Friday, June 19, 2009

First images of memories being made: unrelated to smallpox but pretty awesome

Images taken using fluorescent proteins have shown that when memories are formed, new proteins are synthesized locally in synapses. This strengthens synaptic connections and essentially strengthens and reinforces the memory. 

Synapses in the brain are constantly changing and adapting, forming new connections. This mutability is central to learning, creativity, and the forming of new synapses--making memories.

An important question has always been how long-term memories are made and stabilized in this changing environment.  This study helps provide evidence of regulated translation of localized mRNA at stimulated synapses, which could be the molecular basis for long-term memory formation, and for deficiencies in learning and memory. This is really cool.

-Andrew Beck

Book Review: Demon in the Freezer by Richard Preston

Demon in the Freezer was an interesting, accessible book. Most of its faults, and strengths, derive from the fact that the emphasis is on presenting points of view, rather than on laying out an argument based on factual research.

Preston sandwiches the discussion about smallpox between sections about the anthrax attacks in 2001. He starts with the identification of the spores as anthrax and the mounting concern that it is a bioterrorist threat. He then continues to give a brief history of smallpox and its eradication. The story of Peter Los yields a general familiarity with the disease and then major personalities like D.A. Henderson and Larry Brilliant give Preston a launching point for his chapters about the eradication effort. Next Preston tackle bioweapons. Here he belabors the fact that the Soviets were likely developing weaponized smallpox and anthrax, drawing upon accounts from Soviet defectors and American intelligence. Finally, Preston discusses the variola stores elimination debate and then uses Lisa Hensley as the entry point for the story behind the development of an animal model for smallpox. At the very end, Preston concludes the account of the anthrax attacks and mentions, briefly, how the advance of biotechnology makes it easier than ever to engineer microorganisms and viruses.

Preston frames his story in terms of individuals' stories. He always uses a personality to introduce information about smallpox, and structures his chapters in terms of that person's narrative. One of the fantastic outcomes of this approach is that Preston really brings life to the story of smallpox. Most books describe the progression of clinical symptoms of the disease. Preston describes Peter Los' experiences, and pepper in facts about, for instance, how people who have smallpox remain conscious and mentally aware throughout the entire ordeal. He uses the outbreak initiated by Peter Los to describe what it was actually like to get vaccinated. It was fascinating: according to Preston, nurses jab your arm something like fifteen times with a bifurcated needle that has been dipped into vaccine. I found the concreteness of Preston's writing incredibly gratifying. We have all been reading many books about smallpox, and most of these lay out well-researched claims. Demon in the Freezer, however, made me look at what I knew in a more intimate way. Of course smallpox is a horrible and gruesome disease that caused unbelievable suffering. But following one person for several chapters, reading about the actual experiences, not just the symptoms, of victims gave me a better perspective, and one that I think it important. These actual experiences contain the real significance of smallpox's eradication.

I do wish that Preston cited his facts more often. My main and only criticism of the book is that the emphasis seems to fall on drama rather than researched facts at times. He makes claims, especially in the section about bioweapons, that begs question of his sources. At times he seems to give away information that is supposedly classified; undoubtedly, this is an over-dramatization on his part, meant to make a popular book more interesting. However, the reader still wants to know: where did he get this information? Citing sources would add more credibility to his assessments. Furthermore, because he angles his writing to focus on narrative and excitement, some entire chapters are superfluous. The chapter the time Lisa Hensley cut her glove in the Ebola lab was exciting and I enjoyed reading it, but it didn't really add any insights into smallpox.

Anne was telling me about Preston's writing method and I did some research on it myself. He does do a great deal of factual research, but he also spends a lot of time simply shadowing and hanging out with the people that appear in his books. After he has written the book, he reads sections aloud to the people who figure prominently and then solicits feedback. For instance, he probably read the D.A. Henderson sections aloud to D.A. Henderson and asked for comments. The result is that we get good glimpses into these people who played enormous roles in the history of smallpox and thus have better insights than anyone else into the issues at stake in the elimination debate and the bioterrorist threat. And Preston is quite even-handed about this: he presents both D.A. Henderson, an avid destructionist, and Peter Jahrling, a prominent retentionist, in a respectful, reasoned manner. We can identify with both of these people, and understand that they both have noble motives that underly their opinions.

The overall effect, as mentioned before, is a book that is narrative heavy and peppered with facts—good facts, but floating facts. I think Preston could have cited his sources without losing this important and insight-producing narrative approach. Demon in the Freezer is a popular book, an entertaining read. For people who have already learned a lot about smallpox, it is especially enjoyable because it brings the facts we have learned to life. Getting at the real experiences of people who suffered from the disease and of people who eradicated the disease is crucial for truly understanding the issues surrounding smallpox. Demon does this better than any other book I've read for this class, in spite of its flaws.

-Elaine C

Thursday, June 18, 2009

Book Review: "Jenner's Smallpox Vaccine"

Baxby’s Jenner’s Smallpox Vaccine is an impressive history of smallpox and smallpox vaccination, broad in scope and varied in sources (which was refreshing after the one-source Rotting Face). Essentially, Baxby seeks to outline the controversy surrounding the discovery of the vaccine and the mystery surrounding the origin of “vaccinia” the strain of vaccine that eventually become the norm.


I applaud his clarity in framing the debate in the first chapter. Using numbered lists and other organizational devices, Baxby leaves readers with no doubt about the basic issues he wishes to explicate. From here, he moves to a more general description of the disease, before jumping into the lives of his primary historical figures, such as Edward Jenner. I appreciated his use of scientific studies and data to back up his broad historical knowledge, which lent his text a legitimacy many smallpox or science authors lack, being written by historians with only a cursory scientific knowledge. He is, however, often self-referencing, perhaps a product of the little actual or valid scientific scholarship that has been done on the subject. His use of illustrations and photographs was effective as well; for a disease that is so visually manifested, this is a wise choice.


There are elements of the book, however, that I found less than appealing. Baxby often seems obsessed with who, exactly, received or should receive “credit” for the discovery of vaccine, vaccination, vaccinia, and other key components of the debate. Though recognition is important, his overuse of the word “credit,” sounding like a school examination, and the fact that most, if not all, of those worthy of such “credit” are dead made his impassioned cries seem, at times, rather silly. There are points in the text where Baxby seems to delight in vilifying Jenner; more effective, I think, would have been sympathy to the enormous numbers of Jenner fans in the world, while presenting the alternatives in the same rational, reasoned manner. Finally, Baxby would do well to tighten up his language to avoid ineffective and vague sentences, such as “Some critics had very pertinent points to make on these issues [the safety and effectiveness of vaccination], but some approaches were frankly hysterical” (5) in the middle of a paragraph. By diving right into his subject matter instead, Baxby would make his text both shorter and more exciting to read.

In short, Baxby’s text is important in that it presents alternative views of the smallpox vaccine’s early history that often get lost from mainstream view. Less self-awareness in the writing about his being “the first time this is attempted” (8) and a tone more sympathetic to mainstream readers who may hold Jenner as a hero would contribute to a more readable tone, I think, but Baxby’s book is worth reading. His scientific data is what separates this text from many others. 


Wednesday, June 17, 2009

Mad Cow to Cow, to Fish, to Human?

Dr. Robert P. Friedland has published an article today in Journal of Alzheimer's Disease indicating that prion diseases such as Mad Cow could potentially be transmitted via fish. While this may seem like an irrelevant discovery, it is most certainly not. It seems that America's farmed fish are often fed cow meat- or bone-products. This fact, both surprising and ultimately pretty disgusting, proves just how interwoven the nation's food industries currently are. 

Generally, the species barrier provides reasonable protection for non-host animals against infection; even so, Friedland and his team argue, it is possible for a fish to serve as a carrier for the disease without being infected itself. Further, say researchers, it is "possible that eating diseased cow parts could cause fish to experience a pathological change that allows the infection to be passed between the two species." As Mad Cow disease takes decades to show itself in an infected person or animal, conclusive results may not be available until well into the future. Still, Friedland hopes that his article may help sound the alarm and change farmed fish-food before the disease pervades this transmission route. 

From my standpoint, simply hearing that the farmed fish industry uses leftover cow products as fish-food is reason enough to change the practice. After all, said Friedland, "Fish do very well in the seas without eating cows."



Microbiology Porno: The Reproductive Cycle of Variola Major

For your viewing pleasure:

- Molly, Teresa, Kaitlyn, Andrew, and Elaine S.

A Book Review of Smallpox: The Fight to Eradicate a Global Scourge

By David Koplow

Smallpox: the Fight to Eradicate a Global Scourge is a thorough, multi-disciplinary overview of the debate whether or not to destroy the remaining known stocks of smallpox virus in Vector Laboratory in Russia and the U.S. Centers for Disease Control in Atlanta, Georgia. The beginning chapters provide readers with introductory knowledge of smallpox – its biology, its history, its use as a biological weapon, and its place as an issue in international environmental and health policy. Although each chapter in itself does not cover every issue of the subject (theoretically, each chapter could have been expanded upon to become its own book), Koplow presents an incredibly multi-disciplinary understanding of smallpox as a biological, historical, and political agent. For example, a chapter about environmental law and policy may seem unrelated to smallpox at first, but Koplow discusses many policy aspects that ultimately both are affected by smallpox and affect the development, use, and distribution of smallpox. Ultimately, each chapter serves as a building block to Koplow’s final two chapters, one of which presents the argument for eradication and the other against the eradication. Koplow is professional and neutral in his presentation of the background knowledge; readers will not know whether he is for or against the extinction of smallpox until the final two chapters.

