Category: Research Notes

Pandora Report 9.18.2015

by spopescu, posted in Pandora Report, Research Notes, Uncategorized

What an interesting week! Ongoing salmonella cases, imported plague in Michigan, ISIS was found to be using chemical weapons, and a new prion disease was discovered. Pretty busy in the world of biodefense, I’d say. The Pandora Report is also fortunate to share with you a great piece by one of our graduate students, Greg Mercer, who tapped into Google Trends to look at ISIS nomenclature, and an upcoming book written by Dr. Brian Mazanec, regarding cyber warfare. So sit back and relax while we catch up on the week’s biodefense news.

US Confirmation of Islamic State Chemical Weapons

Operational_Readiness_Exercise_121014-F-LP903-827Sulfur mustard traces were found on fragments of ordnance used by the Islamic State, as well as on scraps of clothing from victims in Syria and Iraq. There have been several accounts by Kurdish officials that have claimed chemicals, like chlorine, were dispersed this summer, which is concerning for the ongoing use of these internationally banned substances. Testing done in the US was reported by officials on Friday, September 11, 2015, stating that, “there’s no doubt ISIS has used this,”. Officials have also said that the chemical residue recently found does not match known chemical ordinance that was used in the former Iraqi inventory. Overall, the use of chemical weapons is highly distressing and the method of acquisition, either manufacturing or from undeclared stocks, is under investigation.

Michigan Experiences Imported Plague Case

 A Michigan woman is the second case of bubonic plague that was traced back to the Little Rainbow area of Colorado. The Michigan resident was visiting family in Salida, CO during a music festival in late August. While her exact exposure hasn’t been established, she became ill after returning home and was hospitalized shortly thereafter. Lucky for the diagnosticians, she displayed textbook plague symptoms, leading to CDC involvement and antimicrobial treatment. Fortunately, she was released from the hospital and is beginning the long road to recovery, although it’s probably the last time she’ll attend that particular music festival or go hiking around it….

The So-Called Islamic State 2
By Greg Mercer

In February, I wrote about a topic that had been puzzling me- the contentious nomenclature of the Islamic State, or ISIS, or ISIL, or Daesh.  I decided to revisit this question now that the issue is a staple in the news, and that we’re probably saying it more frequently while thinking less about what we call it.  So I fired up my good friend Google Trends[1] again to take a look.  Google is a decent measure of public interest in a subject.  It’s the most popular search engine[2] in the world, with 66.78% of search volume worldwide as of August 2015.

Last time, I found that ISIS was the most popular term by a fair amount.[3]  This seems to be true this time around too, which isn’t terribly surprising.  Here’s what I got:
Screen Shot 2015-09-17 at 6.24.26 PM

 

 

 

 

 

This time around, ISIS is still the most popular, but Google’s added a feature that tells us a little more.  While I suspected that the terrorist organization was driving most of the searches for ISIS before, it’s true that ISIS is the only of the names that has other popular uses, notably an Egyptian goddess, a think tank, and of course a fictional intelligence organization.  The new “topics” option in Google Trends lets us identify search volume for an entire subject.  The dotted purple line indicates all searches for the organization, regardless of naming specifics.  Since the searches for “ISIS” specifically and all of the searches for the organization are strongly correlated, it’s safe to say that mythology enthusiasts, nuclear scholars, and Archer fans aren’t skewing the trends.

It’s also still the case that search volumes for all of the names spike with major news events- no surprise there.

I also found the search trends by country interesting, here’s a look at the different terms and how they show up globally:

Screen Shot 2015-09-17 at 7.33.14 PM
Click on image to see Google Trend analysis and additional graphs

 

 

 

 

 

 

 

 

 

 

A couple of takeaways:  Looking at the organization as a whole, the two most interested parties (by Google search) are Iraq and Iran.  That’s not too surprising.  Iran is also #1 for “Daesh”, which is used in both Arabic and Farsi and is considered more a disparaging name.  In fact, the Iranian foreign minister told Iranian state media in January (fair warning, this links to Iran Daily) that he hates the term “Islamic State” and prefers “Daesh.”  In my earlier article, I noted that other foreign policy practitioners share this sentiment, and prefer a name that doesn’t recognize the organization as a state or representative of Islam.  This is also definitely the least popular name in mainstream American media.[4]  Ethiopia and Peru are the highest by volume for ISIS and ISIL, respectively, neither of which I would have expected offhand.

It’s interesting to see how these trends break down, and to look at a single massive political issue and international crisis with such a proliferation of terms.  I think the name that finally sticks remains to be seen.

[1] This links to the search parameters I used for this article, so you can play around with the data.
[2] This site is really cool if you’re into this sort of thing- you can see what site users choose based on browser, operating system, and device type.
[3] Personally, I tried ISIL in the name of accurate translation, but I tended to use ISIS when being flippant, and then it ended up sticking.
[4] To get anecdotal, the only person I’ve heard use it is my buddy who does Arabic translation and Middle East studies for a living.

