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LETTERS !"#$%&'(')**$&'+','-./012'34+4

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April, 2010

Dear Harvard Community:

As the desire among undergraduates to gain formative and substantive experiences in research contin-ues to grow and ourish at Harvard, so does the great work of the students who put together e HarvardUndergraduate Research Journal to reveal some of the thought-provoking, inspiring endeavors amongour young scholars across a wide range of disciplines.

Dean Evelynn Hammonds, early in her appointment, described her wish that every undergraduatehave an opportunity to pursue a compelling research experience. Indeed, with programs such as PRISEand the opening of the new O ce for Undergraduate Research Initiatives, Harvard College is poised tofurther support our students who are engaging Harvard faculty and other senior researchers around theworld with imaginative and intellectually stimulating scienti c projects.

e articles that appear in this journal each term endure as a cumulative testimony to some of the im-pressive e orts in research undertaken by our undergraduates. Best wishes and thanks to the THURJ sta not only for reporting to us some of these stories, but for contributing to the further development of ameaningful community among undergraduate scientists as well.

Yours truly,

Gregory A. LlacerDirector Harvard College O ce for Undergraduate Research InitiativesDirector Harvard College Program for Research in Science and Engineering (PRISE)


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Aln Aspuru-Guzik, Ph.D

Assistant Professor of Chemistry and ChemicalBiology

Paul Bamberg, Ph.DSenior Lecturer on Mathematics

Michael Brenner, Ph.DGlover Professor of Applied Mathematics andApplied Physics

Myron Essex, D.V.M., Ph.DMary Woodard Lasker Professor of HealthSciences in the Faculty of Public Health

Brian Farrell, Ph.DProfessor of Biology

Je rey Flier, M.D.Dean, Harvard Medical School, and George C.Reisman Professor of Medicine

Nicole Francis, Ph.DAssociate Professor of Molecular and CellularBiology

Steven Freedman, M.D., Ph.DAssociate Professor of Medicine

Robin Greenwood, Ph.DAssociate Professor of Business Administration

Guido Guidotti, Ph.DHiggins Professor of Biochemistry

David Haig, Ph.DGeorge Putnam Professor of Organismic andEvolutionary Biology

Marc Hauser, Ph.DProfessor of Psychology

Dudley Herschbach, Ph.DFrank B. Baird Jr. Professor of Science

John Hutchinson, Ph.DAbbott and James Lawrence Professor of Engineering and Gordon McKay Professor of Applied Mechanics

David Jeruzalmi, Ph.DAssociate Professor of Molecular and CellularBiology

E himios Kaxiras, Ph.DGordon McKay Professor of Applied Physicsand Professor of Physics

George Lauder, Ph.DProfessor of Biology and Alexander AgassizProfessor of Zoology

Richard Losick, Ph.DMaria Moors Cabot Professor of Biology

L. Mahadevan, Ph.DLola England Professor of Applied

MathematicsDavid Mooney, Ph.DGordon McKay Professor of Bioengineering

Hongkun Park, Ph.DProfessor of Chemistry and of Physics

Steven Pinker, Ph.DJohnstone Family Professor of Psychology

Tobias Ritter, Ph.DAssistant Professor of Chemistry and ChemicalBiology

Eugene Shakhnovich, Ph.DProfessor of Chemistry and Chemical Biology

Irwin Shapiro, Ph.DTimken University Professor

Zhigang Suo, Ph.DAllen E. and Marilyn M. Puckett Professor of Mechanics and Materials

David Weitz, Ph.DMallinckrodt Professor of Physics and of Applied Physics

David Jeruzalmi, Ph.DAssociate Professor of Molecular and CellularBiology Harvard MCB Department

Arthur P. Dempster, Ph.DResearch Professor of eoretical StatisticsHarvard Statistics Department

Bob Westervelt, Ph.DMallinckrodt Professor of Applied Physics and of Physics

Guido Guidotti, Ph.DHiggins Professor of Biochemistry

Shaye J.D. Cohen, Ph.DNathan Littauer Professor of Hebrew Literatureand Philosophy