It is fairly apparent that the book is written for the general public – people who are unfamiliar with smallpox, biological weapons, and public health. For people who know little about these subjects, Koplow writes an incredible introduction to the numerous aspects of smallpox including its basic history and biology and the politics that surround the disease. This book is not tailored for people who are searching for in-depth discussion of the history or biology of smallpox. For people who are more educated about the issues, some sections may be cursory and too general. Still, I appreciated Koplow’s approach to presenting an entire package of information about smallpox.

Perhaps what I enjoyed most about this book is how applicable its content is to today’s world. Through his organization and style of writing, Koplow encourages his readers to think about smallpox as more than just an eradicated virus confined to the pages of a history or biology textbook. He succeeds in equipping the readers with the information and questions necessary to engage in the debate about extinction of smallpox. Furthermore, the framework of analysis and thought he uses to address smallpox could be used for any other infectious disease (such as HIV to which he makes numerous reference). Thus, Koplow doesn’t tell his readers what to think about smallpox but how to think about public health issues in general. Koplow asks the question “should the remaining stocks of smallpox be destroyed?” and he shows that the answer to that question is anything but simple.


Tuesday, June 16, 2009

Structure of HIV Protein Shell

Remember when we learned in class about capsid morphology? We learned that viruses have 3 different types of morphology - icosahedral, helical, and complex - and that HIV falls within the complex category. I was excited to find today that some new research on HIV, published this month in the journal Cell and conducted by researchers at The Scripps Research Institute, builds very nicely on what we already know about the structure of the HIV capsid.

As we learned in class, the protein capsid surrounds the genetic material of the virus. We also saw pictures of several capsids in class, including (I'm pretty sure) one of the HIV capsid. Previously, scientists knew that the HIV capsid was an arrangement of about 250 hexagonal protein building blocks, called the CA. Sets of 6 CA protein molecules make up hexamers, and the ends of shell are completed with 7 and 5 protein pentamers (remember trying to spot the pentamers?). In the past, the group of scientists who conducted this study visualized these hexamers using electron microscopy, and then x-ray crystallography. However, this study is the first to describe the high-resolution molecular structure of the CA. Growing 3D crystals of the CA hexamer had been extremely difficult, but for this study scientists engineered CA proteins that would provide sturdy links between crystals. As a result, they were able to visualize the CA hexamer at a resolution of 2 Angstroms - an unprecedented level of detail. At this resolution, scientists were able to see the precise location of the side chains on the alpha helices that are responsible for stabilizing the structures. They were also able to see "flexibility" in the structure, as well as connections between the C-terminal ends and N-terminal ends of adjacent CA protein molecules.

This kind of detailed understanding of the HIV capsid structure provides new opportunities for interventions that could break apart or destabilize the capsid. For example, interventions could inhibit assembly of the capsid or facilitate its degeneration. The article mentioned, for example, designing small molecules that could be inserted at strategic positions to destabilize the capsid.

I was excited to read about a study that directly applies something we have learned about - viral structure, and specifically capsid morphology - to the real-life problem of HIV. I think this article illustrates beautifully how basic biological principles and understanding, which can often feel far removed from real life, can have huge implications for public health in the future. Whether or not this structure actually leads to the development of an effective intervention remains to be seen, but it seems to me that the greater our understanding of viruses, especially at the atomic level, the greater the chance that we will be able to intervene effectively.

The article can be found at:


Cryptosporidium Enteritis: Swimming Pool Parasite

-C. Paula de los Angeles

I've always been hesitant to swim in public swimming pools, and the recent reports of the sharp increase in recent years of reports of gastrointestinal illness from use of public pools and water parks has only confirmed these fears.

If one thinks that chlorine can kill any parasite and stop the spread of infectious disease, one is wrong. Cryptosporidium has an egglike shell that allows it stay alive in chlorinated water for up to 10 days. Statistics have shown an increase from 7 outbreaks affecting 567 people in 2004 to 31 outbreaks affecting 3726 people in 2007. However, it is unclear whether the increase is a result of an increase in incidence or reporting.

Epidemiologist Michele C. Hlavsa of the CDC has noted that the development of a treatment for the diarrheal disease, cryptosporidiosis, in 2002 could have led to an increase in detection and reporting. Symptoms include diarrhea and dehydration.

To swim or not to swim? Public health officials encourage people to still swim, but to "be smart about it". To them, this means not allowing children to swim when they have diarrhea. Do not swim in cloudy water. Do not swim in pools with slick tiles or without humming filtration machines. Don't use the pool as a toilet.

With that in mind, I'll think twice before I jumped into a pool this summer.

News link here:

Politics and trade offs of swine flu funding

Kaiser Foundation Jun 5 2009 “White House Seeks More Money For Swine Flu”

President Obama has requested an additional $3.1 billion of unspent stimulus funds to be reserved for swine flu, that money coming from a 1% cut “across-the-board” to stimulus programs. The stimulus plan, which so far has mostly been spent on assistance for state Medicate and Social Security, has become an “alluring pot of money” for politicians to take money out of. According to this article, Congress is unlikely to approve Obama’s request, especially with major opposition from Republicans, with the US House Majority leader Steny Hoyer expressing concern about a $2 billion war funding bill that is in congress concurrently with the swine flu proposal.

I find this political funding struggle very interesting because it shows where the government’s priorities lie, and also demonstrate some key questions in the swine flu debate. How much money is appropriate to devote to swine flu? Should we really take money away from stimulus programs, which would help Americans with rising healthcare costs and ameliorate joblessness – problems which we know are happening? Should we take money away from these programs to stockpile vaccines for a disease which for the moment remains mild, with only a potential to become more virulent? It is a question of balancing high probabilities of smaller magnitudes, with small probabilities of larger magnitudes. What effect could Obama’s proposal have on the economy? Will it stall our path to economic recovery, and could it do more harm than good in terms of swine flu? For example, would taking money out of Medicaid, harm our ability to treat swine flu infections in the poorer populations that Medicaid serves – a population which I would guess is more vulnerable to chronic conditions that increase risk of swine flu complications. However, if it comes to a choice between a funding for war or for swine flu, I would choose swine flu any day.


Infant Death in Argentina due to Swine Flu

-C. Paula de los Angeles

One of the concerns about the recent swine flu pandemic is how the flu will fare in the winter seasons.

The World Health Organization has already confirmed 35,928 cases of the virus, including 163 deaths in 76 countries worldwide.

This past week, Argentina, a country now entering its winter months, experienced its first fatality due to swine flu, a 3-month-old baby. Officials do not know how the infant contracted the disease, but its continued perseverance into these colder months is a reason to be concerned.

Questions: What is the ideal environmental/climate of this swine flu to spread?

News article here:

Review: "Scourge: The Once and Future Threat of Smallpox" by Jonathan B. Tucker

It seems that this is a popular book in this class, and rightly so. Jonathan Tucker’s “Scourge: The Once and Future Threat of Smallpox” is a historical tour de force sparingly littered with scientific errors and skillfully dotted by artistic liberties. No conversation is too private, no location too classified for the near-omniscient gaze of The Tucker. The demi-author is able to reproduce a vivid world of facts and events mostly true to their origins and certainly within the toleration of the people he described. That said, this oeuvre was a thoroughly enjoyable read from beginning to end due to its character driven narrative. I think that in a significant way, this book is a dedication to all the people who made the eradication of smallpox possible. It centers on the quirks and genius of eradication giants such as D.A. Henderson, Larry Brilliant, and Bill Foege. The detailed (and somewhat questionable) accounts of conversations and chance encounters reflects not only the research which went into this book, but also the enormous amount of time Tucker took to interview each and every one of the protagonists which populate “Scourge”.

The central story line is remarkable and is a true exemplar of what is achievable when talented and dedicated people are put together and given the chance to make the world a better place. Tucker’s vivid treatment of the events places the reader in the perspective of someone who is along for the eradication effort; from the highest echelons of the WHO bureaucracy to the most common foot soldier in the war against smallpox, the reader is there with the characters. Dispersed in between the various personality-driven narratives are little tidbits of scientific fact which gives insight into the practical challenges confronting the highly translational science of vaccines. The author does an exceptional job at summarizing the key events which led up to zero pox and he makes a good stylistic choice by quoting Brilliant’s reflection of exactly how profound a moment that was for humanity.

The last third of the book is less of an adventure and more of a discussion on bureaucracy and international politics. Tucker can no longer switch between the contrasting personalities of Henderson and Brilliant and their respective cohorts, but almost entirely focuses on Henderson’s frustrating journey through Washington and Geneva politics. Unfortunately, the pace of the narrative drops off but the quantity of information certainly makes up for it; the author takes us into the classified and shady world of Soviet biological weapons research and leaves us wondering about what exactly is in our next breath of air. At times, Tucker makes it seem as though the places and events described were recorded in person while in actuality they were obviously from secondary sources, most likely interviews with people such as Alibek. All in all, “Scourge” is a well written and well researched book about the people who helped to remove smallpox from this world and also others trying to stop those who contrive to bring it back.


New and Hot: Recombination and Antibiotic Resistance in Pneumococcus

In the latest issue of Science researchers in the UK and Finland studied genetic recombination in Streptococcus pneumonia, the bacteria that causes pneumonia and bacterial meningitis.

They analyzed the genetic sequences of recombination loci of 2,024 different pneumococcus genotypes from the MLST database, a database that gives recombination locus sequence data for seven housekeeping genes found in pneumococcal bacteria. Housekeeping genes, according to a quick google search, are simply those genes that are involved in basic cell function are are thus always turned on. Using a Bayesian analysis program, the researchers grouped the genotypes into six clusters based on allele frequencies. They found that half of these clusters matched non-pneumococcal bacteria and the other half matched pneumococcal sub-populations. Most importantly, when they looked at cluster 4, one of the non-pneumococcal clusters, they found that it contained almost all of the non-pneumococcal alleles. Upon further investigation, they found cluster 4 bacteria were associated with higher antibiotic resistance to enicillin, erythromycin, tetracycline, chloramphenicol, and cefotaxime. "In contrast, cluster 1, which almost exclusively contained alleles from one cluster, negatively associated with resistance" (3).

This suggests that those strains of bacteria that exhibit the hyper-recombination, a higher tendency to accept genes from other species, are important in the evolution and spread of antibiotic resistance.

This seems consistent with what we've been learning about viruses--the higher the rate of mutation or recombination, the higher the likelihood a strain will develop drug resistance. What I am not clear on is whether their is a recombination mechanism for pox-viruses as there are for most bacteria? Bacteria, especially when they are of the same species, routinely undergo homologous recombination, "in which short tracts of DNA in the recipient are replaced by the corresponding tract from a donor strain, resulting in a mosaic of DNA from different ancestors" (2). How rare are recombination events for pox-viruses and viruses in general? I know Kaitlyn mentioned theories that vaccinia was a recombination of various strains of pox-viruses...

(1) Science summary
(2) Science article
(3) News summary

-Elaine C

The Greatest Killer: Smallpox in History

By Donald R. Hopkins

If I had to choose only word to describe The Greatest Killer: Smallpox in History by Donald R. Hopkins, it would be “thorough.” The book is comparable to an encyclopedia in its comprehensiveness of the history of smallpox. Hopkins somehow manages to write about smallpox in all five continents and its history in each of those continents. In addition to discussing the fairly well-known history of smallpox in Europe, he thoroughly chronicles smallpox in East and Southeast Asia, the Pacific Islands, and Africa which I think is rarer and sometimes more interesting knowledge. In doing so, Hopkins blends history and medicine and presents himself as both a doctor and historian with the authority to speak about smallpox.

My main criticism of Hopkins’s novel is how he documents the people affected by smallpox. Hopkins writes in his introduction that he “deliberately chose to linger on the illnesses and deaths of prominent persons…first, because they were bound to be of more obvious consequence to history than the illnesses or deaths of numerous less influential folk” (Hopkins xiv). Ironically though, in listing every single member of royalty that was ever infected with smallpox in the history of the world, Hopkins turns these prominent persons into less influential folk in the minds of the readers. At the end of first few chapters of the book, I couldn’t recall one monarch in European history that had been infected with smallpox (except for Queen Elizabeth I) because they all blurred together in my mind. Essentially, there was nothing distinguishing these monarchs from all the other millions of people infected with smallpox because Hopkins only succeeded in pressing upon the reader that A LOT of people were infected with smallpox.

However, when Hopkins is not listing every single prominent person in the history of the world infected with smallpox, he does write an incredibly interesting account of other aspects of the history of smallpox – how it changed the trajectory of numerous empires, how different cultures responded to the disease, and how the “same despair, tragedy, fear, bewilderment, and mistakes…seen in African and Asian villages…[also occurred] in European palaces, North American hospitals, and elsewhere in the not so distance past” (Hopkins xiv). The organization of the book allows for readers to easily observe the evolution of attitudes and behaviors towards smallpox in the different continents (i.e. his last chapter is called “Erythrotherapy and Eradication”), and although very dense, Hopkins’s writing is comprehensive and easy to read.

In 1806, Thomas Jefferson wrote to Edward Jenner that “future generations will know by history only that the loathsome has existed.” I would not be surprised if Hopkins’s book became the main vehicle for knowing the existence and history of smallpox in the future.


Monday, June 15, 2009

Ken Alibek's "Biohazard" Review

Ken Alibek’s “Biohazard”

In Ken Alibek’s memoir about his work at the USSR’s bioweapons organization, Biopreparat, a new take on the scope of the Soviet Union’s bioweapons arsenal and research is revealed. Along with Pasechnik, Alibekov (as he was known as in Russia) was one of the most informative defectors from the USSR, and because of his high status in the USSR’s military-dominated science ministry and biological weapons, his knowledge of the extent of the research involving tularemia, smallpox, plague, toxins, and anthrax was instrumental in the United States’ understanding of their enemies progress. Though the memoir can become melodramatic and a little heavy handed at some points, Alibek attempts to describe the inherent danger of the USSR’s programs and the danger that could still exist today- the dispersion of USSR seed virus strains, scientists, and knowledge to rogue nations and terrorist operations throughout the world. Once a reader is able to get through Alibek’s attempts at flowery writing and dramatic line endings, the foundation of his book is interesting and terrifying. He explains very simply and in layman’s terms the genetic and biological processes to enable increased understanding of the magnitude of the biological weapons and biomanufacturing he was dealing with. All in all, this book was a great introduction and firsthand account of one man’s moral struggle as both a doctor and a biological weapons engineer, in a time when distrust between countries was rampant, and the knowledge and progress of the USSR’s Biopreparat program placed the entire world at danger.


Along the same lines of Elaine’s Presentation….

A mathematical modelist from the University of Texas at Austin is using Facebook to track disease spread and to measure how individuals perceive health threats and health challenges. The following questions were asked on a Facebook group to measure public responses to the H5N1 outbreak:

“When did you first learn about the swine flu outbreak?"

"Have you searched the Internet for additional information on the swine flu outbreak?"

"If a vaccine for swine flu became available, would you want to be vaccinated?"

These three questions appeared on Facebook two days after the panic hit regarding the swine flu. The principal investigators involved in this model were part of the of the “National Institutes of Health research program called the Models of Infectious Disease Agent Study (MIDAS) that develops computational models of how infectious diseases emerge, spread and can be contained. The results can help public health officials plan for and perhaps even prevent contagious outbreaks.”
“Key to the researchers’ MIDAS modeling project is surveying people on how they perceive health risks. The researchers will use this information to build a dynamic model that simulates how changes in decision-making influence patterns of disease spread. The model will help them and others identify the strategies that improve adherence to interventions and reduce the spread of disease.”

One of the interesting things regarding this study was how the researchers were planning on using the results: “the group is interested in tracking how people’s answers change as public health officials issue new information or guidance about H1N1. The differences could reflect what happens to people’s perceptions, behaviors and choices as a disease outbreak evolves. Incorporating this information will truly advance the field of disease modeling.”

Disease modeling, while having serious limitations, is being used in interesting and new ways- measuring how media changes public perception and perhaps even affecting behavioral changes for community members.



Injection Safety

Reports from the Associated Press and the US Army have stated that 16 patients have tested positive for Hep B and C, most likely due to improper injection practices.

“According to the AP, the 16 patients at the William Beaumont Army Medical Center were just a fraction of the more than 2,000 diabetics who may have been exposed to Hepatitis B (HBV) and Hepatitis C (HBC) and other blood borne illnesses. The AP noted that the Army said multiple patients had been administered injections from the same insulin pen. Texas’ El Paso Times reported that each insulin pen is meant for use by one person, but between August 2007 and January 2009, multiple patients were injected with the insulin pens. According to Journal Now, multiple patients were “systematically” injected with the same pen.”

The CDC has been working on a ten year long review of patients put at risk for “potentially deadly, blood-borne infectious diseases”. According to the CDC, over 60,000 patients were places at risk, and thousands of patients have to undergo testing for HBV and HCV due to improper infection control practices.

“According to the CDC’s report, health care personnel failing to follow basic infection control procedures and “aseptic” techniques in injection safety is to blame for the patients’ exposure. The CDC said that syringe reuse and medication, equipment, and device blood contamination were common reasons for the exposure issues.”

The importance of medical hygiene is not an affliction of the past. It’s not only in developing countries- it’s happening in our own backyards, and it’s important that we begin to recognize it and educate our health care workers to the importance of basic hygienic functions.



Infectious Diseases and Cardiovascular Disease

Hepatitis C-infected individuals are shown to have an increased risk of cardiovascular disease: “Hepatitis C virus increases the risk of coronary artery disease, a large American study published in the 15th July edition of Clinical Infectious Diseases (now online) has found. The study involved over 160,000 individuals, approximately half of whom were infected with hepatitis C. Despite having fewer risk factors for cardiovascular disease, the hepatitis C-infected individuals were more likely to have been diagnosed with coronary artery disease.”

Other infectious diseases have been associated with cardiovascular disease risk, including HIV and other individuals who are co-infected with both HIV and hepatitis C.

