Balancing 'hysteria and suspicion': Doctors face new responsibilities in 'bioterrorism era'

Doctors need much more training, say Saint Louis University experts in The Lancet - The emergence of bioterrorism as a threat is creating new responsibilities for the medical community and, for the first time in history, is putting physicians at the forefront of managing disaster, according to an article by Saint Louis University researchers in The Lancet.

"Unlike other forms of terrorism, in which an acute exposure or traumatic injury is rapidly inflicted and quickly recognized, such as the 9/11 attacks, bioterrorism may involve an incubation period of days or even weeks," says Bruce W. Clements, MPH, associate director of the Institute for Bio-Security at Saint Louis University School of Public Health, and the lead author of the article.

"During these events, patients will turn to their most trusted adviser on health issues -- their doctors -- who will be expected to recognize sometimes rare conditions and take appropriate action. This means doctors will be the tip of the sword -- not the military, not the police, not the firefighters."

Clements presents his argument in an article published in the Dec. 18 issue of the medical journal, The Lancet.

Clements, and his co-author R. Gregory Evans, Ph.D., MPH, director of the Institute for Bio-Security at Saint Louis University, argue that this transfer of first-responder status puts greater responsibility on doctors, a responsibility that they currently are not prepared to shoulder.

"They will be in the driver's seat deciding how an outbreak will be managed so they must be trained for it," Clements says. "The challenge lies in finding the balance between suspicion and hysteria."

Clements says it is a delicate balance because most potential bioterrorism agents listed by the Centers for Disease Control and Prevention (CDC) -- such as those that cause smallpox, anthrax, botulism, plague, tularemia -- initially present in patients as flu-like symptoms.

"You don't want to walk into your doctor's office with flu-like symptoms and be told you might have Ebola," says Clements. "On the other hand, if you were exposed to something exotic, such as a biological agent, you would hope your physician has a high enough index of suspicion that he or she may take the extra moment to consider something unusual or atypical."

Clements and Evans urged medical schools to incorporate more information about bioterrorism into their curriculums to prepare doctors to meet the diagnostic challenge.

In addition, continuing medical education programs and community drills (such as a simulated smallpox scenario Evans and Clements developed for the CDC for use by state and local health departments) are critical in preparing doctors, they said. The exercises are designed to help physicians see how things may unfold in an atypical outbreak of smallpox and how different their work environment might be.

"In a bioterrorism incident, physicians will have to interface with the FBI and other government agencies that they've never had to speak with before," Clements says. "This type of communication doesn't come naturally. It's learned."

While physicians stand at the forefront of preparing for bioterrorism threats, Clements and Evans point out in their article that physicians have contributed to the creation and proliferation of these weapons -- both wittingly and unwittingly.

"Ethics must be integrated into all medical school courses, not just a few lectures in the first or second year of training," says Evans, a professor of environmental health.

The Institute for Bio-Security at Saint Louis University School of Public Health was established in 2000 with funding from the CDC. The Institute's original mission was preparing for bioterrorism or an emerging infectious disease. The mission was expanded in 2002, however, to include preparedness for all aspects of bio-security. Saint Louis University School of Public Health is one of only 36 fully accredited schools of public health in the United States and the nation's only School of Public Health sponsored by a Jesuit university.

Biological smoke detector" helps protect against potential bioterrorist attacks

Scientists have developed a new "biological smoke detector" to help protect against potential bioterrorist attacks, according to a study published in the Jan. 1 edition of Analytical Chemistry, a peer-reviewed journal of the American Chemical Society, the world's largest scientific society.

High-traffic facilities like airports, office buildings, rail stations and sporting arenas serve hundreds of thousands of people each day, making them particularly susceptible to silent and invisible biological attacks. Researchers from Lawrence Livermore National Laboratory in California have now developed a new stand-alone detector that can provide early warning to help authorities limit exposure and start treating victims before they show symptoms of full-blown infection.

The instrument, called the Autonomous Pathogen Detection System, or APDS, continuously monitors the air like a "biological smoke detector," says John Dzenitis, Ph.D., a chemical engineer at LLNL and corresponding author of the paper. It is capable of detecting and identifying three types of biological agents: bacteria, viruses and toxins, including such familiar threats as anthrax, plague and botulinum toxin. The machine runs the same tests that molecular biologists would carry out in a laboratory to detect biological agents, providing information that is required before definitive public-health action can be taken.

LLNL has been working on this instrument since 1995, but this new version, tested at the U.S. Army's Dugway Proving Grounds in Utah, is a step-change in capability, Dzenitis says. Now, in addition to simultaneously testing for multiple agents with protein antibodies, the APDS also confirms positive results with a DNA test specific for the agent. No other field system has two independent molecular biology tests. Having two laboratory-quality tests further reduces the probability of a false alarm and gives confidence for effective response.

Generex Biotechnology Working on Vaccine Development Against Bioterror Agents

Collaborates to Use Animal Models and Volunteer Samples to Test Activity Of Novel Smallpox Vaccine -

Generex Biotechnology Corporation (Nasdaq: GNBT) announced today that its wholly owned subsidiary, Antigen Express, has established collaborations with Emory University and the Imperial College of London to develop a novel smallpox vaccine. The vaccine is based on proprietary Antigen Express technology employing modified peptide antigens to stimulate immunity. The collaboration brings together one of the pre-eminent investigators on vaccinia, Dr. Geoffrey Smith of the Imperial College, and the noted immunologist Dr. Rafi Ahmed of Emory University. Dr. Robert Humphreys, founder of Antigen Express, will coordinate the program at Antigen Express.

Antigen Express has developed proprietary technologies that dramatically enhance the immunogenicity of small fragments from viral or tumor-associated proteins. "This is a particularly attractive strategy in the case of bioterror agents such as smallpox," said Robert Humphreys, founder and Chief Scientific Officer of Antigen Express. "The manufacture of small peptides is trivial compared to whole virus and safety concerns are virtually negligible.

We are excited and fortunate to be able to work with such distinguished individuals as Drs. Geoffrey Smith and Rafi Ahmed on this project."

The specter of a smallpox bioterror attack has pointed to the need for a safer smallpox vaccine. The frequency of adverse reactions to the existing vaccinia virus used for vaccination against smallpox is high enough as to prevent mass vaccinations. While attempts have been made at generating safer vaccines, none have been developed that are thought to be safe enough today for widespread use. Dr. Geoffrey Smith of the Imperial College of London has studied extensively the immunological responses to vaccinia and is a recognized leader in this field. His investigations have been instrumental both in identifying the key proteins to use as vaccines as well as model systems wherein to characterized potential vaccines.

Dr. Rafi Ahmed has a long-standing interest in the ability of the immune system to 'remember' prior exposures to an infectious agent and respond appropriately to subsequent infections, focusing both on HIV and vaccinia.

This is of particular interest in the context of Antigen Express technologies for stimulation of T helper cells, which have long been shown to play a key role in immunological memory and are critical in mounting a robust response. Antigen Express has demonstrated the potential of this technology in preclinical models and plans to begin clinical trials in patients with breast cancer during the first quarter of this year.

About Generex

Generex is engaged in the research and development of drug delivery systems and technologies. Generex has developed a proprietary platform technology for the delivery of drugs into the human body through the oral cavity (with no deposit in the lungs). The Company's proprietary liquid formulations allow drugs typically administered by injection to be absorbed into the body by the lining of the inner mouth using the Company's proprietary RapidMist(TM) device. The Company's flagship product, oral insulin (Oral- lyn(TM)), is in late stage clinical trials around the world. Generex acquired Antigen Express in August. 2003. The core platform technologies of Antigen Express comprise immunotherapeutics for the treatment of malignant, infectious, allergic, and autoimmune diseases.

This release and oral statements made from time to time by Generex representatives concerning the same subject matter may contain "forward- looking statements" within the meaning of the Private Securities Litigation Reform Act of 1995. These statements can be identified by introductory words such as "expects," "plans," "intends," "believes," "will," "estimates," "forecasts," "projects" or words of similar meaning, and by the fact that they do not relate strictly to historical or current facts. Forward-looking statements frequently are used in discussing potential product applications, potential collaborations, product development activities, clinical studies, regulatory submissions and approvals, and similar operating matters. Many factors may cause actual results to differ from forward-looking statements, including inaccurate assumptions and a broad variety of risks and uncertainties, some of which are known and others of which are not. Known risks and uncertainties include those identified from time to time in the reports filed by Generex with the Securities and Exchange Commission, which should be considered together with any forward-looking statement. No forward- looking statement is a guarantee of future results or events, and one should avoid placing undue reliance on such statements. Generex claims the protection of the safe harbor for forward-looking statements that is contained in the Private Securities Litigation Reform Act.

Engineers Develop Biowarfare Sensing Elements That Permit Mass Production of Highly Sensitive and Stable Nerve-Gas Detectors

A sensing device tailored for mass production of highly sensitive and stable nerve-gas detectors has been developed by a research group led by a mechanical engineer at The University of Texas at Austin.

The new sensor technology, which was more sensitive and much more stable than its predecessors, was featured on this week's cover of Applied Physics Letters. The researchers' highlighted study demonstrated the sensor's potential ability to detect a single molecule of the nerve gas, sarin, the most toxic of biological warfare agents.