Boards

BusinessRuoyu Zhang, 13Kevin Fan 13

ContentAlissa DGama 11 - Associate Managing

EditorSophie Wharton 11 - Associate Managing

EditorPatrick Snodgrass 13Jung Soo (Tom) Lee 12Stacy Rush 11

Caroline Huang 13Je rey Atwood 13Yi Cai 11

Peer Review and SubmissionsWilliam Sun 13 - Associate EditorHelen Yang 11 - Associate EditorJessica Zeng 12 - Associate EditorPatrick Snodgrass 13 - Associate EditorAbby Schi 11 - Associate EditorAllen Shih 13 - Copy EditorNathan Kim 13 - Copy EditorIsabella Wechsler 13Xuezhi Dong 12Peter Zhang 13

Jeanine Sinanan-Singh 13Keli Liu 13Johanna Lee 13Katherine Xue 13Akachimere Uzosike 13Doris Chen 13Edward Kogan 12Jacob Cedarmaum 12Jacob Weatherly 12John Liu 11Andrew Chen 12Johnny Hu 11Meng Xiao He 11Sway Chen 12Ye Zhao 13Nicholas Tan 12Eva Gillis-Buck 12Vanisha Yarbrough 10Darius Li 12Justine Cheng 13Alex Mays 12Fiona Wood 13

Managing Editor of ContentJen Gong 12

Managing Editor of Peer Review andSubmissionsMonica Liu 12

Executive BoardCo-Editors-in-Chief John Mei 12 and Grace Cho 12

Business ManagerVarun Bansal 13

Design ChairAmanda Lu 13

Manager for Social and PublicRelationsJanet Song 13

Faculty Advisory Board

Faculty ReviewersDesignRitchell van Dams 11 - Associate ChairJung Soo (Tom) Lee 12Allen Shih 13Shimwoo Lee 13

Casey Alcantar 13Peter Zhang 13Chioma Madubata 11

Social and Public RelationsPreya Shah 13 - Associate ManagerCaroline Huang 13Rohini Shivamoggi 13Jeanine Sinanan-Singh 13Jung Soo (Tom) Lee 12Shannon Purcell 12

CONTENTS !"#$%&'(')**$&'+','-./012'34+4


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About Us

e Harvard Undergraduate Research Journal (THURJ) showcasespeer-reviewed undergraduate student research from all science andquantitative social science disciplines. As a biannual publication,THURJ familiarizes students with the process of manuscriptsubmission and evaluation. Moreover, it provides a comprehensiveforum for scienti c discourse on the cutting-edge research that impactsour world today.

At its core, THURJ allows students to gain insight into the peerreview process, which is central to modern scienti c inquiry. AllTHURJ manuscripts are rigorously reviewed by the Peer Review Board(consisting of Harvard undergraduates), and the top manuscriptsthat they select are further reviewed by Harvard graduate students,post-doctoral fellows, and professors. is process not only stimulatesfaculty-student collaboration and provides students with valuable

feedback on their research, but also promotes collaboration betweenthe College and Harvards many graduate and professional schools. Inaddition to publishing original student research papers, THURJ is alsoan important medium for keeping the Harvard community updated onscience research-related news and developments.

Contact

General : [email protected]

Advertising : [email protected]

Subscribing : [email protected]

Submissions : [email protected]

Website : http://www.thurj.org

Copyright 2010 The HarvardUndergraduate Research Journal.

No material appearing in this publicationmay be reproduced without writtenpermission of the publisher, with theexception of the rights of photographswhich may only be granted by thephotographer. e opinions expressedin this magazine are those of thecontributors and are not necessarily shared by the editors. All editorial rightsare reserved.

CONTENTS !"#$%&'(')**$&'+','-./012'34+4


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Features


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FEATURE Volume 3 Issue 1 | Spring 2010

8 The Harvard Undergraduate Research Journal

Since his youth, Adam Cohens passion has been forscienti c inquiry. Growing up in Manhattan, the cur-rent Assistant Professor of Physical Chemistry at Har- vard remembers picking up pieces of electronics fromthe garbage, taking them home, and trying to x them.In seventh grade, he enrolled in a graduate level coursein electronics, which led him to build his own lab in hishouse, complete with all the tools to build complex cir-cuits. Despite his intense interest in science, Cohen doesnot only focus on his research. Electronics led to physics,which he studied as an undergraduate at Harvard. erehe participated in several extracurricular activities: hetravelled abroad in Ecuador as part of Lets Go, a travelwriting program, and taught science to young childrenwith the ExperiMentors, a PBHA group which still existstoday on campus. He also worked in George Whitesidesschemistry lab for all four years as an undergraduate.Coming back to Harvard as a professor showed Cohena di erent side of the university: As an undergrad I was

unaware of all the graduate students, but there are justas many graduate students as undergraduate students,and there is a whole other part of the university goingon independent of the classes.

Cohens chemistry interest came from an unlikely path.As a senior in high school, he built a scanning tunnelingmicroscope as an entry to a science contest. is led himto work in a lab in MIT, helping to develop new scannersto detect land mines, which in turn sparked an interest inphysical chemistry. In Whitesidess lab, he continued toresearch sensor technology. Concentrating in both chem-istry and physics, he described his research as applyingphysical insights to chemical problems. A er earningP.h.Ds from both Oxford and Stanford, he returned toHarvard as an assistant professor of chemistry. Eventhough he has an extensive resum, Cohen still nds timefor his non-research pursuits. Graduate student YiqiaoTang stated that one the reasons he was attracted to thelab was Cohens devotion to his students and researchers.

Despite the change from building electronics at home,to working in a lab at Harvard, the same desire to go

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rey Atwood 13, THURJ Sta

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beyond the bounds of human knowledge motivates his

research. To make a prediction, do an experiment, andsee that prediction born out in reality is amazing, Cohenexplains. His research covers a wide variety of topics,from the theoretical to the practical. For example, oneof his current projects is to gain a basic understandingof mucus and how bacteria cantravel through it, a subject thatthe scienti c world knows sur-prisingly little about. Much of his research, as he puts it, is todevelop tools that other scien-tists can use in order to makediscoveries. We build new waysof visualizing molecules, new ways of controlling theirpositions, and new ways of controlling their internal statesand reactivity. Despite being a relatively young profes-sor, he has already received several prestigious awards,including the Camille and Henry Dreyfus Award for NewFaculty, and the DARPA Young Faculty Award.

One of Professor Cohens most unique projects, how-ever, is not research-based. Over the summer of 2009,Professor Cohen and other scientists traveled to Liberiato try and improve the quality of science education in thatcountry. Cohens connection with Liberia is personal. eadviser for his high school science club was from Liberia,and many times, Cohen would see him collecting schoolsupplies to send to his family in Liberia. e two formed

a personal connection, and as a professor at Harvard, heinvited him to speak, and this gave him the idea to travelto Liberia and see what he could do to help.

In Liberia, the team met with civic and religious leadersand examined the nations educational facilities, from itselementary schools to the sole medical school in the coun-

try. ey even gave sermons at local churches explainingthe bene ts of science education. One of their main nd-ings was that much of the aid to Liberia is wasted. eequipment sent cant be used, either because the citizensdont know how to use it, or because they dont have theinfrastructure. Together, the group focused on ways toimprove scienti c literacy without the equipment andteaching aids that universities in the United States takefor granted. Cohens group showed the students at thelocal medical university how to do a DNA extraction ona tomato, which Cohen called, probably the rst DNA

puri cation ever done in Liberia. ey also tried toteach the people about basic issues that were relevant tothe local community, such as the germ theory of diseaseand malnutrition. He plans to make a return trip in thesummer to lead a workshop at the University of Liberia

in the hopes that these people willeventually teach others and reedu-cate a nation that lost its youngestgeneration of scientists, doctors,and teachers to civil war.

With so many demands, Cohenstill manages to make time to takecare of his lab members and stu-

dents. He throws parties and cooks for his researchers athis house. Perhaps his most important contribution to hisresearchers is to teach them to be unafraid to be curious,and pursue their ideas. Graduate student Yiqiao Tangsummed up his lesson as, Premature is not such a badthing; its always good to talk to people, and to hear theircomments about this idea. As a scientist with a strongconnection to students, Cohen has one word of advicefor young future scientists: Work in a lab. However,he follows up with a word of caution. eres an issuethat people sometimes run into: that doing well in sci-ence classes here has very little to do with being a goodscientist e key to being a good scientist is asking theright questions.