“Even though the individuals infected with hepatitis C had a lower prevalence of traditional risk factors for coronary artery disease, the investigators’ statistical analysis (which controlled for possible confounding factors) showed that the hepatitis C independently increased the risk of such diseases by 27% (adjusted hazard ratio, 1.27, 95% confidence interval: 1.22-1.31). Traditional risk factors for cardiovascular disease were also significant in both groups of patients.”

This is just another example of how little we actually know about the relationship (perhaps symbiotic?) between infectious disease agents, and what used to be considered diseases of lifestyle or unfortunate genetics. Epigenetics are going to be an important part of our medical care in the next few decades, and I think we are going to see many other examples of infectious agents having a role in what were once considered non-infectious diseases and afflictions.



Orthopedic Registries

This isn’t exactly an infectious disease related post, but I’m pretty intrigued- having two ACL repairs and two meniscus repairs, this stuff is pretty important to me!

A few senators are pushing for the creation of an artificial joint registry- surgery patients that have been given artificial joints or had artificial devices implanted in them would be tracked and monitored to ensure that no defective devices are being used, or to just rate the effectiveness of the devices implanted. The system is designed to “track how patients fare, reduce unnecessary surgeries and weed out inferior products”, all part of Obama’s new take on healthcare: “comparative effectiveness” reviews in order to identify the procedures and devices that work best. Funding hasn’t been secured yet, but a registry like this has been implemented in other countries with high success rates and patient satisfaction.

“The types of problems associated with not having a registry were highlighted last year by an episode involving a Zimmer hip component called the Durom cup. Though some doctors warned Zimmer the device was failing at an unacceptable rate, the company kept selling it for months while it reviewed patient records in an attempt to determine how frequently the problem was occurring.”

We’ll see if it gets enough funding to go through!


Book Review - Pox Americana

Pox Americana by Elizabeth A. Fenn
Book review by Cooper Lloyd

Elizabeth A. Fenn’s Pox Americana: The Great Smallpox Epidemic of 1775-82 offers a unique and astonishingly well-researched account of the role of smallpox in America’s formative years. Using a plethora of primary documents to support her arguments, Fenn relates the previously neglected narrative of smallpox during the American Revolutionary War. Her more textbook-like descriptions of historical events are balanced with carefully crafted vignettes and individual stories, and the result is a gripping and thorough account of a disease that, between 1775 and 1782, surely changed the course of history.

Pox Americana relates a couple of different narratives, including both the effects of smallpox in and on the Revolutionary War, as well as the effects of the disease on Native American populations. The book coalesces, however, in its depiction of the virus as a powerful and unrelenting force, and in its implicit argument that an account of American history is incomplete without an understanding of smallpox and its movement between and among populations. Fenn’s ability to pull together disparate documents and data to make these points demonstrates not only scholarly aptitude, but also a strong vision and vivid imagination for the events of the past. This combination of scholarship and storytelling is Fenn’s greatest achievement in Pox Americana.

In the first half of the book, Fenn describes the movement of troops in Boston, Quebec, Philadelphia, Virginia, and the South, while in the second half she expands to the American West and the fur trading industry. While describing smallpox separately in each locale, she also shows connections between different outbreaks that ultimately enabled the disease to spread across the continent. Fenn demonstrates clearly that the outcome of the war was determined not only by the course of Variola among and between populations, but also by the response of the army and civilians to the virus. Perhaps most interestingly, she argues that George Washington’s decision to inoculate the American troops was one of his most important decisions during the war – a claim that is substantially supported, if controversial.

Fenn’s book not only succeeds as a historical narrative, but also as a source that comes to bear on present day. Pox Americana, for example, paints a picture of the conditions in which smallpox, as well as other infectious diseases, thrive: cramped quarters in military camps, close and unhygienic living conditions in cities, and an “unbroken chain of person-to-person connections.” Furthermore, Fenn shows the reader, rather than simply telling, the incredible potential of smallpox as a biological weapon, and the reader cannot help but extrapolate to the future. In this light, her book provides an eerie vision of what the future could hold and, one might argue, a case for the rapid and final extermination of Variola from the planet.

While there is little to criticize about Pox Americana in terms of thoroughness, at times it seems that Fenn’s writing simply includes too much and that the book is overloaded with evidence, dates, and facts. By the end, reader grows weary of the constant deluge of information that characterizes the narrative, and finishing the book can feel like a chore. It is hard to blame Fenn, however, for substantiating her argument so completely. Pox Americana chronicles an often ignored but vital piece of American history, and it deserves to take its place as a major chronicle of both disease and history in America.

Book Review: Scourge: The Once and Future Threat of Smallpox by Jonathan Tucker

Scourge is quite simply the first smallpox-related book that I have enjoyed from beginning to end. Jonathan Tucker truly pulls off a remarkable feat, synthesizing the vast amount of literature into a taut, compelling account of the history of smallpox, the most terrible disease ever to plague mankind. At its core, Scourge is a comprehensive and fairly neutral account of the history of smallpox, from early epidemics in Europe and America to the unparalleled efforts of the WHO eradication campaign to the contemporary debate regarding the fate of the remaining smallpox strains.

Many readers, upon opening Scourge for the first time may wonder: Why do people still care? Wasn’t smallpox eradicated? Tucker answers these questions from the very start with a hypothetical scenario on death row, a potent metaphor for the contemporary debate on whether or not to destroy the remaining smallpox strands. It is a simple device that serves to remind the reader of the current relevancy of smallpox, which helps to support the book in its recounting of early history. He begins the historical account with speculations on the role of smallpox in early civilizations and darts through an account of the epidemics in Europe and America during the 18th century as well as Jenner’s development of the smallpox vaccine.

These events, however, are merely meant to be a primer for the heart of Scourge, which is the discussion of smallpox in the 20th century onward. In the first part of this discussion Tucker devotes full attention to the massive WHO eradication campaign, detailing its early efforts in West and Central Africa to the final push in India and Bangladesh. Tucker wisely anchors the story of the eradication campaign to the personal journey of its director, D.A. Henderson. His rise from an officer of the Epidemiological Intelligence Service to director of the smallpox eradication campaign is rife with ambition and unwitting betrayal, as the unexpected acceptance of his combined smallpox/measles vaccination program proposal strains the resources of the EIS and almost destroys his relationship to his superior, Dr. Alexander Langston. Henderson’s story, as well as the other stories of the individuals involved in the eradication campaign convincingly puts a human face to this chapter in the smallpox story.

The second half of this discussion, focusing on smallpox and biological warfare is compelling as well, although the horrific content would arguably stand on its own in lesser hands. He retraces in detail the Soviet Union’s intentions to weaponize smallpox as an agent of biological warfare and the work of the Vector program, which was devoted to the engineering of viruses for such purposes. Once again Tucker wisely anchors this discussion to the personal stories of the people involved, particularly Kanatjan Alibekov’s progression from aspiring physician to scientist in the Vector program to active anti-biological warfare spokesperson. Tucker captures the perpetual sense of dread and uncertainty regarding whether or not the international community will ever reach a consensus regarding the fate of the remaining smallpox strands. By meticulously recreating the dense web of conflicting interests regarding international security and the possibility of rogue sources of smallpox, Tucker ably conveys the moral and ethical ambiguities characteristic of the debate regarding destruction, which is itself a testament to Tucker’s clear, impartial writing style.

This neutrality is both a source of Scourge’s strength and weakness, depending on the reader’s expectations. Those looking for stirring or controversial commentary regarding the debate on smallpox destruction will be disappointed; Tucker refuses to take a stance, offering general recommendations for the future handling of biological warfare but never personally commenting on whether or not the remaining smallpox strands should be destroyed. Yet the cool, uncalculating eye that Tucker casts on events allows history to breathe and compel on its own; as a result, events like the implementation of coercion tactics in the WHO eradication campaign feel very real and devoid of the sensationalism that generally plagues many historical accounts. While the book may be less controversial because of it, Tucker’s lack of bias preserves the already riveting essence of the narrative and is all the better for it.

As far as smallpox books go, Scourge is hard to beat. Packed to the brim with smallpox history yet accessible to any reader, Tucker’s narrative is a must-read for anyone even remotely interested in smallpox and stands as one of the best introductions to the subject available.

-Andrew Plan

New and Hot: one way the TB bacteria achieves virulence

A few things were known about how the TB bacteria Mycobacterium tuberculosis infects host cells. It had been previously observed that TB bacteria were engulfed by macrophages, where they proliferate. Researchers also observed high levels of cyclic AMP, an enzyme that regulates certain cell functions, in macrophages that were infected with TB. The mechanism that produced this "cAMP burst" was unclear. And if I understand correctly, how the excess cAMP lead to disease was also not well understood.

A recent study conducted by William Bishai et al has filled in some of the gaps in this mechanism. His group found 17 genes in the TB bacteria genome that coded for cAMP production. They injected mice with bacteria that had various combinations of these 17 genes activated. The results suggest that a single gene called Rv0386 is crucial; bacteria with the gene outperformed all other microbes. Hence, they showed that "among the 17 adenylate cyclase genes present in M. tuberculosis, at least one (Rv0386) is required for virulence" (2), that Rv0386 is one of the genes that produces the cAMP burst.

