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: