Author: Siddha Hover

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.
______________________________

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

The Pandora Report 11.29.13

by Siddha Hover, posted in Pandora Report

Highlights include a new Q-fever vaccine, MERS in Qatari camels, revised 2009 H1N1 deaths, black silicon the bacteria slayer, and the new, FDA-approved, H5N1 vaccine. Happy Friday!

Eyeing Terrorist Potential, Pentagon Seeks Vaccine Against Cold War-Era Bioweapon

The Pentagon is pushing forward with plans to develop a vaccine against Q-fever, the disease caused by the bacterial agent Coxiella burnetii. While the majority of Q-fever cases are asymptomatic, C.burnetti is a spore former, and is therefore both hardy and stable. However, as the primary reservoirs of the disease are sheep, goats and cattle, the disease tends to be confined within slaughterhouse workers. The acute form of the disease has a fatality rate of less than one percent, while the chronic form ranges from five to 25%.

National Journal – “The United States investigated the agent’s warfare potential and the Soviet Union fully weaponized it decades ago, long before both countries formally denounced biological arms in the 1970s. The disease also occurs in nature and has affected hundreds of U.S. troops deployed overseas. It can produce fever, pneumonia, and numerous other symptoms associated with a variety of pathogens. Certain antibiotics are considered effective against the bacteria, but no vaccine is presently sold in the United States, according to the Federation of American Scientists. An existing vaccination available abroad reportedly can cause side effects such as abscesses and swollen joints.”

MERS virus found in camels in Qatar, linked to human spread

The Middle Eastern Respiratory virus has been detected in three Qatari camels, according to an unpublished study. While the press release does not detail whether live virus or antibodies to the virus were detected, there have been two confirmed cases of human infection related to the barn housing the infected camels. Although camels and bats are the leading candidates for potential reservoirs of the virus, there still exists too little conclusive evidence supporting either.

Reuters – “British researchers who conducted some of the very first genetic analyses on MERS last September said the virus, which is from the same family as Severe Acute Respiratory Syndrome, or SARS, was also related to a virus found in bats…Ab Osterhaus, a professor of virology at the Erasmus Medical Centre in The Netherlands that worked on the camel study, told Reuters the results were confirmed by a range of tests including sequencing and antibody testing. Dutch scientists said in August they had found strong evidence that the MERS virus is widespread among one-humped dromedary camels in the Middle East – suggesting people who become infected may be catching it from camels used for meat, milk, transport and racing.”

W.H.O. Estimate of Swine Flu Deaths in 2009 Rises Sharply

The WHO has significantly revised its fatality estimates for the 2009 outbreak of H1N1, which are estimated be ten times too low. It’s original numbers were just over 18,000 – according to a study published this week, the number of fatalities from the virus alone was actually closer to 203,000. When fatalities resulting from secondary conditions because of the virus are counted, the number approaches 400,000. There are a couple of  important reasons for revising fatality counts, the first of which is it remedies accusations of sensationalizing the potential threat to sell vaccines.

New York Times  – “The estimated death toll closely matches that of a study published in June 2012 by the Centers for Disease Control and Prevention. That study, based on early data, estimated that 201,000 people died of flu and respiratory causes and another 83,000 died of related cardiac problems. Both counts were many more than the 18,449 laboratory-confirmed cases that the W.H.O. stood by as its official count in 2009 because agency officials were reluctant to guess at fatality rates. Some politicians, particularly in Europe, used the low official W.H.O. death rate to argue that fear of the pandemic had been overblown. They accused vaccine companies of fanning the public’s fears to sell more of their product.”

Bactericidal activity of black silicon

From dragonfly’s wings to black silicon? In a recent study originating from Australia, scientists discovered that dragonfly wings were absolute shredders of bacteria. The structure of the wings destroys bacterial cell walls of both gram positive and gram negative bacteria upon contact. Now, shown that black silicon has similar bactericidal properties as well. While black silicon is not readily mass produced, there are several substances with similar nano features which can be. Our first thoughts here are hospitals and doorknobs.

Nature – “Both surfaces are highly bactericidal against all tested Gram-negative and Gram-positive bacteria, and endospores, and exhibit estimated average killing rates of up to ~450,000 cells min−1 cm−2. This represents the first reported physical bactericidal activity of black silicon or indeed for any hydrophilic surface. This biomimetic analogue represents an excellent prospect for the development of a new generation of mechano-responsive, antibacterial nanomaterials.”

