HURJ Volume 15- Fall 2012

HURJ Hopkins Undergraduate Research Journal

Fall 2012 | Issue 15

Piecing Together Wellness 1

hurj 2012-2013 hurj’s editorial board Editor-in-Chief

Mary Han

Andi Shahu Focus

Elina Tonkova Bridget Harkness

Humanities & Social Sciences

Wallace Feng

Anne Badman Spotlight

Isaac Jilbert

Tara Nicola

Layout Editors

Katherine Quinn

Dev Patel

Publicity

Chloe Reichel

Alex Polise Webmaster

Emily Kashka Faculty Advisor

Dr. Michael Yassa

Our journal also presents the impressive academic work of undergraduate students from diverse intellectual backgrounds. From an interview with the medical advisor from the hit series House MD to an analysis of the Bible’s role in the Israeli-Palestinian Conflict, this issue showcases the distinct depth of research performed by our students across many disciplines.

Best regards,

hurj spring issue 2012 contributors Lydia Liang Dong Kim Elina Tonkova Kimia Grace Ganjaei Michael Yamakawa Camila Prieto Young-Hee Kim Catherine Rose Gabrielle Barr Grady Stevens Meagan Young

about hurj:

The Hopkins Undergraduate Research Journal provides undergraduates with a valuable resource to access research being done by their peers and interesting current issues. The journal is comprised of four sections - a main focus topic, spotlight, science & engineering, and humanities & social sciences. Students are highly encouraged to submit their original work.

disclaimer:

The views expressed in this publication are those of the authors and do not constitute the opinion of the Hopkins Undergraduate Research Journal.

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What is wellness? This issue of the Hopkins Undergraduate Research Journal aims to identify some of the building blocks of wellness. We explore topics ranging from mental health to obesity, issues that are on the forefront of current healthcare policy.

This issue of HURJ was made possible by the dedication of our staff and the diligence of our undergraduate writers. We would like to thank the JHU Student Activities Commission for their continued support. We hope that you enjoy this Fall 2012 issue.

Science and Engineering

Ryan Gallo

Copy Editors

Meredith Haddix

Shereen Shafi

Woojin Kim

Elizabeth Chen

a letter from the editors

Amy Conwell Scarlet Hao Lina Gallego-Giraldo Robert Esinger Justin Halberda Ryan M. Kahn Gisela Teixidó-Turà, MD João A.C. Lima, MD Elzbieta Chamera Alex Schupper

Mary Han

Co-Editor-in-Chief

Andi Shahu Co-Editor-in-Chief

contact us: Hopkins Undergraduate Research Journal Mattin Center, Suite 210 3400 N Charles St Baltimore, MD 21218 hurj@jhu.edu http://hurj.org

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table of contents fall 2012 focus:

table of contents spotlight

pg. 13 .......

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The Art of Diagnosis: A Conversation with Dr. Lisa Sanders

Kimia Grace Ganjaei

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Our Drug War Against Microbes

Michael Yamakawa

Mad Country, Sweet Land of Insanity An epidemic of mental illness in America

Lydia Liang

10 The Extending Reach of Immunology

Camila Prieto 12 Baltimore Healthy Carryouts: Study of Two Model Carryouts

Young-Hee Kim

humanities & social sciences pg. 15 .......

Shifting the Healthcare Debate

Dong Kim

21 How Sexual Values Shaped Sex Education in Public Schools Throughout the Twentieth Century and The AIDS Crisis in the United States

Catherine Rose 24 Seaton’s Pleas With the British Public and the Transmission of Scarlet Fever

Gabrielle Barr 27 The Hero: Greek, Victorian, and Modern; Dominant, Residual and Emerging Conceptions of the Hero in Modern Times

Grady Stevens 30 Use and Misuse of the Bible in Archaeology: The Israeli-Palestinian Conflict

Meagan Young 33 The Rise and Fall of Legend: Geoffrey of Monmouth’s Historia regum Brittaniae in Lewis E 247

Amy Conwell

pg. 18 .......

The Weight of Obesity: Unseen complications of every day life

Elina Tonkova

science & engineering

37 Phenotypic Effects of Lignin Reduction in Model Plant Species

Scarlet Hao, Lina Gallego-Giraldo 41 Ensembles Function as Individual Units for Visual Indexing and Visual Selective Attentios

Robert Eisinger, Justin Halberda 45 The Reproducibility of Measuring Aortic Strain and Pulse Wave Transit Time Through Magnetic Resonance Imagings

Ryan M. Kahn, Gisela Teixidó-Turà, MD, João A.C. Lima, MD, Elzbieta Chamera 49 Progesterone For the Clinical Treatment of Acute Traumatic Brain Injury

Alex Schupper

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hurj fall 2012: issue 15

The Art of Diagnosis:

A Conversation With Dr. Lisa Sanders Kimia Grace Ganjaei, Class of 2013 Behavioral Biology

About Dr. Lisa Sanders is currently an internist and Assistant Professor of Medicine at the Yale University School of Medicine. Fascinated by the process of diagnosis, she serves as a medical storyteller in her “Think Like a Doctor” blog and monthly Diagnosis column in the New York Times, presenting mysterious, seemingly impossible medical cases to her readers. It is this column that inspired Howard Shore’s House, M.D., where she serves as one of the technical advisors.

I’m a big fan of the Think Like a Doctor blog, and it was after reading her book Every Patient Tells a Story: Medical Mysteries and the Art of Diagnosis that I decided to contact Dr. Sanders to learn more about the issues with diagnosis today and the incredible forensic quality of medicine a pre-med can look forward to while they’re looking down at their organic chemistry textbook.

What inspired the ‘Think Like a Doctor’ blog and the NY Times Diagnosis column? Where do these stories come from?

Really what inspired the Diagnosis Column was when I was in medical school—and certainly before I was in medical school—was that I had no idea what diagnosis really was, and I thought it was like multiplication tables, or something that you just memorized and it was something that had a right answer or a wrong answer. It wasn’t a process, it was a thing, it was a fact. Then I went to medical school and everything you learn in medical school makes you think [something specific] is the case. You take multiple-choice tests, you take fill in the blank tests, you don’t take essays—there are no essays questions.

So when I got to my third year and started my medicine clerkship, I went to this reading that everybody goes through everyday in medicine called Resident Report. I saw this tiny mystery being unfolded in front of me, where a single patient is presented with all the complications of what is the foreground and what is the background, what is just the patient, and trying to tease out what all the important information might be. That’s what these residents did everyday

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for this one hour and I was amazed. You know, I’m a huge Sherlock Holmes fan and I saw that there was this little Sherlock Holmes story of deduction. That’s really why I became an internist, and that’s where my column comes from.

Because I’m a slightly disillusioned pre-med student, I have to ask this. Do you think we could incorporate the stories that appear on the Diagnosis Column into premedical education? Is there a certain way of thinking that we can benefit from?

Most medical schools now, because we understand so much more about the way adult human beings learn, especially doctors— we have very peculiar kinds of minds—I think that medical schools teach in a case-based way…When I was in medical school, I sat through as a pre-med, organic chemistry. You know, I memorized all those things but by the time I got to pharmacology in my 2nd year of medical I had totally forgotten all of my organic chemistry.

So really there are these opportunities to make an incredible education that would be wildly useful, but it hasn’t actually happened.

But I think there is an opportunity, and I think there is an effort to actually try and realize that opportunity. Certainly as a way of teaching medicine, I’m sure that when you get to anatomy and physiology there will be an effort to teach it in terms of cases, because learning a bunch of facts turns out not to the best way to learn things if you are going to actually apply medicine to the patient in the bed.

I think there’s a very good chance that pre-med education has very little to do with what it’s actually like to be a doctor. But it does serve an important function in weeding out those who don’t have the grit to put up with all the B.S. Something that pre-med education gets right is that there is this focus on knowledge that is essential, because you can’t diagnose a disease that you’ve never heard of. There might be exceptions…but 99.9 percent of the time, for you to think of a diagnosis, you have to actually know what it is. So that kind of huge knowledge base, even though it’s not necessarily the knowledge base you need, that idea that you need to know a lot, is actually true…

I am putting together a collection of my columns that I think will be useful as [teaching] cases. Not all of my cases are useful, because sometimes the foreground and the background are so complicated, or the presentation is so bizarre that it’s not a useful teaching case. But some of my cases are terrific teaching cases, [for example] in my book the guy who had Still’s disease…absolutely classic. His presentation was textbook. And it wasn’t recognized…because if you don’t know about it, you won’t think about it, as was the case with that resident...

What is the importance of doctors hearing the patient’s entire story? Or is it just a medical courtesy?

Most of the time the patient will tell you what they have. Period.

hurj fall 2012: issue 15 You just have to be there and listen. The odds are very high that the patient has important things to tell you, things that are going to help you make a diagnosis. Unfortunately the patient often does not know what those things are, and the doctor doesn’t necessarily know what those things are. So you just have to be quiet and listen until you have a story and try and be alert for the clues that are sprinkled through the patient’s story.

I think the hardest thing about listening to the whole patient’s story is—you know how you have that relative at family reunions who can’t tell a good story? We call it the “shaggy-dog story.” Because as you hear the patient telling their story you’re trying to think, what’s the meaning? Where is this story going? We are meaning-seeking creatures— that’s the way our brains work—and as doctors, that’s a very important skill, but it’s worse because we know that somebody’s life depends on it. It makes us very anxious, if you ever listen to somebody and you couldn’t figure out where their story was going and what it all means. This is very much what doctors feel when they’re listening to a story. You really have to develop a skill of setting aside the anxiety that uncertainty can provoke. Up to 70% of the time it’s going to be there, probably more.

In your book, Every Patient Tells a Story, there’s a lot of discussion about the changing attitude towards the physical exam. Why do you think the physical exam is not performed as much in hospitals anymore?

I think it was taught incorrectly. But it’s not taught because it’s not valued. We think that other tests will give us the same information. And sometimes that’s true. It will take longer, it will be more expensive, but we will feel more secure about it. [The physical exam] is simply not valued, it’s a relic. I think that we will be forced to bring it back, because insurance companies are going to stop paying for tests in the sort of ransom, come-hither way they have in the past.

And when that happens we will be forced to examine people and come up with the reason why we’re worried about X, Y or Z. But now, no one cares what the murmur sounds like, they only want to know what the echocardiogram shows. And that’s not a bad thing. This is what’s wrong with the way we’re taught: When we look at a murmur, we’re taught that we should know whether this is an aortic regurge murmur or mytril stenosis. Actually that’s not the case.

What we really need to know is this a heart sound that needs further investigation or is this a benign heart sound? That’s the distinction we need to learn. And that’s often overlooked in the way we’re taught.

spotlight We’re flogged for not recognizing a pulmonary artery stenosis, but actually if we knew that certain kinds of murmurs or certain qualities of murmurs that tell you that you don’t need to investigate further or that there are certain qualities that say you need an ECHO to look at this, that’s what we really need to know. We need to incorporate the ECHO into our assessment, rather than just defer everything to it, or insist that the ECHO doesn’t exist. We need to find a way to incorporate our testing with other tools we have available—our clinical exam—to help us make the best diagnosis. I think that’s worthy of thinking about and teaching towards.

How often do you feel doctors have to treat the unknown without much sign of a diagnosis? Is this, in a way, a method of diagnosing someone?

It’s certainly the weakest way to diagnose someone. It also depends what you mean by unknown. If someone comes in with pneumonia, you can see it on their chest X-Ray, but you don’t know what’s causing the pneumonia…the chance that you’ll actually find out what’s causing the pneumonia? Very small. But if somebody with a fever, shaking chills, and he’s hemodynamically stable, you have an obligation not to treat that until you know what it is. You have to know when it’s important to know exactly what you’re treating than when you have to just treat the patient to save their life. But I would say that the kind of willy-nilly therapeutic deployment you see on House is extremely bad medicine, and diagnoses made by response to therapy are the worst diagnoses you can make because people get well by what you do or they can die no matter what you do some of the time. So response to therapy doesn’t necessarily tell you something. You think, that patient seemed to get better when we gave them antibiotics so maybe that means that they have a bacterium but maybe it was viral and the virus has just run its course. That’s the other possibility. We just have to recognize how uncertain those kind of diagnoses are and how undesirable they are.

There’s a lot of interest in studies done on diet and nutrition, a lot of which is seen on the Internet. But it’s hard to know what can be trusted. For example, that antioxidants truly prevent aging or that coffee can prevent cancer. What do you think can be trusted?

Well, we are just beginning. If you knew how little we know…

When I first got to medical school I thought, “Oh my God—we don’t know THAT?” If you knew how much we know compared to how much there is to know, you would just be shocked. We are just beginning to seriously look at the way the body works in a systematic way.

I mean, especially in nutrition, we are just beginning to understand how that all works…Eating the right foods turns out to do good, but isolating one component of that—if there’s anything that is unholistic in the world, that would be it. Identifying one aspect of food that is good for you? I mean, that’s ridiculous. In the end, we haven’t found it to be the case, even with fat. When you look at fat, there’s some kinds of fat for some people that might not be so good, but you know there’s been a 25 year “War on Fat,” and it hasn’t done much but make us all fatter… With antioxidants they can’t find any benefit, and

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spotlight some of them are actually linked to higher rates of cancer when you super-supplement people… It’s a very oversimplified way of thinking: “If a little is good, then a lot must be terrific!” But actually, that’s not the case…

hurj fall 2012: issue 15 [learn] what is needed to be done.

Certainly the way we did do it was probably the worst way, which is to reduce the amount of time a resident has in the hospital, and yet, not reduce the workload.

What is your take on the 80-hour workweek? What are What’s it like to be a technical advisor on HOUSE MD? the benefits and drawbacks of it?

We don’t actually know. I mean, it was imposed because of political pressure. A better way to do it would be to say, “Let’s see if limiting work hours makes the difference in how patients do.” There were studies that proposed that there might be a trend towards better patient outcomes, but in general, those are balanced by studies that show that worse trends in patient outcomes. We just jumped into this without really appropriately thinking or researching it. But the reason research and experiments are useful is because our knowledge is so limited that what seems to make sense at the time doesn’t always work out. And that’s how we learn, by testing something that seems like a no brainer, the null hypothesis… We learn more when the hypothesis we know is turned upside down. So I don’t think anybody really knows whether the 80-hour workweek is a good thing… All we have to do is to figure out how to use the time that we have to

Oh, it’s fantastic. It’s so much fun. I just got an email that says, ‘We need a really fantastic diagnosis for the last episode…’ So I’m scouring over my cases… I’m an unreconstructed collector of weird cases, so I’m pawing through all these cases in the event that something really is special.

Is being on House like the reverse of being a doctor? Is it like you’re giving characters diseases instead of treating them? You take diseases presented on the diagnosis column and send it to the writers to see how it fits into the story of Dr. House?

Yes exactly, exactly! Sometimes I do go to my own column but you know, those I don’t have to search for because I already know by heart. So I go through the other literature, because to write a column I need a lot of information—I need to talk to the doctor, I need to talk to the patient, the patient’s family. For House all I need is the case report, because the first test is to see if they have the symptoms. Cool.

You know, that’s cool because on House the specifics of the story, of the real story, are not important because they’re going to make up a story that goes with it. It’s so much fun, I will so miss it.

It definitely gives you a different perspective to medicine, how it’s very forensic, very “Sherlock Holmes.”s Right, well [Dr. House] is Sherlock Holmes. But you know, my column is “Sherlock Holmes.” Sherlock Holmes would have been a doctor! If there were any diagnostic tests that they could have done, or if it makes a difference about what the diagnosis was. If you have no therapy, diagnosis is meaningless. Doesn’t matter if the answer is right if the patient still dies. But Sherlock Holmes would have been a doctor…he was actually based off of several doctors.

To read the Diagnosis Column online, see: http://well.blogs.nytimes.com/category/doctors/ think-like-a-doctor-doctors/

hurj fall 2012: issue 15

Our Drug WarAgainst

Microbes

Michael Yamakawa, Class of 2014 Biophysics

Microbial Resistance The resistance of microbes towards therapeutics is neither a novel concern nor a surprising natural phenomenon. Evolution, favoring the survival of the fittest, selects for microbial strains resistant to the drugs prescribed to patients. Even after the discovery of the miracle antibiotic (penicillin)in the 1940s, multiple bacterial strains had undergone rounds of evolution to eventually become resistant to it. Today, resistant strains of tuberculosis, malaria, HIV, and even cancerous tumor cells provide obstacles to our healthcare. In the case of malaria, not only did the protozoa responsible for the disease gain drug resistance, but the mosquitos that carry and transmit the infection became resistant to insecticides as well.1 Unfortunately, we have not been able to mount an effective response against microbes and have have arguably only been feeding the growth of drug resistant species through the egregious use of antibiotics. Some infections are becoming resistant to all of their respective prescriptions, while other infections are already resistant to all of the drugs that were designed to eradicate them. it has also become increasingly difficult to discover novel drugs for newly emerging microbes.

If the first round of prescribed antibiotics are ineffective, they are typically succeeded by the more toxic, second-line or third-line antibiotics, which may be as up to 100 times more expensive than the first.

In developing countries, the cost is a major constraining factor of treatment, leaving many with inadequate secondary treatments.In addition, strains can also become resistant to subsequent lines of antibiotics, rendering antibiotics useless in developed countries as well. This trend has necessitated a drastic shift in our strategy in the battle against these microbes, as we are forced to consider how we can circumvent the issue of resistance.

Developing a fuller understanding of how microbes respond to environmental toxins is crucial for future drug discoveries and for eventually bringing these microbes under control.

Multidrug Resistance (MDR) Cells can acquire resistance through methods including but not limited to: evolutionary alterations in the target proteins, decreased permeability of the cell membrane, or metabolism of the drugs. As mentioned before , resistance is not a surprising phenomenon since evolution specifically selects for cells that can render a single class of drugs ineffective. What confounds researchers is the principle of

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multidrug resistance.

Multidrug resistant cells, including bacterial, fungal, and mammalian (cancerous), are able to directly pump out drugs that have entered their system instead of altering their genetic makeup to selectively resist against certain classes of antibiotics. This is achieved by the activation of multidrug (MD) transporters, called efflux pumps, that extrude a broad range of foreign, unrelated, chemical agents out of the cell. MDR cells thus gain resistance towards drugs that they have not been exposed to.2 MD proteins also fail to abide by the conventional “lock-andkey” model of protein-ligand binding, a model that generally suggests great specificity between receptors and ligands (there is usually one “key” for each “lock”).2 Instead, MD receptors undergo what is known as polyspecific binding, allowing them to bind promiscuously with multiple ligands. Scientists question how polyspecific binding could be achieved for a certain set of drugs; why MDR is honed by microbes so readily; and whether there is a clinical solution to eliminating the MDR mechanism which facilitatesthe survival of deadly microbes. Some multidrug resistant stains, such as MRSA (methicillin-resistant Staphylococcus aureus), are responsible for over 200,000 hospital-acquired infections in the United States and cost our healthcare system billions of dollars annually. Thus, it is of vital concern to implement a successful battle strategy against MDR strains.

MD Efflux Pumps and Transcription Factors Superfamilies consist of various proteins that resemble each other in amino acid sequence, structure, and evolutionary origin. MD efflux pumps belong to several superfamilies, including the ABC, MFS, RND, and SMR families, suggesting coevolution over time from different origins. This begs a few more questions: With such architectural disparities between each family, how do MD efflux pumps manage to detect such a broad range of drugs?

Additionally, what mechanisms does each of the proteins undergo in order to expel drugs out?

There is a wealth of information to be gathered from studies on efflux pumps, there is a scarcity of structural data on these proteins. Fortunately, researchers, including Dr. Herschel Wade, PhD, who works in the Department of Biophysics and Biophysical Chemistry at the Johns Hopkins School of Medicine, have focused their research on the transcription factors that control the expression of efflux pumps in order to acquire a deeper understanding of multispecificity in proteins. Transcription regulators are much more manageable for structural studies than efflux pumps, since the latter tend to be very large and difficult to solubilize, purify, and crystallize for research purposes. Since membrane transporters largely interact with non-polar moieties in the membrane bilayer, solubilizing these proteins may not result in the correct physiological fold for accurate study. transcription factors, which are much smaller and solubilized in the cell, can offer an easier avenue for structural studies.

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The expression of efflux pumps is controlled by the concentration of drugs within the system: the respective transcription regulators are activated when drug concentrations increase. These transcription regulators are also multidrug recognizing proteins, promiscuously binding to ligands with similar affinities as their partner efflux pumps. Extensive studies have been performed on two bacterial transcription factors: QacR and BmrR. QacR is a transcription factor for a known efflux pump in S. aureus called QacA. QacR contains multiple binding pockets, which bind to a variety of ligands.3 Structural data have shown that ligands, such as rhodamine and ethidium, bind to two distinct pockets within the protein while other ligands, such as rhodamine and proflavin, bind in the same region. QacR offers a large pocket- with multiple, flexible, mini-pockets and low shape complementarity with ligands that can accommodate drugs with reasonable affinities.4 On the other hand, BmrR, a transcription factor for bmr in Bacillus subtilis, binds promiscuously with a very similar set of ligands with a much smaller pocket and greater rigidity.2,5 Current studies are investigating how such a tight pocket can bind to many ligands. Both QacR and BmrR pockets present hydrophobic moieties that shield lipophilic, cationic drugs from the aqueous phase. Further stabilization of the drug is achieved inside the pocket through van der waals interactions and aromatic residues, which undergo π-π interactions.

Any electrostatic interactions with glutamate or aspartate residues, which are accentuated within a hydrophobic environment due to the exclusion of water dipoles, can stabilize positive charges on the drugs as well.there seem to be overlapping characteristics in these proteins, in structure and residual contributions, which are necessary for MD binding.

Advancing our knowledge of polyspecific binding will be crucial for preparing an attack against multidrug resistant organisms.

If we are able to fully understand how MD transcription factors and MD transporters bind to various drugs and perform their respective functions, we can provide fertile grounds for novel drug designs directly targeting these proteins.

References 1. Knobler SL, Lemon SM, Najafi M, Burroughs T., 2003. The resistance phenomenon in microbes and infectious disease vectors. National Academies Press. 336p.

2. Bachas S, Eginton C, Gunio D, Wade H. Structural contributions to multidrug recognition in the multidrug resistance (MDR) gene regulator, BmrR. PNAS 2011, 108(27):1104611051.

3. Maria A. Schumacher, et. al. Structural mechanisms of QacR Induction and Multidrug Recognition. Science 2001, 294: 2158 4. Wu J, Hassan KA, Skurray RA, et. al. Functional analyses reveal an important role for tyrosine residues in the staphylococcal multidrug efflux protein QacA. BMC sion. The Journal of Biological Chemistry 2008, 283(39): 26795-26804. Microbiology 2008, 8:147.

5. Newberry KJ, Huffman JL, Miller MC, et. al. Structures of BmrR-Drug Complexes Reveal a Rigid Multidrug Binding Pocket and Transcription Activation through Tyrosine Expulsion. The Journal of Biological Chemistry 2008, 283(39): 26795-26804.

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hurj fall 2012: issue 15

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The Extending Reach

of Immunology Camila Prieto, Class of 2012 Biophysics As a biophysics major, I would not have expected to spend the summer before my senior year working in an immunology lab. Even though I had not taken a single immunology course before I began my research, I soon realized that immunology is becoming an increasingly interdisciplinary field in which many students studying a wide range of subjects can apply their skills.

One of the great characteristics of immunology research is the application of bench work to the clinic and vice versa. My principal investigator had a patient with Clericuzio-type poikiloderma with neutropenia (PN), a rare autosomal-recessive genodermatosis. This is a genetic condition characterized by skin poikiloderma, hyperkeratotic nails, chronic neutropenia, and recurrent pulmonary infections. Not only do these patients have great skin concerns with poikiloderma, a skin condition characterized by inflammation and very thick, malformed nails, but they also have an abnormally low number of neutrophils, the most important type of white blood cells.1,2 The scientific community knows very little about this disease other than the gene responsible for the condition. Next generationsequencing and mutations found in unrelated patients identified C16orf57 as the gene responsible for PN disease.3 The identification of the gene was an important step in the treatment of PN patients, as many patients were first misdiagnosed with Rothmund-Thompson (RT) syndrome. RT syndrome shows phenotypic overlap with PN disease, but it is not characterized by immunodeficiency.4 Since little is known about PN disease, my principle investigator was interested in pursuing further research centered on the gene C16orf57 and the protein that it encodes.

My research project thus began with the goal of finding more information on C16orf57. Little is known about C16orf57 and the functions of its proteins, but two independent studies have revealed direct interactions between C16orf57 and Smad4 genes.5,6 Smad4 and C16orf57 are interconnected to the protein RECQL4 through three signaling proteins.3 This model supports that the phenotypic overlap between RT syndrome and PN can be partially explained by a shared common pathway. Additionally, Smad4 proteins are central to the TGF-β (transforming growth factor-β) pathway: transcription regulatory complexes are formed by the association of Smad4 with receptor-phosphorylated Smad2 and Smad3, which transmit the TGF-β signal to the nucleus to regulate TGF-β transcriptional targets.7,8,9,10 Importantly, TGF-β is an anti-inflammatory cytokine in the body and among its many functions is the activation of t-cells, b-cells, and macrophages.

In my research study, I assessed the role of C16orf57 in the TGF-β signaling pathway, specifically with regard to localization and function of Smad4. My research goals were three-fold: to determine the cellular location of C16orf57, whether a direct interaction exists between C16orf57 and Smad4 in human fibroblast cells, and whether knocking down C16orf57 has an effect on Smad4.

To determine the cellular location of C16orf57, indirect immunofluorescence was performed with anti-C16orf57 on cultured

Neutrophil

Fibroblast Cells

human fibroblast cells. Fibroblast cells are commonly found within connective tissues. Tw --o mathematical approaches, Manders’ Coefficient and Li’s Method, were used to determine the colocalization of C16orf57 in the nucleus. In primary human fibroblasts, C16orf57 was cytoplasmic and could be seen surrounding the nucleus. Additionally, the two mathematical approaches did not indicate colocalization of C16orf57 in the nucleus, further supporting that C16orf57 is primarily cytoplasmic.

To investigate whether there is a direct interaction between C16orf57 and Smad4 in human cells, cultured cells were lysed and immunoprecipitation was performed with anti-C16orf57. Immunoprecipitates were subjected to Western blot analysis after 24- and 48hour periods. Immunoblotting was performed with an anti-Smad4 antibody. Immunoprecipitation confirmed the direct interaction between C16orf57 and Smad4 in human cells.

To examine the role of C16orf57, cells were transfected with a C16orf57 knock down vector and treated with LPS for three hours to induce the TGF-β pathway. Indirect immunofluorescence was performed with anti-Smad4 and anti-collagen, a good measure of Smad4 function. In cells with a C16orf57 knockdown, a decrease of Smad4 in the nucleus was seen, and collagen fibril formation was affected after stimulation. The C16orf57 knockdowns affecting the amount of Smad4 in the nucleus and collagen fibril formation suggest that C16orf57 plays a crucial role in the TGF-β pathway.

A better understanding of the role of C16orf57 in the TGF-β pathway is of critical importance to gaining further knowledge about the PN disease and finding ways to help affected patients. Additionally, further research in immunology is needed in order for the scientific community to fully grasp immunodeficiency disorders and successfully treat those who have them.

Grath, J., and Taieb, A. (2008). Poikiloderma with neutropenia, Clericuzio type, in a family from Morocco. Am. J. Med. Genet. A 146A, 2762-2769.

