

Rapid Medical Countermeasure Response to Infectious Diseases

Globalization is by no means a new phenomenon; transcontinental trade and the movement of people date back at least 2,000 years, to the era of the ancient Silk Road trade route. The global spread of infectious disease has followed a parallel course. Indeed, the emergence and spread of infectious disease are, in a sense, the epitome of globalization. Although some experts mark the fall of the Berlin Wall as the beginning of this new era of globalization, others argue that it is not so new. The future of globalization is still in the making. Despite the successful attempts of the developed world during the course of the last century to control many infectious diseases and even to eradicate some deadly afflictions, 13 million people worldwide still die from such diseases every year. On April 16 and 17, 2002, the Forum on Emerging Infections held a working group discussion on the influence of globalization on the emergence and control of infectious diseases. The contents of the unattributed sections are based on the presentations and discussions that took place during the workshop. The Impact of Globalization on Infectious Disease Emergence and Control report summarizes the presentations and discussions related to the increasing cross-border and cross-continental movements of people and how this could exacerbate the emergence and global spread of infectious diseases. This report also summarizes the means by which sovereign states and nations must adopt a global public health mind-set and develop a new organizational framework to maximize the opportunities and overcome the challenges created by globalization and build the necessary capacity to respond effectively to emerging infectious disease threats.

Exploring the Consequences and Opportunities: Workshop Summary

The Impact of Globalization on Infectious Disease Emergence and Control

Health and Medicine Division

On December 4â€"5, 2019, the National Academies of Sciences, Engineering, and Medicine held a 1.5-day public workshop titled Exploring the Frontiers of Innovation to Tackle Microbial Threats. The workshop participants examined major advances in scientific, technological, and social innovations against microbial threats. Such innovations include diagnostics, vaccines (both development and production), and antimicrobials, as well as nonpharmaceutical interventions and changes in surveillance. This publication summarizes the presentations and discussions from the workshop.

Proceedings of a Workshop

Exploring the Frontiers of Innovation to Tackle Microbial Threats

Beginning with the germ theory of disease in the 19th century and extending through most of the 20th century, microbes were believed to live their lives as solitary, unicellular, disease-causing organisms . This perception stemmed from the focus of most investigators on organisms that could be grown in the laboratory as cellular monocultures, often dispersed in liquid, and under ambient conditions of temperature, lighting, and humidity. Most such inquiries were designed to identify microbial pathogens by satisfying Koch's postulates.3 This pathogen-centric approach to the study of microorganisms produced a metaphorical "war" against these microbial invaders waged with antibiotic therapies, while simultaneously obscuring the dynamic relationships that exist among and between host organisms and their associated microorganisms-only a tiny fraction of which act as pathogens. Despite their obvious importance, very little is actually known about the processes and factors that influence the assembly, function, and stability of microbial communities. Gaining this knowledge will require a seismic shift away from the study of individual microbes in isolation to inquiries into the nature of diverse and often complex microbial communities, the forces that shape them, and their relationships with other communities and organisms, including their multicellular hosts. On March 6 and 7, 2012, the Institute of Medicine's (IOM's) Forum on Microbial Threats hosted a public workshop to explore the emerging science of the "social biology" of microbial communities. Workshop presentations and discussions embraced a wide spectrum of topics, experimental systems, and theoretical perspectives representative of the current, multifaceted exploration of the microbial frontier. Participants discussed ecological, evolutionary, and genetic factors contributing to the assembly, function, and stability of microbial communities; how microbial communities adapt and respond to environmental stimuli; theoretical and experimental approaches to advance this nascent field; and potential applications of knowledge gained from the study of microbial communities for the improvement of human, animal, plant, and ecosystem health and toward a deeper understanding of microbial diversity and evolution. The Social Biology of Microbial Communities: Workshop Summary further explains the happenings of the workshop.