The researchers, led by Dr. Li Shi, designed and tested a nanometer-thin crystal of tin oxide sandwiched between two electrodes. When a built-in micro-heater heated the super-thin device, the tin oxide reacted with exquisite sensitivity to gases.

Shi's group experimented with a non-toxic gas, dimethly methylphosphonate (DMMP) widely used to accurately mimic sarin and other nerve agents. The sensor element responded to as few as about 50 molecules of the DMMP in a billion air molecules.

Both the nano-sizing of the metal-oxide and the unique micro-heater element of the sensor gave the detector its high sensitivity, stability and low power consumption, said Shi, assistant professor of mechanical engineering.

The thinner a metal-oxide sensor becomes, the more sensitive it becomes to molecules that react with it. In addition to improved sensitivity, the group found its single-crystal metal-oxide nanomaterials allowed the detector to quickly dispose of previously detected toxins and accurately warn of new toxins' presence.

Shi's engineering collaborator, Zhong Lin Wang from Georgia Institute of Technology, provided single crystals of tin oxide as thin as 10 nanometers, and with the ability to rapidly recover from chemical exposure. The researchers found that the sensor was refreshed immediately after the DMMP molecules were purged from the small flow-through chamber where the sensor element was tested in. By contrast, previous polycrystalline metal oxide thin film sensors could not recover automatically after being exposed to toxic or flammable gases, an effect known as sensor poisoning.

Co-author and collaborator Wang is the first to grow the ribbon-like, single crystals of tin oxide used for sensing DMMP. Other sensors of this type consist of crystals with many imperfections, and recover slowly because molecules previously detected can become trapped in these imperfections.

Shi constructed the accompanying sensor components using traditional computer chip design and fabrication techniques. Specifically, he used microelectromechanical systems (MEMS) fabrication methods.

For instance, MEMS was used to fabricate the platinum electrodes, one of which links to a microfabricated heating element and thermometer to elevate the nano sensor's temperature to a constant 932 degrees Fahrenheit (500 degrees Celsius) with a power consumption of only 3-4 milliwatts. These components allow the sensor to be operated using a battery so that it can be used as a wearable device. To minimize heat loss, Shi's group isolated the silicon nitride membranes attaching the electrodes using trapeze-like strands of microfabricated silicon nitride.

The sensor requires the high temperature to activate the reaction between DMMP molecules and the tin-oxide sensor element. That reaction changes the electrical current across the crystal, which indicates a nerve agent is present.

The paper was based on the dissertation research of the lead author, Choongho Yu. Yu received a doctor's degree in mechanical engineering from The University of Texas at Austin last year, and is a post-doctoral fellow at Lawrence Berkeley National Laboratory.

Shi's group is continuing to develop methods to integrate nanomaterials with MEMS devices more efficiently in order to microfabricate better, lower-cost sensors. Multiple sensor elements would then be packaged together to produce a commercial sensing device that acts as an electronic nose for detecting different toxic and flammable molecules.

Note: This research was funded by grants from the National Science Foundation and the University of Texas at Austin.

Defensins Neutralize Anthrax Toxin

Max Planck scientists from Berlin, Germany discover a new immunotherapeutic approach against anthrax -

Researchers at the Max Planck Institute for Infection Biology in Berlin, headed by Prof. Dr. Stefan H.E. Kaufmann, have developed a new therapeutic strategy against anthrax using defensins, well known bacteriocidal defence molecules of our body. These investigations also revealed a novel biological function of defensins (PNAS, March 14, 2005).

The anthrax attacks in the aftermath of September 11, 2001 in the USA have illustrated the high potential of anthrax for misuse in bio-terrorism. Dissemination of anthrax by letters led to the death of 5 people and chemotherapeutic treatment of 30,000 individuals.

Now the team of Stefan H.E. Kaufmann, his PhD student Chun Kim and co-workers have developed a new therapeutic strategy against anthrax. In preclinical studies, these scientists showed that defensins neutralize the lethal toxin of anthrax bacilli and thus can prevent its deadly effect. Whilst defensins are well known to kill bacteria, toxin neutralization represents a novel function of defensins.

Defensins are capable of perforating the bacterial cell wall thus killing bacterial pathogens. Accordingly, their antibiotic potential is currently exploited although it is not clear when new chemotherapeutic agents on the basis of defensins will be available. The researchers, however, hope that a drug against anthrax toxin can be ready for human use within the next years.

Anthrax causes an infectious disease mostly in pigs, cattle, horses, sheep and goats. The disease is rare in humans and occurs primarily in regions with intensive farming. The lethal toxin (LeTx) composed of the lethal factor (LF) and the protective antigen (PA) is mostly responsible for the high mortality of anthrax. Although Bacillus anthracis can be treated by antibiotics, this chemotherapy frequently fails, in particular if not initiated immediately after infection, because even after eradication of the pathogen, bacterial toxins can remain in the circulation. "For this reason, new intervention strategies are urgently needed", says Stefan H.E. Kaufmann.

Original work:

Chun Kim, Nadesan Gajendran, Hans-Willi Mittr�cker, Mathias Weiwad, Young-Hwa Song, Robert Hurwitz, Matthias Wilmanns, Gunter Fischer and Stefan H.E. Kaufmann Human a-defensins neutralize anthrax lethal toxin and protect against its fatal consequences.
PNAS published March 14, 2005, 10.1073/pnas.0500508102

PDF (68 KB)

Rural America Vulnerable to Bioterrorism and Natural Disaster Threats

Inadequate Systems Need Strengthening to Meet Public Health Emergencies -

The Harvard School of Public Health Center for Public Health Preparedness, in collaboration with the Maine Department of Health and Human Services, and four other schools of public health, has released its latest independent report highlighting rural preparedness challenges and concerns.

Preparing for Public Health Emergencies: Meeting the Challenges in Rural America presents information and recommendations resulting from a conference that was held in St. Paul, MN, Sept. 27 - 28, 2004. The session brought together more than 80 public health preparedness leaders from multiple states to identify important yet unique barriers facing rural public health preparedness and the strategies to overcome those barriers.

The report presents recommendations based on the unique preparedness concerns facing rural America. Specifically:

-- Contrary to the opinion of many, rural America is indeed vulnerable to bioterrorism and other serious public health emergency threats such as storms and other natural disasters, and must be adequately prepared to protect its citizens;

-- Public health and health care systems in rural America need to be strengthened to meet the challenges of these threats;

-- Policy makers at the federal, state and local levels need to make sure that rural America has the financial and human resources required to achieve an adequate state of readiness; and,

-- Public health and health care leaders in rural areas need to work together to assure that emergency preparedness is achieved in a cost-effective manner.

Paul Campbell, Harvard School of Public Health (HSPH) faculty member, and Joshua Frances, research assistant and co-investigator of the report, are leaders in rural preparedness at HSPH's Center for Public Health Preparedness and helped organize the conference. Michael Meit, Director of the University of Pittsburgh's Center for Rural Health Practice, was also an author of the report.

"The conference did not focus exclusively upon bioterrorism," said Campbell. "Participants from across the country emphasized that we need to be prepared for the full range of public health emergencies, including weather events such as ice storms and hurricanes, and emerging diseases like SARS that do not result from terrorist actions."

Campbell continued: "This issue - the financing of preparations for potential bioterrorist attacks- has forced us to confront the inadequacy of our public health defenses in rural areas of this country. A strong national defense requires that we address our weakest links wherever they are."

"Rural areas in the United States bring with them unique challenges that are much different than their urban counterparts," said Frances. "Though many perceive rural areas to be just farmland, plains and dense forest, much of the nation's water supply, food supply and critical industries (power plants and water treatment facilities) are located in rural areas. They pose a unique challenge to protection from terrorism and public health emergencies."

This report will be presented at the National Rural Health Association's annual policy meeting on March 22, 2005 in Washington, DC.

The report, Preparing for Public Health Emergencies: Meeting the Challenges in Rural America, can be viewed at: hsph.harvard.edu/hcphp/Conference_Proceedings.pdf

Requests for a hard copy can be made to Cassie Watters at cwatters@hsph.harvard.edu or via phone at 617-495-9511.

Collaborators on the report and conference:

Harvard School of Public Health Center for Public Health Preparedness

Maine Department of Health and Human Services, Bureau of Health, Office of Public Health Emergency Preparedness

University of Pittsburgh Centers for Rural Health Practice and Public Health Preparedness

Texas A&M University School of Rural Public Health

University of Minnesota

University of North Carolina School of Public Health

Harvard School of Public Health is dedicated to advancing the public's health through learning, discovery, and communication. More than 300 faculty members are engaged in teaching and training the 900-plus student body in a broad spectrum of disciplines crucial to the health and well being of individuals and populations around the world. Programs and projects range from the molecular biology of AIDS vaccines to the epidemiology of cancer; from risk analysis to violence prevention; from maternal and children's health to quality of care measurement; from health care management to international health and human rights.

Scientists seek answers on what activates deadly anthrax spores

Scientists at Wake Forest University Baptist Medical Center and three other institutions are setting out to find what activates the spores in anthrax, the deadly bacterial infection that is back in the news.