FDA approves H5N1 bird flu vaccine

The FDA has approved the first adjuvanted H5N1 vaccine, designed primarily for those who have frequent interactions with poultry. As the vaccine is adjuvanted, less antigen is required to stimulate an immune response. The vaccine, which is administered in two doses three weeks apart, is designed to support existing vaccine supplies in the national stockpile.

Disaster News – “The vaccine, manufactured by GlaxoSmithKline, was developed in partnership with the Biomedical Advanced Research and Development Authority, which is under the Office of the Assistant Secretary for Preparedness and Response of the U.S. Department of Health and Human Services.’This vaccine could be used in the event that the H5N1 avian influenza develops the capability to spread efficiently from human to human, resulting in the rapid spread of disease across the glove.’ Dr. Karen Midthun, director of the FDA’s Center for Biologics Evaluation and Research, said in the news release. Among people who have become infected with H5N1, mortality is about 60%, according to WHO. Health officials have determined the H5N1 strain of influenza has ‘pandemic potential’ because it continues to affect wild birds and poultry populations, and most humans have no immunity to it.”

(image: Bahman Farzad/Flickr)

Image of the week: Salmonella!

by Siddha Hover, posted in Images

In honor of Thanksgiving and our slightly perverse senses of humor, this week’s image is of everyone’e least favorite holiday bacteria – Salmonella! Pictured below is Salmonella typhimurium, the causative agent behind your run of the mill gastroenteritis.  In order to avoid encountering this particularly unfortunate pathogen, we recommend you check out the CDC’s guidelines for a pathogen-free Thanksgiving. Which, incidentally, is what we wish you all!

SALMON_1

Pictured in this lovely SEM, we have Salmonella typhimurium in red, invading human cells.

(image credit: Rocky Mountain Laboratories, NIAID, NIH)

 

WHO: MERS update

by Siddha Hover, posted in News

The World Health Organization released an update on MERS cases today. According to this most recent report, a further three cases of MERS have been detected in Saudi Arabia in the last week. Of the three patients, aged 73, 65, and 37 respectively, two had underlying medical conditions, and two have subsequently died, each within two weeks of becoming symptomatic. None of the three cases had prior, documented exposure to animals.

These most recent cases bring the global count up to 160 laboratory-confirmed cases, with 68 deaths.

For the full update, visit the WHO website here.

This Week in DC: Events 11.25.13 – 12.2.13

by Siddha Hover, posted in Events, Week In DC

A very abridged events round-up due to the upcoming Thanksgiving holiday, which we hope you all enjoy!

Tuesday, November 26

Nuclear Talks with Iran: Potential Pitfalls and Prospects for Success
Heritage Foundation
12:00PM

The rise to power of Iranian President Hassan Rouhani has boosted expectations that the decade-long standoff over Iran’s nuclear weapons program soon will be resolved through a diplomatic agreement. How realistic are these expectations? What is the meaning of the deadlocked talks at Geneva? What negotiating pitfalls must be avoided to construct the framework of an acceptable agreement? What is the role of international sanctions in pressuring Iran and under what circumstances should Washington consider easing sanctions? Join us as the speakers address these and other questions.

Modulation of RNA structure and function using protein, ligands, and RNA
Georgetown University
12:00PM

Speaker: Nathan Baird, Postdoctoral Research Fellow, Ferre-D’Amare Lab National Heart, Lung and Blood Institute.

Foreign Policy Challenges in Obama’s Second Term
Center for a New American Security
12:15 – 1:45PM

On Tuesday, November 26, the Center for a New American Security (CNAS), the New America Foundation and the American Enterprise Institute will host an in-depth discussion on the foreign policy challenges faced by the Obama administration in its second term. With a politically turbulent Middle East, a financially teetering EU, and an increasingly technologically competitive Asia-Pacific region, Obama and his administration will face critical foreign policy decisions in the second half of his final term. Featured speakers: Ambassador Dennis Ross, Anne-Marie Slaughter, Robert Kaplan.