2. Clericuzio, C., Harutyunyan, K., Jin, W., Erickson, R.P., Irvine, A.D., McLean, W.H.I., Wen, Y., Bagatell, R., Griffin, T.A., Shwayder, T.A., Plon, S.E., Wang, L.L. (2011). Identification of a novel C16orf57 mutation in Athabaskan patients with poikiloderma with neutropenia. Am. J. Med. Genet. A 155, 337-342.

3. Volpi, L, Roversi, G., Colombo, E.A., Leijsten, N., Concolino, D., Calabria, A., Mencarelli, M.A., Fimiani, M., Macciardi, F., Pfundt, R., Schoenmakers, E.F., Larizza, L. (2010). Targeted next-generation sequencing appoints c16orf57 as Clericuzio-type poikiloderma with neutropenia gene. Am. J. Med. Genet. 86, 72-76.

4. Van Hove, J.L., Jaeken, J., Proesmans, M., Boeck, K.D., Minner, K., Matthijs, G., Verbeken, E., Demunter, A., and Boogaerts, M. (2005). Clericuzio type poikiloderma with neutropenia is distinct from Rothmund-Thomson syndrome. Am. J. Med. Genet. A 132A, 152-158.

5. Colland, F., Jacq, X., Trouplin, V., Mougin, C., Groizeleau, C., Hamburger, A., Meil, A., Wojcik, J., Legrain, P., and Gauthier, J.M. (2004). Functional proteomics mapping of a human signaling pathway. Genome Res. 14, 1324-1332.

6. Rual, J.F., Venkatesan, K., Hao, T., Hirozane-Kishikawa, T., Dricot, A., Li, N., Berriz, G.F., Gibbons, F.D., Dreze, M., Ayivi,-Guedehoussou, N., et al. (2005). Towards a proteome-scale map of the human protein-protein interaction network. Nature 437, 1173-1178.

7. Chiba, S., Takeshita, K., Imai, Y., Kumano, K., Kurokawa, M., Masuda, S., Shimizu, K., Nakamura, S., Ruddle, F.H., and Hirai, H. (2003). Homeoprotein DLX-1 interacts with Smad4 and blocks a signaling pathway from activin A in hematopoietic cells. PNAS 100, 15577-15582.

8. He, W., Dorn, D.C., Erdjument-Bromage, H., Tempst, P., Moore, M.A.S., and Massague, J. (2006). Hematopoiesis controlled by distinct TIF1γ and Smad4 branches of the TGFβ pathway. Cell 125, 929-941.

9. Karlsson, G., Blank, U., Moody, J.L., Ehinger, M., Singbrant, S., Deng, C., and Karlsson, S. (2007). Smad4 is critical for self-renewal of hematopoietic stem cells. J. Exp. Med. 204, 467-474.

10. Owens, P., Engelking, E., Han, G., Haeger, S.M., and Wang, X. (2010). Epidermal Smad4 deletion results in aberrant wound healing. Am. J. Path. 176, 122-133.

References

1. Mostefai, R., Morice-Picard, F., Boralevi, F., Sautarel, M., Lacombe, D., Stasia, M.J., Mc-

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hurj fall 2012: issue fall 1515

Baltimore Healthy Carryouts: Young-Hee Kim, Class of 2012

Lydia Liang, Class of 2014

Public Health

Neuroscience

The United States is growing fatter. Adult obesity rates have doubled from 15% to 30% since 1980 and have increased in 16 states in the past year.1 Twelve states now have obesity rates above 30% compared to only one state just four years ago. Childhood obesity parallels this dangerous trend. Obesity rates in the United States are significantly larger than that of other countries: the obesity prevalence was higher in the United States in 1999-2002 than in Canada in 20042 and studies show that the prevalence of obesity appears lower in European countries than in the United States.3 Obesity is a chronic disease with disastrous health consequences. Higher grades of obesity are associated with mortality, cardiovascular disease, as well as diabetes and certain cancers.4 However, obesity is not merely a health problem. It is becoming a social and economic epidemic as well. The associated health problems with being overweight or obese have a significant economic impact on the U.S. healthcare system.5 Because obesity places individuals at risk for more than 30 serious diseases, more money and resources are needed within the United States healthcare system in order to provide care for those who are sick.

While the United States is growing fatter, the fattening of the country is not evenly distributed. In the United States, substantial disparities exist in obesity trends based on demographics, geographic region, and socioeconomic status. Racial and ethnic minorities, those with less education, and those who make little money continue to have the highest overall obesity rates. These people tend to live in low-income urban communities and be of African American descent.1 Baltimore, Maryland clearly reflects this phenomenon in the U.S. In 2008 between 59.2% and 63.1% of Baltimore City adults were obese or overweight.6 Research has shown that the food environment in Baltimore, Maryland could contribute to the rising obesity rates: Baltimore City is a “food desert” – healthy, affordable foods are difficult to obtain. Yet, not all parts of Baltimore are “food deserts.”

It has been found that in predominantly white neighborhoods there is a higher availability of healthy foods compared to predominantly black neighborhoods. Access to food source and food source use is associated with healthy and unhealthy food-purchasing behaviors among low-income African American adults in Baltimore City.7 The larger numbers of corner and carryout stores in low-income neighborhoods, which makes them an easily accessible and frequently used food source for many people, compared with supermarkets in higher income neighborhoods, can explain unhealthy food-purchasing behaviors among low-income African Americans.

A large segment of the U.S. population is not yet fully aware of the health consequences of a poor diet.8 Therefore, there has been considerable interest in ecological strategies for health promotion and, more specifically, in environmental interventions aimed at improving health-related behaviors.9 The Baltimore Healthy Carryouts Project is one such intervention: the project aims to persuade carryout owners to sell healthier items and to implement various strategies to convince the low-income Baltimore City residents who use

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Mad Country, Sweet Land of Insanity An epidemic of mental illness in America

Study of Two Model Carryouts

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such carryouts as their food source to purchase healthier foods.

Eight different carryouts in East and West Baltimore were chosen as control and intervention carryouts. In the intervention carryouts, three different phases of intervention were implemented: 1) installation of new menu boards with symbolic menu labeling to indicate healthier, fresher choices, 2) addition of healthy sides, beverages, and desserts, and 3) creation of cheap combo meals with a comparably healthy entrée coupled with desserts, sides, and drinks.

The Baltimore Healthy Carryouts Project is unique because it implements a different kind of menu labeling intervention – symbolic menu labeling – instead of traditional menu labeling (e.g. caloric labels). Moreover, the Baltimore Healthy Carryouts project focuses on carryout stores, a major food source for Baltimore City residents and other populations living in similar low-income, urban communities, which has been unprecedented.

In-depth interviews and analysis of sales data show that the Baltimore Healthy Carryouts project is a feasible and a sustainable intervention. Two intervention carryouts showed significant sales increases of healthier food options with the implementation of Baltimore Healthy Carryouts. The owners have contended that they were open to sustaining the intervention, not only because of the economic advantages gained from the project, but also because of the educational impact the project had on the owners themselves and the satisfaction they gained from helping the community. The success of the Baltimore Healthy Carryouts Project will continue in Baltimore via the bigger Lexington Market and will hopefully be translated into legal policy. Public health research, whether qualitative or quantitative, provides evidence for true changes in people’s lives and health.

References

1. F as in Fat: How Obesity Threatens America’s Future Report. 2011. Accessed at: http:// healthyamericans.org/report/88/.

2. Tjepkema M. Adult obesity. Health Rep. 2006; 17(3):9-25 3. Ogden CL, Flegal KM, Carroll MD, Johnson CL. Prevalence and trends in overweight among U.S. children and adolescents, 1999–2000. JAMA 2002;288:1728–1732.

4. Malnick SD, Knobler H. The medical complications of obesity. QJM.2006; 99(9):565–579.

5. United States Department of Health and Human Services, 2011. Accessed at: http://www. hhs.gov/.

6. Balakrishnan A, Fichtenberg C, Ames A. Baltimore city health department data fact sheet, Baltimore city health Department’s office of epidemiology and planning. 2008. http:// www.baltimorehealth.org/info/2008_07_22.ObesityFactSheet.pdf.

7. Gittelsohn, J., Suratkar, S., Song, H. J., Sacher, S., Rajan, R., Rasooly, I. R., et al. (2010).

Process evaluation of Baltimore healthy stores: A pilot health intervention program with supermarkets and corner stores in Baltimore city. Health Promotion Practice, 11(5), 723-732.

8. Glanz, K., Basil, M., Maibach, E., Goldberg, J. & Snyder, D. (1998) Why Americans Eat What They Do: Taste, Nutrition, Cost, Convenience, and Weight Control Concerns as Influences on Food Consumption. Journal of the American Dietetic Association, 98, 11181126.

9. Green LW, Richard L, Potvin L. Ecological foundations of health promotion. Am J Health Promot. 1996 Mar–Apr;10(4):270–281.

Over the last 50 years, rates of mental illness have increased dramatically in America. Careful analysis of the correlations between this increase and developments in psychiatry suggests that the increase is caused by the distinct concepts and treatments in the field of psychiatry itself. Ambiguity in the term “mental illness” has contributed to the increase and often adds to to difficulties in gathering and analyzing data on the true state of mental disorder in America. The consequences are serious, and understanding the origin of the dangers of blind faith in modern concepts of “mental illness” requires analyzing the transitions in the field of psychiatry.

In less than 100 years, the number of the officially “mad” in America has skyrocketed. The tally of those who are so disabled by mental disorders that they qualify for Supplemental Security Income (SSI) or Social Security Disability Insurance (SSDI) increased nearly two and a half times between 1987 and 2007– from one in 184 American adults to one in seventy-six, adding up to four million adults in the United States who receive a government disability check because of mental illness.1, 2 This increase is paralleled in children, with those receiving a disability check because of mental illness shooting up in a thirty-five-fold increase over twenty years, leaping from 16,200 in 1987 to 561,569 in 2007. Mental illness is now the leading cause of disability in children, well ahead of physical disabilities like cerebral palsy or Down syndrome which were the original reason federal support programs began. The statistics continue to soar, with 850 adults and 250 children added to the rolls daily. Dr. Marcia Angell, editor-in-chief of the New England Journal of Medicine, characterizes the increase as a “raging epidemic of mental illness.” 1

Examining the trends in the mental health of America over the past fifty years is even more astonishing. In 1955, a drug called Thorazine was first used to treat symptoms of schizophrenia and similar disorders. It heralded the “modern era of psychiatry” and a “psychopharmacological revolution.”2 It was the beginning of the first generation of drugs marketed against a spectrum of mental disorders.

At that time, there were 355,000 adults, or about 0.21% of the population, with a psychiatric diagnosis in state and county mental hospitals.

During the next three decades, the focus of psychiatry shifted away from psychoanalysis and towards psychopharmacology and the number of mentally disabled rose to 1.25 million people, about 0.51% of the population.3 Prozac led the second generation of psychiatric drugs in 1988, and

the number of mentally disabled grew towards today’s enormous tally of more than four million adults, roughly 1.28% of the population.

In the modern era of psychiatry, treatment means prescribing psychoactive medicines, or drugs that affect brain function. More of these are being prescribed than ever before. The federal Centers for Disease Control (CDC) published an alarming study last year that found in the years 2005-2008, one in 10 Americans over the age of 12 took antidepressant medication, a 400% increase from 1988-1994.4 Once abundant, training in psychotherapy is now neglected in the field of psychiatry. As recently as 1977, 64% of psychiatric visits were exclusively for psychotherapy with no prescription assigned; in 2002 this was true for less than 10% of visits to psychiatrists.3

The shift in focus from therapy to medication represents the adaptations of psychiatric medicine to advances in neuroscience, especially discoveries of major and highly specific chemicals called neurotransmitters that are essential for proper brain function, and how different drugs alter normal neurotransmitter action in the brain.5 Heavily touted by the pharmaceutical industry, the primary theory of the underlying cause of mental illness over the past four decades has been characterized by “chemical imbalances,” where abnormal levels of different neurochemicals supposedly cause psychiatric disorders and can be adjusted by drugs.1 With antipsychotic medications replacing cholesterol-lowering agents as the top-selling class of drug in the United States, it seems Americans have accepted this theory wholesale.

Despite compliance rates being the highest ever, the rate of mental illness in America continues to increase.

A large survey conducted by the National Institute of Mental Health between 2001 and 2003 randomly selected adults and screened them for mental illness using criteria established by the American Psychiatric Association. An incredible 46 percent met criteria for having had at least one mental illness within four broad categories– anxiety disorder, mood disorder, impulse-control disorder and substance abuse disorder– at some time in their lives with most meeting criteria for more than one diagnosis.3

Recent trends are astounding and beg the questions: Is the prevalence of mental illness truly so high and still growing, or have criteria for mental illness been expanded to the point where half of Americans have a disorder? If more people than ever are on antipsychotic medication, and if those drugs work, shouldn’t we expect the prevalence of mental illness to be decreasing? Untangling these requires first looking at the meaning

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focus of “mental illness.” Researchers and clinicians, in their quest to provide effective patient care, have struggled to pinpoint what defines a mental disorder for centuries. Many others have offered their own perspectives on insanity: “For me, insanity is super sanity. The normal is psychotic. Normal means lack of imagination, lack of creativity.” –Jean Debuffet “Insanity is relative. It depends on who has who locked in what cage. ” -Ray Bradbury “The statistics on sanity are that one out of every four people is suffering from a mental illness. Look at your three best friends. If they’re OK, then it’s you.” -Rita Mae Brown

Unlike physical ailments, the classification of the symptoms of mental disease frequently relies on subjective assessments, creating ambiguity around the term “mental illness” and drawing into question the parameters for collecting statistics. Psychiatry currently relies on a manual called the Diagnostic and Statistic Manual of Mental Disorders (DSM) for clinical and research diagnostic guidelines. The DSM was introduced in the 1950s around the same time as psychoactive drugs and contained 106 diagnoses reflecting the Freudian view of mental illness. At that point, American psychiatry had little interest in neurotransmitters or any other aspect of the physical brain. Instead, it had its roots in unconscious conflicts affecting the mind, seen as a separate and distinct entity from the brain.

Discoveries of psychoactive drugs, shifted the focus to the brain and biological models of mental illness, but hit a snag when emergent side effects called the drugs and the biological model of mental illness into question in the 1970s. Mental health professionals were deeply divided over the nature of mental illness and how to treat patients. In response, the field made intense efforts to “remedicalize psychiatry,” and decided to use a scheduled revision of the DSM to standardize criteria for and language of mental health conditions.6

In making revisions for the third DSM, the American Psychiatric Association (APA) directed Robert Spitzer, the head of the revision committee, to emphasize drug treatment. Spitzer promised to make the DSM-III “a defense of the medical model as applied to psychiatric problems.”1 Published in 1980, the revised DSM-III was expanded to contain 265 diagnoses and came into nearly universal use. The manual introduced a symptoms-based diagnosis system whereby a physician would note how many of nine given symptoms, relevant to a particular disorder, a patient has and would make a diagnosis if the patient had at least five symptoms. This aimed to ensure that different physicians would identify and label a disorder in the same way.

The DSM-III proved immensely successful at bringing a standard of reliability to classification of mental conditions and the current version is psychiatrists’ go-to manual. However, there were, and still are, many problems with this system of diagnosis. Its reliability, or consistency, is not the same as accuracy. The problem with all of the DSM editions (we are on DSM-IV now with 886 pages and 365 diagnoses, with DSM-V to be published in 2013) is that they simply reflect the opinions of their writers. In the case of DSM-III, this meant Spitzer himself, a man who said in a 1989 interview, “I could just get my way by sweet talking and whatnot.”1

Determining the criteria for diagnoses in the DSM mostly meant that a group of men would heatedly discuss their opinions and the most emphatic arguments would win. Thus, the cornerstone of the

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hurj fall 2012: issue 15 psychiatric profession and the basis on which millions of Americans daily receive their diagnoses and treatments is actually quite subjective.

While this hints at the problems in the meaning of modernday mental illness, the picture is incomplete without acknowledgment of the pharmaceutical industry’s influence. As psychiatry became a drugintensive specialty, thanks to the reliability afforded by the DSM, drug companies quickly saw the advantages of a close alliance with the psychiatric profession. The industrial practice of fueling the self-interest of physicians, essentially bribing them to promote and prescribe a particular drug, takes coercively subtle and blatantly lucrative forms. Drug companies shower gifts and free samples on practicing psychiatrists, subsidize meetings of the APA and other psychiatric conferences and especially actively court faculty psychiatrists who publish much of the clinical research on drugs. Of the 170 contributors to the current DSM-IV, 95 had financial ties to drug companies, including all of the contributors to the sections on mood disorders and schizophrenia.7

As Daniel Carlat, MD, a practicing psychiatrist in Boston states, “Psychiatrists consistently lead the pack of specialties when it comes to taking money from drug companies… [because] we have few rational reasons for choosing one treatment over another.”8 The boundaries between normal and abnormal mental functioning are more often than not unclear, and drug companies are quick to take advantage of the blurry boundary between mental distress and mental disorder. In the process of medicalizing the human condition, psychiatrists legitimize their profession and mislead millions of Americans.

The drug companies’ efforts have proven more than effective.

Dr. Ramin Mojtabai, professor at the Johns Hopkins School of Public Health, noted, after reviewing recent psychiatric literature, that “we’ve seen a marked increase in antidepressant use among individuals with no psychiatric diagnosis”; according to his findings, the number of visits where individuals were prescribed antidepressants with no psychiatric diagnoses increased from 59.5 percent to 72.7 percent between 1996 and 2007.9 The troubling thing about psychiatric drug usage is that in many cases these drugs have serious side effects and can be the origin of debilitating symptoms of other disorders.10

The Food and Drug Administration (FDA) is the federal entity responsible for ensuring that drugs are effective and safe before they are put on the market. They require drug producers to demonstrate two clinical trials in which a drug has proven significantly more successful than a placebo trial, where half of study participants unknowingly take a sugar pill to allow comparison of the effects. Unfortunately, there are many loopholes and opportunities for drug companies to present less than the whole truth. Since only two successful trials are required to approve a drug, many drugs are approved and marketed to billions of Americans even when they have not been more effective than a placebo in the majority of the other studies, as well as some that are potentially unsafe. Furthermore, Robert Whitaker, a seasoned medical journalist and writer, notes that while drugs may have their intended short-term effects, not enough experiments on long-term effects have been completed.3 When people stay on medications for many years they experience chronic weight gain, depression, and fatigue, among other symptoms.

According to Carlat, a typical patient might take a dangerous cocktail of medication for depression, anxiety, insomnia and two more medications for the fatigue and impotence that come as side effects of the others.8

Ultimately, understanding the difference between mental distress and mental disorder is an essential component to the classification of diseases, and correctly diagnosing and classifying mental health conditions is crucial to effective patient care. While there is no infallible boundary separating mental distress from mental disorder, this does not mean

hurj fall 2012: issue 15 that “mental illness” is nothing more than an arbitrary social convention.

Clinical science does illustrate that cases of mental illness possess many properties lacking in cases of mental distress. Unfortunately, Americans view psychoactive drugs as the best, and often the only, treatment for mental illness or emotional distress. Emphasis on effective alternatives like psychotherapy and exercise is severely lacking, contributing to the view that a quick fix in the form of a pill is all that is needed to solve unhappiness.

Ideally, science can tell us what has gone wrong with a person and which treatments will work best to fix it. However, it cannot tell us whether we should treat a certain condition so the mental health professions will forever grapple with values as well as facts in their efforts to reduce human suffering. We, as Americans, have a crucial role to play in this too. The nearly half of us who will meet criteria for diagnosis with a mental disorder at some point in their lives are among us; they are working among us, they are our neighbors, our friends and our family– they are us. For the sake of those legitimately suffering from mental illness and for the health of our nation, we must avoid blind trust in medications and advertisements, instead remembering the time-honored medical dictum: first, do no harm.

References 1. Demyttenaere, Koen, “Prevalence, Severity, and Unmet Need” Journal of the American Medical Association, 2004 Jun 2;291(21):2581-90.

2. McHugh, PR. “Striving for Coherence: Psychiatry’s Efforts over Classification” Journal of the American Medical Association, 293 (2005): 2526-2528.

3. Whitaker, Robert. Anatomy of an Epidemic: Magic Bullets, Psychiatric Drugs, and the Astonishing Rise of Mental Illness in America. Crown (Random House, 2010).

4. Pratt LA, Brody DJ, Gu Q. Antidepressant use in persons aged 12 and over: United States, 2005–2008. NCHS data brief, no 76. Hyattsville, MD: National Center for Health Statistics.

2011.

5. Eisenberg, L. and Guttmacher, L. B. (2010), Were we all asleep at the switch? A personal reminiscence of psychiatry from 1940 to 2010. Acta Psychiatrica Scandinavica, 122: 89– 102. doi: 10.1111/j.1600-0447.2010.01544.x 6. Angell, Marcia. The Illusions of Psychiatry. Retrieved from <http://www.nybooks.com/ articles/archives/2011/jul/14/illusions-of-psychiatry/?pagination=false#fn-5> 2011 Jul 4.

7. Cosgrove et al., “Financial Ties Between DSM-IV Panel Members and the Pharmaceutical Industry,” Psychotherapy and Psychosomatics , Vol. 75 (2006).

8. Carlat, Daniel. Unhinged: The Trouble with Psychiatry - A Doctor’s Revelations about a Profession in Crisis (Free Press, New York, 2010).

9. Johns Hopkins School of Public Health, Prescriptions for Antidepressants Increasing Among Individuals with no Psychiatric Diagnosis < http://www.jhsph.edu/news/newsreleases/2011/mojtabai_antidepressant_prescriptions.html>. Published August 4, 2011.

10. Cassels, Alan, Moynihan, Robert. Selling Sickness: How the World’s Biggest Pharmaceutical Companies Are Turning Us All into Patients (Nation Books, New York, 2005)

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Shifting the Healthcare Debate Dong Kim, Class of 2013 Molelcular & Cellular Biology and Psychology

A number of politicians have tried their hand at health care reform and have failed. The most vivid failure, Hillary Clinton’s battle to install the individual mandate, would have made having health insurance a law. Opposition to Clinton’s proposal was largely political and questioned the constitutionality of a health insurance requirement. This misses the point of health care reform: producing a viable system to cut costs and provide quality health care to a larger portion of the population. The debate’s focus on politics rather than determining a fiscally sound solution to the health care problem in the United States underpins the belief among many that there is no economic need for reform. However, the current state of U.S. health care is hurting the population, which urgently needs policy changes.

Currently, much controversy surrounds the U.S. medical system, not just the idea of reform. Many politicians and citizens view American medicine as the best in the world. Meanwhile, critics point out inequality and poor outcomes. Both sides are right; it is true that American medicine is of very high quality, but there are disparities in distribution of health care and in what diseases are tackled by research. Fixing the problem requires introducing preventive health and changing the pharmaceutical industry to decrease costs through policy change. Still, the first step before this must be recognition of problem areas in health care.

The World Health Organization, or WHO, ranks the United States 37th in health care and 1st in spending per capita [1]. This ranking is often criticized for failing to incorporate factors such as culture and diet, which are difficult to measure but have an impact on outcomes, a reflection on the state of health care. However, the critical point is that U.S. spending is at a much higher level than other countries. Currently, the United States spends approximately 17% of its GDP on health care, meaning that just under a fifth of all the services and goods produced by the U.S. are related to the health care field [2].

The U.S. is making a major investment in health, which is understandable as long as the investment makes high returns.

However, the data from WHO shows it does not. The problem is similar to the following: if lemonade costs $1 a cup, the US is paying $5 for only 3 cups of lemonade. The U.S. is putting more money into medicine but not getting the full value; greater life expectancies, more life-saving technologies, and an efficient system to provide more of the population with proper health care is still out of reach [3].

The difference between the value of what is put into and what comes out of the healthcare system is clear when comparing health outcomes of two countries that spend differently, such as Taiwan and the U.S. The Taiwanese spend only 7% of their GDP on healthcare, but there is no evidence that their medical system suffers any disadvantage compared to the US [3.5]. There is a gap in which the value of what the US is putting in is not coming out but is simply lost. Countries that invest less do not experience this sort of loss.

However, there are also upsides to the way the US invests in health, such as excellence in chronic disease treatment [4]. The

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WHO defines these as diseases of long duration and slow progression, cidence of the associated diseases and thus their respective emergency such as heart disease, diabetes, stroke, and cancer [5]. The modern era treatments. of medicine has ushered increasingly effective and expensive treatments The best form of prevention is use of long-term public health and technologies for such diseases. But playing favorites leaves other measures, such as those called for in the Universal Health Care Choice dimensions of health care underdeveloped; while chronic disease treat- and Access Act, which calls for more resources for education and prement flourishes, initiatives such as preventive care are ignored, bringing vention [10]. Senator Tom Coburn, M.D., an author of the Act, predicts down the rate of successful treatment outcomes. This may be the biggest savings of billions of dollars, but economists predict the savings will be problem of the American health care system, resulting in an expensive, delayed by the time necessary to shift attitudes about public health. While and unsustainable, system. the effectiveness of such prevention programs is undisputed, they receive

As early as 1996, five chronic diseases (mood disorder, diabetes, only 0.1% of the total health care expenditures compared to 4.5% spent heart disease, hypertension, and asthma) accounted for 62.3 billion dol- on biomedical research [11]. This is partially due to America’s focus on lars, or 49% of the health care budget [6]. A recent report by the WHO salient, visible results from short-term investments. In contrast, public projected the costs of chronic disease to balloon to 47 trillion dollars by health initiatives usually have fewer measurable results and require a lon2030 [7]. The costs are amassed by both the government and the private ger-term investment. Prevention programs won’t provide instant gratimarkets to provide a standard of care deemed humane. Unfortunately, fication, which is an expectation that isn’t compatible with meaningful the American medical system does not encourage interventions to re- reform to the American health care system. duce costs. The main culprit of this is the system of multiple health insur- Beyond preventive measures, there are a number of other apers. proaches to decrease cost. Peter Provonost, M.D., Ph.D., a well-known

“The more fragmented the insurance system, the less incentive advocate of public health effectiveness, created a simple checklist to inindividual insurers have to care about prevention, whose benefits may crease efficiency and reduce mistakes during routine procedures. For exaccrue to other insurers,” notes David Hemenway, Ph.D., an expert at the ample, doctors often need to follow several steps to prevent patient infecHarvard School of Public Health. “It tion when inserting an intravenous seems that countries with national infusion line to deliver medication.

“The more fragmented the insurance system, the health insurance often provide Following use of Provonost’s checkmore incentives for prevention.” list, infection rates went down to 0 less incentive individual insurers have to care about

In a fragmented insurance percent and resulted in thousands prevention, whose benefits may accrue to other insurers.” system, those with insurance can of lives and millions of dollars -David Hemenway, Ph.D., an expert at the Harvard School of have multiple tests, such as MRI’s, saved in the average hospital [11.5]. x-rays or other analyses, done with Though the effectiveness of the tool Public Health minimal personal cost. There is lithas been confirmed, states have tle motivation to make an effort to been slow to adopt the checklist, instay healthy and to use as few medidicating the struggle to change and cal procedures as possible. Meanwhile, the lack of preventive care means implement policies to improve wellness [12]. Most importantly, the need those without insurance might develop persistent health problems. With- for the checklist has pointed to a major problem: the lagging efficacy of out interventions that would follow from having routine health screen- basic medical delivery in comparison with the push for increasing comings, these individuals can end up requiring costly emergency services. plexity in medical development.

These costs in turn drive up the overall cost of health care in countries The U.S. biomedical research industry is huge. It is worth $100 such as the U.S. This problem affects about 50 million Americans who billion and has produced some of the best health care technologies and lack insurance and an additional 30 million who are under-insured [8]. pharmaceutical products in the world [13]. Many of the most highly At a time when the health care costs are continuously rising, there is only regarded medical technologies in history have come from American one clear way forward: prevention, a medical approach that introduces companies or universities. Among these are statins, a class of cholesterolwellness, as opposed to health as it is traditionally understood, as a goal. lowering compounds that have been refined into drugs such as the well The theme of wellness has entered the vernacular of health poli- known Lipitor, which nets the company Pfizer about $10 billion per year, cy experts as well as politicians. Wellness can be defined as those acts per- or 14% of their revenue in 2011 [14]. Research on statins was first started taining to maintaining good health through lifestyle decisions and public by a Japanese scientist, but the research turned into a market drug only health initiatives. This is achieved by treating the patient as a whole rather when American companies took a risk on investing in and developing it. than as the sum of many organs and their functional status. For instance, Recent data suggests that developing a drug is causing private an unhealthy pancreas might be made healthy through costly treatments, markets to incur increasingly more costs [13]. Furthermore, the number but minding nutrition to keep the pancreas healthy in the first place of drugs entering human trials in the last two decades has fallen. The reacontributes to an individual’s wellness. Hence, a major part of wellness son for this isn’t that drugs are harder to make but that there is an increase is education and awareness of having a balanced diet and exercising to in regulation. Other countries are making huge advances and producing improve the outcome of most diseases and as a preventive measure to better biomedical research environments, but this is a matter of policy reduce many risks of illness.

[15]. Policy and the environment it produces makes the difference be Public health officials estimate a vast number of deaths could tween successful biomedical research and not. be prevented using proper health interventions; they are deaths associ- Some believe the current system provides the best treatments in ated with smoking (465,000 deaths per year), hypertension (395,000), the world because of how it is structured (as opposed to despite how it is obesity (216,000), physical inactivity (191,000), high blood glucose levels structured). Specifically, there is an idea in the health care debates that the (190,000), and high levels of low-density lipoprotein cholesterol (113,000) current system is the reason for U.S. dominance in biomedical research.

[9]. Identifying preventable deaths helps target public health education Thomas Boehm, M.D., a former post-doctoral fellow and current mediand prevention efforts, giving hope for cutting costs by reducing the in- cal director at a private firm, is a proponent of this idea; Boehm believes

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hurj fall 2012: issue 15 the U.S. system has a particular culture and system that drives the development of medical technologies and drugs [16]. According to Boehm, U.S. resources allow for risk-taking, which leads to results. Boehm’s hypothesis introduces an exciting idea that is liked by many proponents of the current system, but there’s no evidence for it; it is unproven and dubious that the U.S. pharmaceutical industry is unique.

This belief is challenged by the reality that the U.S. is faltering the face of world competition due to lack of government intervention and a lack of focus on cost-effective pharmaceutical targets. The U.S. pharmaceutical and biomedical industries are losing ground to competing governments which are adopting policies similar to those of the US. For example, the Bayh-Dole Act, a bill which offered universities the opportunity to commercialize products from their research, illustrates how governments can pass policies to foster environments that promote research innovation and development. The explosion of biomedical technology industry in Southeastern Asia, most notably in Singapore and Japan, not only proves the success of policies such as Bayh-Dole, but also that there is nothing inherent in US industries that makes them succeed [15].

Health care in the U.S. emphasizes treatment of chronic disease and the average consumer of health care is someone with a high income who is in need of cures, not preventive care. This leads to underfunding of public health measures, which could save money for the government and produce better patient outcomes. In part because of this landscape, treatments are expensive and costs have begun to reach a point where fewer people have the resources to pay. A 2007 study in the American Journal of Medicine concluded medical costs directly caused 62.1% of bankruptcies with 92% of those families struggling to pay an average of $5000 [17]. Compounded with impeded access to primary care – a necessity for implementation of prevention measures – this paints a bleak picture for the US [18]. The future of American health care cannot be guided by fear of upsetting the biomedical research markets and disrupting innovation. Health care reform is desperately required and debates must shift from a political argument on the role of government to one based in sound economic data to provide cost effective and sound health care.

focus 2010 [10] Heritage Lectures, Competition: A Prescription for Health Care Transformation, No. 1030, 2007 [11] Hemenway, David. Why We Don’t Spend Enough on Public Health.

NEJM. 2010 [11.5] Anft, Michael. Check That. Johns Hopkins Magazine, November 2008.

[12] Tierny, John. To Explain Longetivity Gap, Look Past Health System.

New York Times, September 2009. http://www.nytimes.com/2009/09/22/ science/22tier.html?_r=1 [13] The New England Journal of Medicine, Biomedical Research and Health Advances, 2011 [14] http://www.pfizer.com/files/annualreport/2011/proxy/proxy2011. pdf [15] The Global Biomedical Industry: Preserving US Leadership, 2011, Milken Institute [16] Journal of Medical Marketing, How can we explain the American dominance in biomedical research and development?, 2005 [17] The American Journal of Medicine, Medical Bankruptcy in the US, 2007: Results of a National Study [18] Reinhardt, Uwe. Keeping Health Care Afloat: The United States vs.

Canada, The Milken Institute Review, 2007

Endnotes [1] The World Health Report, WHO, 2000 [2] Health Spending Projections Through 2019: The Recession’s Impact Continues, Truffer et. Al, Vol. 31, No. 4, April 2012 [3] Gerard F. Anderson, et al, It’s the Prices, Stupid: Why the United States is so Different from Other Countries, Health Affairs, 22, no.3 (2003): 89-105 [3.5] Ian Williams (2007-10-07). “Taiwan gets healthy”.

The Guardian. http://commentisfree.guardian.co.uk/ ian_williams/2007/10/taiwan_gets_healthy.html.

[4] Preston, Samuel H. and Jessica Ho. 2009. “Low Life Expectancy in the United States: Is the Health Care System at Fault?” PSC Working Paper Series PSC 09-03 [5] www.who.int/topics/chronic_diseases/en/ [6] Benjamin G. Druss, et. Al, Comparing the National Economic Burden of Five Chronic Conditions, Health Affairs, 20, no. 6 (2001): 233-241 [7] The Global Economic Burden of Non Communicable Diseases, World Economic Forum, September 2011 [8] http://money.cnn.com/2011/09/13/news/economy/census_bureau_ health_insurance/index.htm [9] Murray, Christopher J.L., Ranking 37th- Measuring the Performance of the US Health care System, The New England Journal of Medicine,

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The Weight of Obesity: Unseen complications of every day life Elina Tonkova, Class of 2012 Molecular & Cellular Biology The obesity epidemic stands in the national spotlight before an audience that has easy access to all of the statistics. Most of us know about the rate of obesity in the United States, the plethora of related medical problems, and the fact that obesity is a sinkhole for healthcare funds.

However, there are also gaps in our understanding of the complications that have no medical diagnosis; not everything about obesity has been addressed. In fact, looking at obesity and believing that we know the whole picture is the true problem, causing stigma and impeding effective interventions.

Over one third of Americans are obese, a weight that is related to cardiovascular disease, stroke, type 2 diabetes, gallbladder disease, sleep apnea, and some cancers such as breast, prostate, and colon1. It has been reported that every one in ten dollars spent on healthcare goes toward treating obesity and its medical complications, totaling to approximately 150 billion dollars per year, more than the amount spent on the treatment of all cancers combined.2 Someone is considered obese when he or she has a body mass index (BMI) of 30 or greater.3 BMI is measured as weight in kilograms divided by height in meters squared; for example, an individual who is 5’4’’ or 5’9’’ would be considered obese at a weight of 174 or 203 pounds, respectively. Although the World Health Organization (WHO) defines health as “a state of complete physical, mental, and social well-being and not merely the absence of disease of infirmity,” it’s rare that issues other than the conventional physical co-morbidities are considered health problems associated with obesity.4

WHO’s inclusion of not only physical but also emotional and mental health creates a holistic view that might be better explained as an overall feeling of well-being, or wellness. This broadened definition gives a better sense of the total negative “Over one third of Americans are obese, a impact that weight that is related to cardiovascular disobesity can ease, stroke, type 2 diabetes, gallbladder dishave on an ease, sleep apnea, and some cancers such as individual’s wellness, breast, prostate, and colon. “ since “both physical functioning and psychosocial functioning are negatively impacted by excess weight, with greater impairments associated with greater degrees of obesity.”5 Psychosocial function is synonymous with mental and social well-being, both of which are essential for health, but are somewhat abstract and call for further analysis.

Mental well-being is different from mental health, which is constituted by the absence of mental illness. One of the most well-known models of mental wellness was developed by three doctors of counseling

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education: Jane Myers, Thomas Sweeny, and Melvin Witmer. According to their model, mental wellness is based on five fields: spirituality, work and leisure, friendship, love, and self-direction—with sub-fields including sense of worth, problem solving, stress “Appreciating the breadth of effects of management, and obesity is crucial to fully understanding its more.6 According to the model, consequences and their manifestations in an individual’s everyday life.” ability to respond to various life circumstances in an appropriate manner depends on and constitutes that individual’s mental wellness. WHO elaborates on this with the addition that a state of mental well-being requires the realization of one’s potential, productive and fruitful work, and contribution to community.7

These definitions also bring up the idea that healthy functioning is dependent on interaction with others, tying in to social well-being.

The New Economics Foundation is an independent organization with the mission of improving quality of life, not only through research but also through translating their research into actions to help improve well-being worldwide. They have done extensive research on well-being, including social well-being, by using measurements of how people perceive their connections to those around them and how strong those relationships are. Through this they have created a definition of social well-being that hinges on two components. First they identified supportive relationships, or “the extent and quality of interactions in close relationships with family, friends and other who provide support.” Second is trust and belonging, which the Foundation defines as “people’s experiences of trusting other people, being treated fairly and respectfully by them” within the broader social spheres in which they live.8

Mental and social well-being components can greatly affect the broader scope of an individual’s quality of life. Appreciating the breadth of effects of obesity is crucial to fully understanding its consequences and their manifestations in everyday life. Thankfully, attention is being drawn to this. A review of scholarly articles on obesity emphasizes that “quality of life may be one of the most important health outcomes to consider in managing [obesity].”7 Though quality of life may seem like a subjective term, it has been successfully quantified using medical, social, and emotional components.

The Short Form (36) Health Survey, or SF-36, is a commonly used survey to determine quality of life. It was devised by the RAND Corporation as part of a two-year study of the quality of life of patients with chronic medical conditions. The SF-36 is composed of 36 questions scored on a scale

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that cover physical pain and ability, self-sufficiency, emotional stability, and social activity, among others.9 At their core, quality of life measurements such as the SF-36 survey evaluate one’s ability to live as fully and actively as desired, something that obese individuals often lose because of many non-medical consequences of their weight. Unfortunately, the inability of many obese individuals to lead fulfilling lives is as serious as the adverse effects of obesity on morbidity and mortality.10

Complications to the daily routine of someone who is obese can take many forms beyond potentially life-threatening medical comorbidities such as cardiovascular disease or stroke. Robin Frutchey, a psychologist on staff at the Johns Hopkins Weight Management Center affiliated with the Bloomberg School of Public Health, comments on her experience counseling obese clients:

“Every time I conduct an initial assessment with a client, I ask what is motivating the client to seek treatment. More often than not, clients mention that their weight is affecting their overall quality of life. This is especially the case when mobility is affected.”11

The impairment of obesity to daily living comes into play in a variety of ways, all of which prevent individuals from living as they choose and instead forcing them to live only as their bodies allow, dictating what can and cannot be done in the course of a day. While many who are obese experience physical activity positively, enjoy it, or used to, their weight makes it difficult or impossible to partake in it.12 In a study using extensive interviews of obese individuals, researchers reported that many felt strained and uncomfortable in activities requiring them to appear in public, reporting feelings of taking up a lot of space, with a particular focus on chairs when visiting others, going to the cinema or to meetings.13

This struggle puts many who are obese between a rock and a hard spot: getting to one’s destination using public transportation presents a problem, but, as Frutchey notes, “inability to walk very far keeps people from going to zoos, museums, and other attractions with their families.”11 Not participating in social activities because of weight is an example of how the physical obstacles overlap with emotional, mental, and social issues. The “inability to participate fully in social settings...was

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reported as linked to depression and lack of motivation to change the situation.”13 This compromises mental well-being, as well as both aspects of social well-being.

Not only does it jeopardize a sense of belonging within one’s broader community, through instances such as the embarrassment of asking flight attendants for seat extenders or the extreme self-consciousness that comes with wearing a bathing suit at a pool or the beach, but it also complicates close, supportive relationships. Shutting oneself out of social events is not constructive to having meaningful relationships, but it seems that sometimes it’s not within an obese individual’s ability to overcome this. Frutchey comments: “It’s very common for clients to mention that they’re unable to keep up with their children, play ball with them, or get down on the floor to play with them,” straining bonding within families.11

Difficulty maintaining closeness and intimacy within a romantic partnership also arises. In interviews, a typical pattern of response arose whereby “obesity seemed to cause tension in relationships, and two women [out of eleven interviewees] told of relationships that ended, in part because of weight problems, and periods of social isolation.”13 Problems with sexual functioning, such as erectile dysfunction and lack of arousal and satisfaction, can physically be caused by obesity; there is also the negative impact of “the overweight individual suffering from poor body image, depression, and low energy... [and occasionally,] the spouse’s lack of interest.”14, 11

Obesity can not only prevent fulfillment at the personal level but also at the professional level, with many reporting that their obesity keeps them from doing their job as well as they might otherwise, and that the workplace is one of the greatest sources of stigma.15 Frutchey notes that obese individuals frequently perceive prejudice in the workplace and report feeling that coworkers who are a normal weight get more respect and responsibility, regardless of actual talent.11 Despite their qualifications, Frutchey’s clients often get the sense that their weight implies a lack of control, causing them to be passed over for jobs and promotions.11

Given the variety of obstacles that obesity can bring to living a fulfilling life, it’s critical to look beyond medical problems as the sole

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How Sexual Values Shaped Sex Education in Public Schools consequences and realize how obesity can impair quality of life. Many obese individuals report feeling that their weight is so debilitating to their day-to-day life that their accounts are comparable to those with chronic illnesses like inflammatory bowel disease and liver cirrhosis, or to limb amputation.16 Two of the greatest and most common issues are feelings of powerlessness to change the situation, and consequent choices that create a perpetuated cycle of obesity. The worst offenders among poor mechanisms of responding to stigma are over-eating and refusing to diet, avoiding social interaction (thus eliminating the possibility of receiving support), and avoiding physical activity.17 Considering that unhealthy strategies of coping with stigma have a reverberating impact on well-being, acknowledging the consequences of obesity on quality of life is essential for effective interventions. This acknowledgment may improve efficacy measurements for obesity treatments, and, in turn, better the standard of care. Assessing intervention effects on how patients feel and function in their everyday life will simultaneously alleviate symptoms as well as help to motivate patients to maintain longterm weight loss.5 Obesity weighs on people in ways that slip through the fingers of conventional medical diagnosis; stopping the obesity epidemic requires greater awareness and appreciation of the issues beyond those already in the public eye.

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References 1. Demyttenaere, Koen, “Prevalence, Severity, and Unmet Need” Journal of the American Medical Association, 2004 Jun 2;291(21):2581-90.

2. McHugh, PR. “Striving for Coherence: Psychiatry’s Efforts over Classification” Journal of the American Medical Association, 293 (2005): 2526-2528.

3. Whitaker, Robert. Anatomy of an Epidemic: Magic Bullets, Psychiatric Drugs, and the Astonishing Rise of Mental Illness in America. Crown (Random House, 2010).

4. Pratt LA, Brody DJ, Gu Q. Antidepressant use in persons aged 12 and over: United States, 2005–2008. NCHS data brief, no 76. Hyattsville, MD: National Center for Health Statistics.

2011.

5. Eisenberg, L. and Guttmacher, L. B. (2010), Were we all asleep at the switch? A personal reminiscence of psychiatry from 1940 to 2010. Acta Psychiatrica Scandinavica, 122: 89– 102. doi: 10.1111/j.1600-0447.2010.01544.x 6. Angell, Marcia. The Illusions of Psychiatry. Retrieved from <http://www.nybooks.com/ articles/archives/2011/jul/14/illusions-of-psychiatry/?pagination=false#fn-5> 2011 Jul 4.

7. Cosgrove et al., “Financial Ties Between DSM-IV Panel Members and the Pharmaceutical Industry,” Psychotherapy and Psychosomatics , Vol. 75 (2006).

8. Carlat, Daniel. Unhinged: The Trouble with Psychiatry - A Doctor’s Revelations about a Profession in Crisis (Free Press, New York, 2010).

9. Johns Hopkins School of Public Health, Prescriptions for Antidepressants Increasing Among Individuals with no Psychiatric Diagnosis < http://www.jhsph.edu/news/newsreleases/2011/mojtabai_antidepressant_prescriptions.html>. Published August 4, 2011.

10. Cassels, Alan, Moynihan, Robert. Selling Sickness: How the World’s Biggest Pharmaceutical Companies Are Turning Us All into Patients (Nation Books, New York, 2005)

Throughout the Twentieth Century and The AIDS Crisis in the United States Catherine Rose, Class of 2013 History, Political Science Throughout the twentieth century, sex education in public schools, or the lack thereof, was dictated by Americans’ attitudes towards sex and its place in society. Before the 1960s, changes in courtship and dating worried Americans that young people would engage in sexual activity at an early age and “family life education,” was introduced to promote marriage among serious couples and educate them living on a household budget. In the 1960s, in the midst of the sexual revolution, sex education programs became more prevalent in public schools but their content varied greatly between states and school districts. In the 1970s and 1980s, social conservatism resurged and the federal government under the influence of social conservatives began to regulate sex education. Congress passed the Adolescent Family Life Act, which made it difficult for girls under eighteen to have abortions and gave funding to sex education programs that exclusively taught abstinence.

However, government regulation of sex education programs under the Adolescent Family Life Act soon became detrimental to the welfare of students. When the AIDS epidemic hit America, the government refused to allow sex education programs to inform their students of technology and methods that could stop them from getting AIDS if they chose not to abstain from sex. The government thought that AIDS could be contained through abstinence. Unfortunately, many students did not abstain and contracted the disease in part due to the failure of sex education. In the end, it was America’s social conservative values and morals about sex that prevented sexual education programs from effectively helping students during the AIDS crisis.

Sex Education Pre-1960 Before the sexual revolution of the 1960s, American attitudes about sex were heavily influenced by Judeo-Christian beliefs, which preached that it was wrong for two people to engage in sex if they were not married. Men did not want to marry women who were not virgins, but society was more forgiving in judging men than women who were promiscuous. Young men dated outside of their social class and engage in sexual activity with young women of a lower class, but married chaste young women of their own social standing. Parents might have encouraged dating, but they expected their children, especially their daughters, to observe limits. Colleges imposed curfews on their female students and had strict rules about visiting hours. Advice books aimed at high school students discouraged sexual contact and the most popular guide of the postwar year, Facts of Life and Love for Teenagers, warned that anything beyond “that goodnight kiss” could lead to trouble. Before the 1960s, the ideal woman was one who was pure and moral and although it was more acceptable for a man to seek sexual activity before marriage, sex before or outside of marriage was in no way encouraged.

In the 1930s, information about sex and sexuality was limited with the exception of information included in female hygiene products. They included diagrams and discussed female anatomy, but began to venture outside of the information necessary for instruction and into topics like dating and other problems facing adolescent girls. In the 1940s, penicillin drastically changed healthcare in the United States but did nothing to affect venereal diseases, which in spite of Americans’ alleged views of extramarital sex, were becoming increasingly prevalent. The federal government expanded funding

for programs sponsored by the Public Health Service in hope that educating adults would stop the rapid spread of syphilis and gonorrhea. This increased funding set a precedent for federally funded sex education programs.

Sex Education in 1960s Alfred Kinsey’s famous studies, published in 1947 and 1953, proved that Americans’ sexual behavior did not reflect the principles that most people claimed to support. In the 1950s there was an extreme increase in the rates of pregnancy and venereal disease among teenagers. Cold War anxieties added to concerns about the deterioration of American families.

An editorial in the Journal of Social Hygiene said, “Nothing could please the ironic enemies of democracy more than to witness the corrosion of American family and community life in the very course of our efforts to defend both.” The actions of America’s youth, evident in Kinsey’s publications, did not support the image of strength and unity that America wanted to project to the Soviet Union. States did not mandate sex education programs, but if they existed, they were developed into “family life education.” These programs encouraged couples that wanted to engage in sexual activity to get married, gave lessons on how to manage a household budget.

In 1956, teenagers accounted for half of all new cases of syphilis and gonorrhea. By 1960, federally funded research concluded that women were more likely to contract a venereal disease at eighteen than another age, meaning that teenage women were becoming more likely to engage in risky sexual behavior and that problems associated with unprotected sex were “not confined to any sex, race, social group, or section of the country.” The CDC called for “a new war on sexual ignorance” to target all Americans but include, for the first time, a specific program for the nation’s adolescents.

Sex education developed to mirror the sexual attitudes of Americans before the 1960s. The prevalence of venereal diseases and teenage pregnancy threatened American values and thus, “family life education” was born to encourage marriage before sexual activity and prepare students for married life. These curricula did not cover how to prevent venereal disease or pregnancy because schools believed that if people embraced morality and chastity, they would not have to deal with those problems. Many schools that offered sex education in the 1960s only included simple instruction about privacy, hygiene, and respect. A few older students had instruction about dating, marriage, premarital intercourse, and rarely, a teacher took questions about masturbation, birth control, and homosexuality. Moreover, communities were concerned that children were too young to be exposed to sex and some thought that sexuality should be veiled as it had been in the past because of tradition. One mother blamed the school for “taking away from my children the mystery, the wonderful experience of my wedding night.”

Sex education programs of 1960s had books that were more direct than their immediate post-war counterparts, but the stigmas about appropriate gender roles and behavior had not changed to reflect the new attitudes of American youth. The young people of the sixties were experimenting with drugs, protesting the Vietnam War, fighting for civil rights, and “making love not war,” but the majority of authors condemned premarital sex, homosexuality and mentioned sexual pleasure only as a caution against masturbation. Time magazine blamed the change in sexual culture on the availability of pornography, indecent clothing, Hollywood’s growing tendency to push the limits, and pressure in schools to engage in adult behavior in order to be considered “cool.” Time said that the majority of Americans probably still

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humanities & social sciences humanities lived by old religious morality or at least tried to, but unlike in the past, many others, especially young people, were now living by “permissiveness with affection,” meaning that they believed morals were a private affair and love justified premarital sex. The magazine warned Americans that, “When sex is pursued only for pleasure, or only for gain, or only to fill a void in society or in the soul, it becomes elusive, impersonal, ultimately disappointing” and said, “Perhaps it is time that modern Americans, who know a great deal about sex, once again start talking about love.” The popular press was concerned about changing behavior among adolescents and SIECUS emerged as an attempt to bridge the gap between the two groups The Sex Information and Educational Council of the United States, or SIECUS, formed in 1964 and wanted to redefine sex and popularized the term “sexuality” as part of one’s life and personality. SIECUS supported abstinence, hoping that it would not only encourage safe and responsible sex but also condemned traditional sexual restrictions like religious guilt and ignorance. They encouraged young adults to create their own sexual values system based not on religion, but on their individual, moral compass. Opponents argued that education about sex, protection from venereal diseases, and pregnancy would only fuel the fire of the sexual revolution and encourage the destruction of the family and parental authority. Religious attacks in the 1970s made SIECUS less popular.

Sex Education since the 1970s: How It failed to address AIDS

For some, sex education was a symbol of cultural decline and acceptance of the sexual revolution. The conservative party took it upon themselves to support those who wanted to fight against the sexual revolution and the party found success in subsequent elections. Issues like abortion and sex education formed unprecedented coalitions between Catholics and other Christians, conservative Jews, and Muslims and pro-family politics became a cornerstone of American government. Even though Roe v. Wade made abortion legal in the United States in 1973, legislative initiatives after the ruling made it difficult for the poor and underage to have abortions.

Conservatives attacked sex education by calling educational materials pornography, calling sex educators not only communists, but pedophiles, and claiming that talking about sex only encouraged experimentation. Between 1969 and 1971, public support for sex education in public school fell by 6%.

Despite the position of the Republican Party, increasing numbers of teenagers received some form of sex education in the 1970s, but content varied.

One study, performed in 1979, revealed that only 10% of American teenagers had ever had a course that covered a wide range of topics including sexually transmitted diseases, masturbation, and contraception and the typical course was only a few hours of classroom time per year. By the end of the 1970s, it was less common to hear accusations that sex education was Communist-inspired, but it was increasingly common to hear that sex education undermined parental authority and destroyed families.

Despite calls to eliminate sex education, President Reagan reformed it along the lines of social conservatives with the 1981 Adolescent Family Life Act (AFLA), which denied funds to programs that provided abortion or abortion counseling and mandated abstinence education in the sex education programs that it funded. AFLA made “abstinence education” popular for the first time on the national scene because it was an alternative to comprehensive sex education that many Americans felt gave children too much information. It diverted federal money, “that would otherwise go to Planned Parenthood into groups with traditional values.” Religious conservatives were thrilled that their support of abstinence was getting deserved national attention, but others thought AFLA interrupted progress on establishing comprehensive sex education programs: The national government more or less ignored sex education in the 1970s and early 1980s, except when they used AFLA to encourage abstinence-only education. Many conservatives did not believe that sex education had a place in schools, but as a compromise to states and school districts,

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fall2012: 2012:issue issue14 15 hurjhurj spring the federal government under conservative leadership gave an incentive for the states and schools to support abstinence-only education, in line with conservative values and pro-family politics. Abstinence education became increasingly popular as AIDS captured the attention of the nation.

The first cases of what became known as HIV/AIDS occluded in the late 1970s… In mid-1982, good evidence that the disease was sexually transmitted finally surfaces; at the conclusion of summer, 505 cases had been reported, with 202 dead.

President Reagan was slow to react to the news about HIV/AIDS. It was not until Rock Hudson, a friend of Reagan’s from his acting days, passed away from AIDS in 1985 that Reagan made any public comment or asked the White House physician for more information about the disease. He did not speak of AIDS again until 1986 when he instructed the Surgeon General, C. Everett Koop, to report on the problem. Reagan did not endorse the use of condoms and ignored Koop’s report, but in June 1987, his administration formed a presidential commission to investigate the disease and recommend solutions.

Koop released The Surgeon General’s Report on Acquired Immune Deficiency Syndrome in October 1986 and included information about how the disease spread, what people could do to protect themselves, and the of importance education. He said that some people were not receiving necessary information and others, “erroneously dismiss AIDS as a topic they need not be concerned about. They must be convinced otherwise.”

Koop believed that education should begin in schools: Many people—especially our youth—are not receiving information that is vital to their future health and well-being because of our renitence in dealing with the subjects of sex, sexual practices, and homosexuality.

This silence must end. We can no longer afford to sidestep frank, open discussions about sexual practices—homosexual and heterosexual.”

Schools could reach as high as 95% of the young people and educate them before they put themselves at risk. Reagan made no public comment on Koop’s Report, but his administration did suggest that Koop “update” the Report, meaning they hoped her would remove the word “condom.”

The Reagan administration’s conservative values did not accept Koop’s recommendations because they did not support any sort of education that was not exclusively supportive of abstinence.

The Report of the Presidential Commission on the Human Immunodeficiency Virus Epidemic was presented to President Reagan on June 24, 1988. In its recommendations for future prevention, it included a section called “School-Based Education” and recommended a two-step approach.