"A key aspect of anthrax spore biology concerns the germination process through which the dormant spore becomes a reproductive, disease-causing bacterium," explained Al Claiborne, Ph.D., the principal investigator. "The potential importance of such a germination control mechanism in anthrax is clear, as spore germination and outgrowth are fundamental to proliferation."

Claiborne, co-director of Wake Forest's Center for Structural Biology, added, "Basic understanding of the regulatory signals that promote germination will enable discoveries leading to drugs that block the process."

The research is being paid for by a $152,687 grant from the Southeast Regional Center of Excellence in Biodefense and Emerging Infections, based at Duke University, one of eight such regional centers funded by the National Institute of Allergy and Infectious Diseases.

The other institutions in Claiborne's project include a co-investigator at Virginia Tech and collaborators at the U.S. Army Medical Research Institute of Infectious Diseases in Frederick, Md, and the University of California, San Diego.

The research stems from lessons learned from studying the bacteria that cause Staphylococcus infections and two other bacteria in the same group as anthrax.

Claiborne said the group proposes that a vitamin B5 derivative known as Coenzyme A plays a crucial role in the germination of the anthrax spores. They have already shown that anthrax is missing a similar cofactor called glutathione that is common to many other bacteria, as well as humans.

The researchers are working with a non-pathogenic strain of anthrax. The genome sequences of four strains of the bacteria, known scientifically as Bacillus anthracis, have been determined.

The group also will be exploring the three-dimensional structures and the functions of the proteins involved. State-of-the-art facilities at the Center for Structural Biology will be used to determine how genetic information in the anthrax chromosome translates into a vast array of protein structures, Claiborne said. Once they know the structures, they may not only be able to provide new details on how anthrax develops, but also pick out structural vulnerabilities that are key to designing new therapeutic agents to prevent anthrax.

Interest in determining how to stop anthrax remains high, not only after the 2001 attacks through the mail that resulted in 18 cases and five deaths, but also after the recent scare at two military mailroom facilities when anthrax alarms went off.

The group also would like to understand another closely related bacterium, Bacillus cereus, one strain of which can produce anthrax-like symptoms.

The research team includes Conn Mallett, Ph.D., Derek Parsonage, Ph.D., graduate students Carleitta Paige, Jamie Wallen, and Tim Colussi, and senior research assistants Bill Boles, M.S., and Sumana Choudhury, M.S. Paige earlier received a $161,000 graduate fellowship from the Department of Homeland Security to support her research.

Media Contacts: Robert Conn, rconn@wfubmc.edu, Shannon Koontz, shkoontz@wfubmc.edu, or Karen Richardson, krchrdsn@wfubmc.edu, at 336-716-4587.

Photos of two microscopic perspectives of the anthrax bacteria are available

About Wake Forest University Baptist Medical Center: Wake Forest Baptist is an academic health system comprised of North Carolina Baptist Hospital and Wake Forest University Health Sciences, which operates the university's School of Medicine. The system comprises 1,298 acute care, psychiatric, rehabilitation and long-term care beds and is consistently ranked as one of "America's Best Hospitals" by U.S. News & World Report.

Officials Simulate Bioterrorist Attack to Test APL-Developed Disease Surveillance System

Public health officials from the District of Columbia, Maryland and the Commonwealth of Virginia gathered today at the Johns Hopkins University Applied Physics Laboratory (APL) in Laurel, Md., to demonstrate the utility of the National Capital Region (NCR) Disease Surveillance Network.

Concerns about the potential for a large-scale bio-terrorist attack or an outbreak of an infectious disease have prompted a growing number of jurisdictions across the nation to launch electronic tracking systems to quickly detect outbreaks. By compiling data from emergency rooms, poison control centers and other sources, disease surveillance can serve as an early warning alarm.

The NCR network uses the Electronic Surveillance System for the Early Notification of Community-based Epidemics (ESSENCE), developed by the Lab with the Walter Reed Army Institute of Research. ESSENCE compiles data containing health indicators, performs analysis and provides information to local and regional public health officials on statistical anomalies that occur to help them identify bio-events early. Such irregularities would include upward trends in rashes, fevers and unexplained deaths, or a sudden surge in over-the-counter drug sales. It is the first system to integrate military and civilian data.

Each local and state public health jurisdiction in the NCR network responds independently to public health alerts and to ensure the health and safety of its residents. With an unprecedented collaborative network among public health programs, the NCR disease surveillance system offers a first line of defense in the national capital area.

Today's exercise was designed to test the system, using a simulated terrorist attack to observe the response from public health authorities. (The scenario was based on a hypothetical situation and was not intended as a forecast of future events.)

"This is giving us an opportunity to see, in real time, how health data are provided under this framework to different people to support a decision-making process that turns into action, and to see if it's done in a coordinated manner" said Thomas J. Lockwood, the U.S. Department of Homeland Security's director of the Office of National Capital Region Coordination. "This exercise is a key building block in protecting our citizens against a bioterrorist attack. NCR's ESSENCE is not the only protective tool we have in this regard, but it's an important one."

The purposes of the exercise were: to reinforce existing partnerships for an integrated response, including strengthening communications between NCR public health jurisdictions; to familiarize jurisdictional leaders with how public health officials use ESSENCE to apply knowledge in the early detection and monitoring of an intentional or naturally occurring emerging pathogen; to identify areas for improvement and enhancement within the system architecture; and to identify specific education and training needs of participants.

"What we've seen in this exercise is that the public health experts from the regions have been able to identify events that have occurred and determine their significance by sharing knowledge across the jurisdictions," said APL's Joseph S. Lombardo, who led the development of the ESSENCE system. "We noticed that when the health departments are so engaged the way they are, enhanced surveillance really does work."

The NCR network is comprised of independent operation centers - known as surveillance nodes - in the District of Columbia, Maryland and Virginia, with a central "regional integration node" operated by APL for performing surveillance across jurisdictional boundaries. It operates 365 days a year, providing information to local and state public health departments.

This exercise culminates the network's first year of operation using ESSENCE. Since it was formed in April 2004, the network has created an Enhanced Surveillance Operating Group to oversee the regional collaboration and formalized its data-sharing agreement. "As we enter our second year, we will formalize our response plan," said APL's Sheryl H. Lewis, the project manager for NCR. "We will also provide the local jurisdictions with the materials to quickly train their personnel on using ESSENCE and continue to fine-tune the system's algorithms based on comments from today's participants."

Comprehensive biodefense text published

A new book, Biological Weapons Defense: Infectious Disease and Counterbioterrorism, deals with the intentional causality of disease. Published by Humana Press, this text is also available in e-Book. Many of the contributors come from the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID), the nation's premier biodefense laboratory.

In this 624-page, hardcover text edited by Luther E. Lindler, Frank J. Lebeda, and George W. Korch, biodefense research experts authoritatively explain the universe of scientific, medical, and legal issues facing the biodefense research community. They describe the origin, effects and treatment of established pathogens that cause diseases such as anthrax, plague, smallpox, brucellosis, glanders, and Q fever, and discuss what is known about the aerosol route of infection and the process of decontamination.

Contained in the 25 chapters is an extensive discussion of preparation and military support for possible acts of bioterrorism, medical count

ermeasures, emerging threats and future preparation, and development of diagnostic tests for identifying biological warfare pathogens. Intended for researchers, physicians, and policy makers, Biological Weapons Defense: Infectious Disease and Counterbioterrorism offers a detailed look at the ongoing efforts to detect and identify these disease-causing agents, including proteomic and genomic analysis as a gateway to better diagnostics, therapeutics, vaccinations, genotyping, and forensics.

USAMRIID, located at Fort Detrick, Maryland, is the lead medical research laboratory for the U.S. Biological Defense Research Program, and plays a key role in national defense and in infectious disease research. The Institute's mission is to conduct basic and applied research on biological threats resulting in medical solutions (such as vaccines, drugs and diagnostics) to protect the warfighter. USAMRIID is a subordinate laboratory of the U.S. Army Medical Research and Materiel Command.

Secret of smallpox's success may lead to bioterror cure

In disease, as in war, offensive strategies can become weaknesses, if the defenders see the enemy coming and compensate for its weapons.

By manipulating what is perhaps the most devastating trick in cellular weaponry of pox viruses like smallpox, Arizona State University virologist and Biodesign Institute researcher Bertram Jacobs believes that he can turn the biochemical machinery of the pox viruses against themselves - and protect the public against catastrophic bioterror attacks.

And if he is correct, Jacobs may not only be able to create a vaccine that can cure smallpox infections in their early stages, but he may also have a powerful tool for fighting a host of other viral pathogens, including HIV.

Jacobs has received a $1 million grant from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health (NIH), to develop an effective post-exposure vaccine for smallpox. The research is one of ten projects funded under Project Bioshield, which gives federal agencies new tools to accelerate research on medical countermeasures to safeguard Americans against chemical, biological, radiological or nuclear attack.

The idea for the vaccine comes from Jacobs and his team's discovery of a gene that gives pox viruses uncanny ability to camouflage themselves from mammalian immune systems. The ability to stay hidden allows the smallpox virus, in particular, time to grow and multiply to the point of causing devastating disease before the immune system detects it and attempts to mount a counter-attack.