Foreign Policy Series: New Hope for Nuclear Negotiations with Iran, or Further Disappointment?
World Affairs Council
6:30 – 8:30PM

For the past month representatives from Iran and six world powers have been attempting to restart negotiations for an agreement related to Iran’s nuclear ambitions. While a deal has seemed imminent, with Secretary of State John Kerry traveling to Geneva during his recent trip to the Middle East, and all sides noting progress, lingering doubts exist. Will an agreement be struck, and if so, how likely are the parties involved to adhere to it?

Monday, December 2

Going the Whole Nine Yards: What Is Needed for an Africa Free of AIDS, Tuberculosis, and Malaria
Wilson Center
10:00 – 11:00AM

In conjunction with the Replenishment Conference for the Global Fund, the Africa Program is co-hosting the conference, “Going the Whole Nine Yards: What Is Needed for an Africa Free of AIDS, TB, and Malaria,” which will take place in the Wilson Center’s 6th floor Flom Auditorium. The effectiveness and benefits that have accrued to Africa since the fund was established and the continuing need to have a fully operational Global Fund will be discussed. At this tipping point in the fight against HIV/AIDS, tuberculosis, and malaria, the Wilson Center’s Africa Program and Friends Africa believe that amplifying the voices of leading advocates in the fight for an African continent free of HIV/AIDS, TB and Malaria is crucial to garner support towards meeting the replenishment target of 15 billion USD.

Dancing with the devil: Lessons from negotiating with rogues and terrorists
American Enterprise Institute
5:30 – 7:00PM

Whether wielding nuclear or chemical weapons, sponsoring truck bombs, or taking hostages, rogue regimes and terrorist groups continue to threaten the United States and its allies. How should America address the rogue threat? Highlighting research from his new book, “Dancing with the Devil” (Encounter Books, February 2014), Michael Rubin will describe not only lessons Americans have learned from decades of engaging Iran, North Korea, the Palestine Liberation Organization, the Muslim Brotherhood, and the Taliban, but also what rogue regimes and terrorists have concluded about dialogue with Americans.

(image courtesy of Dell)

The Pandora Report 11.22.13

by Siddha Hover, posted in Pandora Report

Highlights this week include dengue in New York, detecting ricin, a suspected al Qaeda biological weapons expert, the evolution of flu, and polio and the Taliban. Happy Friday, and have a bacteria-free Thanksgiving!

‘Locally-Acquired’ Dengue Fever Case Reported In New York

For the first time, a locally-acquired case of dengue fever has popped up in the state of New York. The infected individual had not left the region at any point during the incubation period. This suggests that the probable route of infection was a mosquito which had taken a blood meal from an infected person before biting the New York patient. The patient has made a full recovery. However, this case highlights the truly global nature of infectious disease today. Dengue  is considered a “neglected disease” by the WHO, meaning its research on its treatment and cure receive comparatively less funding. This is especially unfortunate as the virus, which is considered “pandemic-prone” causes an estimated 100 million infections every year in 100 different countries. It’s easy to dismiss dengue as a disease which affects other people in far-flung parts of the world, but this simply isn’t the case anymore.  The prevalence of international travel means relative geographical isolation is no longer the protective boundary it once was.

Global Dispatch – “‘Given the recent introduction of Aedes albopictus into New York State and the high level of travel in New York to areas of the world endemic for dengue, it is not surprising that a locally acquired case of dengue has been found in the state,’ said State Health Commissioner, Nirav R. Shah, M.D., M.P.H. ‘This finding emphasizes the need for physicians to be aware of signs and symptoms of diseases common in tropical countries, but may occasionally present themselves in New York.'”

Army Scientists Improve Methods to Detect Ricin

The CDC has sponsored research on decontaminating ricin. While the utility of spending large amounts of money on vaccine development against certain pathogens can sometimes be questionable, decon is an area of real importance that is under-researched. A letter containing ricin may not kill a lot of people, but its particles can linger for a very long time at each of the mail facilities it traveled through.

Military News – “The paper, which is entitled, ‘Surface Sampling of a Dry Aerosol Deposited Ricin,’ examines swab materials commonly used to sample biological threat agents from surfaces. The paper documents his studies, which demonstrates the need for accurate dissemination techniques to effectively evaluate sampling technologies in an environment mimicking the ‘real-world’ environment where the toxin may be present.”

Israel Holding Suspected al-Qaida Bio Weapons Expert

Israel is currently in a bit of a bind over it’s holding of a suspected biological weapons expert. According to court documents released this week,  Samer Hilmi Abdullatif al-Barq was trained as a microbiologist in Pakistan, had military training in Afghanistan, and eventually was recruited by Ayman al-Zawahiri into the al Qaeda weapons program. Israeli courts have yet to try al-Burq, due to lack of sufficient evidence, but his actions in the area, including attempted recruitment of others into al Qaeda, render him too dangerous to release. Moreover, attempts to release him into the custody of neighboring states have been politely declined. It’s clearly a complicated case.

New York Times – “In a document presented to the court, the military prosecutors described Mr. Barq as an operative in the global Qaeda organization with ‘a rich background in the field of nonconventional weapons, with an emphasis on the biological field,’ having studied microbiology in Pakistan. The prosecutors argued that Mr. Barq’s release at this time to the West Bank, where he is a resident, would constitute ‘a point of no return in the development of a significant global jihadist infrastructure in the area.'”

Scientists zero in on flu virus defenses

A recent study published in the journal Science details novel research on the hemagglutinin protein (HA) of the H3N2 flu strain. The work examined mutations in the protein between 1968 and 2003 which prompted structural changes.  In doing so, researchers were able to pinpoint changes in seven key amino acids that prompted evolutionary change in the virus.  Better understanding the virus’ points and methods of evolution could help in the creation of more efficacious vaccines.

ABC Australia – “The researchers confirmed their findings by engineering changes to these seven amino acids and testing the antibody response to the new virus in ferrets. Importantly, the amino acids singled out by Barr and colleagues are close to the site on the HA protein that binds to host cells. This limits the number of amino acid substitutions that are possible as many changes will alter the protein’s structure, interfering with the virus binding process. ‘The virus can evolve in a number of different directions,” says Barr. “If we can narrow that down to a small number of directions then we’ve got a better chance of trying to work out which particular virus might be the one which is going to turn up in a year’s time.'”

The Surge

Wired has an excellent long-form piece on polio vaccinations and the Taliban. The six-part article is interactive, and includes audio interviews, photo galleries, and infographics on why eradicating polio is so important and so challenging. Obviously, we highly recommend it!

Excerpts – “The virus typically infects only the mucosal tissues of the gastrointestinal system for a few weeks, where the immune system clears it before any harm is done. After that, the infected person would be immune to future infections from the same strain. However, in less than 1 percent of infections, the virus attacks the central nervous system and causes paralysis. Typically this affects just the legs. But in 5 to 10 percent of paralytic cases (that is, 0.05 percent of total infections), polio paralyzes the breathing muscles, meaning that without artificial respiration the patient will suffocate. All this explains why polio is so difficult to annihilate. For every one person who actually gets sick, nearly 200 are carrying the virus and infecting others…

“[T]he math of cost-benefit analyses runs aground when it comes to eradication campaigns, because the benefits, in theory, are infinite. That is: No one will ever die from—or spend a dime on vaccinating against—smallpox for the remainder of human history, barring a disaster involving one of the few lingering military stockpiles. According to a 2010 study, polio eradication would generate $40 billion to $50 billion in net benefits by 2035.”

(image:  Sgt. Mike R. Smith, National Guard Bureau)

Reminder: November Biodefense Policy Seminar Tonight!

by Siddha Hover, posted in Events

Just a reminder that our Biodefense Policy Seminar is tonight! Dr. Vogel will discuss bioweapons threats and nonproliferation. There will be free pizza and soda – join us!

November Seminar Title: Project BACHUS: Forecasting Bioweapons Threats with Experiment and Demonstration
Speaker: Kathleen Vogel
Date: Thursday, November 21, 2013, 7:20PM
Location: Meese Conference Room, Mason Hall,  GMU Fairfax Campus

20110912_Fall Scholars 2011Dr. Vogel will describe a 1990s bioweapons threat assessment that involved setting up a mock bioweapons production facility as an “experiment”. The talk will discuss the difference between a scientific experiment and scientific demonstration and why it is important to interrogate what things are labeled as “experiments” and the implications that has for bioweapons assessments. Kathleen Vogel is an associate professor at Cornell, with a joint appointment in the Department of Science and Technology Studies and the Judith Reppy Institute for Peace and Conflict Studies. Vogel holds a Ph.D. in biological chemistry from Princeton University. Prior to joining the Cornell faculty, Vogel was appointed as a William C. Foster Fellow in the U.S. Department of State’s Office of Proliferation Threat Reduction in the Bureau of Nonproliferation. Vogel has also spent time as a visiting scholar at the Cooperative Monitoring Center, Sandia National Laboratories and the Center for Nonprolif­eration Studies, Monterey Institute of International Studies. Her research focuses on studying the social and technical dimensions of bioweapons threats and the production of knowledge in intelligence assessments on WMD issues.