First, in the short term, HIV education should be introduced across the nation in all the states that have not done so already. It recommended that both elementary and secondary school students receive such an education, tailored to their age so “they can make informed decisions about their behavior and avoid those actions that put them at risk for HIV infection.”

Second, in the long term, the Commission recommended the introduction of a comprehensive health education curriculum for kindergarten through twelfth grade. The Commission acknowledged that the HIV epidemic involved personal behaviors, which could be difficult to incorporate into a classroom setting, that many communities did not believe that HIV would ever affect them and saw no need to educate their children, and that the funding necessary for HIV education programs was not readily available. Because adolescence was such a formative period for behavior patterns such as smoking, alcohol and drug use, driving, food intake, relationship patterns including pre-marital sexual activity, the teen years presented a crucial opportunity for “preventative intervention and affirmation of healthful living and self-respect.” The Commission put most of the responsibility for achieving these goals on state and local governments, but encouraged the Department of Education and the CDC to increase funds to national education organizations, school districts, and other educational entities. They recommended that the Secretary of Health and Human Services and the

hurj fall 2012: issue 15 Secretary of Education co-chair a task force to articulate what should be taught at which grade level and to explore the development of incentives for school systems to incorporate these programs into their curricula.

In 1989, the American Public Health Association published “Preventing AIDS: A Guide to Effective Education for the Prevention of HIV Infection,” which came to similar conclusions as Koop and Reagan’s Commission, but went into greater detail about why youth was such an important group to educate, in spite of the fact that their prevalence of infection was very low. Half of all adolescents had had sex by age nineteen and 16% of teenage women had had four or more partners. Only half of all teenagers used contraception their first time and 33% had never used contraception at all. 20,000 high school students in the United States had tried heroin and millions of others had used other drugs that could be injected intravenously.

Adolescence is a time of taking risks and experimentation with alcohol and drugs only increases the possibility of engaging in risky sexual behavior.

While Koop and the Commission laid out clear guidelines of how to implement HIV education in the curricula of public schools, the attitudes of many communities about sex and the virus made it difficult to do so. Many of the initial victims of the virus were gay men, prostitutes, minorities, and injection drug users. In 1985, Margaret Heckler, the director of the Department of Health and Human Services presented an “us and them” mentality about the virus when she said, “We must conquer AIDS before it affects the heterosexual population…the general population. We have a very strong interest in stopping AIDS before it spreads outside the risk groups, before it becomes an overwhelming problem.” Even within the federal government, Americans were unwilling to accept AIDS as something that could affect them because its victims were not of the most desirable populations.

Throughout the 1980s, it became increasing apparent that HIV/AIDS was not staying contained to the risk groups and more states mandated K-12 AIDS education. Of the 27 published state-approved curricula in 1989, only eight addressed both abstinence and strategies of prevention for sexually active students, while all others exclusively encouraged abstinence. All programs, however, encouraged students to examine and develop their own values, but 75% of all of these teachers believe that students should only be taught to “say no” to sex. Despite the efforts of these programs, the number of adolescents diagnosed with AIDS doubled every fourteen months until 1989 and one fifth of all people with AIDS were in their twenties. Although the programs were young, it was apparent that America’s youth was still participating in risky behaviors, potentially because they were not aware of effective ways to protect themselves. Only 8% of males and 2% of females said that they used condoms after their AIDS education classes, either because they ignored it or has received an abstinence-only education. In 1990, a survey of students revealed that they learned more about HIV/AIDS from the media and interpersonal sources, or their friends and families, than they did in school. They described their teachers as ill informed, reluctant to talk about disease and sexual activity, and students even requested “more extensive and intensive education, beginning earlier, and including presentations by people with HIV/AIDS, target information about prevention, condom availability, and discussion of the psychosocial impact of the disease.”

Under the Welfare Reform Law, passed in 1996, additional federal grants were made available to states that established programs whose exclusive purpose was the “promotion of abstinence only education.” Many states submitted school-based proposals even though national and worldwide research proved that these programs are less effective, if effective at all at when compared to comprehensive sex education programs in preventing STDs and unwanted pregnancy among teens. As of 1996, no federal funding was available for such programs.

While America’s adolescents were ready for the information that would protect them, the older Americans in charge of school committees and the federal government were stuck in the past. Their opinions about sex and sex education prohibited students all over the country from receiving a complete

humanities & social sciences education about HIV/AIDS. The reaction, or lack of reaction, to the AIDS crisis in terms of sex education proves that Americans feel so strongly about sexual values and principles that they will not even provide information about protection to a group of young people who choose not to live by those values and principles. Sex education, became even more important when the worst thing that could happen changed from an unwanted pregnancy or venereal disease to a disease that could potentially kill anyone who got it. Despite a plethora of knowledge, information, and suggestions from reputable sources like the Surgeon General and the Presidential Commission on the Human Immunodeficiency Virus Epidemic, the federal government refused to mandate education programs that gave information about protection and even in 1996, still provided incentive funds for any program that provided students with an abstinence-only education. Even in the face of a new and dangerous challenge, sexual values and morals dictated the way Americans approached sex education in public schools. American’s cultural views of sex and its place in society prevented information about AIDS and how to prevent it was detrimental to America’s youth, who, had they been more informed, could have made better decisions about their sexual behavior and protecting themselves.

References:

1. John D’Emilio and Estelle B. Freedman, Intimate Matters: A History of Sexuality in America (New York: Harper & Row, 1988), 239, 262-264.

2. David Gudelunas, Confidential to America: Newspaper Advice Columns and Sexual Education (New Brunswick: Transaction Publishers, 2008), 10.

3. Alexandra M. Lord, Condom Nation: The U.S. Government’s Sex Education Campaign from World War I to the Internet (Baltimore: The Johns Hopkins University Press, 2010), 51, 63, 94-96.

4. Jeffrey P. Moran, Teaching Sex: The Shaping of Adolescence in the 20th Century (Cambridge: Harvard University Press, 2000), 136.

5. Ibid, 136.

6. Lord, Condom Nation: The U.S. Government’s Sex Education Campaign from World War I to the Internet, 112-115.

7. Ibid, 112-115.

8. Janice M. Irvine, Talk About Sex: The Battles Over Sex Education in the United States (Berkeley: University of California Press, 2002), 19.

9. Ibid, 19.

10. Ervin Drake, “Morals: The Second Sexual Revolution,” Time, January 24, 1964, accessed May 6, 2011, http://www.time.com/time/magazine/article/0,9171,875692-1,00.html.

11. Irvine, Talk About Sex: The Battles Over Sex Education in the United States, 17-18, 24, 28.

12. Irvine, Talk About Sex: The Battles Over Sex Education in the United States, 186-187, 192 13. Ibid., 38, 43, 47-48.

14. Ibid., 65-66, 73.

15. Irvine, Talk About Sex: The Battles Over Sex Education in the United States, 73.

16. Irvine, Talk About Sex: The Battles Over Sex Education in the United States, 88-89 17. Scales, “Sex Education in the ‘70s and ‘80s: Accomplishments, Obstacles, and Emerging Issues,” 558.

18. Scales, “Sex Education in the ‘70s and ‘80s: Accomplishments, Obstacles, and Emerging Issues,” 559-562.

19. Kristen Luker, When Sex Goes to School: Warring Views on Sex—And Sex Education—Since the Sixties (New York: W.W. Norton & Company, 2006), 222.

20. Irvine, Talk About Sex: The Battles Over Sex Education in the United State, 90-92.

21. Lord, Condom Nation: The U.S. Government’s Sex Education Campaign from World War I to the Internet, 167.

22. Lucas Richert, “Reagan, Regulation, and the FDA: The US Food and Drug Administration’s Response to HIV/AIDS, 1980-90,” Canadian Journal of History (2009), 468.

23. Ibid., 469.

24. C. Everett Koop, “Surgeon General’s Report on Acquired Immune Deficiency Syndrome,” Public Health Reports 102 (1987): 1.

25. Ibid, 1.

26. “Dr. Koop’s Personal Account of the AIDS Controversy,” HealthNewsDigest.com, accessed May 5, 2011, http://www.healthnewsdigest.com/news/National_30/Dr_Koop_s_Personal_ Account_of_the_AIDS_Controversy_printer.shtml.

27. Report of the Presidential Commission on the Human Immunodeficiency Virus Epidemic, chap. 7 (Washington, DC: Government Printing Office, 1988), 99-102.

28. Ibid, 99-102.

29. Ibid, 99-102.

30. Preventing AIDS (Washington, DC: American Public Health Association: 1989), 155-156.

31. Jonathan G. Silin, Sex, Death and the Education of Children: Our Passion for Ignorance in the Age of AIDS (New York: Teacher’s College Press, 1995), 13, 16, 27.

32. Ibid., 56, 72-74.

33. Robert T. Francoeur, Sexuality in America: Understanding Our Sexual Values and Behavior (New York: Continuum, 1999), 280-281.

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Seaton’s Pleas With the British Public and the Transmission of Scarlet Fever Gabrielle Barr, Class of 2012 History

In 1872, the Public Health Act mandated the appointment of a Medical Officer of Health (MOH). Edward Cox Seaton, Jr., a physician and fellow of the Royal College of Surgeons, became Nottingham’s first MOH at the age of twenty-six in 1873 for a salary of £400. This son of Edward Cator Seaton, Sr., a MOH to the Privy Council and Local Government board, followed in his father’s footsteps in addressing the community’s public health concerns; but where the elder Seaton focused on vaccination, the son promoted a variety of initiatives from housing improvements, to unpolluted wells, to advocating that cities notify their populations of current outbreaks of infectious diseases. One of the main aspects of being a MOH was investigating and restricting the transmission of illness; thus, in 1877 Seaton Jr. published a pamphlet entitled “How to prevent the spread of fever,” in which he encouraged the building of hospitals, disinfection of these venues, and the isolation of patients suffering from scarlet fever, typhoid, and small pox into specialized infirmaries. Due to an argument over his salary and the tragedy of his wife’s death, Seaton resigned from this post in 1884 but soon assumed a similar position in Chelsea where he worked in the public health sector until 1915.

As the MOH for Chelsea, Seaton published three editorials between 1886 and 1888 in the Times, a widely read and respected newspaper of the period, concerning the prevention of scarlet fever. Scarlet fever claimed the lives of more than ten thousand British men, women, and children during its most virulent epidemics in the 1860s. A Lancet article from 1865 called it the “deadliest of fevers,” yet even A.B. Whitelegge, Seaton’s successor in Nottingham, commented as late as 1887 that “Scarlet fever... [was] practically always present in every large community.” This malady that afflicted all classes and ages proved to be especially fatal amongst children and the poor. After 1870, fewer people succumbed to scarlet fever for several reasons, among them being the prominence of the less lethal form of the Group A Stremolytic Steptocci; however, this scientific fact was unknown to Seaton and his contemporaries who put forth numerous theories about the disease’s origins and steps that society should take to avoid its transmission. Seaton in 1878 printed his “Memorandum on Precautions against Scalatina,” which attributed the spread of disease to dust particles and therefore promoted the disinfection of clothing and spaces.

However, Seaton’s ideas changed by the 1880s with the introduction of the notion that scarlet fever could be transmitted through milk. Although Michael Taylor of Penrith was the first person to suggest this theory in 1867, several influential individuals such as Ernest Hart, George Newman, and William Power

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also embraced this concept. In 1885, scientists believed that that the outbreaks of scarlet fever in Hendon and Paisley could be traced to families of dairymen.

The local MOH issued a prosecution against a particular dairyman who violated regulations under the Dairies, CowSheds and Milk Edward Cox Seaton Shops Order of the Contagious Diseases (Animals) Act of 1879. Although, by the vague definition of the relevant clause “any person suffering from a dangerous or infectious disease’ or any person in ‘contact’ with an infected person from milking cows and selling milk,” these verdicts were difficult to determine and enforce. Seaton as a MOH had a slightly different reaction to the scientific conjecture than many of the scientists working on this issue, in the sense that he constantly strove to tie research to public health initiatives. Though Seaton’s three editorial articles in the Times varied slightly in tone and focus, they all endorsed the zymotic theory that milk could serve as a vector for the transmission of scarlet fever and they all served as public critiques of the current state of the British public health system.

On July 9, 1886, Seaton wrote his first editorial to the Times, advocating that both public health officials and his lay readers reexamine the accepted origins of scarlet fever and the measures used to quell epidemics. Although the article was entitled “The Prevention of Scarlet Fever,” it hardly focused on that particular disease. Seaton’s editorial introduced a general audience to the scientific theories that might have explained the source of various maladies such as scarlet fever. Seaton did not commence his article by discussing a virulent outbreak of these infectious diseases but rather began his piece by mentioning William Power’s article that he considered “one of the most important reports which have ever been issued by the Medical Department of the Local Government Board.” Power, an investigator from the Privy Council had examined the fatal 1877-1879 outbreak in Easington and Northriding. This report examined the connection between “milk scarlatina” and “Hendon cow disease” and concluded that both cows and humans were susceptible to scarlet fever, which was thought to be communicable. Seaton

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commended Power for his moral qualities “[p]atience, skill, and promoted the conjecture. The scientific angle of the piece from sagacity,” which permitted the scientist to conduct his sanitary citing the temperature in which human scarlet fever bacterium investigations. Even though this comment on Power’s moral can be killed to Klein’s observations illustrates Seaton’s increased character may seem unrelated to the article’s argument, it hu- investment in the technical aspects of the idea. manized a figure that would be unfamiliar to many of Seaton’s However, he had to appeal to his general audience as evireaders. denced by his word choice and the persuasive elements of his Seaton further extolled Power calling his experiment “an writing. Seaton constructed the article to be part of a larger conexample of scientific research by methods of induction” that de- versation surrounding the topic, and therefore mentioned Klein’s served admiration. He believed that this data coupled with Dr. recent lecture at the Royal Institution as well as his previous ediEdward Klein’s observations at the Brown Institution would ul- torial to accentuate the relevancy of his article to a population timately attract the attention of medical and scientific profes- that had not experienced a significant epidemic in more than a sionals. Although Seaton claimed that his purpose in writing the decade. His frequent references to past articles and lectures also article had implications beyond lauding scientific advancements, served as legitimization for the information on which he based pure scientific research was clearly critical to this doctor and his arguments. The lay English readers would not be able to comMOH who spent a significant portion of the piece introducing prehend the complexities of these scientific inquiries, but they these acclaimed studies. would respect the names, titles, and expertise that Seaton cited Seaton had faith that these investigations would impact pub- in the piece, which would ultimately bolster his authority on the lic health by preventing or limiting serious ailments such as scar- subject. let fever. While he admitted that a focus on municipal cleanliness Seaton reiterated numerous proposals to avert the spread of had reduced disease, he proclaimed, as an experienced member scarlet fever from boiling milk to separating the infected cows of the field, that some of his colleagues who promoted cleanliness from the herd. His frequent rhetorical questions presented the as a means to limit all types of fevers stymied the advancement of options as apparent and simple responses against the disease. knowledge and its practical ramificaHe recommended that Britain adopt tions. Seaton mocked these narrowthe German and Austrian example of minded individuals, writing “as if it medical men who were also trained Seaton clearly functioned as the were superfluous to look elsewhere in veterinary science, which he adambassador between the lay and for the origin of the outbreak.” He vocated would be a boon for the field scientific worlds, and he vehemently cited examples of how occurrences of of public health, especially since he scarlet fever and diphtheria were atmentioned the unwillingness of vetdisplayed his irritation towards the tributed to poor housing conditions, erinarians to collaborate with pubpublic’s stubbornness and his antagonism but Seaton questioned the connection lic health officials. These medical towards the medical system that did not between defective sewer drainage and men with a background in sanitation the causes of certain illnesses. Scienwould be able to advise authorities embrace his solutions. tific discovery had influenced mediand supervise the sanitary conditions cine such as the case when Power disof cow sheds and dairies, an imporcerned that an epidemic of diphtheria tant step towards eradicating scarlet correlated with the distribution of a particular milk supply, and fever. His comparison to foreign states and the line that linked that the infectiveness of the milk most likely stemmed from a dis- medical men with hygienic training to “defence in this country ease of the cow known as “garget.” Seaton claimed that too little against easily preventable disease” employed nationalist sentiattention was paid to this “promising line of investigation and re- ments to rouse the people to support his plan of action. search,” which had only became noticed recently because the pubSeaton clearly functioned as the ambassador between the lic mind had become “possessed with the idea that the advocacy lay and scientific worlds, and he vehemently displayed his irof cleanliness must be the sole aim of sanitary workers, and that ritation towards the public’s stubbornness and his antagonism the prevention of zymotic diseases [was] only to be achieved by towards the medical system that did not embrace his solutions. the promotion of structural works for improvements in drainage Throughout the letter to the editor, Seaton’s pessimism and sarand water supply.” casm escalates. In the introduction of the article, Seaton reHis emphatic language and dismissive tone conveyed his marks on the implausibility that the English people would boil frustration with the limited perspective of his colleagues who their milk, but by the conclusion of the piece, Seaton vents, “ were unwilling to explore alternative possibilities to the Chad- At present, as is well known, the appointment of medical offiwickian model of public health. Interestingly, despite his support cers of health in the majority of sanitary districts is nothing but for scientific inquiry, he also doubted the effects it would have in a sham, the officers being appointed to perform nominal duties eradicating or suppressing disease. Thus, Seaton initially encour- for nominal salaries.” This harsh appraisal of the situation conaged his readers to be open to various possibilities more than he trasted with the easily attainable model that Seaton suggested endorsed a single theory. that would be highly compensated for their important work.

Seaton’s second editorial published on June 1, 1887 focused The emphasis on skills and qualifications shed light on the unentirely on preventing scarlet fever through controlling the milk satisfactory jobs performed by those of England’s public health supply. Unlike his first letter to the editor that merely suggested infrastructure. It also might indicate the resentment Seaton the possibility of the milk theorem, the second article strongly had towards the public health bureaucracy after they refused

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humanities & social sciences to raise his salary when he acted as the MOH in Nottingham. Thus, Seaton turned to Britain’s taxpayers, i.e. his readers, to make the decision between his proactive ideas and the expensive, infectious disease hospitals supported by the state with public funds.

Seaton’s third letter to the editor that appeared in the Times on June 6, 1888 projected the most directed and forceful argument of his three editorials. Just as in the last article, Seaton did not need to furnish the same level of background, which gave the piece a more delineated focus. Seaton concentrated on the role of scientific studies from Power’s report to Dr. James B. Russell, a medical officer of health of Glasgow’s experiment, played in confirming the contaminated milk theory’s credibility. He commented frequently on these individuals’ astute capabilities and status to illustrate the sophisticated research in which the milk theory was grounded. Seaton now readily championed this explanation and used these investigations to support his case. Though he admitted to the improbability of the idea being overwhelmingly accepted in its initial stages and the need for more “independent and equally able observers,” he remained committed to the notion of using words like “unquestionable” and “sufficient certainty” to describe previous findings and citing a Lancet article that discussed Russell’s correlating observations.

However, the scientific evidence did not readily support Seaton’s broad conclusions. Professor G.T. Brown’s 1888 report “Eruptive Diseases of the Teats and Udders of Cows in Relation to Scarlet Fever in Man” included a range of annotated documents, illustrations, and graphs of different inquiries that neither completely confirmed nor rejected the milk theorem. This report generally promoted the possibility of infected cows and milk leading to human scarlet fever, but it also questioned the part of external circumstances such as human agency had on the transmission of the disease. Many scientists including Russell expressed the importance of not drawing premature inferences. As a government briefing, Brown had the liberty to explore more of the subtleties of the issue than Seaton who had to craft a shorter, compelling argument for the masses.

The lack of concluding evidence may have prompted Seaton to make the abrupt transition from the description of Russell’s examination of cattle to harmful government research policies. Towards the end of the piece, Seaton lashed out against the state-enforced, restrictive regulations, which he bitterly labeled as “mistaken” and characterized as “[fettering] scientific observers in conducting researches intended to lessen the sum of human misery resulting from preventable disease.” He spitefully told those responsible for the imposition of such laws to review John Simon’s “Experiment as a Basis of Preventive Medicine” with the same anger he conveyed in his other editorials.

Nevertheless, Seaton’s appeal to human sympathy seems far more important to his message. The use of the word “surely” demonstrates that Seaton believed that his readers would agree with his moral premise, and his choice of the phrase “human misery” as opposed to “cause deaths” or “save lives” gave his argument more of an emotional impact. Whereas the first two articles underscored the his points of intellectual openness and efficiency, Seaton’s last plea demonstrated the absurd human suffering the regulations were causing, which would conflict with the civil values of his readers, in the hopes that popular support could transform a problematic system.

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hurjhurj spring fall2012: 2012:issue issue14 15 Edward Seaton’s perception of the milk theory noticeably changed from his first editorial, where he proposed the conjecture to be a pliable idea to his last article where he emphatically defended the concept and the right for science to have less confined limits in order to have the capacity to prevent disease.

Seaton’s three letters to the editor encapsulated the spirit of the complex investigation’s findings and involved a lay community into a pertinent scientific dialogue. While Seaton focused on the prevention of scarlet fever, he evoked themes such as intellectual openness to novel hypothesis, efficiency of the health care, and state’s role in science, which transcend his narrow topic into medical and sanitary issues around the world throughout time.

References

[1] Amos, Denise. “Early Medical Officers of Health” The Nottinghamshire Gateway 20 Jul. 2008 < http://www.nottsheritagegateway.org.uk/people/ moh.htm.> >; “Edward C. Seaton, M.D., F.R.C.P., Consulting Medical Officer Of Health, Surrey County Council” The British Medical Journal 1:2826 27 Feb. 1915, 402-403.

[2] Hardy, Anne. The Epidemic Streets: Infectious Disease and the Rise of Preventive Medicine 1856-1900. Oxford: Clarendon Press, 1991. 56 [3] Hardy 59, 67, 70, and 77; Wohl, Anthony S. Endangered Lives: Public Health in Victorian Britain. Cambridge: Harvard University Press, 1983. 129 [4] Woodward , John. ‘Medicine and the City: the Nineteenth-Century Experience.” Urban Disease & Mortality in Nineteenth-Century England.

Robert Woods & John Woodward, eds. New York: St.Martin’sPress, 1984, 64; Delmege, Anthony. Towards National Health: Health and Hygiene in England from Roman to Victorian Times. New York: The MacMillian Company, 1932.

175; Cliff, A.D., M.R. Smallman-Raynor, D. Hagget, D.F. Stroup, and S.B. Thacker. Emergence and Re-Emergence: Infectious Diseases: A Geographical Analysis. Oxford: Oxford University Press, 2009. 91-92 [5] Hardy 178 [6] Smith ,F.B. The People’s Health 1830-1910 . New York: Holmes & Meier Publishers, 1979. 178 [7] Seaton, Edward. “The Prevention of Scarlet Fever.” The Times 9 Jul. 1886, 13.

[8] Smith 140 [9] Morris, Malcolm. The Story of English Public Health. London: Cassell and Company, 1919.178 [10], [11], [12]Seaton, Edward. “The Prevention of Scarlet Fever.” The Times 9 Jul. 1886, 13.

[13], [14], [15] Seaton, Edward. “The Prevention of Scarlet Fever.” The Times 1 Jun. 1887, 4.

[16] While public health officials made great strides in the send half of the nineteenth- century, they encountered many difficulties, particularly in a legislative capacity. Among the people, however, they were generally viewed a pragmatic and respected individuals, which certainly differed from the manner Seaton portrayed them. Anne Hardy, “Public Health and the Expert: The London Medical Officers of Health, 1856-1900” Government and Experts: Specialists, Administrators, and Professionals, 1860-1918 Roy MacLeod , ed.

(Cambridge: Cambridge University Press, 1988), 131, 137, and 141.

[17] Amos, Denise. “Early Medical Officers of Health” The Nottinghamshire Gateway 20 Jul. 2008 < http://www.nottsheritagegateway.org.uk/people/ moh.htm.> >; “Edward C. Seaton, M.D., F.R.C.P., Consulting Medical Officer Of Health, Surrey County Council” The British Medical Journal 1:2826 27 Feb. 1915, 402-403 [18], [19] Seaton, Edward. “The Prevention of Scarlet Fever.” The Times 6 Jun. 1888, 15.

[20] Brown, G.T. “Eruptive Diseases of the Teats and Udders of Cows in Relation to Scarlet Fever in Man.” London: Eyre and Spottiswoode, 1888.xiv [21] Seaton, Edward. “The Prevention of Scarlet Fever.” The Times 6 Jun. 1888, 15.

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The Hero: Greek, Victorian, and Modern; Dominant, Residual and Emerging Conceptions of the Hero in Modern Times Grady Stevens, Class of 2013 Philosophy, Classics In the 1856 novel Tom Brown’s School Days, Thomas Hughes praises boys who are great sportsmen or take brave actions in sports and showcases them as heroic figures. He does this by chronicling the early years of the protagonist Tom Brown, as Tom goes through his time at The Rugby School, an English Public School. Throughout the novel, Hughes praises the ability of sportsmen; he also sees sports as a moral educator for young boys. In fact, Hughes treats the athletes in his novel as heroes, praised for their actions. To Hughes, a hero is a sportsman whose actions reflect a superior quality of character because of the moral education received while playing sports. This concept of the hero can be described as the Victorian hero.

However, different cultures within the Western tradition have had different understandings of heroism. For the Greeks who founded the Western tradition, the only requirement for heroism is excellence in war, like that of Achilles, the prototypical Greek hero. Unlike the Victorian conception of the hero, the Greek conception did not require any moral superiority; it allowed for heroes to be corrupt as long as their performance is still superhuman. Furthermore, modern culture has inherited both Victorian and Greek conceptions of the hero. Because of the inherent incompatibility between the Victorian and Greek conceptions, the residual culture of the Victorian era is in constant tension with the residual culture of the Greeks in modern society. Additionally, with the rise of “heroes” like soccer star David Beckham, there is a possibility of a new emerging cultural conception of the heroic, which is of a completely different sort than the Modern, Victorian or the Greek. In this paper, I will focus on the Sportsman as the epitome of a hero; however, this does not mean that the sportsman is the only lens through which one can view the heroic, as individuals like politicians and soldiers could also been seen as heroes in those times.

In order to understand the term “hero,” we must understand the meaning of this word in the past. “Hero”, as we understand it, comes from the Ancient Greek noun ἥρως; which means ‘demi-god’. It has no connotation of morality; the only requirement is excellence on a superhuman level. Heroes are a mixture of divinity and man, as the term demi-god shows; they are almost gods because they have a divine lineage. As a result, their abilities were considered to be greater than other men. By greater, I simply mean above or more, in the sense that a higher quantity is superior; accordingly, their actions were also expected to be greater than other men’s. Therefore, their μῆνιν, which is Greek for “wrath” or “rage,” should be greater than that of other men.

This may seem counterintuitive until one understands a basic explanation of the actions of the Greek gods; through such an explanation, an understanding of traditional Greek morality can emerge.

The actions of the mythological Greek gods are nothing short of immoral and hedonistic. Zeus is notoriously a womanizer and Hades is a rapist, not to mention the vast amount of infidelity amongst the

other gods. The Trojan War is started over a beauty contest, the Judgment of Paris. Hera holds a grudge against Herakles for his entire life, and tries to murder him as a baby. Zeus overthrows his father. Kronos eats his children. Zeus and Hera are brother and sister, as well as being husband and wife. Dionysus is constantly intoxicated. Basically, the faults of the gods are the same as mankind’s. The only difference is that their power and status allows them to do actions normally considered terrible by men, for no other reason than because they have the power to do so. In the Greek mind, might is right. The gods were simply capable of greater—more—joy, hatred, love, and sexual desire than men; moreover, because heroes lie between these two levels, their emotions must be amplified above Human normality as a result.