Jacobs notes that there have been clues to this property of the virus present in historical results from using vaccinia, or cowpox, to immunize against smallpox. In most people, exposure to vaccinia generally only causes a mild infection in humans before the immune system responds and eliminates the virus, also leaving immunity to smallpox and other pox viruses in its wake.

"And there has been anecdotal evidence that if you get exposed to smallpox and get vaccinated within 4 days of exposure, the vaccine will protect you," Jacobs said. The immune system is apparently better able to detect the vaccinia virus than it is smallpox, and thus vaccinia alerts the immune system in time to counteract the smallpox infection.

Jacobs' idea for a post-exposure vaccine is to strengthen the immune response to the vaccinia virus by completely eliminating the viral gene that allows pox viruses to hide. The more visible the vaccinia virus is to the immune system, the stronger the immune response should be and the better the body should be able to fight off a smallpox infection.

Over the past 15 years, Jacobs has developed a variety of mutant vaccinia viruses that lack the camouflage gene, and have proved harmless to mice that otherwise get sick from vaccinia. Currently, he is testing these strains for their ability to protect mice that have already been exposed to a particularly lethal strain of vaccinia, or to mouse pox, another pox virus.


"We want to look at all of our mutants and see which ones work best in this post-exposure prophylaxis," explained Jacobs. Though results are preliminary, several strains look promising.

Jacobs' experimental results verify that the de-cloaked viruses not only do not cause disease, but improve disease resistance when they are present. When a mouse has been exposed to a lethal vaccinia virus and then is vaccinated with a very low dose of the mutant virus - only 100 virus particles - the mouse gets sick but eventually recovers. The more mutant virus the mice are given, the less sick they become.

"If you give them a million particles, they don't even get sick -- the animals stay healthy," notes Jacobs.

"The body reacts and it fights off both the mutant, and also the normal virus that normally would hide itself," said Jacobs. "The more you put in, the more likely it is for the immune system to say 'Hey, wait a minute! There is something going on here! I need to start fighting a virus infection!' and so it fights the mutant virus and a normal pathogenic virus as well."

The gene that Jacobs has isolated and eliminated from the mutants is a special adaptation of pox viruses that appears to help the viruses hide double-stranded RNA, a form of RNA that only viruses produce and that animal immune systems have learned to recognize.

"It's what we call a 'pathogen associated molecular pattern' - a biomarker that is only present in your body when you are infected with a virus and that the body knows to look for and respond to," said Jacobs. "The body responds in a lot of different ways, but the main way is it starts producing an immune response - double-stranded RNA is very powerful in eliciting this.

"What this gene in pox viruses does is make a protein that binds up all the double-stranded RNA like a little sponge, and this is how the viruses hide infection from your cells," he explained. "Take the gene out and now we have a vaccinia virus that can no longer hide itself - it can't camouflage its signature anymore from the cells in its body."

Once the virus calls attention to itself, the immune system begins a complex immune response, including developing antigens that specifically target the virus. Because the virus's double-stranded RNA signal is very clear, the immune response tends to be very strong when the quantity of the uncloaked virus is high.

According to Jacobs, the uncloaked vaccinia virus has the potential to be useful for developing novel post-exposure vaccines for other dangerous viruses as well, making available a who new arsenal of weapons against disease. Antigen-eliciting genes from hard-to-treat viruses such as HIV could potentially be added to the mutant vaccinia virus, which would draw the immune system's attention to the target virus's proteins, thus creating a strong immune response to the target virus. Though perhaps controversial, such a method could ultimately provide effective protection from some of humankind's most challenging viral enemies.

Jacob's current attempt to develop a post-exposure smallpox vaccine is also not with its challenges. Because of the extreme dangerousness of the smallpox virus, the effectiveness of the vaccine cannot actually be tested through clinical trials on humans. Instead, the vaccine is tested on mice and other animal models, using viruses closely related to smallpox that are lethal to those animals.

"We're testing with vaccinia and mousepox in lab mice, and in dormice with monkeypox. These are good model systems - if we can protect against mousepox in mice, then we have a high level of certainty that the vaccine will be able to protect against smallpox in humans," Jacobs said.

"Since you can't test in people, the FDA's animal efficacy rule applies. If you can show efficacy in several animal models, then you can presume efficacy in humans, if it is for a disease that you can't ethically expose people to in trial. The vaccine will go through safety studies in humans, though."

Because of the importance of the research for national security, Jacob's work is on a fast-track, with the studies projected to yield a usable vaccine virus within eighteen months. At that point, the virus will go to a commercial manufacturer, who will be responsible for developing and then producing a complete nasal-delivery vaccine. If all is successful, a large number of doses will then be produced and put into storage for possible use in case of emergency, in accordance with the procedures of Project Bioshield.

Though the final product may take a while to be produced and, one hopes, may never have to be used, Jacobs has a feeling now of years of research coming to fruition.

"This is the result of work that we have been doing for 15 years now and I think we are really very close to producing some really important findings, especially now that we are engaged in these fast-track projects," Jacobs said. "It's really exciting."

New biosensor helps detect toxic biological agents more quickly developed by Houston University student

A University of Houston student has made an award-winning breakthrough in biosensors that could help bioterrorism researchers in their ability to quickly and accurately detect toxic biological agents.

Mrinal Shah, a doctoral student in chemical engineering at UH, has developed new methods in the use of biosensors that could provide one of the first steps in developing a protein-based biosensor that would help the government in safeguarding the nation.

Working under the direction of Peter Vekilov, a world-renowned expert in the field of nucleation and a chemical engineering professor at the UH Cullen College of Engineering, Shah employs liquid-liquid phase separation - a technique that is similar to the concept behind how oil and water separate. His research makes use of the proteins needed in biosensors and accurately controls the nucleation of those proteins.

"The development of a successful biosensing chip has potential uses that are manifold and urgently needed with several applications that are immediately significant," Shah said. "If there is biological warfare somewhere, and you put this chip into that environment, you would know exactly what is in that environment, and safety precautions could be taken. That's the ultimate achievement that every scientist working in protein chips dreams about."

Biosensing chips are already in use for studies such as the quality control of water and checking glucose levels. Shah's involvement in the biosensing application began with his initial interest in protein nucleation that occurs with diseases such as Parkinson's, sickle cell anemia and Alzheimer's. While his methods may prove useful in the early detection of these diseases, Shah said he is not searching for any cures. He said that what basically happens is the protein is normal inside the body, but then suddenly something happens for it to just start nucleating. The protein misfolds, denatures and begins to aggregate together forming into the disease.

"We're not finding cures ourselves, but we are finding the mechanisms that follow the formations of these fibers," Shah said. "Once we know the mechanism, then we also can know by what methods to reduce the rate of its formation. The physics behind the mechanisms is much more interesting to us."

Shah says there are a number of other applications for the chip, as well, including combating mad cow disease and anthrax.

While working on the initial part of his project - studying the kinetics and the thermodynamics involved to better understand what mechanisms govern the phase separation of nanoscale droplets of protein solution - Shah came up with the idea that could lead to a new potential way of making biosensors that would be fast and easy. He found that control over nucleation is essential to the creation of biosensors.

"It was a difficult project, because we were hoping that one of two approaches would work, and neither of them did," Vekilov said. "We tried electrophoresis and dielectrophoresis and neither worked. But Mrinal kept working, kept trying new things and finally developed his own method. What we discovered is that the solution has a time-dependent, non-uniform electric field, and this is what causes the nucleation."

"The next step will be to tag the protein molecule onto the micro-area electrode," Shah said. "That will be a challenge, but we already have several promising strategies in mind."

Since winning second place at last year's Keck Annual Research Conference, Shah has been able to replicate his results, using a more widely used biosensing protein - horseradish peroxidase. The W.M. Keck Center for Computational and Structural Biology is designed to unite modern biological, physical and computational sciences in addressing problems in biology and biomedicine. Its six member institutions include UH, Rice University, Baylor College of Medicine, The University of Texas Health Science Center at Houston, The University of Texas Medical Branch at Galveston and The University of Texas M.D. Anderson Cancer Center.

About the University of Houston

The University of Houston, Texas' premier metropolitan research and teaching institution, is home to more than 40 research centers and institutes and sponsors more than 300 partnerships with corporate, civic and governmental entities. UH, the most diverse research university in the country, stands at the forefront of education, research and service with more than 35,000 students.

About the Cullen College of Engineering

UH Cullen College of Engineering has produced five U.S. astronauts, ten members of the National Academy of Engineering, and degree programs that have ranked in the top ten nationally. With more than 2,600 students, the college offers accredited undergraduate and graduate degrees in biomedical, chemical, civil and environmental, electrical and computer, industrial, and mechanical engineering. It also offers specialized programs in aerospace, materials, petroleum engineering and telecommunications.

New 'biosensor' screens Air Force personnel and equipment for contamination within minutes

Air Force personnel will soon know within minutes if they or their equipment are contaminated with a biological agent, thanks to a new technology developed by the Air Force and a national laboratory.