Decoding Nipah, One Protein at a Time

by Siddha Hover, posted in News

Researchers at the Scripps Research Institute have used X-ray crystallography to solve the structure of a key protein in Nipah’s pathogenicity. The decoding of the protein’s structure has provided researchers with further information on Nipah’s mechanism of replication. Nipah, which many of you may recognize as the basis for the virus in the film Contagion, is a zoonotic virus capable of causing symptoms ranging from respiratory distress and comas to  severe, fatal encephalitis. Currently, there is no vaccine or effective theraputic against the virus, which has an average case fatality rate of 75%.

From Science Daily – “When the scientists solved the crystal structure of the P protein, they found that it forms a tetramer, with four proteins that join to form a single unit. ‘It was surprising to us that this structure is so similar to those from measles and mumps viruses, even though they are only 5 to 26% identical in sequence,’ [first author and researcher Jessica] Bruhn said. ‘If two proteins have high sequence identity then you would expect that they would have similar 3D structures, but to see such similarity in proteins with such low identity was surprising.’ She said this speaks to the importance of structural conservation over sequence conservation — meaning that regardless of whether a protein has an identical sequence of amino acids or not, the structure could still be similar, especially when that structure has the important function of replicating the virus’s RNA genome. ”

Read more here.

(image: Mike Lehmann/Wikimedia)

This Week in DC: Events 11.18.13 – 11.22.13

by Siddha Hover, posted in Events, Week In DC

Our featured event this week is the November Biodefense Policy Seminar this Thursday, featuring biodefense and non-proliferation expert, Dr. Kathleen Vogel. The event is free and open to the public – stop by!

Tuesday, November 19, 2013

Emergency Preparedness Conference
Politico
8:00 AM

Join POLITICO for a conversation about how key players in emergency and disaster response allocate critical resources, plan for the unexpected and come up with innovative solutions to resolve unfinished business from 9/11 as well as prepare for the future.

New Realities: Energy Security in the 2010s and Implications for the U.S. Military
Strategic Studies Institute
All day

The rapidly changing global energy supply situation, coupled with a host of social, political, and economic challenges facing consumer states, has significant implications for the United States generally and for the U.S. military specifically. The U.S. Army War College will gather experts from the policymaking community, academia, think tanks, the private sector, and the military services at the Reserve Officers Association headquarters in Washington, DC on 19-20 November to address first the major ‘new realities’ both geographically and technologically and then the specific military implications. Following the conclusion of the conference, the U.S. Army War College will produce an edited volume consisting of contributor comments/papers, as well as a series of two-page decision-maker executive summaries that will be designed to shape U.S. national security policy and the American response to the ‘new realities.’

TRIA Triage: A Discussion of the Terrorism Risk Insurance Act
National Journal
8:00 AM – 10:00AM

Following the September 11th attacks, many insurers stopped providing terrorism risk coverage after suffering what was then the most costly disaster in the history of insurance. In the wake of the financial disruption, the government enacted the Terrorism Risk Insurance Act; a public-private cost-sharing arrangement that requires private insurance companies to provide terrorism risk coverage in exchange for federal financial backing. Without Congressional intervention, TRIA is currently scheduled to sunset on December 31, 2014. Join National Journal for a policy summit that will convene the nation’s top security, financial and insurance experts for a robust discussion concerning TRIA’s future. The discussion will explore questions such as: Is TRIA a common-sense solution that benefits insurers and policyholders alike, or do taxpayers bear the burden of unnecessary insurance bailouts? What other costly disasters might be on the horizon, and should TRIA be reauthorized at the end of next year?

