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 The board weighed the risks and the benefits of the work and recommended that the papers not be published as written, but only in a highly redacted form that would prevent the rapid and direct replication of the work.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).

Recent events in the U.S. have raised concerns about the safety and security of research with hazardous microbial agents, particularly with regard to the insider threat. The anthrax letters of 2001 and several technical surprises in legitimate infectious disease research, led to a series of high-level committee recommendations on safety and security of the ongoing work. When a scientist from a U.S. military high-containment laboratory was implicated in the anthrax letters case, the president and congress called for more regulation. Subsequently, a series of steps to reduce the risk have been proposed: from armed guards, pathogen accountability and medical and psychological exams for scientists to training, ethical frameworks, codes of conduct and standards of quality research. Franz will discuss the implications of these events on both security and productive research in support of public health and the life-sciences enterprise, and the important role of leadership and culture in enhancing both safety and security.

About the speaker: Dave Franz is a Vice President and Chief Biological Scientist at MRIGlobal. He served in the U.S. Army Medical Research and Materiel Command for 23 of 27 years on active duty and retired as Colonel. He served as Commander of the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) and as Deputy Commander of the Medical Research and Materiel Command. Prior to joining the Command, he served as Group Veterinarian for the 10th Special Forces Group (Airborne). Dr. Franz was Technical Editor for the Textbook of Military Medicine on Medical Aspects of Chemical and Biological Warfare released in 1997. He serves on numerous national committees and boards. Dr. Franz holds an adjunct appointment as Professor for the Department of Diagnostic Medicine and Pathobiology at the College of Veterinary Medicine, Kansas State University. The current focus of his activities relates to the role of international engagement in the life sciences as a component of national security policy.

Infectious diseases, especially those transmitted from person to person through the respiratory route, continue to pose a threat to the global community. Public health surveillance systems and the International Health Regulations are intended to facilitate the recognition of and rapid response to infectious diseases that pose the risk of developing into a pandemic, but the response to the 2009 H1N1 influenza pandemic illustrates the continuing challenges to implementing appropriate prevention and control measures. The response to the 2009 H1N1 influenza pandemic will be discussed and its implications examined.

Speaker biography:

Antibiotics have represented the primary line of defense for treating bacterial infections since 1935 when the first sulfur-containing compounds were introduced. Many antibiotic compounds are produced naturally by microorganisms while some more recently developed antibiotics are chemically designed based on a knowledge of susceptible biochemical pathways or physiological processes in pathogenic bacteria. Ciprofloxacin (“cipro”), a synthetic broad-spectrum antibiotic, functions by interfering with DNA replication.

Increased use and mis-use of antibiotics has led to increased numbers of pathogenic bacteria that are resistant to one or more antibiotics. Some resistant microbes possess mechanisms that allow continued growth in the presence of multiple antibiotics. These multiply drug-resistant pathogenic bacteria may also possess pathogenic properties that result in significantly more severe disease than their drug-sensitive cousins. Medical misuse of antibiotics – prescribing antibiotics for viral infections, failure of patients to complete treatment with the full regiment of antibiotics, or application of antibiotics based on inaccurate or incomplete tests can lead to selection of antibiotic resistant bacteria that can then cause infections that cannot be treated with the antibiotic(s) to which they are resistant. Multiple drug resistance can quickly reduce or eliminate all antibiotic-based treatment options. Infections caused by antibiotic resistant bacteria are very difficult to treat and can sometimes lead to death of the patient.

Antibiotic resistance can also result from selection based on exposure to antibiotics present in the environment. More than 70% of the antibiotics sold in the U.S. are used as supplements to animal feed. The intestinal bacteria in the animals provided with such feed often show resistance to the antibiotics in the feed and, in some documented cases, have transferred this resistance to pathogenic microbes with which they share the environment.

A brief of history of antibiotic use and the medical and public policy factors that are, in part, responsible for increased antibiotic resistance in pathogenic microbes and for a decrease in the development of new antibiotics will be presented. An introduction to new directions that are being taken to develop a next generation of antibiotic compounds will also be provided.

Speaker Biography:

Paul Jackson received his Bachelor's of Science degree from the University of Washington in Cellular Biology and his Ph.D. from the University of Utah in Molecular Biology. He became a CISAC Visiting Scholar in September 2011. He was previously a CISAC affiliate.

For the past 18 years he has been studying bacterial pathogens, first working to develop DNA-based methods of detecting these microbes and their remnants in environmental and laboratory samples, then developing methods to differentiate among different strains of the same pathogenic species. Research interests include the study of different methods of interrogating biological samples for detection and characterization of content, and development of bioforensic tools that provide detailed information about biothreat isolates including full interrogation of samples for strain content and other genetic traits.

Methods he developed have been applied to forensic analysis of samples and aid in identifying the source of disease outbreaks. He contributed to analysis of the Bacillus anthracis present in the 2001 Amerithrax letters and conducted detailed analyses of human tissue samples preserved from the 1979 Sverdlovsk anthrax outbreak, providing evidence that was inconsistent with Soviet government claims of a natural anthrax outbreak.

His current work continues to focus on development of assays that rapidly detect specific signatures including antibiotic resistance in threat agents and other pathogens. More recent activities include identification and characterization of new antimicrobial compounds that are based on the pathogens' own genes and the products they encode. These include development of such materials as therapeutic antimicrobials, their application to remediate high value contaminated sites and materials, and their use to destroy large cultures and preparations of different bacterial threat agents. Efforts to address issues of antibiotic resistance and treatment of resistant organisms have recently been expanded to look at non-threat agent pathogens that cause problematic nosocomial or community-acquired infections of particular interest to the military.

Paul spent 24 years as a Technical Staff Member at Los Alamos National Laboratory where he was heavily involved in development of the biological threat reduction efforts there. He was appointed a Laboratory Fellow at Los Alamos in recognition of his efforts. He moved to Lawrence Livermore National Laboratory in 2005 where he is presently Senior Scientist in the Global Security and Physical and Life Sciences Directorates. In addition to his work at the National Laboratories, he has served on the FBI's Scientific Working Group for Microbial Forensics, on NIH study sections and review panels, and continues to serve on steering and oversight committees for other federal agencies.