Personnel will use the biosensor system to collect and isolate samples, detect and identify agents, and assess the seriousness of the threat.

"The system will provide an increased capability for Air Force Special Operations personnel to rapidly determine the presence of biological warfare agents in a combat environment," said Dr. Richard Stotts, counterproliferation branch chief within the Air Force Research Laboratory's Human Effectiveness Directorate. The device is compact, quickly identifies agents, can be used repeatedly and requires very little maintenance to keep it running in the field."

The system consists of a spray, developed at the directorate's Brooks City-Base, Texas, facilities, and a hand-held "green box," which determines if agents are present. The green box, or DNA Capture Element instrument, was developed by researchers at the Department of Energy's Pacific Northwest National Laboratory. The box uses an Air Force-developed biochemical assay based on aptamers, or single chain DNA fragments.

"We've used our lab's expertise to develop an instrument that's complementary to the Air Force's technology and that simultaneously satisfies the speed, specificity, sensitivity, portability, durability, health and safety needs," said Mike Lind, a senior advisor at PNNL. "The rapid detection capability of this instrument will be useful in a variety of applications, even outside of the armed forces."

With the prototype system, the user sprays the suspected contaminated area, creating a sample that can be picked up by a swab. The sample material on the swab is suspended in liquid by rinsing it in a container. Once in a liquid form, the sample is injected into a special flow cell, the place where the assay occurs.

The flow cell is currently designed for one-time use. Since the cell is sealed, it can be decontaminated by immersion in a bleach solution and then safely transported to a forensic laboratory for further analysis where it can be opened to retrieve the sample material.

A liquid crystal display, or LCD, provides a quantitative readout of the concentration of targeted material present, and a set of red, yellow, and green light emitting diodes provides an easily interpreted reading of the threat level. For instance, "no threat" is green, a barely detectable to medium level of an agent is one or two yellow dots, and a high detection level is red.

The biosensor system is designed to be reliable, disposable and cost-effective. The Air Force will continue testing the device over the next several months.

PNNL (http://www.pnl.gov) is a DOE Office of Science laboratory that solves complex problems in energy, national security, the environment and life sciences by advancing the understanding of physics, chemistry, biology and computation. PNNL employs 4,000, has a $650 million annual budget, and has been managed by Ohio-based Battelle since the lab's inception in 1965.

Post-9/11 Immigration Enforcement Lowered Demand For Undocumented Workers

A recent study in the Journal of Policy Analysis and Management shows that as a result of a variety of interior enforcement initiatives implemented in 2002-2005, such as the ramping up of the Social Security no-match program, employers' demand for undocumented workers fell. This led to an erosion of the wages and employment opportunities of recent low-education male immigrants from Latin America with potentially negative implications for U.S. taxpayers.

The study's results show that increases in immigration-related law enforcement since September 2001 unfavorably affected the labor market for low-education, male immigrants from Latin America, a group that composes the bulk of undocumented workers in the U.S.

Consequently, their wages, employment, and hours worked all fell relative to similar low-education black and Hispanic native men and immigrants who have been in the U.S. longer.

"Interior enforcement without comprehensive immigration reform can be a lose-lose proposition," the authors conclude. "As illegal immigrants and their families are pushed closer to poverty and into greater dependence on public assistance, both the immigrant and the taxpayer may lose out."

Social Networking For Terrorists

A new approach to analyzing social networks, reported in the current issue of the International Journal of Services Sciences, could help homeland security find the covert connections between the people behind terrorist attacks. The approach involves revealing the nodes that act as hubs in a terrorist network and tracing back to individual planners and perpetrators.

Dr Yoshiharu Maeno, Founder Management Consultant of the Social Design Group and Dr Yukio Ohsawa, Associate Professor at the School of Engineering, University of Tokyo, Japan, explain that their analytical approach to understanding terrorist networks could ultimately help prevent future attacks.

Terrorist attacks can cause significant loss of life, have intense social and environmental impacts, and large economic losses. Maeno and Ohsawa explain that responding to a terrorist attack is akin to dealing with a natural disaster, with one important difference. Disaster recovery management is required with both, but in the case of a terrorist attack there is the added pressure of short-term responses to the terrorists themselves and in the long-term the need to identify and weaken the covert foundation underpinning an organized attack.

The team explains that by combining the prior understanding of expert investigators with graph theory and computational data processing, it should be possible to analyze a terrorist network and reveal latent connections and patterns. The researchers have carried out such an analysis of the network responsible for the 9/11 attacks in 2001 in order to evaluate the performance of their approach.

Fundamentally, their technique is a mathematical one involving "node" discovery. The nodes of a network are the hubs at which different members of the network are connected. Usually, ordinary members have one or two connections, nodes can have several and the critical nodes, the hubs, have many more.

The scheme is analogous to the structure of the world-wide web where individual web pages may have one or two connections, small organizations may have a few more. Major hubs, such as the big search engine companies, such as Google and Yahoo, news sources like CNN and the BBC, and social media networks such as Facebook and MySpace have many, many more. These big nodes act as the hubs through which individual and smaller sites are interconnected.

The team's computational analysis of the terrorist network associated with the 9/11 attacks revealed nodes that were not apparent to security experts in advance of the attacks. Such latent nodes appear to have been critical to the attacks but superficially do not appear to be particularly important individuals acting as hubs.

The analysis revealed a connection not known in advance of 9/11 between Waleed Alshehri and Mohand Alshehri, who share a name but are unrelated, which indicated the existence of Mustafa Ahmed Al-Hisawi as an important individual in the network.

In retrospect the connections seem obvious, but they were not seen initially, but the Japanese team's analysis could have unearthed them much sooner. Mohand Alshehri helped Mohammed Atta hijack the AA11 and fly it into the North Tower of the World Trade Center. Mohand Alshehri hijacked the AA175 and flew it into the South Tower of the World Trade Center. Waleed Alshehri had six links and is, the researchers demonstrate, the keystone person.

Having such network insights sooner rather than later would allow investigators to gather information on associates, friends, and relatives of a suspect terrorist and so bring the perpetrators to justice that much sooner or perhaps even unravel a network plotting future attacks.

"If the investigators had had a warning information on the 19 hijack planners (including WA and MA) before 9/11, our analysis could have aided the investigators in quickly understanding the complete picture of the organized attack including the covert foundation (like MAAH)," Yoshiharu says, "I am not sure, however, whether even a very quick investigators' understanding and action could have prevented the attack. Our analysis seems more suitable to satisfying the long-term need than the short-term need."

New Detectors For Nuclear, Radiological Material In Cargo Should Not Be Acquired Until Testing Deficiencies Fixed, Cost-Benefit Analysis Completed

A thorough cost-benefit analysis that includes an assessment of meaningful alternatives is needed to reveal the potential security advantages of deploying new detector systems to screen cargo for nuclear and radiological materials at U.S. ports and border crossings. It is likely that the costs will exceed the savings gained from improved efficiency of the screening systems, says a new report from the National Research Council. There are shortcomings in the U.S. Department of Homeland Security's testing of these new detector systems, therefore the DHS secretary cannot conclude whether they will consistently outperform the current ones. DHS should not proceed with further procurement of these new detector systems until the issues are addressed and the systems have been shown to be a favored option in the cost-benefit analysis.

The 2006 SAFE Port Act requires that all containers coming into the United States through major entries be scanned for radiation, and "to the extent practicable, the Secretary shall deploy next generation radiation detection technology" to enable such scanning. In response, the department's Domestic Nuclear Detection Office (DNDO) requested proposals for advanced spectroscopic portals (ASPs), the next generation of radiation detectors for cargo screening, to replace the current system of radiation portal monitors and handheld radioisotope identifiers, which have known deficiencies. Before DHS can proceed with full-scale procurement of ASPs, Congress required the secretary to certify that they will provide a "significant increase in operational effectiveness" over continued use of the existing screening devices. If ASPs are certified, DHS may spend more than $1 billion to purchase these detector systems, with a possible net lifecycle cost of more than twice that figure. Currently, DHS is testing and evaluating the ASPs to inform the secretary's decision.

Congress asked the Research Council to advise DHS about testing, analysis, costs, and benefits of ASPs before this certification decision is made. The ASP testing and evaluation program encountered some delays in 2008, which created the opportunity for this interim report to provide advice on how testing, evaluation, and the cost-benefit analysis should be completed.

Testing of ASPs before 2008 had serious flaws, a number of which DNDO has acknowledged and addressed, said the committee that wrote the new interim report. In 2008, DNDO carried out physical tests to evaluate some of the limits of the ASP systems, but inadequacies remain. These include a lack of modeling to complement the physical tests and small test sample sizes that limit the confidence of comparison testing between the old and new detector systems.

The committee recommended an iterative testing approach, using computer models to simulate performance of the detector systems and physical experiments to test the models and identify needs for refinements. Then the needed model refinements could be undertaken. This iterative modeling and testing approach will allow DHS to gain a better understanding of the detector systems' performance, the committee said.


Rather than focusing on a single procurement to replace current screening technology, testing of ASPs should be viewed as a first step in improving and adapting the detector systems, the committee recommended. DHS should develop a process for continuous improvement that could address and exploit changes in technology and the nature of commerce so the system is not outdated or obsolete by the time it is fully deployed. DHS should begin this process by deploying the unused ASPs they already own in real ports of entry.