Workshop Summary

The Social Biology of Microbial Communities

Pathogens transmitted among humans, animals, or plants by insects and arthropod vectors have been responsible for significant morbidity and mortality throughout recorded history. Such vector-borne diseases â€" including malaria, dengue, yellow fever, and plague â€" together accounted for more human disease and death in the 17th through early 20th centuries than all other causes combined. Over the past three decades, previously controlled vector-borne diseases have resurged or reemerged in new geographic locations, and several newly identified pathogens and vectors have triggered disease outbreaks in plants and animals, including humans. Domestic and international capabilities to detect, identify, and effectively respond to vector-borne diseases are limited. Few vaccines have been developed against vector-borne pathogens. At the same time, drug resistance has developed in vector-borne pathogens while their vectors are increasingly resistant to insecticide controls. Furthermore, the ranks of scientists trained to conduct research in key fields including medical entomology, vector ecology, and tropical medicine have dwindled, threatening prospects for addressing vector-borne diseases now and in the future. In June 2007, as these circumstances became alarmingly apparent, the Forum on Microbial Threats hosted a workshop to explore the dynamic relationships among host, pathogen(s), vector(s), and ecosystems that characterize vector-borne diseases. Revisiting this topic in September 2014, the Forum organized a workshop to examine trends and patterns in the incidence and prevalence of vector-borne diseases in an increasingly interconnected and ecologically disturbed world, as well as recent developments to meet these dynamic threats. Participants examined the emergence and global movement of vector-borne diseases, research priorities for understanding their biology and ecology, and global preparedness for and progress toward their prevention, control, and mitigation. This report summarizes the presentations and discussions from the workshop.

Global Health Impacts of Vector-Borne Diseases

Years of using, misusing, and overusing antibiotics and other antimicrobial drugs has led to the emergence of multidrug-resistant 'superbugs.' The IOM's Forum on Microbial Threats held a public workshop April 6-7 to discuss the nature and sources of drug-resistant pathogens, the implications for global health, and the strategies to lessen the current and future impact of these superbugs.

Implications for Global Health and Novel Intervention Strategies: Workshop Summary

Antibiotic Resistance

As the human population grows--tripling in the past century while, simultaneously, quadrupling its demand for water--Earth's finite freshwater supplies are increasingly strained, and also increasingly contaminated by domestic, agricultural, and industrial wastes. Today, approximately one-third of the world's population lives in areas with scarce water resources. Nearly one billion people currently lack access to an adequate water supply, and more than twice as many lack access to basic sanitation services. It is projected that by 2025 water scarcity will affect nearly two-thirds of all people on the planet. Recognizing that water availability, water quality, and sanitation are fundamental issues underlying infectious disease emergence and spread, the Institute of Medicine held a two-day public workshop, summarized in this volume. Through invited presentations and discussions, participants explored global and local connections between water, sanitation, and health; the spectrum of water-related disease transmission processes as they inform intervention design; lessons learned from water-related disease outbreaks; vulnerabilities in water and sanitation infrastructure in both industrialized and developing countries; and opportunities to improve water and sanitation infrastructure so as to reduce the risk of water-related infectious disease.

Global Issues in Water, Sanitation, and Health

Individually and collectively, resident microbes play important roles in host health and survival. Shaping and shaped by their host environments, these microorganisms form intricate communities that are in a state of dynamic equilibrium. This ecologic and dynamic view of host-microbe interactions is rapidly redefining our view of health and disease. It is now accepted that the vast majority of microbes are, for the most part, not intrinsically harmful, but rather become established as persistent, co-adapted colonists in equilibrium with their environment, providing useful goods and services to their hosts while deriving benefits from these host associations. Disruption of such alliances may have consequences for host health, and investigations in a wide variety of organisms have begun to illuminate the complex and dynamic network of interaction - across the spectrum of hosts, microbes, and environmental niches - that influence the formation, function, and stability of host-associated microbial communities. Microbial Ecology in States of Health and Disease is the summary of a workshop convened by the Institute of Medicine's Forum on Microbial Threats in March 2013 to explore the scientific and therapeutic implications of microbial ecology in states of health and disease. Participants explored host-microbe interactions in humans, animals, and plants; emerging insights into how microbes may influence the development and maintenance of states of health and disease; the effects of environmental change(s) on the formation, function, and stability of microbial communities; and research challenges and opportunities for this emerging field of inquiry.