In order to understand traditional Greek views on heroism, one must look no further than Homer’s Iliad. The Iliad focuses on the events in the 10th year of the Trojan War. The plot is moved by the actions, or inactions of Achilles, who is the driving force for the plot.

In Book I, it is his decision to withdraw from the fighting that causes many of the problems the the Greeks face during the Iliad. Regarding heroism, the nature of the Greek heroic pantheon is a hierarchical model. Achilles is the best fighter and thus Achilles is the greatest hero.

Odysseus can be understood as second best, over Ajax, because Odysseus inherits the armor of Achilles. Odysseus, however, is heroic in a different way than both Achilles and Ajax. He is heroic because of his “many wiles” that allow him to trick people and gain the upper hand in this manner. This does not make him the greatest hero; ancient Greeks referred to Achilles as the greatest Greek hero simply because he was the best fighter. Thus, an aspect of the Greek conception of the hero was someone who not only possessed great rage but who also could fight extremely well.

Achilles’s famous rage is the driving force for the action in the Iliad.

The Iliad begins with Achilles’s rage being sparked by Agamemnon for taking one of his prizes of war—Briseis. Achilles is not angered by Briseis the person being taken, but by one of his possessions being taken from him. This insult from Agamemnon makes Achilles decide to withdraw from fighting. Despite this, no other hero calls Achilles less of a hero, nor do they really care about his childish behavior. As shown in Book IX, Odysseus, Ajax, and Phoenix persuade Achilles to fight again. They only care that Achilles does come back and fight, regardless of what his personal beliefs are. Because of this, the Greek notion of the hero can be seen as someone who is quite simply capable of actions greater than that of other men; it does not require any sort of moral character.

Although the Greek view of the hero still influenced the Victorian age, the Victorian idea of the hero was significantly different. The Victorian culture of the 19th century emphasized the character of the hero, as a man who is morally superior; this moral superiority results in heroic actions. The sportsman was as the prototypical hero in this era due to the astonishing fame of W. G. Grace, who was arguably England’s most famous man during the Victorian era. The sportsman was closer to home than the soldier, and as such makes for a better, more

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humanities & social sciences humanities accessible hero—because their heroic actions were seen more often.

Therefore, if people saw sportsmen act heroically in a consistent manner, such sportsmen would become heroes.

This conception of athletes as heroes resulted from the fact that many sports games in the Victorian era lacked referees; thus, it was of the utmost importance that the participants followed the rules, because this was the only possible way to have an organized-game. In Tom Brown’s School Days, there is a great deal of trust put into the schoolboys by the praepostors, who are essentially prefects in the English Public Schools. This trust is a crucial part of the type of heroism that was dominant in the Victorian era; it is evidenced by how the whole of schoolhouse is supposed to play football at three o’clock, but none of the praepostors took any measure to check attendance: “They trust to our honor, they know very well that no school-house boy would cut the match. If he did we’d very soon cut him, I can tell you.”

In the first Football game of the novel, there is strong evidence that the boys are honest about the rules. During the game, there are shouts of “off your side,” “down with him,” “put him over,” and “bravo.” The athletes govern themselves. Foul plays are frowned upon and fair play is extolled. The peer pressure to act honorably shows that the boys understand the importance of morality.

The Victorians believe that the moral quality in the hero would lead to heroic actions. In this early part of the novel, a character called old Brooke is portrayed as the prototypical hero, captaining the schoolhouse football team. In a speech given to his teammates, old Brooke calls for an end the bullying that was rampant in school and stands up for the Headmaster of the Rugby School, Thomas Arnold. Arnold enacts strict rules on the boys that are unpopular; despite their unpopularity, Old Brooke understands the value of the rules and makes sure that the other boys were aware of it as well. Both of these are unpopular opinions, but as a hero, it is old Brooke’s responsibility to be morally superior to the rest of the boys and act on his beliefs. The unstated but implied message that Hughes wants to send is that old Brooke is able to do the heroic actions on the pitch because of his moral character: performance is reliant on moral character.

Victorian heroes were also supposed to have courage and mental toughness. In one of the football games, the main character and hero, Tom, is in disbelief when he first sees the differences in number between his team and the opposition: “You don’t mean to say that those fifty or sixty boys in white trousers, many of them quite small, are going to play that huge mass opposite?” The response made by a friend of Tom’s, East, is quite to the mark: “Indeed I do, gentlemen; they’re going to try at any rate, and won’t make such a bad fight of it either.” This is

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hurjhurj spring fall2012: 2012:issue issue14 15 an extraordinary expectation; the schoolhouse boys were expected to compete against an overwhelming number of opponents. This clearly illustrates the importance of courage for this conception heroism.

The football match also demonstrates the mental toughness of the players. During the game, two young players get caught up in the moment, and rush forward into the scrimmage without thinking. Old Brooke, however, “keeps his head” and puts all of his energies into his work to produce a positive effect for his team. Hughes praises old Brooke’s actions with the words, “take a leaf out of his book, you young chargers.” By praising old Brooke, Hughes demonstrates the values of mental toughness in the hero-athlete.

Furthermore, in a Victorian hero, the act of sacrificing oneself for a greater cause is one of the noblest possible actions. Sport is the only forum for the boys in Tom Brown’s School Days to practice this virtue every day. East exemplifies this virtue in his attempt to prevent a much larger boy from getting a chance to score. Hughes writes: “They rush together, the young man of seventeen and the boy of twelve, and kick it at the same time. Crew passes without a stagger; East is hurled forward by the shock.” The description of East, preventing Crew from scoring with his heroic self-sacrificing action, was roused with cheers of “bravo” from the schoolhouse, and his action was seen as “the pluckiest charge of all that hard-fought day.” By praising East’s sacrifice, Hughes argues that sacrificing oneself for the preservation of the collective is heroic and should be emulated.

The dominant view of heroism in this time was succinctly put by the British Prime Minister from 1908-1916 and Oxford Balliol man Herbert Asquith. He described it as “the tranquil consciousness of an effortless superiority.” In addition, the Victorian view of heroism is fundamentally embodied by the amateur, someone who plays the sport—but the sport is not their means of making an income; they play for the love of the game as the name denotes. The Modern conception fits very well with the idea of the professional athlete, a person whose life is devoted to the sport; the sport is his trade, it is what he practices in order to get a paycheck. The Victorian conception faded away at the same time as the fall of the amateur hegemony in 1961 when the English Football Association removed the cap on a player’s salary, and professional soccer players could get paid any amount of money for their work.

humanities humanities & social sciences

hurj fall 2012: issue 15 On the other hand, not every great sportsman of the Victorian age exemplifies this view of the heroic. One such exception was the English Cricket player W. G. Grace, who was and still is considered the greatest cricketer of all time. Yet, the one aspect of his game that can be called into question is his sportsmanship. It has been said that Grace “approached cricket as if he were fighting a small war.” His approach to cricket was as intense and focused as that of a soldier going into battle. He is well known to have gotten into fights with referees about calls and act in a generally ungentlemanly manner. This analogy is quite apt to modern athletics. If the reader has ever heard the rhetoric of modern competitive sporting events, the most common metaphor is undoubtedly that the upcoming game, match, etc. is going to be a war and that the participants must prepare themselves for battle. This new emergent heroism, which Grace embodies and which I will dub the Modern hero, appears to have more in common with the Greek than the Victorian.

The Modern view of heroism also dictates that heroes should have strong work ethic, because of a belief engrained in Western postindustrial societies that “all men are created equal.” What separated a hero from a non-hero were work ethic and the will to win. W. G Grace is an outlier and innovator in his time because he was unashamedly zealous about his passion for cricket and the amount of work he put into it.

It is easy to see how this new modern conception of heroism conquered the old Victorian one. In the Victorian conception, the view is that a person’s character will manifest itself in sport. Furthermore, one’s actions in sport are a reflection of one’s character, not one’s skills. This then gives no reason to enhance the skills needed to play the sport at a high level. However, the Modern conception of the heroic states that practice and hard work create a superior athlete, not the person’s character. In this way, it follows that the Modern hero will work harder and become a more accomplished technician of the movements required to excel in a sport than the Victorian hero. This is the case because the Victorian hero does not need practice to be great; their moral superiority is supposed to show itself in heroic acts during the contest.

The pitfall to this new Modern hero is a rejection of the moral superiority of the hero. Quite simply, the modern view treats sport as a craft which is to be mastered, not a game which is to be loved for itself.

One way in which this view has manifested itself is in the soccer player Diego Maradona. He was voted to have the goal of the century in 1999 and was voted player of the century by a FIFA poll in 2000. Other players speak of him in awe of his abilities on the pitch. His career on the field is nothing short of phenomenal. He is an excellent practitioner of the skills requisite to play soccer at the highest levels; nevertheless, he has had many personal issues with drugs, squabbles with FIFA, as well as the Football Federation in Argentina. To some, Maradona’s skills and dedication to work hard to improve were the only requisites for a hero, and therefore, to them, he automatically counts as a hero.

The link to the old Greek notion is clear; what qualifies Maradona as a hero is his superior talent. That is all that is requisite, and he meets those requirements. As such, the modern version of the hero has absorbed legacies from the Victorian age, because in some circles Maradona does not qualify wholly as a hero simply because of his athletic achievements. However, there are some very clear legacies remaining from the ancient Greek notion of Heroism. At the same time, these two are in constant tension because a Greek hero has no semblance of morality, but the Victorian hero must be moral.

I believe that a new concept of the hero is currently emerging.

The epitome of this emergent cultural conception of the heroic is Da-

vid Beckham. David Beckham is an unusual case of heroism; not only because of his personal athletic journey, but also because of his ability to expand beyond athletics into commercial society and be known not even for his athletic achievements but simply for his name and fact.

He is not praised as a hero because of his phenomenal work ethic and his desire to be the best, unlike George St. Pierre of the UFC, Michael Jordan, or Michael Phelps, who are sports heroes in the traditional modern sense. David Beckham’s heroism seems to have transcended the traditionally masculine and competitive, which has never been done before by any other athlete or hero. He is an ambassador for his country, a sex symbol, and an entrepreneur all in their own right, and not because he is a great footballer. Other heroes have also had some of these qualities, like W. G. Grace, but none have done it without constant reference to their heroic achievements as sportsmen.

W. G. Grace will always be heroized as the greatest cricketer; Maradona will be heroized as arguably the greatest footballer. Beckham can singularly be seen as a new emerging post-modern conception of the hero. The borders of what this new conception is to look like and be defined as are hazy and, as of yet, open-ended. All that can really be said about this new trend is that it is happening, and there is a possibility that heroes may begin expanding beyond what at first made them heroic. Additionally, this is only an emerging conception of heroism; it is yet to be seen whether it will become the dominant cultural norm for heroes to expand beyond their realms of original success without constant reference to their previous greatness.

References: Print.

1. Williams, Raymond. Marxism and Literature. Oxford [etc.: Oxford UP, 1992.

2. Homer, and Allen Mandelbaum. The Odyssey of Homer: a New Verse Translation. New York: Bantam, 2003. Print 3 3. Holt, R. (1996) ‘Cricket and Englishness: the Batsman as Hero’, in R. Holt, J.A. Mangan and P. Lanfranchi (eds) European Heroes: Myth Identity, Sport, London: Frank Cass.

4. Hughes, Thomas, and Andrew Sanders. Tom Brown’s Schooldays. New York: Oxford UP, 1999. Print. 101 5. Hughes 105 6. Hughes 121 7. Hughes 121-125 8. Hughes 103 9. Hughes 103 10. Hughes 106 11. Hughes 106 12. Hughes 106 13. Hughes 112 14. Hughes 112 15. Tomlinson, A and Young, C (2007) A Time for Heroes? The Nature of the Heroic in Past and Present, with Particular Reference to Selected Cases from Football (Soccer) In: Thomas Schierl (ed.), Prominenz in den Medien. Zur Genese und Verwertung von Prominenten in Sport, Wirtschaft und Kultur. Herbert von Halem Verlag, Koln: Deutschland, pp. 302-327.

16. Allison, L. (2001) Amateurism in Sport: An Analysis and a Defense, London: Frank Cass 17. Birley, Derek (1999). A Social History of English Cricket. Aurum. Print 111 18. Holt, R. (1999) ‘Champions, Heroes and Celebrities: Sporting Greatness and the British Public’, in J. Huntington-Whiteley (ed) The Book of British Sporting Heroes, London: National Portrait Gallery 54 19. Allison 111 20. ‘Maradona’, directed/produced by Marc de Beaufort, broadcast Monday 13th May 1996, Channel 4 Television (UK).

21. ‘Maradona’, directed/produced by Marc de Beaufort, broadcast Monday 13th May 1996, Channel 4 Television (UK).

22. Whannel, G. (2001) ‘Punishment, Redemption and Celebration in the Popular Press: The case of David Beckham’, in D. Andrews and S. Jackson (eds) Sport Stars: The Cultural Politics of Sporting Celebrity, London: Routledge. 138-146 23. Whannel 149

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hurjhurj spring fall 2012: issue 15 hurj fall2012: 2012:issue issue14 15

Use and Misuse of the Bible in Archaeology: The Israeli-Palestinian Conflict Meagan Young, Class of 2012 Civil Engineering, Archaeology

Ancient and modern civilizations alike can typically be connected to some sort of religion, whether it is the worship of a primeval fertility goddess, Greco-Roman gods or a monotheistic God. Knowledge of past civilizations is owed largely in part to the work of archaeologists worldwide. In recent years, the study of one particular region has been pulled into an infamous international political debate: the archaeology of the modern states of Israel and Palestine. Although scores of past scholars approached the situation with biased conclusions, a few modern scholars are attempting to address the argument from a more neutral perspective in order to explain the history of this important region.

However, the major problems remain in the interpretation of the archeological evidence from this region.

The history of the Israeli-Palestinian conflict began in the 1940s when the United Nations created the Jewish state of Israel following World War II. The British government selected a portion of land on the Levantine Coast to be the new Israeli nation, exclusively for the Jewish people to call their “homeland.” This move was and still is hotly debated by Israeli and Palestinian people as well as scholars of the region. The disputed territory is known by a variety of names in academia, including Israel, Syro-Palestine, the “Holy Land” and the Levantine Coast, among others. The use of a particular name for the region “reflects the preference of the individual authors,” so the selection of one name over another does not imply more than an individual preference.

In this essay, the land in and around the modern nation of Israel will be referred to as the “Levant,” or “Levantine Coast,” as the name is geographical rather than political. Most other terms infer a political or religious tie to the region, whereas a reference to

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the land itself remains immune to the changing of political and religious affiliations over time.

Based on ancient religious scripture, the Levant is connected to the three major world religions: Christianity, Judaism and Islam. People turned to the archaeological evidence in an attempt to settle the debate over the land by confirming or disproving biblical texts and thus the right of the Israeli people to the land in the Levant. While the intentions are good, the analyses of the archaeological finds are skewed by political and religious agendas.

Because of these faulty analyses, archaeologists have begun to ask the question: to what extent should the Bible and other ancient religious texts be used as a factual reference for archaeology? The very inclusion of the Bible in these archaeological studies has not only raised a debate in and of itself but also caused many problems in the interpretations of archeological evidence in the late 20th and 21st century.

The field of biblical archaeology began as an attempt to excavate archaeological “truths” to confirm the stories of the Bible.

From the 1920s through the 1960s, William Foxwell Albright was one of the leading archaeologists of his time who “established biblical archaeology as a legitimate enterprise.” Albright’s influence on the field led to “the deliberate choice of biblical sites for excavation” and sought to confirm the events of the Bible with archaeological evidence. Albright’s work also had political repercussions; various influential individuals in politics and in academia during the 20th century often cited his methodologies and results to justify their nationalist agendas.

After the 1960s, archeologists began to debate whether the Bible was necessary in the interpretation of archeological data in the Levant. Some scholars jump straight to the ancient source of the biblical narrative, which is shrouded in mystery enough as it is. There was a revisionist movement among archaeologists to move away from the Bible and from politics. In the article “Archaeology, Ideology, and the Quest for an ‘Ancient’ or ‘Biblical’ Israel,” William Dever states that “revisionists” in the field are taking a deconstructive stance, arguing that there is no meaning in texts except that which scholars provide. In particular, they argue that the Bible has no intrinsic meaning for the time it describes since it was written hundreds of years later; rather, it should be used as a source indicative of the time it was written. They cite that a major flaw of the early and continued study of biblical archaeology is the assumption that biblical text could be taken as fact, and any subsequent discoveries could be taken to be a part of the religious narrative to benefit the Israeli argument.

Still, Dever and his supporters assert that even these revisionists’ attempts at unbiased interpretations result in stories about the history of Israel “to suit the demands of our modern situation.” Dever focuses on the shortcomings of textual research of other scholars who do not acknowledge specific archaeological evidence like the Bible, and he draws on pieces of archaeological evidence that he believes to have connections to biblical texts.

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From his evidence, Dever contends that there actually is enough Biblical stories. One major source of concrete information for archaeological evidence to confirm facts within the ancient bibli- scholars is material culture. Material culture is typically defined cal narrative, including architecture and various forms of mate- as the physical evidence left behind by a civilization that archaerial culture. Dever suggests that the Tel Dan stele, for instance, ologists recover and analyze. In the case of ancient civilizations, stands as a confirmation for certain parts of the Bible as it is “a material culture is largely pottery. The use of this evidence, historical datum fixing the ‘house of David’ and Israel into the however, can be cause for some concern in reaching fair conbedrock of the Iron Age.” clusions about the history of the Levant. Some politically and Other scholars like Nadia Abu el-Haj take exception to De- religiously charged individuals will fit archaeological discoverver’s findings and believe that this evidence does not necessarily ies into a preconceived mold, here the biblical narrative, which lead to this same conclusion. In her article “Positive Facts of Na- benefits the Israeli side of the Israeli-Palestinian debate. There tionhood,” el-Haj contends that nationalism, archaeology and the is a modern attempt at unbiased archaeological analysis, but reBible are all connected to one fundamental argument: whether cent politics have gone so far as to skew or exaggerate scientific or not the original settlers of Canaan were Israelites. Although facts. Robert Draper brings up an interesting statement by Barshe does not have a conclusive answer to this argument, el-Haj Ilan University archaeology professor Avraham Faust who states notes that no one in the past has questioned the assumption that that “… [a]rchaeology is a very convenient tool for creating nathe original Canaanites were Jews. She believes that those who tional identities.” Israel is different in a way in that “[i]ts natake the assumption for granted might be susceptible to reckless tional identity came well before any digging. What’s dug up can interpretation of historical evidence. In particular, she takes issue only confirm that identity…or not.” The national identity is the with Albright’s identification of a certain type of pottery as “Isra- charge for determining the origins of the pottery, and therefore elite” which sets a precedent for a circular argument; any subse- creates the motive for the biased characterization of significant quent pottery found within the region was then used to mark the archaeological evidence as biblical in nature. presence of “Israelites.” From pointing out this circular reasonUsing both archeological and biblical evidence raises many ing, el-Haj explains that difficulties still exist in trying to connect problems of interpretation. For instance, some scholars attrithe historical and textual references of the Israelite people in the bute a specific type of pottery found at certain sites to be from Bible to the archaeological evidence the Israelites, a group of people from in excavations and she makes the case biblical narratives, but this classififor a cautious interpretation of archecation raises concerns over preconDespite the problems of subjectivity, ological data. ceived ideas about ancient people In fact, el-Haj argues that using through biblical text and underlying most archeologists today believe that the Bible is a biased approach since nationalist agendas. Material culthe Bible and archeological evidence this system of analysis assumes that ture has been used as a supplement the evidence in the Bible is true, and to historical context in tours of sites should be analyzed together. thus shies away from using it as a and excavations to support the presprominent source for analysis. The ence of Israelites in the region. In the use of historical or biblical texts tends case of a presentation at the site of to present more bias since these writings are subject to the selec- Hazor, “there was never any doubt that the Israelites did contive bias of the author, who can modify and rewrite records as he quer and settle Hazor and the Upper Galilee, that a particular chooses to suit his political interests. In the case of the Israeli- Iron I pottery assemblage is Israelite pottery, [and] that destrucPalestinian conflict, el-Haj and a few other archeologists believe tion levels are evidence of Israelite conquest.” The pottery in that extremely limited use of biblical texts will yield the most ob- question is known as “Albright’s collared-rim type.” This type jective result. of pottery has been found at the site called “Izbet Sartah,” just Despite the problems of subjectivity, most archeologists to- north of Gezer. According to Dever, the material culture at this day believe that the Bible and archeological evidence should be farming site varied drastically from finds at Gezer. This pottery analyzed together. There are two possible reasons for this prac- has been stated to belong to the “Israelites,” and was done so tice. First, some of these scholars may genuinely see the Bible as without any confirmation aside from biblical texts. It matched a valid historical document and in their research, they carefully what the archaeologists were looking for at the time and fit into take into account the context in which it was written. They under- a convenient narrative for a new nation of Israeli people. While stand that the Bible was written hundreds of years after the events the Bible might not be wrong, Dever’s neglect to substantiate his it documented and that therefore, the Bible was more indicative claim with other sources allowed archeologists to give physical of the time at which it was written than the time it narrates. Other confirmation to the texts and thus the existence of the Israelite archeologists incorporate the Bible as a source possibly because people, which unjustifiably causes bias and sways the debate in political and nationalistic motivations encourage them to use the the favor of the Israelis.

Bible as a justification for their existing preconceptions of the In fact, the appearance of a new type of pottery in the arLevant. In both cases, present-day scholars encounter many re- chaeological record does not necessarily mean a new group of search problems in their archeological interpretations. people or chronology can be associated with it and thus raises the In their fieldwork in the Levant, most modern archeolo- question of how to define culture. Culture varies from place to gists incorporate non-biblical evidence as an attempt to validate place and even between groups of people. Since groups of people

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humanities & social sciences are dynamic, ideas and styles flow in and out of cultures. Just as these various ideas are free to move between cultures, so are different types of pottery. Now apply this concept to ancient civilizations. Consider modern Tupperware. The idea was originally from an American man, China then produced the containers on a grander, more global scale, and people from various countries all over the world now use them. However, Tupperware is not indicative of one particular culture. In the same way, pottery does not necessarily indicate a specific group of people– for the sake of this discussion, the appearance of Israelites in the chronological record. It can suggest a new group or culture, but in this case the characterization of the pottery as “Israelite” is misleading.

A larger issue develops as a result of the practice of using both the Bible and the material culture as sources of archaeological analysis: are the modern Israeli people really direct descendants of the ancient Israelites? The debate is centered on which group of people first settled the land thousands of years ago. This, in turn, is based on the assumption that the modern people are the same culture as their supposedly ancient counterparts. The type of civilization scholars are recognizing was probably not well established, at least according to the archaeological record thus far. Modern Egyptians are by no means a part of the same culture as ancient Egyptians, just as modern Americans are not a part of the same culture as their ancient counterparts. By extension, modern Israelis are not the same as their supposed ancestors of the Levant. The connection between modern people and the ancients described in the Bible complicate political and nationalist matters much further than they should.

If the Israelis were to focus on more recent ancient history during the time of the Roman Empire, their argument may have a more solid foundation with respect to who initially inhabited the land. Historical evidence confirms the expulsion of the Jewish people from the land around the second century C.E. Based on this fact, the Israeli people could refute that they indeed inhabited the land before the spread of Islamic peoples in the eighth cen-

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hurj fall 2012: issue 15 tury C.E. However, complete expulsion of the modern Palestinian people would be no less than hypocritical as they have inhabited the disputed land for more than the past thousand years. While it was not right to have dispersed the Israelite people in the first place, is it any more right to expel the Islamic people who have lived there for the last fifteen hundred years?

According to many archeologists today, the Bible is a necessity when studying the history of the ancient Near East. However, the Bible must be viewed as a compilation of many years of stories and cultural influences not only from the time which it describes but also the time in which it was written. Science requires the analysis of facts in an objective manner. In this case, religion is tied into a political debate, which then draws upon science to pick sides. With the use of the Bible in light of interpretation of archeological evidence, complications inevitably occur and modern religious connections make it difficult for the Israelis and Palestinians to objectively analyze the biblical texts for factual information. Nationalism, politics and religion play large roles in creating biased interpretations of archaeological data. While there may indeed be some facts hidden within the ancient narratives of the Bible, the most objective conclusions might be reached only when the Bible is left out of the Israeli-Palestinian debate altogether.

References

1. Ben-Tor, Amnon.

“The Archaeology of Ancient Israel.” (1992). 2 2, 3 Meyers, Eric M. “Biblical Archaeology,” in The Oxford Encyclopedia of Archaeology in the Near East, Volume 1. New York: Oxford University Press, 1997. 315 4. Dever, William G. “Ideology and the Quest for an ‘Ancient’ or ‘Biblical’ Israel,” in Near Eastern Archaeology, Volume 61, Number 1 (March 1998). 40 5. Dever 42 6. Draper, Robert. “Kings of Controversy,” in National Geographic, (December 2010). 83 7. Draper 83-84 8. el-Haj, Nadia Abu. Facts on the Ground: Archaeological Practice and Territorial Self-Fashioning in Israeli Society. Chicago: The Univesity of Chicago Press, 2011. Chapter 5, “Positive Facts of Nationhood.” 127 9. el-Haj 127 10. el-Haj 115 11. Dever 47 12. el-Haj 120

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The Rise and Fall of Legend: Geoffrey of Monmouth’s Historia regum Brittaniae in Lewis E 247 Amy Conwell, Class of 2012 Writing Seminars, Classics

Codex* “Lewis E 247,” held in the free library of Philadelphia’s Special Collections, contains two twelfth century works: Geoffrey of Monmouth’s Historia regum Britanniae (History of the Kings of Britain) and William of Malmesbury’s Gesta regum Anglorum (Deeds of the English Kings). These pseudohistorical texts chronicle England’s history in different ways. Both texts are in Latin, written in narrow, angular, Gothic letters, and are incomplete: The Historia regum Britanniae (HRB) (ff. 1r-25v) breaks off in the middle of chapter xvi of Book XII, ending with the line, “…facile ill[e] subdenda[m] si i[n] illam…” The Gesta (ff. 26r-55v) begins, “D[omi]no ven[er]abili et famoso comiti filio regis rodberto…” and contains only its first three books.

Geoffrey of Monmouth (c.1100-1155 CE) completed his Historia regum Britanniae in 1138, but continued to release recensions (revised editions) until about 1147. The HRB and the King Arthur Legend that it popularized “swept through Britain and northern France…” in the 12th century. It grew to such popularity that over 215 manuscripts (MSS) survive today, of which a majority were written in the 12th century, like the Lewis E 247 HRB. Monmouth’s apostolic network and the text’s political utility begot the HRB’s tour de force popularity. Monmouth’s ordination as a monk (arguably Benedictine) and consecration in 1151 as Bishop of St Asaphs in Wales, demonstrate the Anglican Church’s continued support of his work. HRB MSS had? a strong presence among the scriptoria of Northern England, in the 15th century at the Cistercian houses of “Furness, Whalley, and Meaux,” the 14th century at the Augustinian houses of “York and Bridlington,” the far North at “Tynemouth” and “perhaps Hulne.” Monmouth also enjoyed the patronage of the

Anglo-Norman crown; his early HRBs are arguably political motivated, propagandizing the need for unity of the English crown and establishing England’s precedent for authority in and allegiance from continental nations such as France.