The Evolution of Cyber War

Screen Shot 2015-09-18 at 6.39.11 AMGMU’s very own, Dr. Brian Mazanec, delves into the world of cyber warfare and the reality of this threat. “Already, major cyber attacks have affected countries around the world: Estonia in 2007, Georgia in 2008, Iran in 2010, and most recently the United States. As with other methods of war, cyber technology can be used not only against military forces and facilities but also against civilian targets. Information technology has enabled a new method of warfare that is proving extremely difficult to combat, let alone defeat.” Available on November 1, 2015, we’re excited to share Brian’s phenomenal work!

Stories You May Have Missed:

  • Flu vaccination rates went up a bit for the 2014/2015 season, however, the efficacy was only 18% due to an antigenic drift. Fortunately, vaccination compliance for healthcare workers increased and overall rates showed that women were more likely than men to get vaccinated.
  • The Australian government will pass a new law, the “No Jab, No Pay Bill“, that will penalize parents who don’t vaccinate their children by withholding child care and other payments.
  • An additional 77 cases of Salmonella Poona were reported since September 9, 2015, related to the multi-state cucumber outbreak. The total infected is now 418 people across 31 states, with 91 hospitalizations.
  • A new prion disease has been identified by a team of scientists led by Stanley Prusiner. Their report outlines the discovery and the potentially infectious nature of this new prion.

Biodefense Graduates: Brian Mazanec

by juliadhomstad, posted in Program News, Research Notes

GMU Biodefense Graduate Brian Mazanec’s Deterring Cyber Warfare: Bolstering Strategic Stability in Cyberspace (written with Bradley Thayer) was released on December 5. The book looks at cyber warfare, which is especially relevant after the latest North Korean cyber attack on Sony. The description of the book follows:

Deterrence theory was well developed during the Cold War for the deterrence of kinetic attacks. While the deterrence of cyber attacks is one of the most important issues facing the United States and other nations, the application of deterrence theory to the cyber realm is problematic.
This study offers an introduction to cyber warfare and a review of the challenges associated with deterring cyber attacks. Mazanec and Thayer recommend efforts in three specific areas to aid the deterrence of major cyber attacks: by cultivating beneficial norms for strategic stability; by continuing efforts in the area of improving cyber forensics and defences; and, finally, by developing and communicating a clear declaratory policy and credible options for deterrence-in-kind so as to make escalation unavoidable and costly. This timely study reflects increased international interest in cyber warfare, and is based on the recognition that information networks in cyberspace are becoming operational centres of gravity in armed conflict.
Deterring Cyber Warfare is Prime eligible which means, if you’re a member, you can get it just in time for Christmas! You can order online here.

Mason Researchers Looking for Fresh Answers in a Medieval Disease

by juliadhomstad, posted in News, Research Notes

George Mason University’s National Center for Biodefense and Infectious Diseases has been researching the causative agent of plague–Yersinia pestis.

George Mason University professor Ramin M. Hakami is searching for new ways to treat modern ailments by studying bacterial and viral biodefense agents, including the medieval disease notoriously known as the Black Death.

Along the way, he’s also coaching the next generation of researchers. The two endeavors are equally critical, says Hakami, who knows firsthand how crucial mentoring can be to young researchers from when he himself was a student earning his doctorate in biochemistry in the laboratory of the Nobel Laureate Professor Har Gobind Khorana at the Massachusetts Institute of Technology (MIT).

Read the full article here.

 

Image credit: George Mason University

International Cooperation to Eliminate Syria’s Chemical Weapons

by Gregory Koblentz, posted in Research Notes

While the delays in Syria’s transfer of chemical agents has received significant media attention lately, less attention has been paid to the impressive international coalition that has been assembled to remove and destroy these chemicals. Although the original agreement for Syria to join the Chemical Weapons Convention (CWC) and destroy its chemical weapons was the result of U.S.-Russian diplomacy, implementing this agreement has become a truly international initiative. Within only a few months, the international community devised a plan to eliminate Syria’s chemical weapons program and put in place the resources necessary to achieve this objective.

The extent to which Syria’s chemical disarmament has been internationalized is reflected in a recent fact sheet published by the Organization for the Prohibition of Chemical Weapons (OPCW), the international organization charged with implementing the CWC and destroying Syria’s chemical weapons. The fact sheet provides details on the financial and in-kind contributions made by states to the organization’s program to eliminate Syria’s chemical weapons. While the OPCW received approximately $1.2 million when it won the 2013 Nobel Peace Prize, this amount is only a fraction of the expected cost of destroying Syria’s stockpile of 1,390 tons of chemical weapons. So far, twenty-six countries have pledged or contributed more than $86 million to support this effort. Fifteen nations have also provided in-kind assistance to the United Nations or to Syria to facilitate Syria’s chemical disarmament. Granted, the provision of field kitchens by Belarus and ambulances by China might sound mundane, but in war-torn Syria such resources are in short supply.

