Biosecurity
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From the 1950s through the 1970s, the success of antibiotics and vaccines in controlling or eradicating infectious diseases (ID) worldwide resulted in decreased emphasis on development of ID therapeutics. The emergence in the past three decades of HIV, SARS, West Nile, avian flu, swine flu, Ebola, and the potential for bioterrorist attacks has reversed this trend and renewed interest in treatment and prophylaxis of ID. Unfortunately, because many diseases are prevalent primarily in developing nations (e.g., malaria, TB, Chagas), potential sales of bioterrorist pathogens are limited mainly to orders for government stockpiles (e.g., anthrax, smallpox, botulinum toxin), and the cost of anti-infective clinical trials is high, traditional large pharmaceutical companies have cut back R&D resources in this arena. To combat this investment shortfall, a new paradigm has emerged where public-private partnerships between the NIH, World Health Organization, private foundations, academia, and non-profits, are beginning to function like pharmaceutical companies to advance the development of promising ID drugs, even when there is little opportunity for profit. This talk will discuss the growing need for ID therapeutics, present some new models for discovering and developing them, and provide examples of public-private partnerships that have advanced therapeutics for specific infectious diseases.


About the speaker: Dr. Jon C. Mirsalis is Managing Director of the Biosciences Division and Executive Director of Preclinical Development at SRI International in Menlo Park, CA. Dr. Mirsalis is an internationally recognized expert in the development of drugs for infectious diseases. He manages two large programs for the National Institute of Allergy and Infectious Diseases (NIAID) for the development of promising therapeutics for the prevention and treatment of a broad range of infectious diseases including TB, malaria, influenza, polio, anthrax, plague, and Ebola. He has personally been involved in the development of over 50 therapeutics that have entered clinical trials and several have already reached the market. Before joining SRI in 1981, Dr. Mirsalis was a postdoctoral fellow at the Chemical Industry Institute of Toxicology, where he developed the in vivo-in vitro hepatocyte DNA repair assay, which is now widely used as a screen for potential carcinogens by government and industry. He is the author of over 140 publications and abstracts. Dr. Mirsalis received his B.S. degree in zoology/molecular biology from Kent State University, his M.S. degree in genetics from North Carolina State University, and holds Ph.D. degrees in toxicology and genetics from North Carolina State University. Dr. Mirsalis has an adjunct faculty appointment with the University of California-Santa Cruz, where he lectures regularly on genetic toxicology and carcinogenesis. He has recently served on the Board of Scientific Councilors for the National Toxicology Program, the Advisory Board for the Critical Path Institute, and is a past member of the FDA’s Over-the-Country Product Review Committee. Dr. Mirsalis has been certified by the American Board of Toxicology since 1983.

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Jon Mirsalis Managing Director, Biosciences Division Speaker SRI International
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Many of my colleagues and fellow investigators in the life sciences were surprised in late 2011 to hear about the deliberate laboratory manipulation of highly pathogenic avian influenza viruses for the purpose of creating derivative strains with enhanced capacity for respiratory transmission among mammals— strains with pandemic potential and serious global consequence. More importantly, few were prepared to undertake a reasoned and dispassionate assessment of the risks and benefits of such research and of its publication. This is unfortunate, not only because the resulting paucity of scientific leadership on this topic led to emotional and often unproductive discourse, but because new  instances of concerning research will be increasingly frequent and ever more consequential as the ongoing revolution in the life sciences unfolds.

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David Relman
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David Relman, a Stanford microbiologist and professor of infectious diseases, has taken up the mantle as CISAC co-director alongside Stanford law professor Tino Cuéllar, both of whom intend to broaden the center’s research in biosecurity and the life sciences.

Relman, the Thomas C. and Joan M. Merigan Professor at Stanford’s School of Medicine and chief of infectious disease at the VA Palo Alto Healthcare System, has advised the U.S. government about pathogen diversity, dual-use technology and biosecurity. He also is the current president of the Infectious Diseases Society of America.

“The appointment of a life scientist who focuses on infectious diseases and biosecurity is an innovative step for our work in international security and cooperation,” said Gerhard Casper, president emeritus of Stanford University and director of CISAC’s umbrella organization, the Freeman Spogli Institute for International Studies.