Next, they suggest a further mechanism for how the cAMP burst contributes to the disease. Not only does the Rv0386 gene encode for cAMP, it also facilitates the delivery of the bacterial cAMP into the macrophage cytoplasm. In the cytoplasm, the excess cAMP sets off a chain reaction that results in the host cell producing a lot of TNF alpha, a protein that causes inflammation. Mice with the activated Rv0386 gene activated produced ten times as much TNF alpha in their lungs than mice that lacked the gene. Furthermore, excess inflammation caused by TNF alpha may be linked to the formation of lesions characteristic of TB called granulomas.

(1) News Story
(2) Nature Article

-Elaine C

Book Review - Smallpox: The Fight to Eradicate a Global Scourge

Smallpox: The Fight to Eradicate a Global Scourge by David Koplow
Book review by Cooper Lloyd

David Koplow’s Smallpox: The Fight to Eradicated a Global Scourge is a perfect read for the newcomer to the study of smallpox. Koplow sets out to provide a basic overview of the disease and its surrounding debates, and he successfully realizes this goal. Extremely detailed discussions are left for other writers; Koplow’s aim is to appeal to reader who has little scientific knowledge or background in the issues surrounding smallpox, and to leave him or her equipped to understand the virus’ continuing significance and engage in the debates surrounding its extinction.

Koplow structures Smallpox in chapters that, one-by-one, build up a multi-disciplinary understanding of smallpox. Koplow begins by discussing the history and biology of smallpox – the bread and butter, really – but then adds additional layers of understanding while ultimately crescendoing to a debate of sorts over whether smallpox should be exterminated from the planet. In terms of chapter content, the book moves from the history, biology, and use of smallpox as a biological weapon, to some related background in environmental law and policy, to the role of the WHO and the morality of extermination, and finally to the arguments both for and against extermination.
In the first two thirds of the book, Koplow provides a well-rounded, if cursory, understanding of the disease and the fundamental issues at stake in its continued existence. Koplow’s treatment of the history of smallpox is compressed into only a few pages, yet he mentions most of the important points, touching on the origins of the disease, its role in ancient history, past treatment regimes such as inoculation, and the global eradication program. In the following chapter on biology, Koplow describes viruses from ground zero, also treating topics such as genetic engineering, genetic alteration of smallpox, and the goals of smallpox research. Koplow next discusses smallpox as a biological weapon, moving chronologically through history to situate the current situation within the context of policies that have evolved over time. The chapter on Environmental Law and Policy raises issues that are often neglected in the study of smallpox, such as biological diversity and the bearing of both US and international law in the debate over the extermination of smallpox. Finally, the chapter on the WHO discusses smallpox within the context of the organization that has been such a major player in its eradication, while also answering the readers’ questions about where the current variola stocks reside and why the extermination of the virus is taking so long; the chapter on morality treats the philosophical debates about the role of man in the manipulation of nature.

Koplow uses all of these chapters bring up various points to which he will return in the last two chapters, the first of which treats the case for extermination and the second the case against extermination. These two chapters synthesize the arguments from various disciplines, allowing the reader to understand how several lines of argument apply to this complex question. While some arguments may at first appear to repeat points brought up earlier in the book, the reader ultimately emerges appreciative of Koplow’s attempt to draw together all of the information presented in the preceding chapters. Furthermore, Koplow organizes these final chapters in terms of numbered arguments and rebuttals, which provide a clear framework and allow the reader to move back and forth constantly, considering both sides of the arguments. The arguments themselves are written in non-technical language – the kind of arguments that one might encounter when talking to a friend (for example, Argument 1 in The Case for Extinction: It costs more money to continue to store and work on this stuff). The clarity of these arguments helps draw the new scholar of smallpox into the debates at the very heart of the disease.

In his conclusion, Koplow offers 12 recommendations for the future, including his own take on whether or not to retain the stocks of variola (you’ll have to read the book to find out his opinion); having taken us through the arguments on both sides of the debate, it only seems appropriate that Koplow allow the reader to understand in the end where he comes down on these issues. Appropriately, however, he reserves this injection of personal belief for the very end of the book and thus spends the majority of his time presenting the arguments and rebuttals quite impartially. Koplow’s policy prescriptions are insightful if controversial, but one wonders whether anyone besides the casual reader will ever see them. Furthermore, they are often too general to be very helpful; for example, Recommendation 7 states that we should, “Address the burgeoning bioterrorism threat directly.” The two paragraphs that follow provide no clear vision of how this should come about.

Ultimately, Smallpox is an accessible read and one that fills a gap in the smallpox literature by addressing the debates over the extermination of smallpox in a simplified way that the general public can understand and take part in; however, to a reader more educated in the issues surrounding smallpox, Smallpox will surely be too simplistic to be of much use. One of Koplow’s best devices throughout the book is the structuring of his chapters using questions as headings; for example, a biology section is entitled, “Is a virus alive?”. Throughout the book, Koplow anticipates the readers’ questions, but in the end, the reader is left with a million unanswered questions. Perhaps, however, this is Koplow’s great achievement; he provides the reader with a base knowledge that equips him or her to ask questions with a new level of sophistication, to tackle more detailed works about smallpox, and to engage constructively in the ongoing debate.

Book Review: Smallpox the Fight to Eradicate a Global Scourge by David Koplow

Smallpox: the Fight to Eradicate a Global Scourge is a thorough treatment of the debate about whether or not to eliminate the last known stocks of variola. Koplow's writing is lucid and accessible, and he is good about delineating purely speculative evidence from more substantial evidence.

His book is thorough. The first six chapters either cover general background about the disease or lay the groundwork for arguments forwarded in the final three chapters. This includes general background on the history of the eradication effort, the biology of viruses and the history and authority of the WHO. Koplow also gives background to orient the reader for arguments laid out in chapters 7-9. He discusses environmental law, especially as it relates to biodiversity and endangered species legislation to prepare for later questions about whether the virus should be protected on environmental or moral grounds. Because some of the most important arguments about whether or not to eliminate the variola stocks relate to national security concerns, he discusses biological weapons (BW)—international agreements on BW use, previous instances of BW use, perceived threats in post 9-11 world.

At times Koplow is overly thorough. Although he admirably wishes to give the reader a strong understanding of the history of environmental legislation, most of this background is not pertinent to smallpox. He readily admits this, writing: “In sum, the law of environmental not directly relevant to the question of extermination of the variola virus” (136). His treatment of bioweapons is a little better, but he fails in many places to relate his examples back to the question at hand. For instance, Koplow mentions the anthrax scare multiple times, but only to convince the reader that BW is a real threat. He could have drawn more specific and useful connections to smallpox by, for instance, discussing relevant epidemiological differences between anthrax and smallpox, or whether one disease is more weaponizable than the other, or whether one is easier to identify and diagnose.

On the good hand, Koplow's insistence on covering issues that don't directly relate to smallpox leads us to think about issues in broader or more interesting terms. In spite of the fact that environmental law is largely irrelevant, it was interesting to consider the smallpox extermination debate in terms of endangered species protection. More than anything, such considerations shed more light on our feelings about endangered species than on smallpox. For instance: “Why do we extend special recognition to big creatures and not small?”

Finally, a minor flaw in the last three chapters was Koplow's tendency to show his hand while supposedly giving even-handed accounts of the extermination debate. It is clear, for instance, that he believes elimination would be hubristic when he portrays the side in favor of extermination as saying that humans “play God all of the time” (195). Nevertheless, the critical reader will be able to discern Koplow's biases and can still learn a lot from this book.

Elaine C

Sunday, June 14, 2009

Pox Americana Book Review

Pox Americana: The Great Smallpox Epidemic of 1775-82

Elizabeth A. Fenn’s Pox Americana is a well-researched account of smallpox in North America, from its role in the American Revolution, to its presence in Mexico and the decimation of populations it caused in the American West. The sheer amount of information in Fenn’s book is remarkable, and each page is filled with first-hand accounts, cited statistics and figures that would otherwise be lost to history. Fenn begins with a recent history of smallpox, then works backwards, offering insight and little known facts, from laws in Pennsylvania that forbid variolation, to the fact that Native American treatments were as ineffective as European treatments, a South Carolina ordinance that called for guards outside pox-infested homes, and a Massachusetts law ordering red flags to be flown outside houses with smallpox victims. A book that admirably accounts for multiple fronts of the battle against smallpox in North America, Pox Americana recognizes European efforts to help Native Americans counter smallpox in addition to chronicling the biological warfare that settlers often used against indigenous peoples. In a style that is concise as much as it is conscious of the profound impact smallpox has had on the American psyche, Fenn uncovers an obscure chapter of history with sensitivity and scholarship.

Elaine Su

Book Review: Demon in the Freezer by Richard Preston

In Demon in the Freezer, Richard Preston presents a chilling revelation of the threat of bioterrorism in the 21st century. Using the lens of the anthrax “Amerithrax” attacks in the U.S. following September 11th, Preston dissects the current international biological weapons climate, focusing on the threat posed by humanity’s most feared and devastating killer—smallpox, or the variola virus.

Preston opens the book in October, 2001, with the discovery of an anthrax-laden letter addressed to U.S. Senator Tom Daschle. The investigation of the source of this crime and the fear that smallpox was involved forms a loose plotline for the book, with many tangents providing historical background recounting the eradication of smallpox in humans and the subsequent debate regarding the destruction of the reserves of the virus. Preston astutely draws upon the fear that arose from the anthrax scare to contextualize the threat of similar use of the variola virus, which has otherwise been forgotten by most of society because of its successful eradication, but which would have even more condemning implications than anthrax if it were successfully deployed in an attack.