Perhaps his most importantcontribution to his research-ers is to teach them to beunafraid to be curious , and

pursue their ideas.

Professor Cohen teaches a class to Liberian students.

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By Stacy Rush 11, THURJ Sta

H opi Hoekstra likes mice. A professor in HarvardsOrganismic and Evolutionary Biology depart-ment, Hoekstra is cracking the fundamental relationshipbetween genes, traits and the e ect of the environmenton survival and reproduction. She originally worked withgrizzly bears but quickly realized that to answer any largequestions she needed large sample sizeswhich neces-sitated the use of small organisms. Mice breed proli cally,are easily maintained in a lab settingand, as Hoekstraadds, they do happen to be very cute.

While doing her postdoctorate, Hoekstra spent hertime trapping rock pocket mice in sunny Arizona. Shefound that mice that lived on lava owsdark coloredrocktended to have dark coats, while mice living in alighter environment tended to have light coats. In otherwords, coat color closely [matched] the environmentin which [the mice] inhabit. On the black lava light-colored mice were big targets for predation because they are these bright golden beacons running around on thisblack lava.

But Hoekstras small subjects held big lessons in store.Back in the lab, scientists tracked down a genetic sourcefor the phenotype. Hoekstras team pegged the melano-cortin-1 receptor gene ( Mc1R ) as a key ingredient for thedi erence. A mutation allowed mice to camou age withtheir environmentsan impressive example of evolutionin action.

Hoekstra did not stop there. She found the same phe-nomenon in Floridian populations of beach mice. OnFloridas Gulf coast, mice displayed a dark coat color

compared to mice on the Santa Rosa Island (Hoekstraet. al., 2006). e color di erence was driven by selec-tion for camou age, as many predators are visual hunt-ers. Hoekstras team pegged the same Mc1R gene as acontributor to the adaptive pattern. A single nucleotidechange weakens the receptor so that it does not respond tosignaling as well, creating a light-colored coat phenotype.

at the coat color of the mice matches their surround-ings is only evident through eld observations, whichis why Hoekstra stresses the importance of a hands-onapproach. You just walk out on these brilliant whitesand beaches where you see theres very little vegetativecover and it just makes sense that mice that are lighter incolor are going to be more camou aged, she says. isresearch led National Geographic to hail Hoekstra as anew Darwin just in time for Darwins 200th birthday,which was this past year.

Hoekstra has since branched out to study other micecharacteristics, including tail length variation, repro-ductive traits, and behaviors. According to Jesse Weber,a graduate student in her lab, every diverse thing youcan think of for adaptation in rodentsis fair game inthe lab.

Weber is currently studying the evolution and genetics

Above: Hopi Hoekstra observing a eld mouse.

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of instinctive burrowing in two species of Peromyscus, ordeer mice. Peromyscus polionotusbuilds complex burrowswhile Peromyscus maniculatus builds simple burrows.

e simple burrow consists of just one entrance whilethe complex burrow also contains an escape exit that isdug up to just below the surface. is allows the miceto make a hasty getaway in times of danger. When P.maniculatus and P. polionotus are crossed and then re-crossed, the hybrid progeny mice will build variations of the complex and simple burrows. To enable observationof just this sort of behavior, the lab houses giant four-by- ve feet sandboxes which Hoekstra calls phenodomes

because thats where we measure phenotype. e miceare put in the phenodomes for two days and allowed tobuild a burrow. ey are then removed and researchersmake a cast of their burrow using a kind of hardeningfoam. e cast is then studied just like any other mor-phological trait. is is what Richard Dawkins calls an

extended phenotypeits not actually held within ourskin, yet its controlled by genes, explains Hoekstra. Forfurther research, the lab also has what Hoekstra calls amouse farm - similar in concept to an ant farm. Youcan videotape [the mice] burrowing in a two-dimensionalstructure and they will build these complex burrows,Hoekstra says.