Relman succeeds Siegfried S. Hecker, a nuclear scientist and director emeritus of the Los Alamos National Laboratory, who was the CISAC co-director since 2007. One of the world’s foremost experts on plutonium, nuclear weapons and nonproliferation, Hecker is on sabbatical in New Mexico and the Vienna Center for Disarmament and Non-Proliferation. He is working on a book about his historic efforts to foster collaboration between U.S. and Russian nuclear labs, as well as traveling to meet his nonproliferation counterparts in parts of Europe and Russia.

Hecker will return to CISAC this summer to resume his teaching in the Department of Management Science and Engineering, as well as his writing and research as a senior fellow at CISAC and FSI.

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President Obama and Mitt Romney meet for their third debate to discuss foreign policy on Monday, when moderator Bob Schieffer is sure to ask them about last month's terrorist attack in Libya and the nuclear capabilities of Iran.

In anticipation of the final match between the presidential candidates, researchers from five centers at Stanford’s Freeman Spogli Institute for International Studies ask the additional questions they want answered and explain what voters should keep in mind.


What can we learn from the Arab Spring about how to balance our values and our interests when people in authoritarian regimes rise up to demand freedom?  

What to listen for: First, the candidates should address whether they believe the U.S. has a moral obligation to support other peoples’ aspirations for freedom and democracy. Second, they need to say how we should respond when longtime allies like Egypt’s Hosni Mubarak confront movements for democratic change.

And that leads to more specific questions pertaining to Arab states that the candidates need to answer: What price have we paid in terms of our moral standing in the region by tacitly accepting the savage repression by the monarchy in Bahrain of that country's movement for democracy and human rights?  How much would they risk in terms of our strategic relationship with Bahrain and Saudi Arabia by denouncing and seeking to restrain this repression? What human rights and humanitarian obligations do we have in the Syrian crisis?  And do we have a national interest in taking more concrete steps to assist the Syrian resistance?  On the other hand, how can we assist the resistance in a way that does not empower Islamist extremists or draw us into another regional war?  

Look for how the candidates will wrestle with difficult trade-offs, and whether either will rise above the partisan debate to recognize the enduring bipartisan commitment in the Congress to supporting democratic development abroad.  And watch for some sign of where they stand on the spectrum between “idealism” and “realism” in American foreign policy.  Will they see that pressing Arab states to move in the direction of democracy, and supporting other efforts around the world to build and sustain democracy, is positioning the United States on “the right side of history”?

~Larry Diamond, director of the Center on Democracy, Development, and the Rule of Law


What do you consider to be the greatest threats our country faces, and how would you address them in an environment of profound partisan divisions and tightly constrained budgets? 

What to listen for: History teaches that some of the most effective presidential administrations understand America's external challenges but also recognize the interdependence between America's place in the world and its domestic situation.

Accordingly, Americans should expect their president to be deeply knowledgeable about the United States and its larger global context, but also possessed of the vision and determination to build the country's domestic strength.

The president should understand the threats posed by nuclear proliferation and terrorist organizations. The president should be ready to lead in managing the complex risks Americans face from potential pandemics, global warming, possible cyber attacks on a vulnerable infrastructure, and failing states.

Just as important, the president needs to be capable of leading an often-polarized legislative process and effectively addressing fiscal challenges such as the looming sequestration of budgets for the Department of Defense and other key agencies. The president needs to recognize that America's place in the world is at risk when the vast bulk of middle class students are performing at levels comparable to students in Estonia, Latvia and Bulgaria, and needs to be capable of engaging American citizens fully in addressing these shared domestic and international challenges.

~Mariano-Florentino Cuéllar, co-director of the Center for International Security and Cooperation


Should our government help American farmers cope with climate impacts on food production, and should this assistance be extended to other countries – particularly poor countries – whose food production is also threatened by climate variability and climate change?

What to listen for: Most representatives in Congress would like to eliminate government handouts, and many would also like to turn away from any discussion of climate change. Yet this year, U.S. taxpayers are set to pay up to $20 billion to farmers for crop insurance after extreme drought and heat conditions damaged yields in the Midwest.

With the 2012 farm bill stalled in Congress, the candidates need to be clear about whether they support government subsidized crop insurance for American farmers. They should also articulate their views on climate threats to food production in the U.S. and abroad.