An international flotilla of ships from six nations has assembled in the Mediterranean to support the removal and destruction of Syria’s chemical arsenal. So far, the Dutch and Norwegian cargo ships Ark Futura and Taiko have picked up three loads of chemicals from the Syrian port of Latakia, comprising about 11% of the Syrian stockpile. The centerpiece of this maritime “coalition of the willing” is the U.S.-supplied MV Cape May which will use a Field Deployable Hydrolysis System to destroy 560 tons of Syrian chemicals at sea. Italy has offered the use of the port of Gioia Tauro for the transfer of chemicals from the Dutch and Norwegian cargo ships to the Cape May. Warships from China, Denmark, Norway, Russia, the United Kingdom and the United States will protect these vessels during the removal and destruction process.

In addition to this at-sea destruction, the United Kingdom has agreed to destroy 150 tons of chemical weapon precursors at a commercial facility and a state-owned enterprise in Germany will dispose of the waste generated by the destruction of the chemical warfare agent mustard. On February 14, the OPCW awarded contracts to private firms in Finland and the United States to destroy and dispose of the remainder of Syria’s chemical stockpile.

Thanks to the efforts of the United Nations and OPCW, supported by the financial and material contributions of thirty nations, there is now a comprehensive system in place to safely and securely remove and destroy Syria’s stockpile of chemical agents. Syria has already missed two deadlines for getting rid of its stockpile. The time for delay is over. The international community has done its part. Now it is up to Syria to deliver on its promise of chemical disarmament.

Gobble Gobble, A New Test for Toxins?

by Siddha Hover, posted in News, Research Notes

By GMU Biodefense graduate student, Blain Johnson

Do you find yourself reminiscing about the holidays, back when the bitter cold was mitigated by winter cheer? Cast your mind back to November. Every Thanksgiving millions of families sit down and eat a pleasant turkey dinner, after all, what would the holiday be without the signature dish in the center of the table? But what if you were told that turkeys are good for something other than eating?

A recent University of California Berkeley study has found that it is possible to create a sort of ‘plastic card’ that can be sample air to detect the presence of dangerous toxins or chemicals. The finding was inspired by the turkey, a bird whose skin color changes based on the level of stress around it. Inspired by this unique ability, researchers constructed a molecule, similar in shape to collagen, which contains a specific bacteriophage capable of self assembling into colorful, readable patterns if it detect a given toxin or chemical.

The Berkeley bioengineers tailored their virus to bind to specific sites on particles of TNT explosive. The result was that their new sensor could detect trace amounts of airborne TNT particles. Their development is the newest biosensor that, ironically, contains a living virus. Their bacteriophage can be genetically engineered to change color in the presence of any number of toxins, chemicals, and other viruses. While the discovery is an enormous breakthrough, the lead scientist, Dr. Seung-Wuk Lee, says she hopes to develop more sensitivity for the test in the coming months capable of producing even smaller measurements, such as  sugar levels in diabetic patients.

This new innovation goes beyond medicine; the ability to detect harmful toxins and chemicals is a major breakthrough in our ability to prepare for emergency situations and warn citizens of a possible disease outbreak or terrorist attack before it reaches a critical juncture. Imagine testing a room by waving a plastic card in the air and being able to definitively say the area is safe. This is an important discovery for the Emergency Management field and will hopefully lead to safer and more prepared communities.

So the next time you decide to eat a turkey sandwich, tell your nearest neighbor that you are eating a bird which inspired a  biosensor capable of detecting TNT at 300 parts per billion and see what they say.

Delving Deeper: Emergency Preparedness

by Siddha Hover, posted in News, Research Notes

By Yong-Bee Lim

As the past two years of disaster events have displayed, it is more important than ever for individuals, families, and organizations to prepare for self-sufficiency for extended periods of time.[1] However, there is a universal human tendency to avoid thinking about negative events such as possible emergencies.[2] This deliberate lack of attention to local emergency plans and personal emergency preparedness can be vividly seen in a 2006 study by “The Council for Excellence Government Report”. This report, composed post-Katrina, displayed that only a 1/3 of the population lacked knowledge of local government plans, roughly half did not have an alert emergency situation in their community, and only 8% of the public has done everything required to fully prepare supplies and plans for an emergency incident.[3]

This lack of preparedness in the U.S. population is a large problem for a number of reasons. In emergency situations, a majority (52%) of Americans have reported the loss of electricity for 3 or more days. This, among other issues, creates a number of negative implications, which include:

1)       Potential lack of potable water[4] and other nutritional media (breast milk)[5]

2)       Lack of food, whether in the household or the local grocery store[6]

3)       Diminished visual, security, and communication capability[7]

These types of disruptions are likely to negatively impact populations as natural routines are disrupted. Furthermore, different types of disasters will occur in different areas of the United States; while earthquakes may occur more often in California, tornadoes may more likely affect the Midwestern regions. While parents are likely to be negatively affected by the effects of disaster incidents, children are likely to be affected more severely; due to their psychological, social and physical development differences, children are particularly vulnerable to feelings of powerlessness[8]. The fact that children are exponentially impacted represents a problem as children comprise 25% of the U.S. population.[9]

Emergency Preparedness: Child “Ambassadors”

While events such as natural and man-made disasters cannot be completely eliminated, there are ways to bolster emergency preparedness awareness and implementation. Furthermore, there are not only means to not only empower children by including them in the emergency planning and preparedness process, but means to actively engage children in the emergency planning and preparedness process. This not only provides children with the confidence to deal with unexpected situations, but also helps in mitigating feelings of anxiety and powerlessness in an actual emergency.