Surveillance and Foreign Intelligence Gathering in the United States: The Current State of Play
Georgetown Law
9:30 AM

On Tuesday November 19, at 9:30 am (in Hart Auditorium), the Center and the National Security Law Society will co-host the second event in our three part series: Surveillance and Foreign Intelligence Gathering in the United States: Past, Present and Future.

Wednesday, November 20

New Visions for Citizen Science
Wilson Center
1:00 – 5:00 PM

Citizen science projects range from classifying galaxies and collecting environmental data to collectively solving the structure of an AIDS-related enzyme through a protein-folding game. The Commons Lab within the Science and Technology Innovation Program at the Wilson Center, in collaboration with TechChange and the Wilson Center’s Environmental Change and Security Program and Africa Program, invite you to join a conversation on open innovation and citizen science: What technologies support public participation in scientific research? How can projects ensure high-quality data collection and analysis, and support meaningful engagement with volunteers? How can federal agencies build partnerships to leverage these new approaches? What are the impacts to science, management, and policy, and how do we measure success? Opening remarks by Kumar Garg, Assistant Director for Learning and Innovation, Technology and Innovation Division, White House Office of Science and Technology Policy. Keynote by Bob Perciasepe, Deputy Administrator, U.S. Environmental Protection Agency.

Terrorist Groups in Syria
U.S. House Committee on Foreign Affairs, Subcommittee on Terrorism, Nonproliferation, and Trade
1:30 PM

Witnesses Mr. Brian Michael Jenkins, Senior Adviser to the President, RAND Corporation; Mr. Phillip Smyth, Middle East Research Analyst, University of Maryland; Mr. Barak Barfi, Research Fellow, The New America Foundation

A New Model for Defense Intelligence
Brookings Institution
3:00 – 4:00 PM

The exponential rate of change in the present global environment makes today’s security landscape particularly challenging, and projections promise that the challenges will only increase. In this complex and uncertain future, intelligence, cyber, Special Operations Forces and international partnerships will take on more prominent and critical roles in the nation’s defense and warfare for decades to come. On November 20, the Intelligence Project at Brookings and the National Intelligence University will co-host a discussion with Lieutenant General Michael T. Flynn, director of the Defense Intelligence Agency (DIA), to examine this uncertain future, DIA’s role in this complex security environment and a new model for defense intelligence that ensures preparedness to address these challenges and the crises of tomorrow. Flynn has also served as the director of intelligence at the U.S. Central Command, director of intelligence for the Joint Staff and director of intelligence for International Security Assistance Force-Afghanistan and U.S. Forces-Afghanistan. Brookings Senior Fellow Bruce Riedel, director of the Intelligence Project, and President of the National Intelligence University, David Ellison, will provide introductory remarks, and Riedel will moderate the discussion. Following his remarks, General Flynn will take questions from the audience.

Thursday, November 21

Biodefense Policy Seminar – Project BACHUS: Forecasting Bioweapons Threats with Experiment and Demonstration
Meese Conference Room, Mason Hall, GMU Fairfax Campus
7:20 PM

Dr. Kathleen Vogel will describe a 1990s bioweapons threat assessment that involved setting up a mock bioweapons production facility as an “experiment”. The talk will discuss the difference between a scientific experiment and scientific demonstration and why it is important to interrogate what things are labeled as “experiments” and the implications that has for bioweapons assessments. Kathleen Vogel is an associate professor at Cornell, with a joint appointment in the Department of Science and Technology Studies and the Judith Reppy Institute for Peace and Conflict Studies. Vogel holds a Ph.D. in biological chemistry from Princeton University. Prior to joining the Cornell faculty, Vogel was appointed as a William C. Foster Fellow in the U.S. Department of State’s Office of Proliferation Threat Reduction in the Bureau of Nonproliferation. Vogel has also spent time as a visiting scholar at the Cooperative Monitoring Center, Sandia National Laboratories and the Center for Nonprolif­eration Studies, Monterey Institute of International Studies. Her research focuses on studying the social and technical dimensions of bioweapons threats and the production of knowledge in intelligence assessments on WMD issues.