The Lewis E 247 MS, like many contemporaneous HRB MSS, was most likely financed, copied, later illuminated, and indefinitely housed in a monastery. The Lewis E 247 HRB was produced between 1165 and 1200 in the North of England on late 12th century vellum support. It was bound with Malmesbury’s Gesta in the 18th century, most likely in or around 1732, , with brown calf over wooden boards: Four initial and four final paper fly-leaves precede and follow the two MSS. “Galfridi Historia M.S.” is stamped in gold on the spine, and the text block edges are painted red.

The Gesta seems to have been considered the lesser of the two texts in this codex: not only is its title omitted from the backstrip of the codex (Figure 1), but it is also physically the secondary manuscript (MS).

Figure 1

Unlike many HRB MSS, the Lewis E 247 contains no book divisions or rubrication. The extant manuscript comprises 25 folios (ff), leaves of parchment numbered sequentially as if the text was complete. However, as some ff are missing from the codex, including the last leaf and the third quire, either the ff were numbered prior to binding (and the missing ff were lost, or deliberately excluded), or the binder was well informed as to the original content of the codex.

Palaeographic analysis of the MS reveals two 12th century hands.

The first hand (ff 1v-16r) runs Figure 2 56 to 58 lines per page. The second hand (ff 17v-25v) runs 50 to 56 lines per page. The first hand is so similar to the script of “Facsimile 180” (Figure 2) found in palaeographer Sir E. M. Thompson’s An Introduction to Greek and Latin Paleography that noted Arthurian scholar Acton Griscom posits they may be

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humanities & social sciences science & engineering reports the work of the same scribe. Thompson comments on 180, “In Germany a less elegant style was followed, as will be seen from the specimen here given from a MS of the Commentary of Petrus Lombardus on the Psalms… written for Hartwig, Archbishop of Bremen, in A.D. 1166.” Despite strikingly similarities in the two scripts and the MSS’ close production dates, Thompson’s scribe was problematically located in Germany, and Griscom posits that the Lewis E 247 HRB was copied in Northern England.

The HRB was widely circulated, recopied, adapted, compiled, edited, and translated. Three variations of dedications (to Archdeacon Walter of Oxford, RobFigure 3 ert, earl of Gloucester, and Waleran, count of Meulan) occur in these various manuscripts, implying that Monmouth composed or approved of more than one version of the whole work in the period between the chronicle’s initial release in 1138 and his final revision in 1147. Lewis E 247 is dedicated to Walter and Robert, dux Claudiocestrie (Figure 3: Walter at top; Robert at bottom).

Although historical precedent suggests the Lewis E 247’s HRB MS was cloistered away during the period between its production and binding, the physical condition of the HRB offers little corroborating evidence.

Figure 4 Initial capital letters were illuminated post-production; their ornate filigree most likely dates the illumination to the 13th century at which time “delicate diaperings” and foliage typically surrounded initial letters.

This is demonstrated in the first illumination in Lewis E 247 (Figure 4).

The color of these ornamental letters alternate between red, blue, and irregularly, green. They begin the first word of each paragraph and mark paragraph divisions. Several mistakes indicate the MS was subject to a sloppy illuminator: iniFigure 5 tials are omitted and added at a later date in brown ink (Figure 5), and some letters are incorrect (i.e. folio 3, column b).

Medieval scholars were interactive readers annotating texts as they read; their marginalia included individual reflection, edits, and summary. In accordance

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fall2012: 2012:issue issue14 15 hurjhurj spring with this custom, marginalia found in the Lewis E 247 elucidate or summarize. Marginalia were written in faded brown ink by four different hands, one contemporary to the writing of the text and three dating to the 15th and 16th centuries. On the first page before the text begins, the cursive inscription “historia galfridi” testifies to the presences of these commentators. Griscom calls this script “a contemporary cursive hand,” thus presumably dating it to the late 12th century, whereas J. Crick dates it to the 14th century. It is likely that the Lewis E 247 MS commentators and readers were monks.

The Lewis E 247 codex measures 10 1/2 by 7 1/8 inches. Although the entirety of the HRB text was maintained in the binding process, the lower margins were cropped, and marginalia were wantonly cut out Figure 6 and/or sewn so close together (Figure 6) as to render them almost indecipherable.

This destruction of marginalia corroborates the palaeographic dating of the commentators to the pre-binding period.

The recto (hair side) of the first fly-leaf bears the signature “Alex(r) Boswell Auchinleck” and is dated 1732 (Figure 7).

Both Boswell and Auchinleck are written in the same ink and thus presumably at the same time.

As fly-leaves were added in during the binding process to frame the manuscripts, the Lewis E 247 codex was probably procured and bound if not by Auchinleck’s decree then at least at his behest. It may have been intended as a witty celebration of Alexander Boswell’s new lordship or it may have simply appeased his scholarly incliFigure 7

nations. A book lover, later in life Auchinleck rescued the family’s “Auchinleck Manuscript” from a local professor just as it was about to be destroyed. Margaret Montgomerie, Auchinleck’s daughter-inlaw, compiled a catalog of his library which testified to his status as a “fine classical scholar.”

The care taken with the codex’s binding, gold stamped title, and red page edges points to a moneyed financer, such as Lord Auchinleck. The collecting preferences of later owners of the MS further attest to the value of the binding: Booksellers J. & J Leighton took a particular interest in old and rare bindings as demonstrated at the bottom of an advertisement found in an 1894 booksellers directory (Figure 8). Additionally, William E. Moss is known for his collection of “books and papers on bookbinding” donated posthumously to the Bodleian Library.

The codex was lucky in its owners: book lovers and academics, they took proper measures to ensure its preservation. Lewis E 247 was housed in private libraries and handled with respect (evi-

hurj fall 2012: issue 15 denced in part by the lack of marginalia in the post-binding period). Lewis E 247’s binding also aided its longevity, especially considering its frequent travel from owner to owner in the 20th century; however, the codex did not escape unscathed: seven illuminated letters were later cut out between ff 50 and 56, and the stubs of two quires indicate that several preliminary vellum leaves, as well as five other leaves throughout the HRB MS, were cut out. At least eight leaves were also removed from the Gesta. One leaf of the codex resides at the Columbia University Library, where it is cataloged under the shelfmark “Plimpton MS 267.” After graduating from Columbia University in 1913, Acton Griscom donated texts to his alma mater’s collection; it is likely that he donated the Lewis E 247 leaf as a thank you for Columbia University Library, aid in his HRB MS research.

Several inscriptions mark the front inner cover and initial fly-leaves of Lewis E 247. “Geoffrey of Monmouth & William of Malmesbury first 3 books 1180-1200” is written in pencil on the inside front cover.

“139” is written in pencil in the upper left-hand corner and “7452” in the bottom left-hand corner of the inside front cover. “Alexr Boswell Auchinleck 1732” is written in brown ink on the recto of the first flyleaf and “Galfridi Historia MS” is written below. “Lear & Cordelia fol.

7 recto Cymbeline fol. 11 verso” is written in pencil on the recto of the first fly-leaf. The signature “Acton Griscom” is written in ink on the recto of the first fly-leaf. Lastly, a collation in pencil (Figure 9) is listed on the recto Figure 9 of the second fly leaf. These inscriptions indicate ownership ex libris style (i.e.

Auchinleck; Griscom), delineate the contents of the codex (i.e. GofM & WofM first 3; GH MS; L&C fol.7; the collation), and possibly denote the codex’s placement in its owners’ collections (i.e. 139; 7452).

From 1732 to 2011 the Lewis E 247 codex survived in the libraries of its various owners. It first traveled from the residence of Alexander Auchinleck in Edinburgh, Scotland to the new Auchinleck house built in East Ayrshire, Scotland. Lewis E 247 might have been bound for Auchinleck by Auchinleck, for Auchinleck by another individual, or completely independent of Auchinleck. In this latter instance, any postulation would be mere guesswork. This uncertainty of acquisition prevents conclusive deductions as to the binding’s financial backing, location, and purpose. Still, it is at least clear that the ff comprising Lewis E 247 traveled from their original production site in Northern England to Edinburgh, Scotland, and Figure 8

humanities & social sciences then to East Ayr, Scotland (Figure 10), where the Lewis E 247 codex was bound.

Second-hand booksellers Messrs. J. and J. Leighton bought Lewis E 247 in 1907, transported it to their London shop on 40 Brewerst., Golden-sq., and listed it as “no. 107” in the Leighton 1912 catalog.

The bookstore, established in 1798, dealt in “Antiquarian, standard, Rare, and curious” texts. Ac- Figure 10 cording to James Clegg’s early 20th century directory of second-hand bookstores, historical treasures were often to be found in country estates— it was common practice for booksellers at that time to seek texts from estates like that of the Auchinlecks. The Clegg directory also explicates the monetary value of an autographed text; although Clegg emphasizes the great value of authorial autographs, it is noted that any autograph adds value to the text. Thus, there was a monetary motive for the Auchinlecks to sell their codex.

Lt.-Col. William E. Moss (1875-1973), an English rare book collector, bought the codex from J. & J. Leighton sometime between their 1912 listing of the text and his donation of it to Acton Griscomin 1928. While in Moss’ possession, Lewis E 247 resided in the renowned and valuable library in his Manor house at Sonning-on-Thames, Berks, England. There is no record of the date Griscom procured the codex from Moss. Griscom notes “it reached me too late to be collated with the three selected for the text” (the text being his 1929 critical edition of the HRB), so he must have received the codex close to his work’s publication date.

It is unclear whether Griscom personally requested Lewis E 247 from Moss, or if he sent out a general probe as to the availability of any HRB MSS. Griscom labeled the codex “E.17” and studied it from his library in Highpoint, New Jersey; the codex had to be exported from Great Britain to the United States of America to reach him. According to early 20th century exportation laws, books over 20 years old could pass from Great Britain into the USA duty free. However, all exported texts still had to file three invoices, “stating the titles of the Books and the years of publications… the prices of all the Books that are duty free… These invoices must be taken to the United States’ Consulate, and an affidavit made by the principal (or duty authorized manager), that the said invoices contain full and true particulars of the entire consignment… The Consul’s fee… is 13s [$00.60 in 1928; $7.60 in 2011].

Consignments under 2 pounds value [$9.60 in 1928; $121.63 in 2011] need not be sworn before the Consul, but must have the total value of Books dutiable and Books duty free declared…” “The tax on …autographs… is raised from 25 percent to 35 percent.” Lewis E 247 should have been declared via three invoices, and Auchinleck’s autograph would have been taxable by 35 percent. It is unknown whether the Moss-Griscom exchange went through the proper channels.

Griscom gave Lewis E 247 to Samuel Frederick Houston (1866-

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science & engineering reports humanities & social social sciences sciences humanities & 1952), an associate of Griscom’s father with historical interests (vice president of the National Episcopal Church Historical Society; member of the Historical Society of Pennsylvania) on May 27th, 1946.

Griscom’s father, Clement A. Griscom (1866-1952) and Houston both graduated from the University of Pennsylvania in 1887 with a Ph.B. The codex would have been held at Houston’s home, “Druim Moir” on Willow Grove Ave., Chestnut Hill, PA where he lived with his mother, two sons, daughter, and second wife. Houston’s daughter, Mrs. L.M.C. Smith (1910-1987), known for her work as a conservationist and for her philanthropy (she served two terms on the Historical Commission of Pennsylvania) came into possession of the codex, likely in 1952 as part of her inheritance. She donated the Lewis E 247 in February of 1977 to the extensive medieval manuscript collection of the Free Library of Philadelphia where it still resides today.

Aaron Thompson had first translated Geoffrey of Monmouth’s Historia regum Brittaniae into English in 1718 (Figure 11) With HRB’s release as an English language text, its readership spread beyond the educated confines of the court and cloisters. HRB’s accessible English translation testified to the Figure 11 triumph of the national language over Latin, the standard language of literature. The translation enhanced HRB’s already nationalistic stance, renewed popular interest in the text, and likely attracted the attention of the scholarly Auchinleck.

Similarly, J. A. Giles’ 1848 updated translation renewed popular interest in the HRB in the late 19th century (prompting the Messrs. J. J. Leighton to seek out Lewis E 247). This interest instigated the massive accumulation of Historia regum Brittaniae scholarship in the early 20th century, including the seminal work of Acton Griscom, and increased the presence of the King Arthur legend in literature (i.e. Tennyson’s “Idylls of the King,” T.S. Eliot’s “The Wasteland”) and eventually in film.

References: * Codex: an ancient manuscript text in book form [1] A. Griscom, ed., The Historia Regum Britannia of Geoffrey of Monmouth (London and New York: 1929), 378 [2] Free Library of Philadelphia, Rare Books Department. “Manuscript Level: Codices, Lewis E 247.” (Curatorial Record) [3] Michael D. Reeve, “The Transmission of the Historia Regum Britanniae,” in The Journal of Medieval Latin, 1, (Belgium:1991), 73 [4] Julia C. Crick, The Historia Regum Britannie of Geoffrey of Monmouth, IV. Dissemination and Reception in the later Middle Ages, (Great Britain: 1991), 192- 214 [5] Edwin Burton, “Geoffrey of Monmouth.” The Catholic Encyclopedia. Vol. 6, (New York: Robert Appleton Company). http://www.newadvent.org/cathen/06428a.htm.

[6] Alan Lupack, “The Oxford Guide to Arthurian Literature and Legend,” (Oxford: Oxford University Press, 2005), 24.

[7] A. Griscom 38 [8]Lewis E 247 Historia MS, Free Library of Philadelphia, Rare Books Department.

(Personal photograph, 2011) [9] Julia C. Crick, The Historia regum Britannie of Geoffrey of Monmouth, col. 3, A Summary Catalogue of the Manuscripts (Cambridge: 1989), 297.

[10] A. Griscom, ed., The Historia Regum Britannia, 38 [11] Sir. E. M. Thompson, Greek and Latin Palaeography, (Oxford: Clarendon Press, 1912), 442.

[12] Sir. E. M. Thompson, Greek and Latin Palaeography, 444.

[13] Michael D. Reeve, “The Transmission of the Historia Regum Britanniae,” 73.

[14] Lewis E 247 Historia MS [15] Medieval-Spell, “Illuminated Letters.” http://www.medieval-spell.com/Illuminat-

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hurjhurj spring fall 2012: issue 14 15 ed-Letters.html.

[16] Lewis E 247 Historia MS [17] A. Griscom, ed., The Historia Regum Britannia, 39.

[18] Lewis E 247 Historia MS. [19] A. Griscom, ed., The Historia Regum Britannia, 39 [20] Julia C. Crick, The Historia regum Britannie of Geoffrey of Monmouth, col. 3, 297.

[21] Lewis E 247 Historia MS. [22] Free Library of Philadelphia, Rare Books Department. “Manuscript Level: Codices.”

[23] Lewis E 247 Historia MS [24] A. Griscom, ed., The Historia Regum Britannia, 38.

[25] Alan Lupack, “The Oxford Guide to Arthurian Literature and Legend,” 24.

[26] Irma S. Lustig, “Boswell, Alexander, Lord Auchinleck (1707–1782).” Oxford Dictionary of National Biography, (Oxford University Press, 2004), online ed., May 2005. http://www.oxforddnb.com/view/article/2946.

[27] Irma S. Lustig, “Boswell, Alexander, Lord Auchinleck (1707–1782).” Oxford Dictionary of National Biography, (Oxford University Press, 2004), online ed., May 2005. http://www.oxforddnb.com/view/article/2946.

[28] James Clegg, The International Directory of Booksellers and Bibliophile’s Manual: Including Lists of the Public Libraries of the World, Publishers, Book Collectors, Literary and Scientific Societies, Universities and Colleges; Also a Select Bibliography of Bibliographies (Rochdale: 1894), VII. 22.

[29] “Colonel William E. Moss.” Bodleian Library University of Oxford. Rare Books Provenance. http://www.bodley.ox.ac.uk/csb/rbdkm.htm [30] Seymour De Ricci, Census of Medieval and Renaissance Manuscripts, 1161.

[31] Consuelo W. Dutschke, “Rare Book and Manuscript Library.” (Letter to Ms. Cornelia King. 15 Dec. 1997) Rare Book Department, Free Library of Philadelphia, Philadelphia, Pennsylvania [32] Free Library of Philadelphia, Rare Books Department. “Manuscript Level: Codices.”

[33] Trustees Meeting,” Columbia Alumni News 10.1 (New York: 1918), 274.

University of Pennsylvania Archives and Records Center. “Members of the Class of 1887, University of Pennsylvania University Archives.” http://www.archives.upenn.edu/ histy/features/1800s/1887/studt_list.html [34] Robert Sommerville, “Some Remarks on the Early History of Columbia University’s Collections of Medieval and Renaissance Manuscripts,” in Medieval and Renaissance Manuscripts at Columbia University (New York), 4.

[35] Free Library of Philadelphia, Rare Books Department. “Manuscript Level: Codices.”

[36] Lewis E 247 Historia MS. [37] “The Ancient Monuments and Archaeological Areas Act 1979.” (Scotland: County of Ayr, 1993). (Map) [38] James Clegg, The International Directory of Booksellers and Bibliophile’s Manual: Including Lists of the Public Libraries of the World, Publishers, Book Collectors, Literary and Scientific Societies, Universities and Colleges; Also a Select Bibliography of Bibliographies (Rochdale: 1894). 22 [39] James Clegg, The International Directory of Booksellers, 297 [40] James Clegg, The International Directory of Booksellers, 295-98 [41] James Clegg, The International Directory of Booksellers, 330.

[42] “Colonel William E. Moss.” Bodleian Library University of Oxford. Rare Books Provenance. http://www.bodley.ox.ac.uk/csb/rbdkm.htm.

[43] A. Griscom, ed., The Historia Regum Britannia, 37.

[44] James Clegg, The International Directory of Booksellers, 98.

[45] DollarTimes. “Inflation Calculator: The Changing Value of the Dollar.” http://www.dollartimes.com/calculators/inflation.htm.

[46] James Clegg, The International Directory of Booksellers, 98.

[47] DollarTimes. “Inflation Calculator: The Changing Value of the Dollar.” http://www.dollartimes.com/calculators/inflation.htm.

[48] James Clegg, The International Directory of Booksellers, 97 [49] Seymour De Ricci, with the assistance of W. J. Wilson, Census of Medieval and Renaissance Manuscripts in the United States and Canada, vol. 2 (New York: 1935-40), 1161, no 6.

[50] University of Pennsylvania Archives and Records Center. “Members of the Class of 1887, University of Pennsylvania University Archives.” http://www.archives.upenn.edu/histy/features/1800s/1887/studt_list.html.

[51] University of Pennsylvania Archives and Records Center. “PENN BIOGRAPHIES: Samuel Frederic Houston (1866 - 1952).” http://www.archives.upenn.edu/people/1800s/ houston_saml_fred.html [52] Freeport Historical Society. “Eleanor Houston and Lawrence M.C. Smith.” http:// freeporthistoricalsociety.org/freeport-history/eleanor-houston-and-lawrence-mcsmith [53] De Ricci, Seymour, Census of Medieval and Renaissance Manuscripts, 1161.

[54] “Aaron Thompson’s Translation of Geoffrey of Monmouth’s Historia regum Britannie.” http://faculty.arts.ubc.ca/sechard/geofftom.htm

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science & engineering reports

Phenotypic Effects of Lignin Reduction in Model Plant Species Scarlett Hao1, Lina Gallego-Giraldo2 1 Department of Biology, Johns Hopkins University, MD 2 Plant Biology Division, Noble Foundation, The Samuel Roberts Noble Foundation Abstact The secondary cell wall polymer lignin is key to structural support and physical defense in plants, but remains a persistent obstacle in biofuel production and forage quality. Recent research on reducing lignin has focused on manipulating expression of genes in the lignin biosynthesis pathway. While there has been success in lignin reduction with this method, there are also adverse consequences such as dwarfism and vasculature collapse. This review reports the current findings on the phenotypic effects on modifying expression of some genes encoding lignin biosynthetic enzymes with a focus on two model species–Arabidopsis and N. benthamiana (tobacco)– and on two industrially prevalent species–alfalfa and poplar.

Figure 1. Monolignol biosynthesis pathway as currently understood. The enzyme names are next to arrows symbolizing a reaction. Gray color indicates monolignol units not predominant in wildtype.1

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science & engineering reports Introduction Lignin is a highly abundant plant polymer, second only to cellulose. Found in secondary cell wall and woody tissues, lignin’s complexity as a heterogeneous polymer gives structural strength, enabling plants to resist gravity and grow to great heights. Other functions include serving as a primary barrier to pathogen attack and making vascular tissue impermeable to water to expedite water transport. The polymer is a mosaic of different subunits–monolignols–all derived from the amino acid phenylalanine. The three main monolignols are p-coumaryl alcohol, coniferyl alcohol, and sinapyl alcohol, abbreviated respectively as H, G, and S subunits.

The lignin biosynthetic pathway is a metabolic grid. While each monolignol is made in a step-by-step set of reactions, little is known about lignin polymerization. Plants can use different combinations of monolignols, depending on plant tissue and developmental stage, to synthesize the final polymer, enabling the plant to adapt its metabolism to different environments. Evidence of this change in lignin composition in response to the environment can be seen in monocots that have increased lignin with higher temperatures2 or Populus plants with low S/G ratios when growing under high nitrogen conditions.3 In terms of gene manipulation, evidence of a change in composition can be seen in antisense knockdown of the enzyme CAD in tobacco, where the plants had normal quantities of lignin but with higher levels of coniferaldehyde.4 The plasticity of the lignin polymer is a testament to the molecule’s importance to plants.

Naturally, lignin is an obstacle to industries that utilize plant biomass. For the bioethanol and forage agriculture industries that utilize only the cellulosic fibers, the lignin matrix obstinately protects the cellulose by blocking and absorbing hydrolytic enzymes, and even bits of degraded lignin can interfere with later steps in the industrial processes.5 Bioethanol production must use costly and polluting acid-pretreatment steps in order to remove the lignin and access the cellulose, making the process difficult to commercialize and not economically feasible in comparison to current more popular sources of gasoline.6,7 Reducing lignin in forage plants has also been shown to improve digestibility, increasing the quality and efficiency of feeding in animal husbandry.8,9,10 In response, a great deal of research is now focused on genetically removing lignin from plants in order to negate the need for these expensive pre-treatments and improve the efficiency of these industries. An example of this type of study can be seen in Chen and Dixon’s work. An analysis of saccharification efficiency in antisense down-regulation of six lignin pathway genes in alfalfa revealed C3H, HCT, and C4H as the best candidates for improved sugar releases from the cell wall, which directly reduces the need of pre-treatment in biomass processing.11 However, while the biosynthesis pathway is easily interrupted

by RNA interference or antisense suppression, the undesired side effects of lignin-reduced mutants are not so easily avoided. The most common characteristic is dwarfism,11,12,13,14 as commonly seen with down-regulated HCT. Severe lignin reduction can even lead to male sterility.15 There seems to be no simple cause-and-effect explanation behind this phenomenon: there is much variation in the effects on lignin content and composition depending on the gene that has been targeted for down- or up-regulation. For instance, knocking out different enzymes or combination of enzymes produce varying degrees of growth reduction, and sometimes even no growth reduction at all.

It is further complicated by the fact that specific knockdowns have a myriad of effects depending on the plant species studied. A study of

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hurj fall 2012: issue 15 the recent research on lignin reduction via three popular enzyme targets for down-regulations–one initiatory, one intermediate, and one endpoint enzyme of the pathway–may indicate where future practical application has the most potential.

Effector of Lignin Reduction on Plant Phenotype HCT: The enzyme hydroxycinnamoyl-CoA shikimate/quinate hydroxycinnamoyltransferase (HCT) initiates a branch point in the pathway to begin G and S subunit synthesis. HCT is encoded by one gene in both Arabidopsis and N. Benthamiana.16,17 It has been shown in alfalfa and Arabidopsis that down-regulated HCT results in severe dwarfism, darker-colored green leaves10,18 and increased branching in the inflorescence stem.11 In addition, the alfalfa antisense HCT has less than 50% of the lignin content in wild-type, and develops very small and highly distorted vascular cells.11,19 Silencing HCT in N. Benthamiana also produces a dwarf, but with only 15% lignin content decrease.13 This, however, may be due to the method of virus induction to silence the gene. Virus-induced silencing cannot affect lignin deposited prior to introducing the virus20 and is also not uniform throughout the plant.13

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CAD: Cinnamyl alcohol dehydrogenase (CAD) catalyzes the final reaction in the synthesis of all the canonical monolignols,15 and is encoded by nine genes in Arabidopsis.17 Downregulation of CAD produces the irx4-“irregular xylem”-phenotype, where the wild-type well-rounded xylem vessels instead have crinkled or folded-in walls; however, this mutant is not dwarf.6 A mutant in either the CADc or CADd isozyme or even a double mutant of both CADc and CADd in Arabidopsis shows normal size but with stem lignin content reduced by 40%.26,27

Growth Restoration in Lignin-Downregulated Plants HCT: Is it possible to reverse the dwarfism of HCT down-regulation?

There has been recent work in lignin-reduced alfalfa plants which report an increase of salicylic acid (SA), jasmonic acid, hydrogen peroxide–all defense pathway molecules–and increased expression of several defense-related genes. These indicate a constitutive defensive response active in the down-regulated plants as compared to wild-type plants.28 These features could be linked to plant growth defects seen in lignin down-regulation. The dwarfism associated with lignin downregulation cannot be rescued with simple application of growth hormones (Figure 4), and the activity of these defense genes may explain why. SA negatively affects plant responses to plant growth hormones like gibberellins, rendering HCT down-regulated plants insensitive to gibberellins.28 Evidence supporting this theory came about recently in a study showing that combining HCT down-regulation with SA down-regulation restored gibberellin-induced growth.29 This represents a new possibility of utilizing down-regulated HCT in practical application.

CCR: CCR mutants also accumulate SA but not to the degree with HCT down-regulation. Unlike HCT mutants, they are sensitive to gibberellin treatment and partially recover growth with little change in the reduced lignin content. Down-regulated CCR Arabidopsis shows less dwarfism than their HCT down-regulated counterparts [unpublished work]. These observations indicate a CCR mutant is

Figure 3. Comparison of Control (CT) and antisense CCR (B3) in tobacco.22

a sort of intermediate between wild-type and the extreme dwarfism of HCT mutants, so CCR down-regulation may have potential for practical application.

CAD: For tobacco and alfalfa, although the lignin content is unchanged with CAD downregulation, it has been shown to have increased digestibility.6 Antisense CAD in poplar has no change in the lignin amount or S/G ratio, but is characterized by red xylem.30 There already exists an example of practical application of downregulated CAD. A variant of sorghum x sudangrass hybrid was developed with the bmr phenotype–“brown midrib” which describes the characteristic brown color in the middle of the leaf. bmr

Figure 2. Phenotype of RNA silenced HCT in Arabidopsis.13

CCR: Cinnamoyl-CoA reductase (CCR) is the first enzyme whose catalysis commits the molecule to monolignol biosynthesis.21,22 It is encoded by two definitive genes (CCR1 and CCR2) and five CCRlike genes in Arabidopsis.17 Retrotransposon insertion in CCR1 in Medicago has a greater impact than in CCR2. The insertion lines ccr1-1 and ccr1-2 homozygotes produce dwarf plants that do not survive past flowering, but heterozygotes appear normal.23 These mutants also show a significant decrease in S lignin as compared to G lignin, altering the S/G ratio.23 The CCR2 transposon lines show more decrease in G lignin as compared to S lignin, but no visible phenotype.23 For alfalfa, CCR down-regulation results in reduced biomass, 30% reduction in lignin content in mature stem internodes, and an increase in S/G ratio.24 In addition, down-regulation of CCR dramatically reduces lignin levels in poplar25 and tobacco22 and is detrimental to growth (Figure 3).