To this end, several interactive resources have been made available (both online and in educational settings) to impress, educate, and promote the importance of emergency preparedness in the youth population. Furthermore, as youth “ambassadors” of emergency preparedness, these youths can spark discussions, spur action, and educate their parents and communities about the importance and need to address all aspects of emergency planning and preparedness.

Government Resources

FEMA: The Federal Emergency Management Agency has a number of sources to educate children in the importance and practices of emergency preparedness. Some of these include:

  1. Flat Stanley and Flat Stella: These two characters, crafted as ambassadors for children to teach emergency preparedness, promote students to be child ambassadors by provide information such as the necessary facts, plans, and instructions to build a kit for emergency purposes: http://www.ready.gov/flatstanley
  2. Teen CERT: The Teen Community Response Team is a 20-hour program that provides teenagers with both tacit and experiential learning in regards to readiness and response skills; beyond just relaying the information of their learning to others, these students gain techniques in controlling a variety of emergency-related situations: https://www.citizencorps.gov/cert/teencert/images/Teen_CERT_Brochure.pdf

Private Resources

1)       Sesame Street [Let’s Get Together!]: This series of videos, documents and worksheets, all of which includes fun visuals and Sesame Street character cameos, engages both parents and children in the purpose of, efficacy, creation, and basic planning for emergencies: http://www.sesamestreet.org/parents/topicsandactivities/toolkits/ready

2)       American Red Cross’ [Master of Disaster]: This series of programs (numbering over 200), which are specifically tailored to lower elementary (K – 2), middle elementary (3 – 5), and middle school (6 – 8) are meant to educate children through a series of ready-to-go lesson plans that help students not only prepare for emergency events, but to also be able to adapt in the fact of unexpected events: http://www.redcross.org/prepare/location/school/preparedness-education

Regional Sources

1)       Virginia’s Emergency Preparedness: This document provides a step-by-step process for children and families to go through the emergency preparedness process, as well as offer resources in the State of Virginia for emergency issues: http://www.chkd.org/documents/CareConnections/EmergencyPreparednessforFamilies.pdf

2)       Texas’ Project SECURE Gulf Coast [through CIDRAP]: This project developed a disaster curriculum for Houston schools intended to promote preparedness education for children, and between children and families. An ambassador (known as the Disaster Ambassador Preparedness Program [DAPP]) was created to educate schoolchildren who, in turn, educated their parents. Learned skilled included how to make a family emergency plan, items to store in a family emergency supply kit, ways to receive up-to-date information during a disaster, and how to sign up for transportation assistance: http://www.publichealthpractices.org/practice/curriculum-trains-children-act-disaster-preparedness-ambassadors-their-families

Conclusion

While these programs have yet to display true efficacy data (through the use of a longitudinal study), the results of projects (like Project SECURE) appear to display significant improvements in both emergency planning and preparedness. Following the 2-year Project SECURE program, many families have followed recommended guidelines for emergency planning and preparedness for hurricanes, and the program is to be continued at the schools it was implemented at.

While man-made and natural disaster incidents are difficult to speak of due to a number of emotional and ethical reasons, it is clear that properly advanced preparation and planning is the key to mitigating the harm that might arise from any form of incident. It is, therefore, important to instill the concepts of emergency planning and preparedness early in our nations’ youth.  These youth, who will end up being our future, will also be empowered to aid their families and communities with the knowledge they have been given.

(image: Kakela/Flickr)

[1] FEMA, Ready.Gov Online. Accessed 12/13/12. http://www.ready.gov/make-a-plan

[3] The Council for Excellence in Government Online. Accessed 12/12/12. http://www.citizencorps.gov/downloads/pdf/ready/pri_report.pdf

[6] Columbus Community Hospital Online. Accessed 12/19/12. http://www.preped.org/Resources/20Wkstockpiling.pdf

[7] Pacific Disaster Center Online. Accessed 12/18/12. http://www.pdc.org/iweb/hazard_info_checklist.jsp

[9] ChildStats Online. Accessed 12/20/12. http://www.childstats.gov/americaschildren/tables/pop1.asp

Koblentz on Viral Warfare, Cyber Security, Chem/Bio, and Nuclear Weapons Accidents

by Siddha Hover, posted in Research Notes

GMU Biodefense Deputy Director Dr. Gregory Koblentz has a slew of new publications out of topics ranging from the nexus of bioweapons and cybersecurity to new frameworks for understanding chem/bio threats.