To determine whether the costs for these systems are reasonable and justified, a careful assessment will be needed to reveal the advantages of ASPs among alternatives, the committee said. The cost-benefit analysis should include a clear statement of the objectives of the program; an assessment of meaningful alternatives; and a comprehensive, credible, and transparent analysis of in-scope benefits and costs. The benefit assessment should show how the procurement contributes, relative to other possible DHS efforts and expenditures, to improving security with respect to prevention of the detonation of a nuclear or radiological device, which is the primary objective of the ASP program. A cost-benefit analysis that is silent on this subject would be incomplete, the committee noted.

The study was sponsored by U.S. Department of Homeland Security. The National Academy of Sciences, National Academy of Engineering, Institute of Medicine, and National Research Council make up the National Academies. They are independent, nonprofit institutions that provide science, technology, and health policy advice under an 1863 congressional charter. Committee members, who serve pro bono as volunteers, are chosen by the Academies for each study based on their expertise and experience and must satisfy the Academies' conflict-of-interest standards. The resulting consensus reports undergo external peer review before completion.

Anthrax Attack Requires Early Detection & Quick Response

A large attack on a major metropolitan area with airborne anthrax could affect more than a million people, necessitating their treatment with powerful antibiotics. A new study finds that in order for a response to be effective, quick detection and treatment are essential, and any delay beyond three days would overwhelm hospitals with critically ill people.

The results of a computer simulation study appear in the July/August edition of the journal Medical Decision Making -- one of two studies by Dr. Nathaniel Hupert of Weill Cornell Medical College in the issue.

"No matter how well-organized and prolonged a treatment program is, it must be quickly implemented. In fact, our analysis shows that time-to-treatment is roughly twice as important as the duration of the distribution program," says lead author Dr. Nathaniel Hupert, associate professor of public health and medicine at Weill Cornell Medical College.

"Crucial to rapidly implementing a treatment program is early detection, including thorough use of advanced biosurveillance technologies and live, person-to-person communication," continues Dr. Hupert, who is also director of the new Preparedness Modeling Unit at the U.S. Centers for Disease Control and Prevention (CDC). "But most important of all are multilateral diplomatic efforts to prevent bioterrorist attacks from ever happening."

The study predicts that a campaign initiated two days after exposure would protect as many as 87 percent of exposed individuals from illness -- a rate considered successful by the CDC. Each additional day needed to complete the campaign would result in an average of up to 2.9 percent more hospitalizations in the exposed population. And each extra day of delay to the start of the program beyond two days would result in up to 6.5 percent more hospitalizations. Anthrax attack scenarios typically involve the release of one kilogram of weaponized anthrax from a small airplane flying over a major city. The invisible powder could be inhaled by thousands or hundreds of thousands, who would start becoming sick anywhere from 24 hours to a week or more after the attack. With appropriate and timely administration of an antibiotic treatment program, exposed individuals would be spared from developing inhalational anthrax infection.

Co-authors include Daniel Watson of Washington University School of Medicine in St. Louis, Mo.; Jason Cuomo of Operation USA, Culver City, Calif.; and Weill Cornell's Dr. Wei Xiong, and Eric Hollingsworth and Kristof Neukermans, formerly research data specialists in the Weill Cornell Department of Public Health, reporting to Dr. Hupert.

The study is funded by the U.S. Department of Health and Human Services, Agency for Healthcare Research and Quality, and the National Institutes of Health.

Guidelines for Computer Modeling of Disaster Response

Dr. Hupert is co-author the first-ever position paper of the Society for Medical Decision Making -- also appearing in the July/August edition of the journal Medical Decision Making. The study tackles a challenge in the emerging field of disaster response planning -- the confusing variety of approaches to computer modeling.

Computer modeling is increasingly used to predict and plan for disaster response. But because there are so many different modeling methods, researchers have been unable to compare results between models. Dr. Hupert and his co-authors looked at various approaches and recommend several best practices: models should address real-world problems, be designed for maximum usability, strike the appropriate balance between simplicity and complexity, include appropriate outcomes, and be designed to evaluate the many uncertainties inherent in disaster response. Finally, the authors stress that clear and complete reporting of model results is particularly critical for disaster response models.

The study's lead author is Dr. Margaret Brandeau of Stanford University. Additional co-authors include Jessica McCoy, Jon-Erik Holty and Dena Bravata of Stanford University.

Weill Cornell Medical College

Weill Cornell Medical College, Cornell University's medical school located in New York City, is committed to excellence in research, teaching, patient care and the advancement of the art and science of medicine, locally, nationally and globally. Weill Cornell, which is a principal academic affiliate of NewYork-Presbyterian Hospital, offers an innovative curriculum that integrates the teaching of basic and clinical sciences, problem-based learning, office-based preceptorships, and primary care and doctoring courses. Physicians and scientists of Weill Cornell Medical College are engaged in cutting-edge research in areas such as stem cells, genetics and gene therapy, geriatrics, neuroscience, structural biology, cardiovascular medicine, transplantation medicine, infectious disease, obesity, cancer, psychiatry and public health -- and continue to delve ever deeper into the molecular basis of disease and social determinants of health in an effort to unlock the mysteries of the human body in health and sickness. In its commitment to global health and education, the Medical College has a strong presence in places such as Qatar, Tanzania, Haiti, Brazil, Austria and Turkey. Through the historic Weill Cornell Medical College in Qatar, the Medical College is the first in the U.S. to offer its M.D. degree overseas. Weill Cornell is the birthplace of many medical advances -- including the development of the Pap test for cervical cancer, the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial of gene therapy for Parkinson's disease, the first indication of bone marrow's critical role in tumor growth, and most recently, the world's first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient.

Scientists Move Closer To A Safer Anthrax Vaccine

Researchers at Albert Einstein College of Medicine of Yeshiva University have identified two small protein fragments that could be developed into an anthrax vaccine that may cause fewer side effects than the current vaccine.

The research is significant because anthrax is considered a major bioterrorism threat. The current anthrax vaccine is intended mainly for members of the armed forces serving in areas considered high risk and for individuals involved in homeland biosecurity.

"Our research was motivated by the fact that the current anthrax vaccine has significant limitations and there is great need for a better one," says lead author Nareen Abboud, Ph.D., an Einstein postdoctoral fellow and lead author of the study, which appears in the current issue of The Journal of Biological Chemistry. The study's senior author is Arturo Casadevall, M.D., Ph.D., Leo and Julia Forchheimer Professor and chairman of microbiology & immunology.

Anthrax, a disease caused by the bacterial species Bacillus anthracis, occurs when anthrax spores (the microbe's dormant stage) are inhaled, ingested or enter the body through an open wound. Anthrax is a common disease among grazing animals such as cows, goats, and sheep but can also result from bioterrorism.

Eighty to 90 percent of people infected through inhalation will die if not treated, according to the U.S. Department of Health and Human Services. In 2001, five people died after inhaling anthrax spores contained in envelopes mailed to U.S. lawmakers and media personnel. Typical treatment post-exposure includes the antibiotics ciprofloxacin, doxycycline and penicillin.

Anthrax results in part from toxic proteins, or toxins, that the multiplying bacteria secrete. The current anthrax vaccine employs one of these proteins, which elicits protective antibodies when injected into people.

While this 40-year-old vaccine can prevent disease, it has significant drawbacks. Immunity is temporary, and five injections over the course of 18 months are needed to sustain it. One in five vaccine recipients develop redness, swelling or pain at the injection site, and a small number develop severe allergic reactions. A recent article in the journal Clinical Infectious Diseases states that nearly seven million doses of the anthrax vaccine were administered to more than 1.8 million Americans between 1998 and 2008.

In their study, the Einstein scientists focused on the protein toxin used in the current vaccine, looking for the smallest protein sections (known as peptides) that could trigger the production of protective antibodies when injected into animals.

The researchers injected the current vaccine into mice and recovered six different "pure" strains of antibodies known as monoclonal antibodies. They then mixed each type of antibody with the 145 peptides formed by chopping up the vaccine protein. The researchers looked for peptides that were "recognized by" (became bound to) an antibody an indication that those particular peptides might themselves be able to stimulate the production of protective antibodies on their own.

Ultimately, the researchers found that two of the 145 peptides fit the bill: Each peptide elicited antibodies when injected into mice, and these antibodies protected macrophages from death that would normally have occurred when the macrophages were exposed to anthrax toxin. (Macrophages are protective white blood cells involved in the body's immune response to foreign invaders.) The next step in the Einstein research will be to inject the peptides into an animal model to see if the peptides can protect against anthrax infection.

"An ideal anthrax vaccine contains only the proteins needed to provide protection against disease, and none of the extraneous protein material that triggers the adverse reactions caused by the current vaccine," says Dr. Abboud. "We're hopeful that the two peptides that we have identified in this study can offer these benefits."

The simple structure of these peptides one is only five amino acids in length, the other six means it should be easy to synthesize the peptides and inexpensive to produce a vaccine containing them, Dr. Abboud notes.