Without a substantial crop insurance program, American farmers will face serious risks of income losses and loan defaults. And without foreign assistance for climate adaptation, the number of people going hungry could well exceed 15 percent of the world's population. 

~Rosamond L. Naylor, director of the Center on Food Security and the Environment


What is your vision for the United States’ future relationship with Europe? 

What to listen for: Between the end of World War II and the end of the Cold War, it was the United States and Europe that ensured world peace. But in recent years, it seems that “Europe” and “European” have become pejoratives in American political discourse. There’s been an uneasiness over whether we’re still friends and whether we still need each other. But of course we do.

Europe and the European Union share with the United States of America the most fundamental values, such as individual freedom, freedom of speech, freedom to live and work where you choose. There’s a shared respect of basic human rights. There are big differences with the Chinese, and big differences with the Russians. When you look around, it’s really the U.S. and Europe together with robust democracies such as Canada and Australia that have the strongest sense of shared values.

So the candidates should talk about what they would do as president to make sure those values are preserved and protected and how they would make the cooperation between the U.S. and Europe more effective and substantive as the world is confronting so many challenges like international terrorism, cyber security threats, human rights abuses, underdevelopment and bad governance.

~Amir Eshel, director of The Europe Center


Historical and territorial issues are bedeviling relations in East Asia, particularly among Japan, China, South Korea, and Southeast Asian countries. What should the United States do to try to reduce tensions and resolve these issues?

What to listen for: Far from easing as time passes, unresolved historical, territorial, and maritime issues in East Asia have worsened over the past few years. There have been naval clashes, major demonstrations, assaults on individuals, economic boycotts, and harsh diplomatic exchanges. If the present trend continues, military clashes – possibly involving American allies – are possible.

All of the issues are rooted in history. Many stem from Imperial Japan’s aggression a century ago, and some derive from China’s more assertive behavior toward its neighbors as it continues its dramatic economic and military growth. But almost all of problems are related in some way or another to decisions that the United States took—or did not take—in its leadership of the postwar settlement with Japan.

The United States’ response to the worsening situation so far has been to declare a strategic “rebalancing” toward East Asia, aimed largely at maintaining its military presence in the region during a time of increasing fiscal constraint at home. Meanwhile, the historic roots of the controversies go unaddressed.

The United States should no longer assume that the regional tensions will ease by themselves and rely on its military presence to manage the situation. It should conduct a major policy review, aimed at using its influence creatively and to the maximum to resolve the historical issues that threaten peace in the present day.

~David Straub, associate director of the Korea Studies Program at the Walter H. Shorentein Asia-Pacific Research Center

 

Compiled by Adam Gorlick.

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President Obama and Mitt Romney speak during the second presidential debate on Oct. 16, 2012. Their third and final debate will focus on foreign policy.
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Dr. David Relman investigates the secrets of the life sciences to help build a safer world.

The Stanford microbiologist and professor of infectious diseases has been named the next co-director of the university’s Center for International Security and Cooperation (CISAC). An adviser to the federal government on emerging biological threats, Relman believes his new role at CISAC will strengthen its core mission of making the world a safer place.

“There is a strong link between microbiology, infectious diseases and international security,” Relman said. “It is increasingly clear that the destabilizing effects of human population growth and displacement, environmental degradation and climate change are all mediated in part through the emergence and spread of infectious diseases. In addition, rapidly evolving capabilities of individuals in the life sciences around the globe make it increasingly likely that this science will be used to cause harm.”

Relman, the Thomas C. and Joan M. Merigan Professor at Stanford and chief of infectious diseases at the VA Palo Alto Healthcare System, has advised the U.S. government about pathogen diversity, biosecurity and the future of the life sciences landscape. He is a member of the National Science Advisory Board for Biosecurity (NSABB), chairs the Forum on Microbial Threats at the Institute of Medicine in Washington, D.C. and has participated in a number of studies for the National Academies of Science.

"David Relman is one of the nation’s top scientists exploring the mysteries of infectious disease, a thoughtful adviser to policymakers, and an extraordinary colleague,” said Tino Cuéllar, a Stanford Law School professor and the center’s co-director. “He will make tremendous contributions to CISAC's leadership as we expand our activities on public health and biosecurity while continuing our work on arms control and nuclear security."