His article, “Regime Security: A New Theory for Understanding the Proliferation of Chemical and Biological Weapons”, is available in this month’s Contemporary Security Policy. Here’s the abstract:

“The literature on the proliferation of chemical and biological weapons (CBW) emphasizes the role of external security threats as the primary motive for states to acquire and use these weapons. As recent events in Syria demonstrate, governments lacking political legitimacy may use these weapons to repress domestic challenges to their rule. The concept of regime security provides a theoretical framework for understanding how the threat of military coups, insurgencies, or domestic rivals influences the acquisition and use of CBW by authoritarian regimes. The cases of South Africa and Iraq illustrate how a government’s concerns about internal security threats can impact its CBW proliferation decision-making. Omitting regime security as a factor in CBW decision-making may lead to the adoption of inappropriate nonproliferation and deterrent strategies. In light of Syrian President Bashar al-Assad’s use of chemical weapons against his own people, developing a deeper understanding of the influence of regime security on the acquisition and use of chemical and biological weapons should be a priority.” (available here)

Dr. Koblentz also co-published an article with GMU Biodefense PhD student Brian Mazanec, “Viral Warfare: Security Implications of Cyber and Biological Weapons” – the article examines the relatively emergent threats of biological and cyber warfare, exposing several commonalities between the two. The article was published in the November issue of Comparative Strategy, available here (access required).

Abstract – “Since the beginning of the twenty-first century, two new threats have received increased attention: biological warfare (BW) and cyber warfare. While it may appear that these two threats have little in common, they share several characteristics that have significant implications for international security. This article examines the two modalities side-by- side to review these common characteristics. In light of these commonalities and due to the extensive experience and rich history of dealing with BW threats, strategies for enhancing cyber security could advance more quickly by drawing meaningful insights from the biological warfare experience, such as the prospect of developing constraining international norms.” (available here)

Finally, Koblentz has a new review out  in Foreign Affairs, on Eric Schlosser’s new book, Command and Control: Nuclear Weapons, the Damascus Accident, and the Illusion of Safety.  The first paragraph is below – read the rest here.

Between 1950 and 1980, the United States experienced a reported 32 “broken arrows,” the military’s term for accidents involving nuclear weapons. The last of these occurred in September 1980, at a U.S. Air Force base in Damascus, Arkansas. It started when a young technician performing routine maintenance on a Titan II missile housed in an underground silo dropped a socket wrench. The wrench punctured the missile’s fuel tank. As the highly toxic and flammable fuel leaked from the missile, officers and airmen scrambled to diagnose the problem and fix it. Their efforts ultimately failed, and eight hours after the fuel tank ruptured, it exploded with tremendous force. The detonation of the missile’s liquid fuel was powerful enough to throw the silo’s 740-ton blast door more than 200 yards and send a fireball hundreds of feet into the night sky. The missile’s nine-megaton thermo­nuclear warhead — the most powerful ever deployed by the United States — was found, relatively intact, in a ditch 200 yards away from the silo.

(image: CDC)

Ben Ouagrham-Gormley on Bioweapons Proliferation

by Siddha Hover, posted in Research Notes

GMU Biodefense’s Dr. Sonia Ben Ouagrham-Gormley evaluates the effect of increased state efforts to deter bioweapons threat in her recent article, ” Dissuading Biological Weapons Proliferation”. Check out the abstract below, and look for the full article in this month’s issue of Contemporary Security Policy.

Abstract – “The terrorist and anthrax attacks of 2001 spurred many countries to raise defences against a possible biological weapon attack, and potentially dissuade state and non-state actors from developing these weapons. Yet these programmes’ dissuasive value – creating strong barriers to entry – has never been analysed. This article argues that current biodefence efforts are counterproductive and more persuasive than dissuasive, because they rest on a biological threat narrative that emphasizes the benefits of bioweapons rather than their problematic development and use, and they fail to impose a high cost of entry in the bioweapons field. The dominant biological weapons narrative perpetuates several misconceptions, including that there are no barriers to biological weapons development, that expertise is easily acquired from scientific documents, and that new technologies are black boxes with de-skilling effects. The net result is popularization of a cost/benefit analysis in favour of bioweapons development. To remedy the situation, I suggest correcting these misconceptions by reshaping the biological threat narrative, and recommend policies to achieve a greater dissuasive impact, stressing the role of the Biological Weapons Convention, preventing access to tacit biological weapons skills, and criminalizing bioweapons proliferation by making the development and use of biological weapons a crime against humanity.”

The full journal article is available here (access required).