After establishing the potential for disaster of smallpox-laced anthrax, Preston launches into a brief history of smallpox and its eradication, introducing the ambiguity of current locations of strains of the virus. Despite the existence of only two World-Health-Organization-sanctioned holding places (the Center for Disease Control in Atlanta and the Vector Laboratories in Russia), there is fear that smallpox still exists in back-room “freezers” elsewhere in the world, resulting from either innocent oversight or, more frighteningly, insidious intentions.

The majority of Demon in the Freezer is devoted to establishing the real potential of a biological attack using smallpox, and the devastation that would result. Preston accomplishes this by weaving together brief chapters and anecdotes following different characters, such as introducing the stories Vladimir Pasechnik and Kanatjan Alibekov (Ken Alibek)--two ex-Soviet scientists specializing in biological weapons who defected--to reveal the scale of the Soviet biowarfare program of the 1990s, and following the lives of government scientists and officials such as Peter Jahrling in their pursuit of progress in developing antiviral treatments for smallpox.

Whenever authoritarian knowledge of smallpox and wise insight regarding its use as a weapon is desired, Preston turns to D.A. Henderson, head of the Smallpox Eradication Program, and consensus smallpox know-it-all. Henderson serves almost as an omniscient, mystical character, whose interviews are cited whenever he really wants to hammer a point home. According to Henderson, “dropping an atomic bomb could cause casualties in a specific area, but dropping smallpox could engulf the world.” And regarding how best to solve our current dilemma: “What we need to do is create a climate where smallpox is considered too morally reprehensible to be used as a weapon.”

This technique of introducing concepts, details, and arguments through individuals’ eyes is one that Preston relies heavily on, and it works. Because of it, Demon reads like a sci-fi page turner, and through our sympathy with each new character we feel the triumph of eradication, the heartbreak of the world’s paralysis in destroying the last strains, and the very real fear of the potential for a biological attack using smallpox. Seemingly every chapter ends with a generic all-encompassing statement summarizing—in case we’ve forgotten—the stakes of such an attack. On page 285, Preston exemplifies this by saying, “virus engineering is cheaper than a used car, yet it may provide a nation with a weapon as intimidating as a nuclear bomb.”

All in all, though such textbook suspense-novel cliffhangers run rampant in Demon in the Freezer, Preston has clearly done his homework, and the reader emerges with a very clear and entertaining overview of the history of smallpox eradication and the post-eradication tension, after having encountered everything from suspense to historical accuracy to scientific introduction along the way. Yes, Demon in the Freezer can be enjoyed by the average fiction reader, but it is a true, incredibly informative, and resonating account of an issue with a historical importance and a current relevance that deserves as much attention as it can get, so, despite some simplifications and corny devices, Preston’s attempt at bringing the smallpox issue to the mainstream is more commendable than anything.

-Andrew Beck

New and Hot: Vaccines for Babies!

Researchers at the Children's Hospital in Boston have potentially found a way to stimulate immune responses in newborns. This could reduce infant infection rates and increase the efficacy of vaccines given at birth.

During her guest lecture Dr. McShane mentioned that one advantages of vaccinating at birth is that it is doctors can vaccinate a greater number of people when they do not rely on follow-up appointments. But, as we discussed last Thursday, there are problems with vaccinating at birth. First, newborns have inherited immunity from their mothers for a few weeks or months after birth. Second, the immune responses of infants are impaired (2), which leaves them vulnerable to infection and decreases the efficacy of most vaccines. These are two of the reasons why most vaccines are administered when the baby is two months old (except for Hep B and BCG which are given at birth).

Dr. Ofer Levy 's research suggests that one of the key differences between adult and newborn immune responses is the efficacy of their Toll-like receptors, or TLR's. According to Wikipedia TLR's are receptors on the surface of white blood cells that recognize molecules derived from microbes and activate an immune response. TLR's are part of the first line of defense against infection.

It turns out that in infants, TLR's generally trigger a weak immune response with the exception of TLR8, which triggered a robust immune response in antigen-presenting cells. Stimulating TLR8 could enhance immune response in newborns, reducing infection levels and increasing efficacy of some vaccines administered at 2 months. With funding from the Bill and Melinda Gates Foundation, Levy is now testing TLR8 stimulators in human cells and in animal models.

-Elaine C.

(1) News Story about Levy's Research
(2) Review Article on Vaccination for Infants

Friday, June 12, 2009

Now that we're in a Swine Flu pandemic, what about vaccines?

-Crystal Zheng
This is in response to: “Drugmakers rush to produce a swine flu vaccine” Associated Press

With yesterday’s raise of the pandemic flu level to phase six, signaling the start of the first flu pandemic since 1968, a natural question that arises is that of vaccines. As of right now, there is no vaccine for swine flu, and seasonal flu does not seem to provide immunity (although no studies have been done to this effect). Prior to yesterday’s announcement, the WHO website indicated that a swine flu vaccine could be ready within six months. However, now that we are officially in a pandemic, vaccine companies have pushed up that deadline, with many including GlaxoSmithKline and Sanofi-Aventis announcing that they would be ready to mass produce a vaccine for swine flu within weeks. The traditional flu vaccine is made in chicken eggs, but Novartis has developed a swine-flu vaccine that uses a cellular method, which may be faster. However, this new technology will not contribute significantly to our vaccine stocks, since the majority of vaccines will still be made using chicken eggs. The WHO estimates 2.4 billion doses of swine flu vaccine could be ready within a year.
Still, I have a lot of questions: first, who will get access to those vaccines? How will we prioritize vaccination? Will we vaccinate everybody, or promote vaccination for only at risk populations? Most of the developed countries began preparing for a pandemic long ago by signing contracts with vaccine companies to acquire sufficient supply for its populations. Many less developed countries will not have access to vaccine, not only because of cost but also due to politics. The WHO has asked vaccine companies to reserve a portion of their supply for poor countries. While some companies have helped, for example GlaxoSmithKine has donated 50m doses of vaccine, in practice, vaccines generally don’t leave the country of production until everyone in its home country is vaccinated, regardless of promises.
The lack of vaccines in developing countries is particularly disconcerting because these countries are more vulnerable during a pandemic. Their populations have higher incidences of underlying conditions, such as chronic disease and malnutrition; development lags behind, making them more susceptible to secondary infections; the population is younger and more densely packed in urban areas, facilitating spread; finally, health systems are not adequate to treat the large influx of patients that would seek treatment in the case of a pandemic. While it could be considered fortunate that so far swine flu has been contained to the more developed countries, its spread to less developed countries may not be far away.
Another challenge is to balance production of swine flu vaccine with seasonal flu vaccine. The production capacity of vaccine companies is limited, and resources shifted to swine flu vaccine will have to trade off with seasonal flu. What is the right balance to strike, considering that swine flu so far has generally caused mild symptoms and has a smaller mortality rate than seasonal flu, which will continue to kill tens of thousands.
In my opinion, we cannot allow swine flu to let us forget completely about seasonal flu. To this end, we must promote and prioritize strategies that would have benefits for both swine and seasonal flu, such as improving access to antivirals and antibacterials that can be used as treatment options for both flus, promoting basic health behaviors and knowledge at the individual level, and capacity building, such as training emergency health technicians.

It's Official: Swine Flu Pandemic

The WHO yesterday (June 11th) raised the worldwide alert on the swine flu outbreaks to level 6, the highest possible level. This upgrade in alert status is due to the fact that the H1N1 flu, which is now found in over 70 countries, has transitioned from travel-related spreading to community spreading, which is when secondary cases are rapidly spreading. This announcement has nothing to do with the severity of the virus, however, since the current alert gradations do not account for lethality (see my previous blog post). It is rather merely an acknowledgement that the virus is now spreading within the populations which it gained access to after being carried from one continent to another (level 5).

While there are new guidelines and procedures recommended by the WHO that accompanies this declaration, the situation does not become much different. Governmental health ministries from countries around the world have been bracing for larger scale outbreaks than have been seen in the previous few months. In the US, efforts are underway to produce an effective vaccine, although there are still questions as to whether the putative vaccine will be produced in quantities high enough to protect the entire population.



Thursday, June 11, 2009

Thinking outside the box for malaria vaccines

Scientists at the University of Maryland are working to create a genetically-modified super-mosquito, capable of carrying many more of the parasites responsible for causing malaria in humans. They're doing so because Sanaria, Inc. is trying to develop a vaccine using live malaria. The motivation is based off tests that were held years ago on Sanaria's CEO and some colleagues, in which they purposely exposed themselves to low-levels of malaria. The parasite stayed harmlessly in their livers, but they developed immunity to malaria for about 10 months. Sanaria is now developing a vaccine, but it takes 3000 mosquitoes to produce one dose, so they're trying to genetically engineer mosquitoes with more capacity.

Another lab at Maryland University is also helping to do just the opposite--hinder mosquitoes' malaria-carrying capacity and infectivity.

Both are ways of "thinking outside the box" about malaria vaccines, but as of now, both are very small, rudimentary steps. But steps, nonetheless.