Founded nearly three decades ago, CISAC’s mission is to produce cutting-edge research and spread knowledge to build a safer world. Now a part of the Freeman Spogli Institute for International Studies (FSI), the center has a tradition of appointing co-directors – one from the social sciences and the other from the natural sciences – to advance the center’s interdisciplinary mission.

Relman will take up the post in January, when Siegfried Hecker’s term concludes after having served as co-director since 2007. Hecker, a nuclear scientist and director emeritus of the Los Alamos National Laboratory, is one of the world’s foremost experts on plutonium, nuclear weapons and nonproliferation. He will remain at CISAC and continue to teach in the department of Management Science and Engineering.

“It has been a personal pleasure to work with Sig,” said Cuéllar. “He has been an enormous asset to CISAC.  He will continue to be a visionary leader on nuclear security and arms control issues throughout the world.”

Relman joined Paul Keim, acting chair of the NSABB, to address a CISAC seminar in March about their work in advising the government on the potential dangers of laboratory-engineered H5N1 avian influenza.

The advisory board had been asked to review two manuscripts that described the deliberate modification of the H5N1 avian influenza virus so as to be transmissible for the first time from mammal to mammal via a respiratory route. This provoked a debate in the scientific community about the risks of such work and whether the details of these experiments should be published – details that would enable anyone skilled in the art of virology and molecular biology to recreate these highly virulent and transmissible viruses. Some argued that the research could end up in the wrong hands. The board eventually recommended in a split decision that this research should be published.

“Life scientists need to be involved in discussions about the oversight of risky science and the responsible conduct of science, so that the potential benefits can be realized while the risks are minimized,” Relman said.

Relman will continue to run his research lab at the Stanford University School of Medicine and the VA Hospital in Palo Alto, where his focus is on the beneficial communities of microbes in the human body. He is president-elect of the Infectious Diseases Society of America and a member of the Institute of Medicine at the National Academies of Science. He received his S.B. in biology from MIT in 1977 and an M.D. from Harvard Medical School in 1982. He completed his clinical training in internal medicine and infectious diseases at Massachusetts General Hospital in Boston.

“The appointment of a life scientist who focuses on infectious diseases and biosecurity is an innovative step for our work in international security and cooperation,” said Gerhard Casper, president emeritus of Stanford University and director of the Freeman Spogli Institute for International Studies.

Relman tells a story that illustrates his passion for scientific discovery. On a routine visit to his dentist about 15 years ago, he brought along his own test tube. He asked the dentist to give him some plaque that he had scraped off Relman’s teeth. He wanted to study his own bacteria.

“As a clinician, I can tell you my colleagues were not looking for new microbes to worry about,” Relman said. “Some of them believed there might well be some really weird new microbes in soil or in the ocean, but that the human microbial ecosystem was something that we understood quite well. Of course – that was wrong.”

Using DNA sequencing technology, he has since discovered hundreds of new bacteria in the human body.

“Our ability to predict the next important technical or conceptual advance in the life sciences is miserable, as is our ability to anticipate how these advances will be used,” Relman said. “But we can at least hope to engage the scientific community and the general public in discussions about our goals and our understanding of risks – and how best to mitigate them.”

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The book The Soviet Biological Weapons Program: A History by Milton Leitenberg and Raymond A. Zilinskas is scheduled to be published on May 14, 2012 by Harvard University Press. This book describes and analyzes in detail the Soviet biological warfare (BW) program, from its inception in 1928 to likely termination in 1992. The two most vexing questions that the authors attempt to answer are; in the final analysis, what were the Soviet BW program’s accomplishments? Second, might Soviet accomplishments related to enhancing biological weaponry be made available to future national or terrorist BW programs? This presentation will explain why these questions are difficult to answer but nevertheless will propose answers to them. The authors have a basis for doing so because they have been able to collect and analyze information from primary resources in archives and special collections, as well as in the course of hundreds of hours spent on interviewing scientists who operated the Soviet BW program. During his presentation, Zilinskas will discuss tentative findings that encompass subjects such as whether the application of genetic engineering, which resulted in among other accomplishments the development of multiantibiotic resistant Bacillus anthracis, Francisella tularensis, and Yersinia pestis, actually resulted in improved weaponry and whether genetically engineered strains remain in Russian cell culture collections and from there might escape or be made available to those who seek to acquire biological weapons.