(Image: a single Bacillus anthracis colony, credit CDC/J. Todd Parker; PhD and Luis Lowe; MS; MPH)

Delving Deeper: Living in the Post-Antibiotic Era

by Siddha Hover, posted in News, Policy Review, Research Notes

By Yong-Bee Lim

The Post-Antibiotic Era Problem: What are the Issues, and How Can Adaptive Clinical Trials Potentially Help?

Nostalgia is a powerful thing. When people get nostalgic, they are cognitively living in the past; in this constructed past, the past seems rosy, and often conceived of as more positive than the present. That said, even with rose-tinted glasses, it is hard to argue that life (if defined as survivability) was better before the introduction of antibiotics. For example, mortality rates from pneumococcal pneumonia were 30-35% in the pre-antibiotic era, with the therapy often being quarantining patients.[1] Antibiotics have allowed for both the morbidity and mortality rates of pneumococcal pneumonia to drop to nearly zero in developed countries.[2] Furthermore, antibiotics allow procedures that would have been impossible in a pre-antibiotic era; organ transplants, invasive procedures, and intensive care units would not be possible without effective antibiotics.

A recent piece of news to hit the public health radar involves a man in New Zealand named Henry Pool. Pool, while teaching English in Vietnam, was operated on following a brain hemorrhage. When flown following the operation to a Wellington hospital, it was discovered that he carried a bacteria strain identified as KPC-Oxa 48: a strain of bacteria that is resistant to every antibiotic currently available to man. To contain the possibility of the strain of bacteria getting out, Pool was forcibly quarantined for 6 months until he passed away. [3]

This recent death in New Zealand highlights a threat that looms ever closer in the public health horizon: the post-antibiotic era. Due to a number of factors, including over-prescription of antibiotics to patients and over-use of antibiotics in farming and animal cultivation, bacteria have undergone evolutionary pressures to resist and overcome the mechanisms of our current arsenal antibiotics; several adaptations include the production of enzymes to modify antibiotics, cell wall changes that prevent the ingress of antibiotics inside the bacterium, and the creation of pumps to transfer antibiotics outside of the cell before the antibiotic’s effects are actualized. Furthermore, evidence points to the fact that multiply-resistant bacteria are not staying confined to hospitals as they traditionally have; certain bacteria such as Streptococcus pneumonia and Staphylococcus aureus with partial/complete resistance to penicillin have been detected in community populations.[4]

The concept of antibiotic resistance is not a foreign one to scientists and individuals in the public health sector. Staphylococcus aureus was actually noted to have started developing antibiotic resistance to penicillin as early as the 1940s.[5] Despite this knowledge that antibiotic resistance could, and would, develop over time, very little is available in regards to innovative new antibiotics to counter the rising threat of antibiotic-resistant bacteria. There has been “no major classes of antibiotics introduced” between the years of 1962 and 2000;[6] furthermore, while representatives of novel antibacterial classes (linezolid: 2000, daptomycin: 2003, retapamulin: 2007) have been registered, the chemical classes from whence these representatives originate were patented or reported historically (oxazolidnones: 1978, acid lipopetides: 1987, pleuromutilins: 1952).[7]

If the threat is realized, then, why is there such paucity in the development and production of novel and effective antibacterial therapies? Part of the equation has to do with the society we live in; money is important to companies.  Over the past several decades, a number of large pharmaceutical companies have drastically cut funding and maintaining the internal capacity for R&D of antibacterial therapies. It is often argued that this decline is partially explained by the fact that pharmaceutical companies seek to shift R&D resources from antibacterial drug discovery programs to other, more profitable therapy areas such as musculoskeletal and central nervous system (CNS) drugs.[8],[9] The net effect of various economic barriers involved in the development of an antibiotic (if successful) is a net loss of $50 million dollars compared to a $1 billion gain for a new musculoskeletal drug at the time of discovery.[10] In addition, mergers and take-overs of pharmaceutical companies often result in a restructuring of priorities and personnel; these restructures have often included the loss of research groups with expertise in antibiotic drug discovery.[11]

So if part of the issue is economics, what can be done to better galvanize and incentivize pharmaceutical companies to come back and do R&D on antibacterial drugs? One area where companies often hemorrhage money is in the clinical trials necessary to prove both the safety and efficacy of a product. Oftentimes, the bulk of R&D funds are spent on clinical trials. Clinical trials (depending on the size of the sample needed to test the product, the cost of developing the product itself, and other factors) can run in the ballpark of $100 million dollars per trial; with a minimum of 3 phases of clinical trials (with a high probability of repeating at least one phase of a trial), it is easy to see a successful product would cost a minimum of $400 million dollars in clinical trials alone.[12]

Under the current model of clinical trials, trials are clearly demarcated between phases (Clinical Phase 1, Clinical Phase 2, and Clinical Phase 3) that must be done in a sequential fashion. Furthermore, these trials are rigid in the fact that parameters may not be changed during the course of a trial; all participants must be kept throughout the trial, dosages may not be altered, and trials (except under certain circumstances) must be completed until the end. Among a number of situations, this lock-step approach inflates costs when observations might indicate:

–          A certain subset is not responding to a dose (perhaps the dose is too low)

–          The entire sample is not responding to the product (at any dose)

Using innovative, high-level Bayesian biostatistics, a new avenue of clinical research design is being explored that may help alleviate some of the costs of clinical trials. Adaptive clinical trials are specifically designed studies that are meant to “adapt” as a clinical trial proceeds; these adaptations occur through an analysis of the accumulated results in a trial.[13] As opposed to the lock-step and rigid clinical trial structure that is currently used, adaptive clinical trials allow modifications to be introduced during the trial phase. These modifications could include, but are not limited to:

–          Sample size re-estimation: If the number of people for a trial is too small or too large, this can be adapted during the trial.