Nuclear Weapons in the 21st Century
Heritage Foundation
12:00 – 1:00 PM

Nuclear weapons are as relevant today as they were decades ago. In 2009, President Obama advocated for a “world without nuclear weapons,” and recently reaffirmed this pledge during his speech at the Brandenburg Gate in Berlin. The President stated that he intends to reduce U.S. deployed strategic nuclear weapons by up to one-third below the New Strategic Arms Reduction Treaty level. Meanwhile the U.S. nuclear triad continues to age. The Administration’s policy of “no new weapons,” potential unilateral reductions, and a lack of commitment to sustain U.S. nuclear weapons infrastructure are raising questions about U.S. commitment to keep the weapons safe, secure, and reliable, and maintain its commitment to provide a nuclear umbrella to its allies around the world. Join us as our guests discuss the continued importance of U.S. nuclear weapons for our national security in light of today’s diverse challenges.

The Convergence of Crime and Terrorism
Potomac Institute for Policy Studies
12:00 – 2:ooPM

The nexus between crime and terrorism challenges US law enforcement in unique ways. Since the 1980s and 1990s, evidence has linked narcotics trade to ties between terrorism and transnational organized crime. Operating without borders and in areas of government instability, Latin American gangs such as MS-13 and Mexican cartels have been financing terrorist operations through the drug trade. Narco-trafficking is a lucrative business, and terrorist organizations such as the FARC, Hezbollah, and al-Qa’ida take advantage of this revenue stream. As Hezbollah linked Los Angeles gangs and Al-Shabaab linked groups in Minnesota have demonstrated, terrorist operations via the drug trade continue to operate in the United States. The panelists will discuss important issues surrounding these tactics on the national and local level.

Friday, November 22

Talking Science: Environmental and Health Communications in a Skeptical Era
Wilson Center
1:00 – 4:30PM

How can communications professionals, policymakers, and academic experts effectively communicate environmental and health issues in a skeptical era? In the first of two panels, communications directors from US and UN agencies and environmental and health NGOs will discuss the relationships and negotiations that underlie action (or inaction) in a major policy-making capital like Washington, D.C. In the second panel, five speakers will explore the cultural and social causes and consequences of climate change skepticism (especially American climate change skepticism) and consider the implications for national and international efforts to address global climate change. This discussion is sponsored by the Environmental Communication Division of the National Communication Association.

The Pandora Report 11.15.13

by Siddha Hover, posted in Pandora Report

Highlights include H7N9 vaccines, using bacterial toxins as antibiotics, updated numbers for the Mexican cholera outbreak, the dolphin morbillivirus, Albania refusing to host the Syrian CW arsenal, H6N1, and MERS in camels. Happy Friday!

Vaccines for H7N9 Ahead of Pandemic Fears
As the Northern Hemisphere braces for winter, fears of a resurgence of H7N9 cases are rising. Although the cooler weather has brought a few new cases, it’s still to early to tell whether another large-scale outbreak is imminent. Luckily, both Novartis and Novavax have developed vaccines capable of eliciting strong immune responses to H7N9. The Novavax vaccine generated a significant immune response in 81% of study participants, while the Novartis vaccine generated an 85% response. The real story is the time frame – it took both companies just a few months to have a viable vaccine in clinical trials, which is both impressive and encouraging should an outbreak occur.

Fierce Biotech – “Novartis and partners at the Craig Venter Institute in San Diego were able to launch a clinical trial in August after the virus was identified in March. The project was funded by BARDA. The H1N1 scare back in 2009 spurred a global, multibillion-dollar effort to stockpile vaccines. The campaign highlighted just how long it took to develop and manufacture new vaccines and then spurred a backlash after governments around the globe rushed to buy stockpiles only to see the threat evaporate. In Europe some health officials accused pharma companies of capitalizing on the fear of a lethal pandemic, and memories of the controversy will likely influence any new moves to guard against a new outbreak. This winter’s alarm may also fizzle, but these companies have demonstrated that new vaccines can be developed in record time.”

Bacterial Toxins Suggest New Antibiotic Targets
A group of researchers at MIT have found a bacterial toxin which may result in the development of novel antibiotics. The toxin, SocB, is used as a part of the toxin/antitoxin interplay by Caulobacter crescentu to check bacterial growth if necessary. It binds to a highly conserved protein, DnaN, suggesting the possibility of developing new, broad-spectrum antibiotics.