Andrew Beck

Wednesday, June 10, 2009

W.H.O Recommends Rotavirus for All Children

-C. Paula de los Angeles

In a statement last week, the World Health Organization recommended that all children be vacinnated against rotavirus, a disease that causes fatal diarrhea in 500,000 children a year. Without the vaccination, almost all children get infected with rotavirus by the age of three. Fortunately, children are administered rotavirus drops in the United States. An overwhelming 85% of the yearly deaths due to this disease occur in developing countries in Africa, Asia, and Latin America this is not the case.

The endorsement by the W.H.O will allow donor money to be used for the vaccine. The urging of the WHO to recommend this vaccination stems from clinical trials in South Africa and Malawi showing that the GlaxoSmithKline vaccine worked even in areas with "poor sanitation competing virus, high infant death rates, and mothers with AIDS". A competitor Merck vaccine is being tested in other countries.

Where does the money come in? Currently, the vaccine costs $20 and must be refrigerated (which is difficult in places that lack electricity). Much of the donor money has come from Dr.Tachi Yamada, president of global health at the Bill & Melinda Gates Foundation, very much an advocate of the vaccine.

Personally, I think this is a great example of the power of W.H.O. Not only do people care what the W.H.O recommends, but such an endorsement allows for donor money to be used for the vaccine. In some ways, I think it reminds me of the need for institutional help and financial aid to support the idealistic views of many public health workers or citizens of the world who want to effect change in the places that need it the most.

New arenavirus discovered as cause of hemorrhagic fever outbreak

A new arenavirus called the Lujo virus was identified as the cause of a highly fatal hemorrhagic fever outbreak in Lusaka, Zambia and Johannesburg, South Africa in September and October of 2008 in South Africa after the air transfer of a critically ill person from Zambia. Of the five cases observed, four passed away (the originally ill patient, a paramedic, a nurse, and a member of the hospital staff who cleaned the patient's room). It is the first new hemorrhagic fever-associated arenavirus from Africa identified in nearly four decades. Using genetic extracts of blood and liver from the victims, researchers found through unbiased high-throughput sequencing that the virus is distantly related to Lassa virus and Lymphocytic choriomeningitis virus (LCMV). Lassa virus causes an acute hemorrhagic fever that causes approximately 5,000 deaths a year in West African countries. Lymphatic choriomeningitis is a rodent-borne viral disease that causes meningitis or encephalitis. About 5% of the US population is infected with the virus.

As mentioned before, the researchers used a technique called unbiased high-throughput sequencing to identify the new virus within just 72 hours. Lipkin, one of the professors responsible for the identification of the virus, said, "it is reassuring that we now have the tools needed to rapidly detect and respond to the challenges of unknown pathogens. A key challenge that remains is deployment of these technologies to the 'hot spots' where new killer viruses frequently emerge. We remain committed to this important public health effort as it represents a unique opportunity to prevent the next pandemic, be it a threat like HIV or SARS." It is exciting that we possess the technology to identify new viruses, but like Lipkin said, can we feasibly use this technology in these "hot spots" which often have weak infrastructure and a lack of resources? I think this case highlights the gap between research conducted in laboratories and action on the ground. There needs to be an effective and feasible delivery mechanism, and I hope that there is more research performed to make this technology more accessible.

For the full article:


US To Fund More Biodefense Programs

The National Institute of Health is renewing funding for research centers that study infectious diseases and the bioterrorist efforts that could arise from particular disease. Ten of the existing centers are receiving $455 million over five years, and this includes the creation of another center in the Pacific Northwest.

Do we think smallpox will be included in this new funding???



Semantics in the Health World?

The NY Times printed an article recently regarding the medical jargon and issues with communication that arises in the international health world. With the recent swine flue epidemic, the various words and definitions that are associated with public health became glaringly apparent. What exactly does "pandemic" even mean? Health officials have yet to tell the public exactly what the word even entails, even though the word is instrumental to the WHO's six stages of outbreak levels for infectious diseases.

"Dr. William Schaffner, the chairman of preventive medicine at Vanderbilt University, said that “we, the public health community, deserve to be chided” about the confusion.

“We ought to be able to do a better job in communicating in an understandable way,” he said in an interview.

Scientists like to assert that theirs is an exact discipline. But like the terms “evidence -based medicine” and “peer review,” pandemic turns out to be another example of imprecise vocabulary that doctors use every day, assuming everyone understands their meaning. "

Although journals and textbooks seem to use "pandemic" liberally, they rarely, if ever, actually define the term.

For posterity's sake, here's what Merriam Webster says:

pandemic- a pandemic outbreak of a disease; occurring over a wide geographic area and affecting an exceptionally high proportion of the population

Super helpful, right?

Health needs to become more accessible and communication routes between health officials and communities need to be more clearly defined and traveled more often. This is the only way health will become a global effort and a global success. Everyone needs to become involved; jargon and foggy words cloud the efforts.



Tuesday, June 9, 2009

The Evolution of a Virus

-C. Paula de los Angeles

Science reporter specializing in plagues and pestilences , Donald G. McNeil Jr., speculates on the possibility of a virus, like swine flu, evolving into something more lethal (so far, there have been only 139 confirmed deaths worldwide). Citing numerous scientists, McNeil uses Darwinian logic and rhetoric to argue that there are no evolutionary or selective pressures for the current swine flu to evolve into anything else, despite flu viruses being highly mutable in general .

It's ability to invade human noses and spread through merely coughing is "near-perfect", according to Dr. W. Ian Lipkin, director of the Center for Infection and Immunology at Columbia University’s Mailman School of Public Health.

Structurally, flu viruses are merely eight short strands of RNA that code for 11 proteins. One of most compelling reasons for the current swine flu virus to stay as it is and not develop into a more vicious one is its lack of essential genes, the ones that code for proteins PB1-F2 and NS-1, thought to be involved in lethality.

However, there is a potential of a more vicious swine flu in the possible development of resistance to the antiviral drug Tamiflu, which is currently used to treat it.

Hopefully, the swine flu stays as it is, but perhaps only time will tell...

pandemic defined, for the people

-C. Paula de los Angeles
\pan-ˈde-mik\: occurring over a wide geographic area and affecting an exceptionally high proportion of the population

The rhetoric of science is powerful. As we've witnessed time and time again, the public's interpretation of science can be dangerous and needs to be given careful consideration. In today's New York Times, Lawrence K. Altman discusses what the word "pandemic" means to the general public, especially in light of the recent media attention on the swine flu pandemic.

To the average, non-scientist citizen, pandemic is an emotionally charged and scary word. Is this just a question in semantics? Perhaps not. The World Health Organization uses a six-level staging system for declaring a pandemic that informs the actions of countries in such situations.

According to Altman, the word pandemic implies that there is a "rapid spread of an infectious disease to many countries in different regions, hitting each with more or less the same severity". He questions the validity of this implication, saying that the severity of an infectious disease spread varies from region to region, and certainly does not affect every country. The severity is affected by many variables, including the percentages of people dying, a specific population's vulnerabilty to the disease, and quality of health care.

In the past, the WHO posted a definition on their website saying that pandemics led to "enormous numbers of deaths and illness", however, this was recently changed due to the anxiety caused. If one of the missions of public health is communicating accurate risk assessment, scientists and doctors need to be more careful with their words.

Is it the role of the scientist to make her work accessible or for the layperson to stay a reliably informed citizen of the world? Who carries most of the responsibility? For now, I think the word pandemic needs to be more explicitly defined and concrete statistics should always follow its use.

news article link:

Nambian HIV/AIDS Implementor's Meeting

Hey guys,

So this one is so new and hot that it hasn't even happened yet. On June 10th of this year H.E. Hifikepunye Pohamba, President of the Republic of Namibia, will welcome more than 1,500 HIV/AIDS implementers from around the globe at the opening of the 2009 HIV/AIDS Implementers’ Meeting in Windhoek, Namibia.

The five-day meeting will be hosted by the Government of Namibia, and co-sponsored by the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR); the Global Fund to Fight AIDS, Tuberculosis and Malaria; The Joint United Nations Program on HIV/AIDS (UNAIDS); UNICEF; the World Bank; the World Health Organization; and the Global Network of People Living with HIV. Namibia was selected to host the 2009 conference in recognition of the country’s leadership in fighting HIV/AIDS.

This year’s conference theme is “Optimizing the Response: Partnerships for Sustainability.” From June 10-14, the meeting will bring together practitioners from around the world to discuss best practices and lessons learned during the implementation of multi-sector HIV/AIDS programs. The program will focus
on boosting the impact of prevention, care and treatment programs; enhancing program quality; promoting coordination among partners; and encouraging innovative responses.
With the goal of building a sustainable response to the pandemic, the meeting will allow implementers to share information that will directly impact their programs in the upcoming year.

The conference is the only meeting of its kind focused specifically on HIV/AIDS program implementation.

Very cool.

GPS phones track swine flu and other diseases

The Japanese government and mobile operator Softbank are about to enter the first phase of tests for new mobile phone technology that, incorporating GPS technology, tracks disease carriers. Details for how the test is set-up follows: The first phase will be conducted on 1000 elementary school students. They will be provided phones with the tracking program pre-installedy. A set number of the students will be selected to represented the infected population and monitored as they go about their lives normal, providing researchers a pretty good notion of how many others are potentially exposed to the 'disease.' Ultimately, the program is to provide the user with valuable and up-to-date advice such as when to stay indoors and when to go get a health check. Both mentioned parties behind the program's development are eager for the results, hoping they will confirm their predictions that the technology will prove successful in decreasing the number of contacts a disease makes and preventing massive outbreaks.