–          Early stopping of clinical trials: In the event that there is evidence that the product isn’t performing the way it is supposed to (lack of efficacy), trials can be shut down to save funds and resources.

–          Dropping suboptimal groups: In the event that there is evidence that the product isn’t effective in a subgroup of the trial sample (perhaps a group with a low dose is not presenting results), then the group could be dropped to save funds and resources.

–          Overlapping trials: Adaptive trials could overlap phases (the tail end of phase 1, for example, could overlap the beginning of phase 2), resulting in faster clinical trial completion and, hopefully, swifter licensure.

It should be noted that this type of approach is very new, and is only just garnering use in various areas that require clinical trials. For example, it has not been used, as of this post, for the development of Medical Countermeasures (MCMs). However, if it can be successfully executed, it holds possibilities in significantly cutting down both the temporal constraints, as well as the financial burdens, of attaining the novel and effective antibiotics that are necessary to help curb the growing antibiotic-resistant bacteria threat.

Perhaps the phraseology “post-antibiotic era” is too strong; it seems to evoke a sense of fear, and fails to address the idea that future innovations exist in the pipeline to potentially deal with issues of current levels of antibiotic resistance. However, what can be said is that we are starting to run out of options in our bag of tricks, and it will take more than a wave of a wand and an “abracadabra” to resolve this threat to the status quo: a public health era in which antibiotics work against bacteria to increase survivability. While there are multi-faceted issues contributing to this issue, the ability to help make antibacterial R&D more financially viable for pharmaceutical companies (through the use of innovations such as adaptive clinical trials) could help in dealing with this public health concern.
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Yong-Bee Lim is a PhD student in Biodefense at George Mason University. He holds a B.S. in Psychology and an M.S. in Biodefense from George Mason University as well. Contact him at ylim3@masonlive.gmu.edu or on Twitter @yblim3.

[1] Shai Ashkenazi. (2012). “Beginning and possibly the end of the antibiotic era,” Journal of Pediatrics and Child Health, 49 (3): pp. 179 – 182.

[2] RP Wenzel and MB Edmond. (2000). “Managing antibiotic resistance,” New England Journal of Medicine, 343: pp. 1961 – 1963

[3] “Kiwi dies with bug no drug could beat,” New Zealand Herald, accessed 11/23/2013: http://m.nzherald.co.nz/nz/news/article.cfm?c_id=1&objectid=11159413

[4] LF Chen, T Chopra, and KS Kaye. (2009). “Pathogens resistant to antimicrobial agents,” Infectious Disease Clinics of North America, 23: pp. 817 – 845

[5] “Methicillin-Resistant Staphylococcus aureus (MRSA),” National Institute of Allergy and Infectious Diseases, accessed 11/26/2013, http://www.niaid.nih.gov/topics/antimicrobialresistance/examples/mrsa/pages/history.aspx

[6] MA Fischbach and CT Walsh. (2009). “Antibiotics for emerging pathogens,” Science, 325: pp. 1089 – 1093

[7] Lynn L. Silver. (2011). “Challenges of antibacterial discovery,” Clinical Microbiology Reviews, 24 (1): pp.71 – 109

[8] S. Projan. (2003). “Why is big pharma getting out of antibacterial drug discovery?” Current Opinion in Microbiology, 6 (5): pp. 427 – 430

[9] R Finch and P Hunger. (2006). “Antibiotic resistance – action to promote new technologies,” Journal of Antimicrobial Chemotherapy, 58 (Suppl): pp. 3 – 22

[10] Priya Sharma and Adrian Towse. (2011). “New drugs to tackle antimicrobial resistance: Analysis of EU policy options.”