Bio-IT World – “To regulate their own growth and proliferation, bacteria maintain an intricate network of toxin-antitoxin (TA) systems, in which they produce a mix of toxins and targeted antitoxins that can skew toward a disruptive level of toxins in poor environmental conditions to limit growth. Some bacteria have been found to contain as many as 50 of these TA systems, all prepared to check bacterial growth should anything trigger a reduction in antitoxins…[SocB] inhibits replication in Caulobacter crescentus by binding to a protein that participates in numerous crucial reactions in the replisome, playing roles in mismatch repair, translesion synthesis, and especially DNA replication itself.”

WHO: Update on Cholera Outbreak in Mexico
The cholera outbreak which began in September is continuing apace in Mexico, with four cases in the last week bringing the total laboratory-confirmed case count to 180. The majority of the cases are concentrated within the state of Hidalgo, just north of Mexico City. This is the first outbreak of cholera in Mexico in over a decade. The strain is 95% identical to that of the Haitain outbreak, which was caused by an influx of infected UN aid workers following the 2010 Haitian earthquake. The Haitian outbreak, described as the “worst in recent history” by the CDC, is ongoing, with 684,085 cases to date.

WHO – “The health authorities of Mexico continue to strengthen outbreak investigation and surveillance at the national level and continue to ensure the availability and quality of care in medical units. Health professionals at different levels of the health care system are being trained in prevention and treatment of the disease. Measures are being implemented to ensure access to drinking water and basic sanitation at the community level. Awareness campaigns, particularly around safe water and food consumption are being carried out in Spanish and indigenous languages. An antimicrobial susceptibility test for Vibrio cholerae O1 Ogawa was conducted by the Institute of Epidemiological Diagnostics and Reference (InDRE) which demonstrated that the bacterium was susceptible to doxycycline and chloramphenicol, with reduced susceptibility to ciprofloxacin and resistance to trimethoprim/sulfamethoxazole.”

Dolphin-Killing Virus Spreads South, May Be Infecting Whales Too
There’s been a lot of coverage recently of the morbillivirus infecting dolphins, killing 753 of the animals since July.  The virus has subsequently spread to two species of whales, humpback and pygmy respectively. In humans, measles belongs to the genus Morbillivirus, but to date there have been no documented cases of strains of morbillivirus jumping from a dolphin or other marine mammal to a human, and the likelihood of it doing so remains very low. However, the virus may be able to infect dogs, so if you see a stranded dolphin, keep Fido away as you’re calling animal control.

Wired – “The outbreak began along the coast between New York and Virginia this summer. Now, carcasses are washing ashore in the Carolinas and Florida. Researchers have identified the cause as dolphin morbillivirus, a pathogen that’s related to human measles and canine distemper…The die-off has already been classified as an Unusual Mortality Event by the federal government – a designation that frees up resources and sends investigators and responders to the hardest-hit areas. It’s already exceeded the pace set by the last major morbillivirus outbreak on the East Coast, an event that lasted for 11 months, between June 1987 and May 1988, and ultimately claimed 742 dolphins.”

Albania shuns Syria chemical weapons destruction
How does one destroy a chemical weapon? It’s a question we’ve asked before here on the Pandora Report, and one which our October Biodefense Policy Seminar Speaker, Dr. Paul Walker, answered pretty clearly – very carefully (for a slightly more detailed answer, his full talk is available on our YouTube channel). According to the BBC, there has been a slight hiccup in the destruction of the Syrian arsenal. Following mass protests, the Albanians, who were supposed to host and destroy the materials, have flat out refused to do so. This has left the poor OPCW investigators scrambling to find a different destination for the weapons before the Friday deadline for submission of final plans lapses. Someone get these people (another) medal!

BBC – “The Balkan nation recently destroyed its own chemical stockpile, and the US had requested that it host the dismantling of Syria’s arsenal. Under the deal brokered by Russia to remove Syria’s chemical weapons, it was agreed that they should be destroyed outside the country if possible. Mr Rama attacked the Albanian opposition for having criticised the government’s willingness to consider the idea. A key meeting of the Organisation for the Prohibition of Chemical Weapons (OPCW) – the international watchdog supervising the destruction – had adjourned for several hours, awaiting Albania’s decision.”

In case you missed it:

– First Human Infection with H6N1
– MERS Confirmed Live in Camel

(image: Docklands Tony/Flickr)