Microbial Ecology in States of Health and Disease

Fungal diseases have contributed to death and disability in humans, triggered global wildlife extinctions and population declines, devastated agricultural crops, and altered forest ecosystem dynamics. Despite the extensive influence of fungi on health and economic well-being, the threats posed by emerging fungal pathogens to life on Earth are often underappreciated and poorly understood. On December 14 and 15, 2010, the IOM's Forum on Microbial Threats hosted a public workshop to explore the scientific and policy dimensions associated with the causes and consequences of emerging fungal diseases.

An Emerging Threat to Human, Animal, and Plant Health: Workshop Summary

Fungal Diseases

Globalization of the food supply has created conditions favorable for the emergence, reemergence, and spread of food-borne pathogens-compounding the challenge of anticipating, detecting, and effectively responding to food-borne threats to health. In the United States, food-borne agents affect 1 out of 6 individuals and cause approximately 48 million illnesses, 128,000 hospitalizations, and 3,000 deaths each year. This figure likely represents just the tip of the iceberg, because it fails to account for the broad array of food-borne illnesses or for their wide-ranging repercussions for consumers, government, and the food industry-both domestically and internationally. A One Health approach to food safety may hold the promise of harnessing and integrating the expertise and resources from across the spectrum of multiple health domains including the human and veterinary medical and plant pathology communities with those of the wildlife and aquatic health and ecology communities. The IOM's Forum on Microbial Threats hosted a public workshop on December 13 and 14, 2011 that examined issues critical to the protection of the nation's food supply. The workshop explored existing knowledge and unanswered questions on the nature and extent of food-borne threats to health. Participants discussed the globalization of the U.S. food supply and the burden of illness associated with foodborne threats to health; considered the spectrum of food-borne threats as well as illustrative case studies; reviewed existing research, policies, and practices to prevent and mitigate foodborne threats; and, identified opportunities to reduce future threats to the nation's food supply through the use of a "One Health" approach to food safety. Improving Food Safety Through a One Health Approach: Workshop Summary covers the events of the workshop and explains the recommendations for future related workshops.

Improving Food Safety Through a One Health Approach

In the past half century, deadly disease outbreaks caused by novel viruses of animal origin - Nipah virus in Malaysia, Hendra virus in Australia, Hantavirus in the United States, Ebola virus in Africa, along with HIV (human immunodeficiency virus), several influenza subtypes, and the SARS (sudden acute respiratory syndrome) and MERS (Middle East respiratory syndrome) coronaviruses - have underscored the urgency of understanding factors influencing viral disease emergence and spread. Emerging Viral Diseases is the summary of a public workshop hosted in March 2014 to examine factors driving the appearance, establishment, and spread of emerging, re-emerging and novel viral diseases; the global health and economic impacts of recently emerging and novel viral diseases in humans; and the scientific and policy approaches to improving domestic and international capacity to detect and respond to global outbreaks of infectious disease. This report is a record of the presentations and discussion of the event.

