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.

The production and distribution of counterfeit medications has become a significant global public health issue. Though not as rampant in the United States, the Food and Drug Administration (FDA) has seen a 10 fold increase in the number of cases investigated, particularly a rise in illegally imported and diverted medications entering our legitimate drug supply. In order to curb these illegal activities, California and the federal government have introduced various pieces of legislation to address this. In addition, international entities, State Boards of Pharmacy and the FDA have begun promoting utilization of radio frequency identification technology and other technology to effectively track the medication supply. In a recent California survey, pharmacists felt strongly that the presence of counterfeit medications poses a problem in their pharmacy practice, but they still face several challenges in identifying counterfeit medications, counseling their patients, and forging their role in implementing legislative requirements.

This presentation will aim to provide an introduction to the international and domestic counterfeit drugs situation, discuss possible factors facilitating patient exposure to counterfeit medications, examine potential sources for counterfeit medications in the United States, identifiy federal legislation issues, discuss various forms of technology being used to combat counterfeit medications, and recognize the role of pharmacists and the challenges they face in dealing with counterfeit medications.

Speaker Biography:

Dr. Elaine Law is currently a Clinical Pharmacist specializing in Adult General Surgery at UCSF Medical Center and an Assistant Clinical Professor in the UCSF School of Pharmacy. She received a B.S. in Molecular, Cell and Developmental Biology from UCLA, earned a Doctor in Pharmacy from UCSF School of Pharmacy and completed a General Practice Pharmacy Residency at UCSF Medical Center. She holds a Board Certification in Pharmacotherapy and her research interests include roles pharmacists can play in public health issues including counterfeit medications and pharmacist-based immunization programs. She is an advocate of patient care in underserved areas and reaches out regularly to the Tenderloin communities and elderly populations of San Francisco through pharmacy health outreach programs.

The large-scale industrial accident at the Fukushima-Daiichi Nuclear Power Plant was the culmination of three inter-related factors: external natural hazard assessment and site preparation, the utility’s approach to risk management, and the fundamental reactor design.

The reactor accident was initiated by a magnitude 9 earthquake followed by an even more damaging tsunami. However, it was the inability to remove the decay heat in the reactor core that led to core meltdown and radioactive release.

A review of the timeline of the major Fukushima accident sequences: The plant first experienced a station blackout (i.e. loss of all offsite and onsite power) due to flooding of backup critical emergency cooling equipment. The lack of an ultimate heat sink led to the fuel overheating. Subsequently, the generation of hydrogen through steam oxidation of of the fuel cladding led to chemical explosions causing significant structural damage.

The focus of this talk (presentation slides below) is on the engineering aspects of the reactor accident and the prospects for local environmental recovery. Radionuclide measurements in space and time provide important evidence for the exact evolution of fuel damage leading to partial core melting in multiple units. A review of the spent nuclear fuel pools is given where isotopic water composition and visual inspection images provide important evidence for the condition of the spent nuclear fuel.

While it will be several months to a year before we will be in a position to learn most of the lessons from this tragdy, several conclusions about defensive design, mitigation actions, and emergency response have been drawn by international organizations.

While the public health impact appears to have been low, the economic and nearby environmental consequences are severe, There is no doubt that land restoration will take over a decade and perhaps much longer. A review is given of actions taken by the Japanese government for land recovery in areas such as decontaminating top soil and local farmland as well as highly radioactive water used during ‘feed and bleed’ cooling of the core.

Professor Wein received his PhD in Operations Research from Stanford in 1988 and has taught core MBA courses in operations management throughout his entire career, both at MIT's Sloan School of Management from 1988 to 2002 and, since 2002, at Stanford's Graduate School of Business, where he is currently Paul  E. Holden Professor of Management Science. He has also been a Senior Fellow (by courtesy) at FSI since 2003.

Since 2001, Wein has analyzed a variety of homeland security problems. His homeland security work includes four papers in the Proceedings of the National Academy of Sciences: one on an emergency response to a smallpox attack,  a second on an emergency response to an anthrax attack, a third presenting a biometric analysis of the US-VISIT Program, and a fourth analyzing a bioterror attack on the milk supply. He has also published the Washington Post op-ed "Unready for Anthrax" (2003) and the New York Times op-ed "Got Toxic Milk?" (2005) and has written papers on port security, indoor remediation after an anthrax attack, and the detention and removal of illegal aliens.  He was also Editor-in-Chief of Operations Research from 2000 to 2005. Wein has won several awards, including the 1993 Erlang Prize for the outstanding applied probabilist under 35 years of age and the 2002 Koopman Prize for the best paper in military operations research.