Einstein will be applying for a patent for the use of the two peptides in an anthrax vaccine.

The paper, "Identification of Linear Epitopes in Bacillus anthracis Protective Antigen Bound by Neutralizing Antibodies," appears in the September 4 online edition of The Journal of Biological Chemistry. In addition to Drs. Abboud and Casadevall, the other members of the Einstein research team are Magdia De Jesus, Antonio Nakouzi, Radames J.B. Cordero, Mario Pujato, Andras Fiser and Johanna Rivera.

About Albert Einstein College of Medicine of Yeshiva University

Albert Einstein College of Medicine of Yeshiva University is one of the nation's premier centers for research, medical education and clinical investigation. It is home to 2,775 faculty members, 625 M.D. students, 225 Ph.D. students, 125 students in the combined M.D./Ph.D. program, and 380 postdoctoral research fellows. In 2008, Einstein received more than $130 million in support from the NIH. This includes the funding of major research centers at Einstein in diabetes, cancer, liver disease, and AIDS. Other areas where the College of Medicine is concentrating its efforts include developmental brain research, neuroscience, cardiac disease, and initiatives to reduce and eliminate ethnic and racial health disparities. Through its extensive affiliation network involving eight hospitals and medical centers in the Bronx, Manhattan and Long Island which includes Montefiore Medical Center, The University Hospital and Academic Medical Center for Einstein the College of Medicine runs one of the largest post-graduate medical training programs in the United States, offering approximately 150 residency programs to more than 2,500 physicians in training.

Asthma Plagues World Trade Center Responders

Responders to the 2001 World Trade Center (WTC) terrorist attacks, who were exposed to caustic dust and toxic pollutants following the 9/11 disaster, suffer from asthma at a rate more than twice that of the general US population, according to new research presented at CHEST 2009, the 75th annual international scientific assembly of the American College of Chest Physicians (ACCP).

As many as 8 percent of the workers and volunteers who engaged in rescue and recovery, essential service restoration, and cleanup efforts in the wake of 9/11 reported experiencing post-9/11 asthma attacks or episodes, compared with 4 percent of the general population. Furthermore, the lifetime prevalence of asthma in WTC responders was marked by a dramatic increase from 3 percent pre-9/11 to a high of 16 percent in each of the years from 2005 through 2007.

"Although previous WTC studies have shown significant respiratory problems, this is the first study to directly quantify the magnitude of asthma among WTC responders compared with the general US population," said Hyun Kim, ScD, Instructor of Preventive Medicine at Mount Sinai School of Medicine (MSSM), New York, NY, and lead author of the analysis which uses data obtained from the federally-funded World Trade Center Medical Monitoring and Treatment Program. "Six years out from 9/11, the World Trade Center Program was still observing responders affected by asthma episodes and attacks at more than double the percentage of people not exposed to World Trade Center dust."

WTC Study Details

In the multicenter clinical study, researchers from the MSSM-coordinated WTC Program reported on health-related findings of 20,843 WTC responders who received an initial medical screening examination during the program's first 5-1/2 years of existence, from July 2002 through December 2007. Asthma outcomes assessed were the following: (1) prevalence of asthma episodes/attacks reported by responders to have occurred during the previous 12 months, and (2) lifetime asthma prevalence, as measured by participants reporting having ever been told by a physician that they had asthma. Results were compared with the US National Health Survey Interviews (NHIS) adult sample data for the year 2000 (pre-9/11) and years 2002 through 2007.

WTC Study Results

In the general population, the prevalence of asthma episodes and/or attacks in the previous 12 months remained relatively constant at slightly less than 4 percent throughout the period from 2000 to 2007. In contrast, among WTC responders, while fewer than 1 percent recalled asthma episodes or attacks during the year 2000, that percentage increased to 8 percent, and then remained constant, through the period from 2005 to 2007. WTC responders were 2.3 times more likely to report asthma episodes/attacks that had occurred during the previous 12 months when compared with the general population of the United States. Additionally, the increase in lifetime prevalence of asthma among responders undergoing their initial program screening any time during the study period grew from a reported 3 percent for (pre-9/11) diagnoses to 13 percent in 2002. The lifetime prevalence of asthma subsequently rose through the years to plateau at 16 percent from 2005 through 2007.

"It is important to note that this report focused on findings from baseline or initial visit examinations," said Philip J. Landrigan, MD, MSc, Ethel H. Wise Professor and Chair of MSSM's Department of Preventive Medicine, and principal investigator of the WTC Program Data and Coordination Center. "Where the data shows an increasing percentage of responders reporting asthmatic episodes, rising to double that seen in the general population, it is clearly vital that we continue to track responders' health and look further into the medical outcomes of this population."

Of the study's rescue and recovery workers, 86 percent were men; 59 percent were Caucasian; and the average duration of work at WTC sites was 80 days. The study followed uniformed and other law enforcement and protective service workers (42 percent), as well as construction workers and other responders who had engaged in paid and volunteer WTC-related rescue and recovery, essential service restoration, and/or debris removal and cleanup efforts.

"Asthma and other chronic lung conditions remain a significant burden for rescue and recovery workers responding to the attacks on the World Trade Center," said Kalpalatha Guntupalli, MD, FCCP, President of the American College of Chest Physicians. "The significant chronic health problems associated with the World Trade Center attacks only reinforces the need for stronger disaster preparedness plans, as well as long-term medical follow-up for 9/11 responders and individuals who respond to disaster-related events."

CHEST 2009 is the 75th annual international scientific assembly of the American College of Chest Physicians, held October 31-November 5 in San Diego, CA. The ACCP represents 17,400 members who provide patient care in the areas of pulmonary, critical care, and sleep medicine in the United States and throughout the world. The ACCP's mission is to promote the prevention and treatment of diseases of the chest through leadership, education, research, and communication. For more information about the ACCP, please visit the ACCP Web site at http://www.chestnet.org.

UIC To Develop Antibiotics Against Potential Bioterrorism Agents

Researchers at the University of Illinois at Chicago have received a $4 million federal grant to develop new antibiotics to treat anthrax, tularemia and plague.

Anthrax, tularemia and plague are caused by naturally occurring bacteria classified as "category-A" agents that could be used in bioterrorism and biowarfare.

These microorganisms pose a risk to national security because they can be easily transmitted and disseminated, result in high mortality, have potential major public health impact and could cause panic, according to the Centers for Disease Control and Prevention.

These infections can be treated with current antibiotics, but none is ideal, says Michael Johnson, professor and director of the UIC Center for Pharmaceutical Biotechnology and lead researcher on the two-year grant. Only one antibiotic, doxycycline, can be used to treat more than one of the three diseases, he said.

Worse, it may be possible for terrorists to develop multi-drug resistant strains for all three diseases, Johnson said.

"Our goal is to develop an advanced series of broad-spectrum antibacterial 'lead' compounds that are safe, efficacious and that can be taken orally," Johnson said.

Anthrax infection can occur by absorption through the skin, by inhalation, or through the gastrointestinal tract. If left untreated, the disease can be fatal.

Tularemia, or rabbit fever, has a low fatality rate if treated, but can be incapacitating. It can be contracted through contact, inhalation, ingestion of contaminated water, or by insect bites.

Plague is caused by a bacterium found in rodents and their fleas in many areas of the world. The typical sign of the most common form of human plague is a swollen and tender lymph gland, accompanied by pain. About 14 percent of plague cases in the U.S. are fatal, according to the CDC.

Funding for the research is through the American Recovery and Reinvestment Act of 2009. It is the largest grant UIC has received through the Act and is funded by the National Institute of Allergy and Infectious Diseases, one of the National Institutes of Health.

Johnson's collaborators include Dr. James Cook, chief of infectious diseases in the UIC College of Medicine; Andrew Mesecar, professor in the UIC Center for Pharmaceutical Biotechnology; and David Case, professor of chemistry and chemical biology at Rutgers University.

Predicting The Unthinkable: New Modeling Work On Nuclear Weapons Presented At Fluid Dynamics Conference

If a nuclear weapon were detonated in a metropolitan area, how large would the affected area be? Where should first responders first go? According to physicist Fernando Grinstein, we have some initial understanding to address these questions, but fundamental issues remain unresolved.

"The predictive capabilities of today's state-of-the-art models in urban areas need to be improved, validated and tested," says Grinstein. "Work in this area has been limited primarily because of lack of consistent funding."

At 62nd Annual Meeting of the American Physical Society's (APS) Division of Fluid Dynamics in Minneapolis, Adam Wachtor - a student who worked with Grinstein at the Los Alamos National Laboratory in New Mexico - will present his efforts to improve the way that models track the movement of radioactive fall-out carried by the wind. His wind models track the aftermath of a plume of hot gas released by a small, one-ton device in a typical urban setting at a three-meter resolution.

Current models use wind direction and wind speed to draw a predicted cone-shape area of fall-out. Wachtor's results show that these models are too simple in some ways. For instance, they do not include the complex dynamics of wind movements around buildings, which can concentrate fall-out preferentially in certain areas. They also indicate that small changes in the location of the blast and the temperature of the plume released can have a large effect on the contamination patterns.