Though the government and Softbank tout the programs potentials, criticizing voices are already accusing it of infringing citizens' rights to privacy if implemented in a large-scale manner. They liken the program's monitoring capability with that of Big Brother's in Orwell's 1984. Whether or not this is the case has yet to be seen.

I am greatly interested in the double-edge sword that many emerging medical and biological technology appear to be. Clearly, the potential benefit such technology as the one discussed can bring society is significant. However, at its core, lies another great potential in the other direction, one that conflicts with standard ethics and herein lies our dillemma. I thought about a possible compromise between the population and the government but I realize that the technology would never generate its intended potency unless the entire population participated in it. The only way that the technology could bring its intended benefit without infringing on the population's privacy is it there are clear guidelines drawn up beforehand defining the limits and privileges of the monitoring operators. Otherwise, there's the potential that a lot personal information would be funneled into a few, wrong hands for their personal, exploitative use.

Anyway, this article really falls in love with what marvels me about technology. I think the power and potential that technology can provide humanity can be partially summed up with this quote from Spiderman. "This is my gift, this is my curse."


Monday, June 8, 2009

Mexican genomes show wide diversity

Mexican genomes show wide diversity

After five years, scientists have mapped the genomes of 300 mestizos, people of mixed Indian and European background, in Mexico. The findings include significant differences between mestizo genetic makeup and those of people with European and Asian ancestry.

Better genetic maps potentially help doctors tailor medicine to the individual. It will be easier to identify genetic risk markers, develop treatments, and prevent diseases including diabetes, hypertension and obesity.

Among the individuals studied, those from northern states were genetically closer to Europeans, while those in southern areas were genetically closer to Native Americans.

Elaine Su

Models’ Projections for Flu Miss Mark by Wide Margin

Models’ Projections for Flu Miss Mark by Wide Margin

At the height of the swine flu panic in April, two supercomputer teams constructed models the projected a mere 2,500 cases of swine flu in the US by the end of May. The CDC currently predicts that there are over 100,000 cases in the country, despite the fact that fewer than 7,500 have been confirmed.

The two companies have not yet updated their estimates, although other experts suspect that at the height of an epidemic, numbers could double in a matter of days.

The team from Northwestern University attributes the miscalculation to plugging in a number that was far too low at the beginning of the process, as well as the unexpected cases that were brought back to New York from spring breaks in Cancun.

Indiana's team claimed that they were misquoted, or had misunderstood the question when giving their answer, and stated that the first model had predicted 9,500 cases by the end of May.

Experts at this point seem to agree that a sophisticated model is no longer needed, as the flu will likely grow exponentially in the following months.

Elaine Su

Saturday, June 6, 2009

Public Health is Not Glamorous

Nicholas Kristof, a NYTimes reporter known for traveling around the world and covering topics often neglected by other news agents from a very personal level, highlights public health in his most recent Times blog entry. What topic are we worst at covering in the news, he asks? Kristof's answer: public health. Public health, he argues, is unglamorous, and it is long-term, two factors that essentially make it unappealing for news agents and readers alike. Rotavirus is the disease Kristof cites here, a diarrheal disease that kills half a million children annually, and yet one that very, very few have even heard of. An exception would be swine flu and other panic-inciting proto-epidemics, though even the media attention swine flu has received recently seems to have been short lived.

I leave you with two questions. The first is the same one Kristof poses to readers at the end of his article:

1. What other important but unglamorous issues are neglected by the media?

2. What can we do to ensure that issues of public health reach the public? Why is that even important?


New Malaria Parasite Found in Chimpanzees!

-C. Paula de los Angeles

Last week, researchers at the Research Institute for Development in Montpellier, France, and the International Center of Medical Research in Franceville, Gabon, discovered a new species of the malaria parasite, and was named Plasmodium gaboni, after closely related Plasmodium falciparum. In order to find this new species, researchers analyzed the blood of 17 chimpanzees, 2 of which had the parasite.

There has been only one other species of malaria parasite resembling Plasmodium falciparum found in primates,Plasmodium reichenowi in apes, so hopefully this new discovery will detail the evolution of malaria in humans and apes, and chimpanzees, their common ancestor.

A major concern of the researchers was the risk of chimpanzee-to-human transmission because of the interaction of chimpanzees and humans in these villages (as pets), as well as the recent jump of a version of the malaria parasite in macaques to humans.

This article brings to light the importance of evolutionary histories of all animals and insects, including parasites. Furthermore, it raises the concern of one of the most dangerous evolutionary adaptations of all, changing hosts. This reminded me of an idea brought up in a lunch we had this weekend with a respect scientist, that it was parasitism that mainly drove evolution. Interesting idea that we can see at work here...

primary article link here:
news article link here:

Book Review: Rotting Face

Rotting Face: Smallpox and the American Indian by R.G. Robertson chronicles the story of smallpox in 19th century North America, where it spread through fur-trading networks and devastated the native populations it contacted.

The book has a unique structure. In odd-numbered chapters, Robertson tells the story of the 1837-1838 epidemic in the Americas, which killed vast numbers of Native Americans and altered the power structure of the Great Plains. In even-numbered chapters, he gives readers a global history of smallpox, starting with an overview of its biology and moving on to its initial introduction in the new world.

That structure, like many aspects of Rotting Face, has its ups and downs. In one sense, I appreciated the “background” chapters because I could apply them directly to my understanding of the chapters on the Americas epidemic. In chapter 2, for example, Robertson reviews the symptoms and progression of smallpox; in chapter 3, he describe the first case in his story—in a European fur trader on the upper Missouri river. Having already given us the relevant disease-related background, Robertson is free to stick to his more creative narrative in describing the fur trader. He knows we’ll understand what is going on, and doesn’t have to stop his story to give a more technical description of smallpox’s biology.

But the alternating structure also makes the book feel disjointed; it loses any “flow” it might have had before. Every chapter, I felt like I had to re-orient myself to Robertson’s changing style and purpose. The structure also means that the paired stories, particularly the 1800’s narrative, move painfully slowly—it takes seemingly forever for anyone on the upper Missouri to get smallpox, let alone for the epidemic to start.

Unfortunately, Robertson’s writing, as well as his structure, contributes to the snail’s pace. In an effort to “set the stage” for the reader, he provides minute details on fur-trading life in the Americas, including several excruciating segments on things like steamboat design and coal-shoveling practices. His intentions are noble and occasionally succeeds—the historical setting sometimes helps explain the epidemiology of the disease. But overall, the description (unless you are an 1800’s-Americas-history buff) makes large sections of the book boring. In the middle of long descriptions of steamboat or Native American life, it was almost possible to forget the book’s main topic.

Robertson’s style (maybe due to his attempt to balance technical information with an exciting story), threw me off the most. The book is an awkward mix of flowery description and technical, almost heartless-sounding narrative. Robertson describes Chardon’s Indian wife, whose “long black hair cascaded over her shoulders like waves of glossy silk.” When she dies suddenly in the next few pages, Chardon “[resigned] himself to her death” and “rode across the prairie, searching for a buffalo.” Sometimes Robertson’s descriptions get downright odd. At one point, he gets vaguely Victorian on us: “many a comely damsel has weathered [smallpox] only to forsake the company of men.” At others, they are just perplexing—“above the Missouri floodplain existed an ocean of grass, an expanse so vast the mind struggled to hold it.”

Robertson’s main source on the 1837-1838 epidemic is the diary of a European fur trader named Francis Chardon. It is fantastic that he went back to a primary document for most of his information. The journal appears incredibly detailed, and captures the culture of the fur-trading life as well as the dynamic between European traders and Indian tribes. Europeans were incredibly dependant on Indians for business as well as supplies, and were organized largely around them, with trading agencies and sub-agencies dedicated to the different tribes. However, I wondered about Robertson’s use of a single source for so much of his information. Chardon, of course, had biases, and Robertson doesn’t seem to acknowledge them in his narrative.

Gaps in Chardon’s diaries lead to more unfortunate stylistic decisions. When Robertson wants to describe a particular scene but doesn’t have enough information to do so factually, he uses qualifiers to a distracting extent. “Aboard the steamer, Jacob Halsey and his wife may have conversed with a passenger…or perhaps they accidentally encountered…then again, the Halseys could have…”. It felt like Robertson was trying to bridge an impossible gap between the type of story he wanted to tell, and the facts he actually had.

Robertson (as Molly and other reviewers have pointed out) seems to take an overly critical and even prejudiced attitude towards Native American culture, describing their “shortcomings” in blunt and unthoughtful terms. He describes Indians as having “no understanding of property rights,” living in huts that were “bunched together at random,” and as unable to “fathom a sickness being passed from one person to another any more than they could imagine a warrior with an arrow in his leg transferring the wound to another.” He doesn’t seem to consider the idea that Indians may have a different, non-European conception of property rights, or community organization, or contagious illness. Perhaps Chardon’s diaries had too much of an influence on Robertson’s own perspective?

Ultimately, the unique and sometimes interesting aspects of Robertson’s book—its alternating structure; its use of Chardon’s diaries—come back to haunt the author in its slow-moving style and impossible gaps in the historical record. This book may be a great reference for perspective on the 1838-1838 epidemic, but I don’t think it’s a good cover-to-cover read.