Figure 4. Comparison of wild-type and HCT knockdown responses to gibberellin (GA) treatment in Arabidopsis.29

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Figure 5. 3,3’-Diaminobenzidine (DAB) stain-revealed H¬2O2 in vasculature of 8-wk-old leaves of uninfected, HCT-downregulated M. sativa compared with control.27

originates from decreased CAD activity. This mutant does have decreased lignin content, and it has been shown that it has both increased digestibility31,32 and increased palatability.6 Compared to CCR and HCT, CAD is clearly an enzyme target for downregulation that has been and can still be developed into usable, more efficient variants for multiple industries.

Is Lignin Modification Worth Pursuing?

In summary, lignin modification is a well-researched approach for reducing cell wall recalcitrance in higher plants. Some genes, such as CAD or CCR, can be targeted to give significant improvements in saccharification efficiency or forage digestibility without significant effects on agronomic properties. Targeting other genes such as HCT can lead to much better improvements in saccharification efficiency, but at the cost of significantly reduced biomass yield. Research into the mechanics behind dwarfism is ongoing: uncoupling the still unknown causal pathway of dwarfism from the lignin biosynthesis pathway could open a multiplicity of options to target the optimal genes in each species needed for a specific industry. There is progress and possibility in utilizing additional breeding or engineering to overcome the negative growth impacts. A possible manipulation may be to remove excess SA, but this is probably not viable for field grown plants, as it may compromise disease resistance.

Only recently has the bulk of current knowledge of lignin biosynthesis been elucidated, and much more remains to be explored.

Genetically reducing lignin has been shown to have practical application, and further research into understanding and reversing the undesirable side effects can open up this technique to increased industrial viability.

References

1. Bonawitz N and Chapple C (2010) The genetics of lignin biosynthesis: connecting genotype to phenotype. Annu. Rev. Genet. 44, 337-363.

2. Ford CW, Morrison IM, Wilson JR (1979) Temperature effects on lignin, hemicellulose and cellulose in tropical and temperate grasses. Austr. J. Agric. Res. 30, 621–633.

3. Pitre F, Cooke J, Mackay J (2007) Short-term effects of nitrogen availability on wood formation and fibre properties in hybrid poplar. Trees – Struct. Funct. 21, 249–259.

4. Halpin C, Knight ME, Foxon GA, Campbell MM, Boudet AM, et al. (1994) Manipulation of lignin quality by down-regulation of cinnamyl alcohol-dehydrogenase. Plant J. 6, 339–50.

5. Keating JD, Panganiban C and Mansfield SD (2006) Tolerance and adaptation of ethanologenic yeasts to lignocellulosic inhibi- tory compounds. Biotechnol. Bioeng. 93, 1196– 1206.

6. Li X, Weng JK and Chapple C (2008) Improvement of biomass through lignin modification. Plant J. 54, 569-581.

7. Wyman CE, Dale BE, Elander RT, Holtzapple M, Ladisch MR and Lee YY (2005) Coordinated development of leading bio- mass pretreatment technologies. Bioresour. Technol.

96, 1959– 1966.

8. O’Connell A, Holt K, Piquemal J, Grima-Pettenati J, Boudet AM, Pollet B, Lapierre C,

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hurj fall 2012: issue 15 Petit-Conil M, Schuch W and Halpin C (2002) Improved paper pulp from plants with suppressed cinnamoyl-CoA reductase or cinnamyl alcohol dehydrogenase. Transgenic Res. 11, 495–503.

9. Reddy MS, Chen F, Shadle G, Jackson L, Aljoe H and Dixon RA (2005) Targeted downregulation of cytochrome P450 enzymes for forage quality improvement in alfalfa (Medicago sativa L.). Proc. Natl Acad. Sci. USA, 102, 16573–16578.

10. Shadle G, Chen F, Srinivasa Reddy MS, Jackson L, Nakashima J and Dixon RA (2007) Down-regulation of hydroxycinnamoyl CoA:shikimate hydroxycinnamoyl transferase in transgenic alfalfa affects lignification, development and forage quality. Phytochem. 68, 1521–1529.

11. Chen F and Dixon RA (2007) Lignin modification improves fermentable sugar yields for biofuel production. Nat. Biotech. 5-27, 759-760 12. Franke R, Hemm MR, Denault JW, Ruegger MO, Humphreys JM, Chapple C (2002) Changes in secondary metabolism and deposition of an unusual lignin in the ref8 mutant of Arabidopsis. Plant J. 30, 47–59.

13. Hoffmann L, Besseau S, Geoffroy P, Ritzenthaler C, Meyer D, Lapierre C, Pollet B, Legrand M (2004) Silencing of hydroxycinnamoyl-coenzyme A shikimate/quinate hydroxycinnamoyltransferase affects phenylpropanoid biosynthesis. Plant Cell, 16, 1446–1465.

14. Jones L, Ennos AR, Turner SR (2001) Cloning and characterization of irregular xylem4 (irx4): a severely lignin-deficient mutant of Arabidopsis. Plant J. 26, 205–216.

15. Thévenin J, Pollet B, Letarnec B, Saulnier L, Gissot L, Maia-Grondard A, Lapierre C and Jouanin L (2010) The simultaneous repression of CCR and CAD, two enzymes of the lignin biosynthetic pathway, results in sterility and dwarfism in A. thaliana. Molec Plant, 4-1, 70-82.

16. Goujon T, Ferret V, Mila I, Pollet B, Ruel K, Burlat V, Joseleau JP, Barrière Y, Lapierre C, Jouanin L (2003) Down-regulation of the AtCCR1 gene in A. thaliana: Effects on phenotype, lignins and cell wall degradability. Planta, 217, 218–228.

17. Raes J, Rohde A, Christensen JH, Van de Peer Y, and Boerjan W (2003) Genome-Wide Characterization of the Lignification Toolbox in Arabidopsis. Plant Physiol. 133, 10511071.

18. Besseau S, Hoffmann L, Geoffroy P, Lapierre C, Pollet B, and Legrand M (2007) Flavonoid accumulation in Arabidopsis repressed in lignin synthesis affects auxin transport and plant growth. Plant Cell, 19, 148–162.

19. Nakashima J, Chen F, Jackson L, Shadle G and Dixon RA (2008) Multi-site genetic modification of monolignol biosynthesis in alfalfa (Medicago sativa): effects on lignin composition in specific cell types. New Phyto. 179, 738-750.

20. Wagner A, Ralph J, Akiyama T, Flint H, Phillips L, Torr K, Nanayakkara B and Kiri LT (2007) Exploring lignification in conifers by silencing hydroxycinnamoyl-CoA:shikimate hydroxycinnamoyltransferase in Pinus radiata. PNAS, 104-28, 11856-11861.

21. Lacombe E, Hawkins S, Van Doorsselaere J, Piquemal J, Goffner D, Poeydomenge O, Boudet AM, Grima-Pettenati J (1997) Cinnamoyl CoA reductase, the first committed enzyme of the lignin branch biosynthetic pathway: Cloning, expression and phylogenetic relationships. Plant J. 11, 429–441.

22. Piquemal J, Lapierre C, Myton K, O’Connell A, Schuch W, Grima-Pettenati J, Boudet AM (1998) Down-regulation of cinnamoyl-CoA reductase induces significant changes of lignin profiles in transgenic tobacco plants. Plant J. 13, 71–83.

23. Zhou R, Jackson L, Shadle G, Nakashima J, Temple S, Chen F and Dixon RA (2010) Distinct cinnamoyl CoA reductases involved in parallel routes to lignin in Medicago truncatula. PNAS, 107-41, 17803-17808.

24. Jackson L, Shadle G, Zhou R, Nakashima J, Chen F and Dixon RA (2008) Improving saccharification efficiency of alfalfa stems through modification of terminal stages of monolignol biosynthesis. Bioen. Research, 1-3, 180-192.

25. Leplé JC, et al. (2007) Downregulation of cinnamoyl-coenzyme A reductase in poplar: Multiple-level phenotyping reveals effects on cell wall polymer metabolism and structure.

Plant Cell, 19, 3669–3691.

26. Sibout R, Eudes A, Mouille G, Pollet B, Lapierre C, Jouanin L, and Sèguin A (2005) CINNAMYL ALCOHOL DEHYDROGENASE-C and -D are the primary genes involved in lignin biosynthesis in the floral stem of Arabidopsis. Plant Cell. 17, 2059–2076.

27. Sibout R, Eudes A, Pollet B, Goujon T, Mila I, Granier F, Sèguin A, Lapierre C, and Jouanin L (2003) Expression pattern of two paralogs encoding cinnamyl alcohol dehydrogenases in Arabidopsis: isolation and characterization of the corresponding mutants. Plant Physiol. 132, 848–860.

28. Gallego-Giraldo L, Jikumaru Y, Kamiya Y, Tang Y and Dixon RA (2010-online, 2011) Selective lignin downregulation leads to constitutive defense response expression in alfalfa (Medicago sativa L.). New Phyto. 190-3, 627-639.

29. Gallego-Giraldo L, Escamilla-Trevino L, Jackson LA, and Dixon RA (2011) Salicylic acid mediates the reduced growth of lignin down-regulated plants. PNAS 108, 20814–20819.

30. Baucher M, et al. (1996) Red xylem and higher lignin extractability by down-regulating a cinnamyl alcohol dehydrogenase in poplar. Plant Physiol. 112, 1479-1490.

31. Cherney JH, Cherney DJR, Akin DE and Axtell JD (1991) Potential of brown-midrib, low-lignin mutants for improving forage quality. Adv. Agron. 46, 157–198.

32. Jung HG and Allen MS (1995) Characteristics of plant cell walls affecting intake and digestibility of forages by ruminants. J. Anim. Sci. 73, 2774–2790.

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science & engineering reports

Ensembles Function as Individual Units for Visual Indexing and Visual Selective Attentios Robert Eisinger1, Justin Halberda1 1 Department of Psychological and Brain Sciences, Johns Hopkins University, MD Abstact The enumeration of a small number of objects has been shown repeatedly to consist of two distinct stages dependent on the number of objects. For 1-3 objects, enumeration is fast and accurate. For more than 3 objects, enumeration is slow and less accurate. The former is coined subitizing and the latter is counting. In this study, we show that enumeration of ensembles identically resembles enumeration of individual objects or items, implying that ensembles function as individual units for visual indexing and visual selective attention.

Introduction Processing objects in a visual scene requires deployment of attentive selection, as does natural scene perception. Regardless of the complexity of the scene, visual selective attention serves as the primary mechanism by which individuals parse a scene into individual items, groups of similar individual items, or a combination of both.1,2 Visual indexing is the mechanism through which certain salient features or objects in a visual display are indexed so that they can be referred to by subsequent cognitive processes. An index may be thought of as a reference to the external world that may be utilized later, similar to the memory references that are inherent to a computer’s architecture. A computer relies on a memory reference—which is simply a value—to enable programs to access particular data later on.

Intuitively, it seems unlikely that indexing a scene (particularly a complex one) is performed through a series of index assignments (references to items) to each individual unit in that scene. In fact, the number of visual indexes employed at once is limited.3 For example, try to track multiple leaves simultaneously falling from a tree on a windy day. It is likely that, while you could get a general impression of the number of leaves and their direction, you would be unable to attend to each leaf as a separate unique individual all at once. A number of authors have suggested that our ability to attend to individual objects is limited to approximately three to four objects at any one time.4,5,6,7,8,9 If seeing relies on visual indexing, and if indexes are limited, then how is scene perception even possible? Visual indexing procedures must be more complex than individual references to individual objects.

One recent proposal for this added complexity is the possibility that viewers might rely on “ensemble features” in a scene. Ensemble features are general statistical descriptions of multiple similar items in a scene; e.g., the approximate number and general direction of the leaves falling from a tree.10 By relying on statistical tendencies, we might choose which items to attend to and which to filter out in a visual scene through a series of parses. To maximize the efficiency of attention, imagine that a group of homogenous items such as a group of 12 blue dots (an ensemble) could be recognized as a single unit: we could attend to those items through just a single reference to the entire group as opposed to requiring the computational power of attending to each item in that group. Here we explore the possibility that each ensemble must be selected and attended to much like a

single object, and that the number of ensembles that may be selected at any one time is limited just as it is for individual objects.

Recent studies suggest that the human visual system accurately computes ensemble statistics for a number of different features such as mean size, orientation, average location, approximate number, etc.2,11,12,13,14,15 Previous research indicates that representing multiple objects as an ensemble enhances visual cognition, but why?10 In this study, we show that an ensemble consisting of N items is assigned a single visual index, rather than N indices, thereby empowering a more efficient use of the limited indexing capacity of visual processing.

To explore this idea, we focused on a well-known process that requires attention to individual items: enumeration. Enumeration for a small set of items is fast and accurate, and is referred to as subitizing.16 For sets of items larger than about three or four, however, a person typically enumerates through a process of verbal counting, and enumeration is thus slower and more error prone, as seen in Figure 1.17,18

Figure 1. Typical enumeration curve for small numerosities. For 1-3 objects, enumeration is fast and constant. For larger numerosities, response time is linearly dependent on the numerosity. This dichotomy results in a subitizing elbow, sometimes referred to as subitizing capacity.

This dichotomy in the response times of enumeration for subitizing and counting has been well established.19,20,21,22 It has been explained as resulting from distinctions in visual working memory and

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science & engineering reports Results

Figure 4. Sequence of a trial: A screen indicating that the subject will begin the trial is shown. The stimulus is displayed and remains on the screen until the subject presses the space bar. A mask is flashed for 200 ms, and then the subject is prompted to enter the number of colors he/she saw.

Figure 2. How many colors do you see? In the example on the left (2a), subjects enumerate individual objects. In the example on the right (2b), subjects enumerate ensembles.

FINSTs, separable neural systems and pattern recognition.22,23,18 The majority of accounts agree that each object in an enumeration task must be indexed, especially for numerosities above four.

It remains unknown whether enumerating groups of items is possible also (e.g., counting the number of teams rather than the number of players). In the case of groups of similar items, it seems highly inefficient to index individual objects if all the objects within a particular group are similar. For instance, it is perhaps unnecessary to visually index every single car in a full parking lot in order to identify it as a single coherent parking lot. A single reference to the “parking lot” is satisfactory.

If we presume that ensembles actually receive a single index and function the same way an object does, then the same dichotomy should also exist for enumeration of ensembles, or groups of items.

In other words, the performance of enumeration response times for individual items as in Figure 2a (i.e., counting each dot) should degrade similarly for ensembles as in Figure 2b (i.e., counting each group). Thus, enumeration of ensembles should result in a relatively constant response time subitizing range for set sizes between about one and three, and a linearly increasing response-time as a function

of set size thereafter, representative of the counting range.

We tested this prediction by presenting subjects with subitizing displays involving whole clusters of items—for instance, seven red dots clustered together but spatially separated from four blue clustered dots (e.g., Figure 1b). We recorded subjects’ response times when asked to report the number of colors (i.e., ensembles) on the screen.

In separate trials, we also tested enumeration for concentrically positioned objects and ensembles (see Figure 3). Previous research shows that the subitization of concentric objects is impossible. Concentric items are difficult to subitize because of their focus; their common spatial position. Each has an inside and an outside that is bounded by a contour, and are necessarily different sizes. Enumeration is difficult, because it is performed not on the basis of the variety of sizes of different items or local proximities. As a result, the task of subitizing concentric objects has been deemed impossible.22 In such cases, response time is linear as a function of the set size and a subitizing elbow is not observed—i.e., a fitting algorithm leads to a single-lined best fit, as opposed to the bilinear fits of a subitizing elbow, suggestive of verbal counting across all numerosities as op-

Figure 3. Illustration of the four different types of trials presented in Experiment 1: No-Overlap Clusters, No-Overlap Rings, Concentric Clusters, Concentric Rings. Note that the rings are not intended to represent the cluster displays shown above them.

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posed to the traditional subitizing of lower numerosities.

We predicted that subjects would also be unable to subitize concentrically positioned ensembles. If enumerating ensembles results in a subitizing elbow, and concentric ensembles are not subitized, this would support the claim that ensemble groups function as a single unit for visual indexing and visual selective attention, akin to being an individual object.

Materials and Methods Seventeen undergraduates received academic credit for participating. They viewed 300 trials on a Macintosh iMac computer with a viewable area measuring 29.5 cm by 22.5 cm.

Figure 3 gives examples of the stimuli types presented to subjects. On each trial, participants viewed an infinite-display stimulus consisting of between one and six clusters, each consisting of between five and fifteen individual dots of the same color. The total area of each cluster was controlled to prevent numerosity judgment on the basis of area. Each of six possible colors was represented evenly throughout the course of the experiment, as were the number of dots within each cluster. This disallowed preference for a particular color or number of dots.

Clusters were assigned optimally enclosed rings defined as the smallest circle enclosing the dots in a cluster. On half of the trials, subjects enumerated rings—which served as object representations of the associated ensemble it would have otherwise enclosed—rather than clusters of dots. Thereby, we were able to test subject’s enumeration abilities for both objects (i.e., rings) and ensembles (i.e., dot clusters) while controlling other variables. Subjects were presented with spatially separated (No-Overlap) clusters or concentrically positioned clusters. No-Overlap and Concentric trials were present in even amounts. On Concentric trials, the number of individual dots allowed within a cluster was increased to satisfy the requirements of concentric arrangement.

Within each cluster in Experiment 1, dot position was randomly determined under a constrained maximum cluster spread, defined as the largest distance between any two dots within a cluster. The 300 trials were presented as a single block but randomized across the four conditions.

Subjects were asked to press the space bar immediately after determining the number of colors in the stimulus. A dialog box then prompted the user to enter this numerosity (see Figure 4 below). Accuracy and response time were recorded.

Results from subjects who had an overall enumeration accuracy of less than 90% (four total) were discarded. Subjects were accurate with errors increasing with set size and with higher errors in the concentric conditions. This suggests that enumerating ensembles is more difficult than enumerating individual objects and that enumerating Concentric displays is more difficult than enumerating No-Overlap displays, as our hypothesis predicted.

For analyses of subitizing elbows, incorrect trials were removed from further analysis because subjects were asked to achieve perfect accuracy in enumeration. For the correct trials, we then removed outlier reaction times for each subject and for each condition according to the procedure advocated by Selsts and Jolicoeur (1994).

Subitizing elbows—the position at which subitizing transitions to counting (also known as subitizing capacity)—were found using nonlinear least squares regression with the constraint that the first slope of the bilinear elbow must be small and positive, the second slope must be greater than the first slope, and the two lines must intersect—as described in other studies.24,25 Averages across subjects were computed. See Table 2 for a summary of our findings, and Figure 5 for averaged elbow plots of No-Overlap and Concentric clusters (ensembles) and rings (objects). The slopes comprising the elbow curves are nearly identical. Elbows were entered into a two-by-two analysis of variance (ANOVA) with a total of two factors—spatial layout and stimulus—each having two levels—No-Overlap and Concentric, and Ensemble and Object, respectively. The ANOVA showed that there is a main effect due to spatial layout, F(1, 12) = 8.33, p = 0.014, suggesting a significant difference in No-Overlap and Concentric trials, as expected. We failed to observe a significant main effect of probe type (ensemble or object), F(1, 12) = 0.009, p = 0.927, further supporting the similarity of ensemble and object subitization. There was no significant effect of interaction, F(1, 12) = 0.525, p = 0.483.

Table 2. Slope and elbow values for non-overlapping clusters and rings with associated standard error values.

Of primary importance is the finding that subitizing ensembles results in an almost identical subitizing elbow curve to that of objects. This suggests that the visual indexing procedure is identical, and visual selective attention is carried out in the same manner for both groups of similar units as for individual units themselves. Irrespective of the empirically valid explanation for the existence of the distinct differences in the subsidizing and counting ranges, this finding suggests that for any valid explanation of the enumeration dichotomy of low set-sizes of objects, the explanation and dichotomy also holds for ensembles.

Secondly, we wanted to test the decay in enumeration performance for concentric objects, a well-known factor of interference leading to decreased enumeration performance. In these cases, both individual objects and ensembles were affected in the same way.

When considering objects and ensembles, the behavior of response time as a function of set size is identical. This further shows that in the concentric condition, when the focus across multiple objects is forced to be the same, ensembles and objects use the same visual

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The Reproducibility of Measuring Aortic Strain and Pulse Wave Transit Time Through Magnetic Resonance Imagings Ryan M. Kahn1, Gisela Teixidó-Turà, MD2, João A.C. Lima, MD2, Elzbieta Chamera2 Johns Hopkins University, Public Health Studies, Baltimore, Maryland, US 2 Johns Hopkins Hospital Heart & Vascular Institute, Baltimore, Maryland, US

1

Abstact

Figure 5: The pattern of subitization is nearly identical for both ensemble and object enumeration. The typical subitizing dichotomy is evident in both cases, and it exists at the typical estimated capacity: about 3.

indexing mechanism.

Taken together, these results closely follow the widely accepted results for the enumeration of individual items; hence, we conclude that ensembles must function the same way as individual items for visual indexing and visual selective attention.

Discussion The goal of this study was to confirm the hypothesis that ensembles are mechanistically treated in the same manner as individual objects. Therefore, visual selective attention must act upon ensembles in the same manner as it acts upon items, regardless of what that manner is. These findings align with our knowledge that the keen human visual system only requires a fraction of a second to extract information from a scene. In fact, there is no loss of efficiency for indexing or attention when processing ensembles, as presented in this study, when compared to processing individual objects.

This finding sheds light onto the nature of the human visual system with respect to its remarkable efficiency in performance.

The pigments found in photosensitive cells of the retina convert light into electrical signals that reach our brains via the optic nerve. The processing of those electrical signals is vision’s true mastery. Visual indexing is essentially an arrow, rooted in the visual brain and pointing out from the external world into the mind. Understanding where those indexes point allows us to understand how the visual machinery selects input that leads to vision’s ultimate output: our immediate understanding of the world. It is precisely that selection and utilization of attention of input that must be efficient to produce rapid output and appropriate behavior in the given context. Targeting ensembles as a single unit helps to explain one of the many ways that vision expedites the processing of inputting the tremendous amount of information right in front of our eyes.

References

1. Cohen, M., Alvarez, G., & Nakayama, K. (2011). Natural-Scene Perception Requires Attention. Psychological Science, 22, 1165-1172.

2. Halberda, J. et al. (2006). Multiple spatially overlapping sets can be enumerated in parallel. Psychological Science, 17, 572-576.

3. Pylyshyn, Z. (1989). The role of location indexes in spatial perception: A sketch of the FINST spatial-index model. Cognition, 32, 65-97.

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4. Cavanagh, P., & Alvarez, G.A. (2005). Tracking multiple targets with multifocal attention.

Trends in Cognitive Sciences, 9, 349-354.

5. Culham, J. C., Cavanagh, P., & Kanwisher, N. G. (2001). Attention response functions: Characterizing brain areas using fMRI activa- tion during parametric variations of attentional load. Neuron, 32, 737-745.

6. Oksama, L., & Hyona, J. (2004). Is multiple object tracking carried out automatically by an early vision mechanism independent of higher-order cognition? An individual difference approach. Visual Cognition, 11, 631-671.

7. Pylyshyn, Z. W., & Storm, R. W. (1988). Tracking multiple independent targets: Evidence for a parallel tracking mechanism. Spatial Vision, 3, 179-197.8. Scholl, B. J. (2001). Objects and attention: The state of the art. Cognition, 80, 1-46.

9. Sears, C. R., & Pylyshyn, Z. W. (2000). Multiple object tracking and attentional processing. Canadian Journal of Experimental Psychology, 54, 1-14. Sternberg, S. (1966). Highspeed scanning in human memory. Science, 153, 652-654.

10. Alvarez, G. A. (2011). Representing multiple objects as an ensemble enhances visual cognition. Trends in Cognitive Sciences, 15, 122-131.

11. Alvarez, G. A., & Oliva, A. (2008). The representation of simple ensemble visual features outside the focus of attention. Psychological Science, 19, 392-398.

12. Ariely, D. (2001). Seeing sets: Representation by statistical properties. Psychological Science, 12, 157-162.

13. Chong, S. C., & Treisman, A. (2003). Representation of statistical properties. Vision Research, 43, 393-404.

14. Dakin, S. C., & Watt, R. J. (1997). The computation of orientation statistics from visual texture. Vision Research, 37, 3181-3192.

15. Rubenstein, B. S., & Sagi, D. (1990). Spatial variability as a limiting factor in texture discrimination tasks: Implication for performance asymmetries. Journal of the Optical Society of America A, 7, 1632-1643.

16. Kaufman, E. L., Lord, M. W., Reese, T, and Volkmann, J. (1049). The discrimination of visual number. American Journal of Psychology, 62, 496-525.

17. Atkinson, J., Campbell, F. W., & Francis, M. R. (1976). The magic number 4 ± 0: A new look at visual numerosity judgments. Perception, 5, 327-334.18. Mandler, G., & Shebo, B. (1982). Subitizing: An analysis of its component processes. Journal of Experimental Psychology: General, 111, 1-22.

19. Aoki, T. (1977). On the counting process of patterned dots. Tohoku Psychologica Folia, 36, 15-22.

20. Klahr, D. (1973). A production system for counting, subitizing and adding. In W. G. Chase (Ed.), Visual information processing (pp. 527-546). San Diego, CA: Academic Press.

21. Oyama, T., Kikuchi, T., & Ichihara, S. (1981). Span of attention, backward masking and reaction time. Perception and Psychophysics, 29(2), 106-112.

22. Trick, L., Pylyshyn, Z. (1994). Why Are Small and Large Numbers Enumerated Differently? A Limited-Capacity Preattentive Stage in Vision. Psychological Review, 101(1), 80-102.

23. Piazza, M., Mechelli, A., Butterworth, B., & Price, C. (2002). Are Subitizing and Counting Implemented as Separate or Functionally Overlapping Processes? NeuroImage, 15, 435446.

24. Jevons, W. S. (1871). The power of numerical discrimination. Nature, 3, 363-372.

25 . Green, C., & Bavelier, D. (2006). Enumeration versus multiple object tracking: the case of action video game players. Cognition, 101, 217-245.

MRI (Magnetic resonance imaging) is the most common method of measuring aortic stiffening. However, due to the high cost and limited availability of MRI techniques, it is necessary to determine whether MRI can be a valid, reproducible approach to measuring aortic strain on a large scale. We performed a quantitative analysis of 30 random samples of cine cardiac MRI images obtained in the Multi-Center Study of Atherosclerosis (MESA). The images were measured for Aortic Area and Pulse Wave Velocity (PWV), two specific indicators of aortic strain. Bland-Altman Plots (concordance correlation coefficient) and Intraclass Correlation Coefficients (ICC) were then used to measure the agreement between the calculations for each the ascending, descending, and abdominal aorta.

Nearly all of the data showed an excellent level of agreeability. The R-values for the max/min area measurements ranged between 0.92-1.0; the aortic strain R-values ranged between 0.74-0.99; and the PWV R-values ranged between 0.98-0.99. There was also a clear distinction that the abdominal aorta showed much less variance when compared to the ascending and descending aorta. The use of MRI to measure arterial stiffening showed a high degree of intra-observer agreement and can be a reliable measure of the onset of aortic distensibility.