The simulation is part of a larger coordinated effort between DHS (FEMA), the National Laboratories, DTRA, NRL, and private contractors, each of which has concentrated on a different piece of the project. Other studies have shown that, depending on the situation, buildings can provide some degree of shielding from the radiation.

The hope of the researchers collaborating in this effort is to eventually provide practical information to guide first responders. "We're preparing for [a possible] crisis," says Grinstein - however unthinkable it may be.

Combating Hospital-Acquired Infections, Deadly Food Poisoning And Bioterrorism Toxins

This study paves the way for developing toxin antidotes to safeguard public health and national security.

A team of scientists from A*STAR's Institute of Molecular and Cell Biology (IMCB) has discovered the secret recipe for 'antidotes' that could neutralize the deadly plant toxin Ricin, widely feared for its bioterrorism potential, as well as the Pseudomonas exotoxin (PE) responsible for the tens of thousands of hospital-acquired infections in immune-compromised patients all over the world. The results of this first ever genome-wide study to understand how the Ricin and PE toxins attack cells may also be useful for designing more effective antidotes against Diphtheria and Shiga-like toxins secreted by infectious strains of E. coli bacteria, such as those responsible for the recent food poisoning outbreak in Germany.

In this study, the team led by IMCB Principal Investigator, Dr Frédéric Bard examined the entire human genome of about 22,000 genes to identify those genes of normal host cell processes which Ricin and PE toxins hijack in order to kill the cell. Of the several host genes identified, the team discovered one called ERGIC2 to be an attractive therapeutic target because it is not only highly essential for Ricin but also required for PE intoxication. "This means that we could potentially develop a generic antidote that is effective against the two different types of toxins by blocking ERGIC2 function," said Dr Bard.

Ricin is an extremely potent poison that can easily be purified from the widely available castor beans. Security experts say an amount roughly equivalent to half a grain of rice is enough to kill an adult, making it 1,000 times more poisonous than cyanide. There are currently no known antidotes for Ricin, and the ease of production of this tasteless, odorless plant toxin is why ricin is feared for its immense bioterrorism potential.

Hospital-acquired infections (HAIs) are a major healthcare problem affecting millions of people around the world. The U.S. Centers for Disease Control and Prevention estimates that HAIs leads to US$45 billion in healthcare cost annually and results in nearly 100,000 deaths per year, making HAIs the fourth leading cause of death. The bacteria Pseudomonas aeruginosa that secretes PE toxin is a common cause of HAIs in vulnerable individuals, including those with burn injuries or receiving intensive care. Unfortunately, HAIs are increasingly difficult to treat because the emergence of antibiotic-resistant bacteria is on the rise. Similarly, the E. coli strain that produces Shiga toxins, found in the recent deadly food poisoning cases in Germany, were also resistant to antibiotics. Moreover, in food poisoning cases caused by such toxin-producing bacteria, doctors refrain from using antibiotics as killing the bacteria actually causes more toxins to be released, bringing on the worst symptoms of the illness. There is therefore a real need worldwide for antidotes against these life-endangering toxins.

Highlighting the significance of this study, Dr Bard added, "Through this genome-wide screen, our understanding of how toxins interact with human cells at the molecular level expanded tremendously. Our hope is that with these new therapeutic targets identified from the human genome, we will be one step closer to finding toxin antidotes that will make hospital-acquired infections and enterotoxic E. Coli outbreaks a thing of the past."

More about protein toxins

Though immunologically different from each other, Ricin, PE, Diphtheria and Shiga toxins all kill by destroying the cell's protein synthesis 'factories', the place where all proteins necessary for the cell's survival are produced. To travel to these protein 'factories' in the cell, the toxins first trick the host cell into turning off a natural defense mechanism that destroys foreign proteins. Next, they exploit the host cell's internal transport pathway to reach the protein 'factories', destroying them and killing the cell. When this happens, cell death is imminent. If not contained, toxins released from dead cells can spread to neighboring healthy cells, resulting in rapid and widespread tissue and organ damage.

By identifying the specific host genes required for these toxins to attack the cell's protein 'factories', this study effectively singled out the attractive therapeutic targets from the entire human genome for developing antidotes that could potentially be effective against any toxins that share the same mode of action. For instance, ERGIC2 was found to be an important component of the cell's internal transport pathway that the toxins hijack to reach the cell's protein 'factories'.

CANARY Event Detection Software Protects Water Utilities From Terrorist Attacks And Contaminants, Boosts Quality

Americans are used to drinking from the kitchen tap without fear of harm, even though water utilities might be vulnerable to terrorist attacks or natural contaminants.

Now, thanks to CANARY Event Detection Software - an open-source software developed by Sandia National Laboratories in partnership with the Environmental Protection Agency (EPA) - public water systems can be protected through enhanced detection of such threats.

"People are excited about it because it's free and because we've shown that it works really well. We would love to have more utilities using it," said Regan Murray, acting associate division director of the EPA's Water Infrastructure Protection Division at the National Homeland Security Research Center.

The software tells utility operators within minutes whether something is wrong with their water, giving them time to warn and protect the public. And it's improving water quality by giving utility managers more comprehensive real-time data about changes in their water.

CANARY is being used in Cincinnati and Singapore, and Philadelphia is testing the software system. A number of other U.S. utilities also are evaluating CANARY for future use.

Sean McKenna, the Sandia researcher who led the team that developed CANARY, said people began to pay attention to the security of the nation's water systems after 9/11.

McKenna and Murray said CANARY could have lessened the impact of the nation's largest public water contamination. In 1993, a cryptosporidiosis outbreak in Milwaukee hastened the deaths of dozens of citizens, made more than 400,000 residents ill and cost more than $96 million in medical expenses and lost productivity, according to reports about the tragedy.

"If you don't have a detection system, the way you find out about these things is when people get sick," Murray said.

Sandia, a national security laboratory, had worked on water security before the 9/11 attacks. So when the EPA was looking for help early in the last decade to better monitor water utilities, they contacted Sandia.

A Sandia-developed, risk-assessment methodology for water focused on physical security of the utility infrastructure, but did not address detection and assessment of the impact of contamination within the water itself. CANARY was designed to meet that need for better assessment, McKenna said.

CANARY, which runs on a desktop computer, can be customized for individual water utilities, working with existing sensors and software, McKenna said.

While some utilities monitor their water using real-time sensors, many still send operators out once a week to take samples, said David Hart, the lead Sandia software developer for CANARY.

Compared to weekly samples, CANARY works at lightning speed.

"From the start of an event - when a contaminant reaches the first sensor - to an event alarm would be 20-40 minutes, depending on how the utility has CANARY configured," McKenna said.

The challenge for any contamination detection system is reducing the number of false alarms and making data meaningful amidst a "noisy" background of information caused by the environment and the utility infrastructure itself.

CANARY researchers used specially designed numerical algorithms to analyze data coming from multiple sensors and differentiate between natural variability and unusual patterns that indicate a problem. For example, the Multivariate-Nearest Neighbor algorithm groups data into clusters based on time and distance, explained Kate Klise, a numerical analyst at Sandia. When new data is received, CANARY decides whether it's close enough to a known cluster to be considered normal or whether it's far enough away to be deemed anomalous. In the latter case, CANARY alerts the utility operator, Klise said.

The computer program uses a moving 1.5- to two-day window of past data to detect abnormal events by comparing predicted water characteristics with current observations. But a single outlier won't trigger the alarm, which helps to avoid costly and inefficient false alarms. CANARY aggregates information over multiple 2- to 5-minute time steps to build evidence that water quality has undergone a significant change, McKenna said.

"We've taken techniques from different fields and put those together in a way they haven't been put together before; certainly the application of those techniques to water quality monitoring hasn't been done before," McKenna said.

CANARY also provides information about gradual changes in the water, McKenna said.

One unintended benefit of the software is that when utility operators better understood the data being sent by their sensors, they could make changes to the management of the water systems to improve its overall quality, McKenna said.

"What we found from utilities we work with is that a better managed system is more secure, and a more secure system is better managed," McKenna said.

Harry Seah, director of the Technology and Water Quality Office at the Public Utilities Board (PUB), Singapore's national water authority, wrote in a letter supporting CANARY that the software provided a "quantum leap" in the utility's practice.

In the past, Seah wrote, the utility depended on preset limits of three water characteristics to determine water quality.

"With the implementation of CANARY, relative changes in the patterns of these three parameters can be used to uncover water quality events, even if each individual parameter lies within the alarm limits," Seah wrote. "This dramatically improves PUB's ability to respond to water quality changes, and allows PUB to arrest poor quality water before [it reaches] the consumers."

As more versions of the software are installed at water utilities, researchers are working on new application areas for CANARY, such as computer network traffic logs and geophysical log analysis used by petroleum drillers to analyze rocks at different depths.

Sandia National Laboratories is a multiprogram laboratory operated by Sandia Corporation, a wholly owned subsidiary of Lockheed Martin Corporation, for the U.S. Department of Energy's National Nuclear Security Administration. With main facilities in Albuquerque, N.M., and Livermore, Calif., Sandia has major R&D responsibilities in national security, energy and environmental technologies, and economic competitiveness.