[11] I. Chopra. (2008). “Treatment of health-care-associated infections caused by Gram-negative bacteria: a consensus statement,” Lancet Infectious Diseases, 8: pp. 133 – 139

[12] “How the FDA Stifles New Cures, Part I: The Rising Cost of Clinical Trials,” Forbes, accessed 11/26/2013, http://www.forbes.com/sites/aroy/2012/04/24/how-the-fda-stifles-new-cures-part-i-the-rising-cost-of-clinical-trials/

[13] Donald A. Berry. (2010). “Adapative clinical trials: The promise and the caution,” American Society of Clinical Oncology, 29 (6): pp. 606 – 609

On Not Falling Prey to Biological Weapons Alarmism in Syria

by Siddha Hover, posted in News, Research Notes

by Dr. Sonia Ben Ouagrham-Gormley

A September 5 Washington Post article raises concern that Syria might resort to biological weapons in retaliation for a Western military strike. The article states that intelligence reports indicate that Syria engaged in bioweapons development in the 1970s and 80s and since then has maintained a “dormant capability,” which some experts interviewed by the Post believe can easily be reactivated to produce biological weapons. it is important to inject a little bit of reality in regard to the question of whether or not  Syria might be able to successfully reactivate a “dormant program” and effectively develop and use biological weapons.

First, we need to define more clearly what capabilities are actually available to Syria. If a “dormant capability” means that Syria has maintained from its 1980s program only a handful of research activities, the country will face tremendous difficulties in launching a crash program capable of producing the quantities of agent required for use as a weapon. If we assume — and this is entirely speculation — that Syria already has stocks of pathogens, its first task will be to produce a sufficient amount of liquid agent for weaponization. Scaling-up, however, has been a stiff challenge for both past terrorist and state bioweapons programs. The passage from a laboratory sample to larger quantities of bioagent is not a straightforward linear process. Because microorganisms are sensitive to their environmental and processing conditions, scaling-up has to be incremental, and each stage requires a revision of the production parameters. For example, when the Soviets launched the large-scale production of their anthrax weapon at the Stepnogorsk production plant in Kazakhstan, their scientists could not maintain the lethal qualities of the agent throughout the production process. They were therefore compelled to review and test each parameter of the production protocol at each stage of the scale-up, a process that lasted about two years. Scale-up also exposes the agent to contamination, which further delays production, as was the case in both the U.S and Soviet programs.  Current biodefense and pharmaceutical companies also routinely face such contamination and scale-up challenges.

Second, it is important to determine what type of expertise is currently available to Syria. If Syria maintained minimal research activities over the past 20 years, it is likely that they will face a shortage of expertise at key points of a weapons development. This includes process development, pilot-scale production, large-scale production, testing, dissemination, and weaponization. For example, the Iraqi program had very few experts with knowledge directly applicable to the agents they selected for use as a weapon. They also had only one fermentation expert, and before his involvement in the program, the fermenters purchased for the program remained in their crates for lack of personnel with knowledge on how to use them. The Iraqis also did not have weaponization experts within the bioweapons program. Weaponization work was conducted by individuals involved in the chemical weapons program, and consisted of adapting existing chemical bombs and warheads for bioweapon use. This resulted in very inefficient weapons, designed to disseminate the agent upon impact, which would have destroyed most of the bioagent. It is worth reiterating also that the Iraqis were only able to produce liquid agents, even though they had access to drying equipment. If active bioweapons programs faced such challenges, one can only imagine what problems a “dormant program” might face.

Were the Syrians able to shepherd enough expertise from the civilian sector, it is not clear whether their skills could be directly relevant to support bioweapons work.  The Japanese terrorist group Aum Shinrikyo had among its members individuals with scientific education, but their lack of practical experience in bioweapons development imposed a steep learning curve, which after six years of effort and about $10 million dollars of investment, resulted in failures at every step of a bioweapon’s development.  The Iraqi program faced similar issues: most of its scientists had no prior bioweapons expertise and required several years of learning and exploratory work before they could start making some headway.

Access to expertise is not the only challenge facing Syria. Making sure that the teams of scientists, technicians, and engineers work together, coordinate their efforts, and work towards the same goal is as, if not more, important. The lack of coordination and cooperation was a major source of delay and failure in the Soviet program, which was arguably the most successful of all state programs. Yet, if creating the conditions required for such cooperation is difficult under normal conditions, it is even more complicated under the stress of maintaining covertness in times of war, particularly under an authoritarian regime.

In sum, it is important to avoid falling prey to alarmist claims similar to those that led to the invasion of Iraq in 2003. The threat of Syrian bioweapons use merits a careful and systematic analysis of the capabilities currently available to Syria and a more nuanced and holistic  appreciation of the challenges they might face.

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Sonia Ben Ouagrham-Gormley is an Assistant Professor in the Department of Public and International Affairs at George Mason University and is primarily affiliated the GMU Biodefense graduate program. Professor Ben Ouagrham-Gormley has conducted research and written on such topics as biological weapons proliferation, weapons of mass destruction (WMD) trafficking in states of the former Soviet Union, biosecurity and bioterrorism, export controls, transfer mechanisms of WMD expertise, defense industry conversion, and redirection of WMD experts. She has received several grants from the Departments of Defense, State, and Energy, as well as from the Nuclear Threat Initiative and the Carnegie Corporation of New York to conduct research on WMD proliferation and contribute to remediation programs such as the DOD-funded Cooperative Threat Reduction Program.

(image: CIAT International/Flickr)