About the speaker: Raymond A. Zilinskas, formerly a clinical microbiologist, is the director of the Chemical and Biological Weapons Nonproliferation Program at the Center for Nonproliferation Studies of the Monterey Institute of International Studies. He is the editor of Biological Warfare: Modern Offense and Defense (Lynne Rienner, 1999) and co-editor of the Encyclopedia of Bioterrorism Defense (Wiley, 2005). He received a PhD from the University of Southern California and a BA in Biology from the University of Stockholm.

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Raymond Zilinskas Director, Biological Weapons Nonproliferation Program Speaker Monterey Institute for International Studies
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The National Science Advisory Board for Biosecurity (NSABB), an independent advisory committee tasked with providing guidance on the biosecurity oversight of dual use research, announced on March 30 that it would recommend the publication of controversial research on the H5N1 avian flu. The issue ignited a debate in the scientific community on publishing research that could threaten public health. The committee sent its recommendations to the federal government for review. 

On March 12, Professor Paul Keim, chairman of the NSABB, and Dr. David Relman, a NSABB board member and CISAC affiliated faculty and professor of infectious diseases and microbiology and immunology at Stanford, discussed the debate over whether to make public scientific papers about the adaptation of the avian flu virus H5N1 to transmission in a mammal. The NSABB had not announced its decision to publish the research at the time of the presentation.

Audio from the March 12 seminar is available online. 

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The life sciences have many examples of where research results and technologies can be used for good, but also for bad purposes. Because such scenarios are so common, it is critical to identify that research which is particularly bad and would be classified as dual use research of concern (DURC). Attributes that might result in a DURC designation include how immediate a threat it represents, the magnitude of the threat, the availability of safeguards to defend against its nefarious use and its relative risk to benefits ratio. Several policy forums have studied this problem and the National Science Advisory Board for Biosecurity (NSABB) is currently the official U.S. government advisory group for DURC policy. Recently, NSABB was asked to review two manuscripts that reported adaptation of the high-path avian influenza virus H5N1 to transmission in a mammalian model. This virus rarely infects humans but when it does, it has catastrophic consequences with ~60% mortality. The board weighed the risks and the benefits of the work and recommended that the papers not be published as written, but only in a highly redacted form that would prevent the rapid and direct replication of the work. NSABB also argued for a communication pause so that the consequences of these papers and this research focus be evaluated by a broad cross section of science, public health and society. The US government accepted these recommendations and the two journals (Science and Nature) have thus far not published the papers. Multiple additional forums are planned to discuss the issues and recommendations. The future for policy development in the area of pathogen research and DURC will be shaped by these recommendations and subsequent activities.

About the speakers:

Dr. Paul Keim holds the E. Raymond and Ruth Cowden Endowed Chair in Microbiology at Northern Arizona University (NAU), where he is also a Regents Professor of Biology. In addition, he directs the Pathogen Genomics Division at The Translational Genomics Research Institute (TGen). Both institutions are based in Flagstaff, Arizona. His biological interests span many types of organisms and microbes, but revolve around genetic diversity and its organization in populations and species. This necessarily has involved systematic and phylogenetic analyses to understand how observable genetic diversity is based upon past evolutionary processes. Biodefense programs have capitalized upon his approach of using genomic analysis to understand bacterial pathogen populations for microbial forensics and molecular epidemiological analyses. His laboratory was heavily involved in analysis of evidentiary material from the 2001 anthrax-letter attacks. He has published extensively on the evolution and population genetics of Bacillus anthracis, Yersinia pestis, Francisella tularensis, Burkholderia pseudomallei, Burkholderia mallei, Brucella spp., and Coxiella burnetii. Recently, these same principles have been applied to other public health-related and clinically important pathogens such as S. aureus and E. coli. In all, he has published over 230 scientific or policy papers. Dr. Keim received his B.S. in Biology and Chemistry from Northern Arizona University in 1977 and his Ph.D. in Botany in 1981 from the University of Kansas. Dr. Keim has previously served on the editorial boards of Crop Science and Molecular Breeding; he currently serves on the editorial boards of Infection Genetics and Evolution, Investigative Genetics, and Biotechniques.