Introduction Over 910,000 deaths per year in the United States alone are attributed to heart disease.1 Aging—a common risk factor—has been found to cause a decrease in vascular distensibility and stiffening of the aorta, ultimately resulting in cardiovascular decay.2 Arterial stiffness, which often goes unnoticed in individuals with no previous symptoms of heart disease, is an early indicator of cardiovascular disease beyond traditional risk factors.3 Therefore, early detection of aortic stiffness can lead to the prevention of cardiovascular disease in patients who may not exhibit common risk factors, namely hypertension or high cholesterol.

The aorta delivers blood from the left ventricle to the peripheral tissues and distributes oxygenated blood throughout the body by systematic circulation.4 During the systolic phase, the aorta distends and accommodates a large proportion of the stroke volume (SV), or volume of blood pumped from one ventricle of the heart during beats. The arterial wall then recoils during the diastolic phase. With

a decrease in aortic distensibility, there is a lower proportion of SV stored in the aorta during systole. Ultimately, there is an increase in pressure in systole and a decrease in pressure in diastole, leading to an overall increase of pulse pressure (PP);5 heightened pulse pressure is known to be a risk factor of coronary heart disease.6 Aortic arch pulse wave velocity (PWV), or the rate at which a flow or pressure wave travels down a vessel, along with the relative changes in ascending aorta (AA) area, are the most specific and sensitive indicators of age-related aorta stiffening.8 Magnetic resonance imaging (MRI) has the ability to assess aortic and ventricular geometry with direct high-resolution measurements of aortic strain, distensibility, and PWV.9 Because of the limited availability and high cost of MRI techniques, it is important to determine whether this method can be reproduced on a large scale. This study determined the precision of the aortic area and PWV through MRI measurements, ultimately measuring whether MRI can analyze aortic strain

Figure 5: A. (1) Arterial Function’s cine ring used to the ascending aorta area and (2) descending aorta area; B. The different values of area in both the systolic and diastolic phase; C. Arterial Function mode of analyzing the PWV of the aorta.11 Teixidó-Turà, Gisela. MRI. Digital image. Arterial Functions.

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science & engineering reports multicenter study. MESA was a prospective epidemiologic study that followed 6.814 men and women (45-84 years of age) over 7 years to measure the progression of cardiovascular disease (CVD).10 30 MRI cine images were then chosen blindly at random and processed in ARTFUN. INSERM U678—a custom-made software program that measures aortic area, aortic distensibility, and PWV. ARTFUN uses a ring to trace the ascending, descending, and abdominal aorta, allowing for the measurement of the maximum and minimum area between the systolic and diastolic phases.The aorta delivers blood from the left ventricle to the peripheral tissues and distributes oxygenated blood throughout the body by systematic circulation.4 During the systolic phase, the aorta distends and accommodates a large proportion of the stroke volume (SV), or volume of blood pumped from one ventricle of the heart during beats. The arterial wall then recoils during the diastolic phase.

The change in aortic area is necessary for the calculation of aortic strain. Aortic strain is defined as: %Strain = (Areamax- Areamin)/ Areamin12; this quantity is essential in the calculation of distensibility.

PWV is calculated by measuring the difference in time of the pulse wave between the ascending and descending aorta.13 Thus, in order to measure the difference in time, the Bramwell-Hill Equation was used: Aortic PWV = D/Δt, where D is the distance between the ascending and descending aortas and Δt is the transit time.14, 15 After extensive training with ARTFUN, the minimum and maximum of the ascending, descending, and abdominal aorta as well as the change in time of the pressure wave between the segments of the aorta were measured among the random samples. These results were then cross-referenced and analyzed with Dr. Teixidó-Turà’s calculations of the same cases. The reproducibility of MRI techniques to measure aortic strain and PWV were calculated through a statistical analysis utilizing Bland-Altman plots and Intraclass Correlation Coefficients (ICCs).

Intraclass Correlation Coefficients measures R-values to determine the degree of intra-observer agreement ranging from 0 to 1—where 1 represents exact linear agreement. According to outside studies, fair = 0.40 ≤ R ≤ 0.59; good = 0.60 ≤ R ≤ 0.74; and excellent = 0.75 ≤ R ≤ 1.16,17 Bland-Altman Plots were another method used to determine intra-observer relatedness. Bland-Altman plots place the difference in measurements between the observers on the Y-axis, and the average for each measurement on the X-axis. These plots formulate a concordance correlation coefficient, which range between 0-1 and represent the degree of agreement very similarly to ICC. However, the concordance correlation coefficient is affected by intra-observer error, whereas ICC measurements are immune to these biases.18

Results Figure 3. Bland-Altman Plots: Shows Bland-Altman Plots for ascending, descending, and abdominal aorta. For each data point, the mean of the two measurements is plotted on the X-axis and the difference is plotted on the Y-axis. Shows valid correlation and association among the measurements. A. Ascending Aorta.B. Descending Aorta. C. Abdominal Aorta.

effectively.

Figure 2. ICC Plots: Shows ICC plots for ascending, descending, and abdominal aorta. Minimal deviation from the line represents significant reproducibility. A. Ascending Aorta, Maximum Area. B. Ascending Aorta, Minimum Area. C. Descending Aorta, Maximum Area. D. Descending Aorta, Minimum Area. E. Abdominal Aorta, Maximum Area. F. Abdominal Aorta, Minimum Area.

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Methods and Materials The aortic MRI images of the cases were obtained from The MESA Study (Multi-Ethnic Study of Atherosclerosis), a large-scale

For the maximum and minimum area measurements, the R values (Intraclass Correlation Coefficient) all showed excellent agreement. The reliability of area measurements were greatest for the abdominal aorta, with max/min values of (1.0/0.99) (Figure 2e,2f; Table 1). Measurements for the ascending and descending aorta were not far behind; the ascending aorta max/min values were observed to be (0.99/0.92), while the descending aorta’s max/min values were (0.99/0.97) (Figure 2a,2b,2c,2d; Table 1).

Strain measurements showed a slightly greater variance, but each R-value still fell in the good to excellent range. Once again, the abdominal aorta showed the highest degree of reproducibility

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science & engineering hurj fall 2012: issue 15 reports

hurjscience fall 2012: issue 15 & engineering Intraclass Correlation Coefficient (ICC)

CI95%

Max area, ascending aorta

0.99

0.99-1.0

Min area, ascending aorta

0.92

0.88-0.96

Max area, descending aorta

0.99

0.98-0.99

Min area, descending aorta

0.97

0.93-0.99

Max area, abdominal aorta

1

1

Min area, abdominal aorta

0.99

0.99-1.0

Intraclass Correlation Coefficient (ICC)

CI95%

Strain ascending aorta

0.74

0.51-0.87

Strain descending aorta

0.77

0.55-0.89

Strain abdominal aorta

0.99

0.98-0.99

Table 1.

Table 2.

Aortic Strain measurement reproducibility

Intraclass Correlation Coefficient (ICC)

CI95%

0.98

0.96-0.99

Time between descending and abdominal aorta

0.99

0.98-0.99

Pulse Wave Velocity measurement reproducibility

with an ICC of 0.99 as well as a concordance correlation coefficient of absolute agreement of 0.99 (Figure 3c; Table 2). The next highest agreement was the descending aorta with an excellent ranged value of 0.77 and a concordance correlation coefficient of 0.87 (Figure 3b; Table 2). The least degree of agreement for strain was observed for the ascending aorta with a good to excellent ICC (0.74) and a concordance correlation coefficient of 0.91 (Figure 3a; Table 2).

Both measurements of the pulse wave velocity (PWV) showed near to exact agreement. Both the measurement for observed pulse wave time between the ascending and descending aorta (0.99) and the observed pulse wave time between the descending and abdominal aorta (0.98) showed excellent precision values (Table 3).

Discussion Although this study was performed on a small scale with only 30 samples and calculations were obtained from two researchers of different experience and credentials, the reproducibility of using MRI and ARTFUN in measuring aortic stiffening was evident.. The ICC values of the area, strain, and PWV were almost all within the range of “excellent” agreement; strain of the ascending aorta was the only measurement with a “good” degree of agreement. Overall, the abdominal aorta measurements showed almost ideal precision, while the measurements of the ascending and descending aorta showed slight variation.

The discrepancy in ascending and descending aorta can be attributed to a clear variation in image quality among the abdominal MRI. The precision of the measurements is directly related to ARTFUN’s ability to track the MRI images of the fluctuations ascending, descending, and abdominal aorta between the systole and diastole phases. Throughout the study, the abdominal aorta was more visible and easier to trace, resulting in almost minimal variance.

This study’s results verify the ability to measure aortic distensibility through MRI on a highly reproducible scale; nearly the entire

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science & engineering reports

Progesterone For the Clinical Treatment of Acute Traumatic Brain Injury Alex Schupper1 Hospital of the University of Pennsylvania, Philadelphia, PA

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Aortic Area measurement reproducibility

Time between ascending and descending aorta Table 3.

hurj fall 2012: issue 15 14 spring 2012: issue

data set demonstrated “excellent” intra-observer agreement. Whether MRI can be used to calculate aortic distensibility still needs to be researched on a larger scale before it can be authenticated. However, the results show that using MRI to measure aortic stiffening can be highly reproducible. The measurements of aortic strain via MRI and ARTFUN can therefore have a major contribution in the prevention of heart disease.

References

1. Carter, M. (2006). Heart disease still the most likely reason you’ll die. CNN Health. Retrieved from: http://articles.cnn.com/2006-10-30/health/heart.overview_1_heart-diseaseamerican-heart-association-obesity?_s=PM:HEALTH. 2. Staessen J, Amery A, & Fagard R. (1990). Isolated systolic hypertension in the elderly. J Hypertens, 8, 393– 405.

3(8,9,12,14). Redheuil A, Yu WC, Wu CO, Mousseaux E, de Cesare A, Yan R, Kachenoura N, Bluemke D, & Lima JA. (2010). Reduced ascending aortic strain and distensibility: earliest manifestations of vascular aging in humans. Hypertension, 55(2), 319–326.

4. Maton, Anthea. (1995). Human Biology Health. Englewood Cliffs, New Jersey: Prentice Hall. ISBN 0-13-981176-1.

5(7). Metafratzi ZM, Efremidis SC, Skopelitou AS, & De Roos A. (2002). The clinical significance of aortic compliance and its assessment with magnetic resonance imaging. Journal of Cardiovascular Magnetic Resonance, 4(4), 481– 491.

6. Lefevre, M., & Rucker, R.B. (1980). Aorta elastin turnover in normal and hypercholesterolemic Japanese quail. Biochimica et Biophysica acta, 630(4), 519 – 529. doi: 10.1016/03044165(80)90006-9.

10. Bild DE, Bluemke DA, Burke GL, Detrano R, Diez Roux AV, Folsom AR, Greenland P, David R, Kronmal R, Liu K, Nelson JC, O’Leary D, Saad MF, Shea S, Szklo M, Tracy RP. Multi-ethnic study of atherosclerosis: objectives and design. Am J Epidemiol 2002.

11. Teixidó-Turà, Gisela. MRI. Digital image. Arterial Functions.

13. Bolster BD Jr, Atalar E, Hardy CJ, & McVeigh ER. (1998). Accuracy of arterial pulsewave velocity measurement using MR. Journal of Magnetic Resonance Imaging, 8(4), 878 888. doi: 10.1002/jmri.1880080418.

15. Laurent S, Cockcroft J, Van Bortel L, Boutouyrie P, Giannattasio C, Hayoz D, Pannier B, Vlachopoulos C, Wilkinson I, & Struijker-Boudier H. (2006). Expert consensus document on arterial stiffness: methodological issues and clinical applications. European Heart Journal, 27(21), 2588 –2605. doi: 10.1093/eurheartj/ehl254.

16. Cicchetti DV, Sparrow SA. Developing criteria for establishing interrater reliability of specific items: applications to assessment of adaptive behavior. Am J Ment Defic 1981.

17. Oppo K, Leen E, Angerson WJ, Cooke TG, McArdle CS. Doppler perfusion index: an interobserver and intraobserver reproducibility study. Radiology 1998.

18. Lin L. A concordance correlation coefficient to evaluate reproducibility. Biometrics.

1989.

Abstact ProTECTTM III is a Phase III, double-blinded, randomized, placebo-controlled, multicenter clinical trial enrolling 1140 patients with moderate to severe (Glascow Coma Scale 4-12) blunt traumatic brain injury. The objective of the trial is to treat patients with acute traumatic brain injury with intravenous progesterone and measure their outcome at six months post-injury. There is a 1:1 randomization scheme of progesterone versus placebo, and outcomes are tested at six months post-injury by the Glasgow Outcome Scale-Extended (GOSE). The trial is still ongoing, but some conclusions can be drawn from the two Phase II pilot trials on human subjects. The results of these trials indicate that progesterone works to prevent apoptosis and is safe to use as a neuroprotective agent.

In addition, progesterone might have potential benefit in decreasing cerebral edema. However, the exact mechanism(s) of actions are not yet currently known.

Progesterone will prospectively prove to be effective in decreasing cerebral edema following blunt traumatic brain injury and in decreasing the rate of death and disability in patients with moderate to severe TBI. If progesterone proves to be effective upon the completion of ProTECT, it may become a widely used drug for the treatment of blunt traumatic brain injury.

Introduction Traumatic brain injury (TBI) has become a prevalent and debilitating form of injury in the United States. Every five minutes someone is permanently disabled from a TBI, and an estimated 1.7 million people sustain a TBI each year1. Although many relate traumatic brain injury to sports-related injuries and assault, the leading known cause of TBI in people in the United States is falls (35.2%) and the leading cause in TBI-related deaths is motor vehicle crashes (31.8%)2. The Centers for Disease Control and Prevention (CDC) estimates that over 50,000 deaths annually are a result of TBI (see Figure 1) and that TBI is a contributing factor in a third of all injuryrelated deaths in the United States3. Additionally, traumatic brain injury has been named “the signature wound of the Iraq war.”4 Approximately 20% of soldiers in combat have suffered a TBI while in active duty during the Iraq and Afghanistan wars5, making TBI a great cause of concern on the battlefield.

Although traumatic brain injury is an endemic injury in the United States, there is currently no pharmacological therapy that has been proven to decrease morbidity and mortality. The current standard of care for TBI in an emergency setting is focused around stabilizing the patient by protecting oxygen supply to the brain and blood flow, ensuring no further brain damage occurs, and recording a Glascow Coma Scale score. In the 1990s, Roberts et al. studied the efficacy of the five available treatments for TBI (hyperventilation, mannitol, cerebrospinal fluid drainage, barbiturates and corticosteroids); however, these results showed none of the known interventions produced a reliable reduction in disability or death5. There have been other treatment attempts to fight the effects of TBI. The use of glucocorticoids was examined, but recent studies have shown them to be ineffective, and in some cases even detrimental6. Therapeutic hypothermia, a treatment widely used for ischemia, was also tested to treat TBI, but has not yet been proven effective for TBI.

In fact, according to Roberts et. al (1998), no new pharmacological treatment has proven to be an effective treatment for TBI in the past 30 years5. As there is no current, effective treatment intervention, researchers have been prompted to search for a pharmacological therapy that can be deemed advantageous.

Figure 1. After 60mM of K+ influx for three hours, many apoptotic neurons were found to have been blocked by progesterone15.

Previous clinical experiences with progesterone and progesterone-based research have revealed useful characteristics of the hormone that led researchers to study it for the treatment of TBI. First, progesterone is a neurosteroid that is naturally synthesized within the central nervous system (CNS) and has a history of being used in men and women, making it unlikely to cause harm in humans6-7.

Second, progesterone is unique in the way that it quickly reaches the

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CNS and achieves equilibrium with the plasma. When Lancel et al. compared progesterone to GABA receptor modulators, progesterone was found to have entered the brain and was at equilibrium with the plasma within an hour post-injection9. This is an important characteristic of the drug because time is of the essence in treatment for traumatic brain injury. From early animal studies in rats, researchers found that although effective when administered in the first 24 hours after injury, progesterone is most effective in decreasing cerebral edema if administered within two hours following the injury13. Since progesterone can enter the brain rapidly, doctors would have a larger time window to administer it than previous therapeutic treatments could offer. These animal trials have additionally shown that early administration of progesterone improves functional outcome (TBI animals with progesterone tested better than a control group with the same injury). It also helps prevent the breakdown of the blood brain barrier, a cascade known to cause inflammation2,12.

Figure 3. CDC statistics of the estimated average number of annual cases of TBI in the United States3.

Figure 3. ProTECT study drug in its distributed vials.

progesterone11.

After over a decade of research including 87 positive publications by 22 labs worldwide and two pilot trials in humans2, the Phase III clinical trial of ProTECT is now underway, with the goal of determining the effectiveness and safety of IV progesterone in the treatment of acute moderate to severe traumatic brain injury. The primary hypothesis is that patients with TBI receiving progesterone will have a more favorable outcome at six months than those receiving placebo.

Materials and Methods

Figure 2. Neuroprotective mechanism of progesterone, identified by Luoma et. Al (2011).

Recently, Luoma et al. provided a potential mechanism for the neuroprotective nature of progesterone. Through culture, cell death assay and cytoplasmic calcium imaging, it was shown that progesterone blocks calcium-induced neuronal death via excitotoxicity (see Figure 2)15.

Two pilot clinical trials in humans also showed promising results. The first pilot trial, a single-center study done in the United States, found no harmful results with the use of progesterone, and showed a trend toward efficacy. However, the trial was not large enough to reach statistical significance10. In the second pilot trial administered in China by Xiao et. al,, the results showed a decrease in morbidity and mortality at six months following the treatment of

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ProTECTTM III is a phase III, double-blind, randomized, placebo-controlled, multicenter clinical trial. It is conducted at Level I and Level II trauma centers (primarily Level I) across the United States, mainly in academic hospitals. The study calls for a sample size of 1140 adult (≥ 18 years old) trauma patients who arrive within four hours of the time of injury (time frame based on animal trial results)13. All subjects have a moderate to severe blunt traumatic brain injury (defined by a post-resuscitation Glascow Coma Scale of 4-12) with no penetrating wounds to the head such as a gunshot wound, stab wound or burn. Subjects have a 1:1 randomization scheme (50% chance of receiving progesterone or placebo). The length of each subject’s participation is from the time of randomization through six months following the injury.

If the four inclusion criteria listed above (age ≥ 18, blunt TBI, GCS 4-12, time of injury < 4 hours) are met, then the exclusion criteria must be assessed. ProTECT III is a Phase III trial with numerous safety considerations; there is an extensive list of 16 exclusion criteria set forth in the protocol2. These criteria range from cardiopulmonary arrest to status epilepticus on arrival to an ethanol level greater than 0.250. If the patient presents with one of these exclusion criteria, the subject may not be enrolled in the trial.

Each patient enrolled in this trial must also be treated according to the Clinical Standardization Team Guidelines. These guidelines aim to reduce variability in background care across sites. The CST guidelines set various parameters to control other conditions. Following the enrollment of a patient, the study coordinator makes daily assessments for transgressions and adverse events. Data is recorded,

including oxygen saturation (O2 Sat), blood pressure, temperature, intercranial pressure (ICP), cerebral perfusion pressure (CPP) and a full lab workup (glucose, platelets, white blood count, hemoglobin, hematocrit, etc.). Each data value has a target range determined by the main study coordinator,. If the value is not in this target range it is a transgression. In the case of each transgression and adverse event, the study coordinator must make sure the clinical care follows the CST guidelines. These data must be compiled and entered into the WebDCU database on a daily basis for the first 30 days following enrollment, or twice a week under discharge if the patient leaves the ICU prior to the 30 days. Before the patient leaves the hospital, the coordinator must schedule an appointment with the patient 6 months from the time of injury, as well as make monthly phone calls to stay up-to-date on the condition of the patient2. The GOSE test, as well several other tests and disability ratings, at this appointment concludes the patient’s enrollment in ProTECT. Although the target number of enrolled patients has not yet been attained, the data will be statistically analyzed once the study is completed. To assess the efficacy of the study drug (the primary hypothesis), the proportion of patients with “favorable outcomes” in each treatment group (progesterone vs. placebo) will be compared.

The term “favorable outcomes” is defined by the ProTECT protocol as the following: “Patients with the most severe injury ([index Glascow Coma Score] or iGCS between 4-5) will have a favorable outcome if the GOSE [Glascow Coma Score Extended] is good to severe; patients with an intermediate severe injury (iGCS 6-8) will have a favorable outcome if the GOSE is good to moderate; and patients with a moderate injury (iGCS 9-12) will have a favorable outcome if the GOSE is good recovery.”2

The term iGCS refers to the index GCS, or the highest reliable GCS taken between the time of injury and randomization. In addition to the iGCS, the GCS is also taken post-resuscitation, once the patient is off sedatives and paralytics. The GOSE will be scored 6 months post-injury. A linear model will be used to test this hypothesis, testing the relationship between the treatment and a favorable outcome. The analysis will examine three covariates; the severity of the injury, gender and age2.

Results As patients are still being enrolled, there are no current results.

The first participant was enrolled in March 2010 and the study is expected to continue enrolling subjects for several more years un-

science & engineering reports til the sample size of 1140 participants is achieved (approximately four years from the first enrollment). The Phase II trials were singlecenter studies performed in the United States and in China. The trial in the United States (Emory University) showed that progesterone did not cause any significant adverse events, and that any adverse events that did occur were at similar rates between progesterone and placebo groups. Those randomized to progesterone were also found more likely to have a better outcome (based on the Disability Rating Scale) than those randomized to placebo in moderate TBI10. The trial done in China yielded similar results, with a lower mortality rate in those randomized to progesterone compared to those randomized to placebo. However, unlike the current Phase III trial, Xiao et. al tested outcomes at both three and six months post-injury11. The study showed that the progesterone group had a significantly lower mortality rate at six months than the placebo group (P < 0.05)11. Since the pilot trials had a similar trial design as the Phase III trial, only on a smaller scale, we hypothesize that the ongoing study will yield similar results. Based on the assessment for the primary outcome in the Phase III trial, one can predict the progesterone group will have a more favorable GOSE than placebo at six months post-injury. The difference between this trial and the pilot studies is that this phase III trial has a much larger sample size (and reduced variability due to the sample).

Discussion If the expected results are found and the data are statistically significant, this could lead to change in the clinical practice in the emergency treatment of traumatic brain injury. If the study drug is found to be effective, doctors could begin administering IV progesterone in emergency departments for their patients who arrive with blunt TBI. This would put progesterone on the fast track toward clinical care. The National Institute of Neurological Disorders and Stroke (NINDS) explains that other than surgery, the only standard of care for TBI patients is monitoring vital signs and recording a GCS14; there is no current pharmacological treatment. If progesterone is found to be safe and effective in increasing favorable outcomes in acute TBI patients, it will be the first drug effectively used for the treatment of acute traumatic brain injury.

There are limitations to this study that must be taken into account. Only adults (ages 18 and older) are being studied, so the results will not be relevant for pediatric TBI victims. There is not currently an ongoing trial in pediatric emergency medicine closely mirroring this study. Two of the three age groups most at risk for suffering a TBI are 0-4 years and 15-19 years3, putting a great emphasis on a need for a pediatric trial. Another aspect of the trial is the possibility of variation in treatment. Although the Clinical Standardization Team (CST) guidelines are presented to the clinical team by the study team, doctors at different hospitals still have different treatment plans, which may result in deviation from these guidelines, causing variation in treatment amongst patients.

The exclusion criteria of the trial must also be considered before putting this drug on the market as a proven treatment for traumatic brain injury. For example, pregnant women were not included in this trial, so how does the clinical team treat a pregnant woman with a traumatic brain injury? Is it worth the risk to the fetus to give the mother progesterone for her head injury? Such questions could be asked for all the criteria, such as whether women with previous reproductive cancers should be given the drug, or if a patient with

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science & engineering reports hypoxia and a traumatic brain injury should be given progesterone. Further studies will give answers to these circumstances. Each situation can be made into a research question, studying whether the patient would benefit from progesterone or if their current condition makes it disadvantageous.

Although it will be years, if not decades, before a descriptive label can be put on the exact usage of progesterone for further treatment of head injuries, this trial will ideally determine whether researchers have found the first effective pharmacological agent for the treatment of acute traumatic brain injury.

References

1. Faul M, Xu L, Wald MM, Coronado VG. Traumatic brain injury in the United States: emergency department visits, hospitalizations, and deaths. Atlanta (GA): Centers for Disease Control and Prevention, National Center for Injury Prevention and Control; 2010.

2. Wright, David W. ProTECT III Protocol Version 7. ProTECT III. National Institute for Neurological Disorders and Stroke, 29 Mar. 2011. Web. 1 Aug. 2011.

3. “CDC - Injury - TBI - Statistics.” Centers for Disease Control and Prevention. Web. 01 Aug. 2011. <http://www.cdc.gov/traumaticbraininjury/statistics.html>.

4. Warden D. Military TBI during the Iraq and Afghanistan wars. J Head Trauma Rehabil.

Sep-Oct 2006;21(5):398-402.

5. Roberts I, Schierhout G, Alderson P. Absence of evidence for the effectiveness of five interventions routinely used in the intensive care management of severe head injury: a systematic review [see comments]. J Neurol Neurosurg Psychiatry. 1998;65(5):729-733.

6. Brain Trauma Foundation. The role of glucocorticoids in the treatment of severe head

hurj fall 2012: issue 15 injury. Journal of Neurotrauma. 1996;13(11):715-718.

7. Allolio B, Oremus M, Reincke M, et al. High-dose progesterone infusion in healthy males: evidence against antiglucocorticoid activity of progesterone. European Journal of Endocrinology. 1995;133(6):696-700.

8. Backstrom T, Zetterlund B, Blom S, Romano M. Effects of intravenous progesterone infusions on the epileptic discharge frequency in women with partial epilepsy. Acta Neurologica Scandinavica. 1984;69(4):240-248.

9. Lancel M, Faulhaber J, Holsboer F, Rupprecht R. Progesterone induces changes in sleep comparable to those of agonistic GABAA receptor modulators. Am J Physiol. 1996;271(4 Pt 1):E763-772.

10. Wright DW, Kellermann AL, Hertzberg VS, et al. ProTECTTM: A Randomized Clinical Trial of Progesterone for Acute Traumatic Brain Injury. Ann Emerg Med. April 2007.

11. Xiao G, Wei J, Yan W, Wang W, Lu Z. Improved outcomes from the administration of progesterone for patients with acute severe traumatic brain injury: a randomized controlled trial. Critical Care. April 2008 2008; 12(R61):1-10.

12. Roof RL, Duvdevani R, Heyburn JW, Stein DG. Progesterone reduces BBB damage following bilateral, medial frontal contusion. Paper presented at: Society for Neuroscience, 1994; Miami Beach, FL. 13. Roof RL, Duvdevani R, Heyburn JW, Stein DG. Progesterone rapidly decreases brain edema: treatment delayed up to 24 hours is still effective. Exp Neurol. 1996;138(2):246-251.

14. “Traumatic Brain Injury: Hope Through Research.” National Institute of Neurological Disorders and Stroke (NINDS). Web. 14 Aug. 2011. <http://www.ninds.nih.gov/disorders/ tbi/detail_tbi.htm>.

15. Luoma, Jessie I., Brooke G. Kelley, and Paul G. Mermelstein. “Progesterone Inhibition of Voltage-gated Calcium Channels Is a Potential Neuroprotective Mechanism against Excitotoxicity.” Steroids (2011): 845-55. Print.

16. “ProTECT Overview.” Protectiii.com. Progesterone for the Treatment of Traumatic Brain Injury. Web. 01 Aug. 2011. <http://protectiii.com/>.

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