The One Health Connection: Workshop Summary

Emerging Viral Diseases

In recent years, a number of chronic diseases have been linked, in some cases definitively, to an infectious etiology: peptic ulcer disease with Helicobacter pylori, cervical cancer with several human papillomaviruses, Lyme arthritis and neuroborreliosis with Borrelia burgdorferi, AIDS with the human immunodeficiency virus, liver cancer and cirrhosis with hepatitis B and C viruses, to name a few. The proven and suspected roles of microbes does not stop with physical ailments; infections are increasingly being examined as associated causes of or possible contributors to a variety of serious, chronic neuropsychiatric disorders and to developmental problems, especially in children. The Infectious Etiology of Chronic Diseases: Defining the Relationship, Enhancing the Research, and Mitigating the Effects, summarizes a two-day workshop held by the Institute of Medicine's Forum on Microbial Threats to address this rapidly evolving field. Participants explored factors driving infectious etiologies of chronic diseases of prominence, identified difficulties in linking infectious agents with chronic outcomes, and discussed broad-based strategies and research programs to advance the field.

Defining the Relationship, Enhancing the Research, and Mitigating the Effects: Workshop Summary

The Infectious Etiology of Chronic Diseases

Over the past several decades, new scientific tools and approaches for detecting microbial species have dramatically enhanced our appreciation of the diversity and abundance of the microbiota and its dynamic interactions with the environments within which these microorganisms reside. The first bacterial genome was sequenced in 1995 and took more than 13 months of work to complete. Today, a microorganism's entire genome can be sequenced in a few days. Much as our view of the cosmos was forever altered in the 17th century with the invention of the telescope, these genomic technologies, and the observations derived from them, have fundamentally transformed our appreciation of the microbial world around us. On June 12 and 13, 2012, the Institute of Medicine's (IOM's) Forum on Microbial Threats convened a public workshop in Washington, DC, to discuss the scientific tools and approaches being used for detecting and characterizing microbial species, and the roles of microbial genomics and metagenomics to better understand the culturable and unculturable microbial world around us. Through invited presentations and discussions, participants examined the use of microbial genomics to explore the diversity, evolution, and adaptation of microorganisms in a wide variety of environments; the molecular mechanisms of disease emergence and epidemiology; and the ways that genomic technologies are being applied to disease outbreak trace back and microbial surveillance. Points that were emphasized by many participants included the need to develop robust standardized sampling protocols, the importance of having the appropriate metadata, data analysis and data management challenges, and information sharing in real time. The Science and Applications of Microbial Genomics summarizes this workshop.

The Science and Applications of Microbial Genomics

The most recent Ebola epidemic that began in late 2013 alerted the entire world to the gaps in infectious disease emergency preparedness and response. The regional outbreak that progressed to a significant public health emergency of international concern (PHEIC) in a matter of months killed 11,310 and infected more than 28,616. While this outbreak bears some unique distinctions to past outbreaks, many characteristics remain the same and contributed to tragic loss of human life and unnecessary expenditure of capital: insufficient knowledge of the disease, its reservoirs, and its transmission; delayed prevention efforts and treatment; poor control of the disease in hospital settings; and inadequate community and international responses. Recognizing the opportunity to learn from the countless lessons of this epidemic, the National Academies of Sciences, Engineering, and Medicine convened a workshop in March 2015 to discuss the challenges to successful outbreak responses at the scientific, clinical, and global health levels. Workshop participants explored the epidemic from multiple perspectives, identified important questions about Ebola that remained unanswered, and sought to apply this understanding to the broad challenges posed by Ebola and other emerging pathogens, to prevent the international community from being taken by surprise once again in the face of these threats. This publication summarizes the presentations and discussions from the workshop.

The Ebola Epidemic in West Africa

Dr. Joshua Lederberg - scientist, Nobel laureate, visionary thinker, and friend of the Forum on Microbial Threats - died on February 2, 2008. It was in his honor that the Institute of Medicine's Forum on Microbial Threats convened a public workshop on May 20-21, 2008, to examine Dr. Lederberg's scientific and policy contributions to the marketplace of ideas in the life sciences, medicine, and public policy. The resulting workshop summary, Microbial Evolution and Co-Adaptation, demonstrates the extent to which conceptual and technological developments have, within a few short years, advanced our collective understanding of the microbiome, microbial genetics, microbial communities, and microbe-host-environment interactions.

Forum on Microbial Threats

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