Dr. David Relman is a professor of medicine – infectious diseases, and of microbiology and immunology at Stanford. He joined CISAC as an affiliated faculty member in November 2011. He is also chief, Infectious Diseases Section, at the VA Palo Alto Health Care System. Among his other activities, Dr. Relman currently serves as Vice-President of the Infectious Diseases Society of America, Chair of the U.S. National Academies of Science Institute of Medicine's Forum on Microbial Threats, and member of the National Science Advisory Board for Biosecurity. He received a S.B. in biology from the Massachusetts Institute of Technology (1977) and an M.D. from Harvard Medical School Medicine (1982).

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Paul Keim Acting Chair, National Science Advisory Board for Biosecurity, The Cowden Endowed Chair of Microbiology, Northern Arizona University and Director, Pathogen Genomics Division, Translational Genomics Research Institute Speaker

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Senior Fellow at the Freeman Spogli Institute for International Studies
Thomas C. and Joan M. Merigan Professor
Professor of Medicine
Professor of Microbiology and Immunology
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David A. Relman, M.D., is the Thomas C. and Joan M. Merigan Professor in the Departments of Medicine, and of Microbiology and Immunology at Stanford University, and Chief of Infectious Diseases at the Veterans Affairs Palo Alto Health Care System in Palo Alto, California. He is also Senior Fellow at the Freeman Spogli Institute for International Studies (FSI) at Stanford, and served as science co-director at the Center for International Security and Cooperation at Stanford from 2013-2017. He is currently director of a new Biosecurity Initiative at FSI.

Relman was an early pioneer in the modern study of the human indigenous microbiota. Most recently, his work has focused on human microbial community assembly, and community stability and resilience in the face of disturbance. Ecological theory and predictions are tested in clinical studies with multiple approaches for characterizing the human microbiome. Previous work included the development of molecular methods for identifying novel microbial pathogens, and the subsequent identification of several historically important microbial disease agents. One of his papers was selected as “one of the 50 most important publications of the past century” by the American Society for Microbiology.

Dr. Relman received an S.B. (Biology) from MIT, M.D. from Harvard Medical School, and joined the faculty at Stanford in 1994. He served as vice-chair of the NAS Committee that reviewed the science performed as part of the FBI investigation of the 2001 Anthrax Letters, as a member of the National Science Advisory Board on Biosecurity, and as President of the Infectious Diseases Society of America. He is currently a member of the Intelligence Community Studies Board and the Committee on Science, Technology and the Law, both at the National Academies of Science. He has received an NIH Pioneer Award, an NIH Transformative Research Award, and was elected a member of the National Academy of Medicine in 2011.

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David Relman Professor of Medicine-infectious diseases, Stanford Medical School and CISAC Affiliated Faculty Member Commentator
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Charles Perrow is famous worldwide for his ideas about normal accidents, the notion that multiple and unexpected failures--catastrophes waiting to happen--are built into our society's complex systems. In The Next Catastrophe, he offers crucial insights into how to make us safer, proposing a bold new way of thinking about disaster preparedness.

Perrow argues that rather than laying exclusive emphasis on protecting targets, we should reduce their size to minimize damage and diminish their attractiveness to terrorists. He focuses on three causes of disaster--natural, organizational, and deliberate--and shows that our best hope lies in the deconcentration of high-risk populations, corporate power, and critical infrastructures such as electric energy, computer systems, and the chemical and food industries. Perrow reveals how the threat of catastrophe is on the rise, whether from terrorism, natural disasters, or industrial accidents. Along the way, he gives us the first comprehensive history of FEMA and the Department of Homeland Security and examines why these agencies are so ill equipped to protect us.

The Next Catastrophe is a penetrating reassessment of the very real dangers we face today and what we must do to confront them. Written in a highly accessible style by a renowned systems-behavior expert, this book is essential reading for the twenty-first century. The events of September 11 and Hurricane Katrina--and the devastating human toll they wrought--were only the beginning. When the next big disaster comes, will we be ready?

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