Re ecting on the challenges of her work, Hoekstrasays that it is very integrative. For any given project toget the complete picture of adaptation, it requires essen-tially working across disciplines. We do ecological work .work at the organismal level work at the devel-opmental level down to the genetics and the molecularbiology. Its hard in some sense to do all of it and all of it well. However, she adds, the combination of all theseaspects of biology makes our work fun. As she said inNational Geographic, Opening a trap with a mouse is alittle like Christm as morning.

Above: Camo auge, a light mouse matching its environment.


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doubt, beyond sane, informed, intelligent doubt, beyonddoubt evolution is a fact. In his preface, Dawkins notesthat in his previous books he has assumed the theory of evolution without providing the facts that con rm it,but catalyzed by the glaring reality of these 40 percentof Americans the history-deniers, he sets out to provethe theory of evolution in e Greatest Show on Earth.

As Dawkins explains in his second chapter, evolutionis o en misunderstood in popular culture as the idea thathumans evolved from other apes. Instead of claiming thatwe evolved from modern chimpanzees or orangutans,the theory of evolution holds that we shared a common

ancestor with them thatwas neither ape norhuman, but would even-tually, over millions of years and a staggeringnumber of generations,evolve into the di er-ent primates that we seetoday. He also dispersesanother common mis-conception by explaining

that evolution itself involves an entire speciesnot justone organism. e mechanisms of evolution only work because of the variation in each species that allows natureto select for certain traits in a population.

A er explaining the basics of evolution, Dawkinsmeticulously discusses the di erent agents of evolutionand the evidence le behind by those paths that we canexamine. He even goes as far as to explain the methodsthat we can use to date the fossils and other remainsand how they can be cross-checked with each other. Hedoesnt state facts; he explains how the processes involvedin evolution and studying evolution work.

It is evident from his writing that Dawkins is an experton the subject of evolution and is well-practiced againstbattling the non-believers. To counter the Creationistidea that the world is less than 10,000 years old, he drawsupon evidence from radioactive dating. In the face of the

By Caroline Huang 13, THURJ Sta

Do you believe in evolution?People either accept evolution as a fact or they dont

believe in itrarely do you meet a person without anopinion. When I posed this question to my roommate Iwas attempting to be diplomatic, but I regretted it almost

immediately a erwards. Was the question too prying?Should I have attempted to segue smoothly into the subject, with some backup topic ready to return to, insteadof opening our conversation with that particular inquiry?It was odd to talk and think about a scienti c theory as if it was a taboosubject; normally only social issuesmerit this aura of untouchability. etheory of evolutionmay be unique in itscapacity to stir upcon ict and discom-fort. I would not feelat all uneasy posinga similar question to my roommate about quantum theory (which is generally much less well-known and under-stood), and likely she would not have paused for one tell-ing second before replying with an air of certainty: no.

November 24, 2009just shy of three months a erRichard Dawkins published his book e Greatest Showon Earth: e Evidence for Evolutionmarked the 150 th anniversary of the publication of Charles Darwins semi-nal work of evolutionary biology, On the Origin of Species.Charles Darwins own 200 th birthday was in February of the same year. e ap of Dawkins newest book informsus that a 2008 Gallup poll found that over 40 percentof Americans deny evolution. Ostensibly they are hisaudience for this book, for he spends most of the rstchapter discussing the viewpoints of his 40-percentersand stating that the message of the book is to convincethe reader that beyond reasonable doubt, beyond serious

Beyond reasonable doubt,beyond serious doubt, beyondsane, informed, intelligent doubt,beyond doubt evolution is a fact.

-Richard Dawkins


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argument that animals are too perfectly evolved to havebeen the product of an unconscious design-by-nature,he shows the ridiculously long detour of the recurrentlaryngeal nerve in a gira es necksome extra 15 feetthat serves as a reminder of its gilled ancestors. Gaps inthe fossil record? We are lucky to have a fossil record

at all, and given the miniscule chances of fossilizationour collection is actually quite large and compelling. Torefute the idea that evolution from a simple, singled-celledorganism, even if it were possible, would have taken lon-ger than the approximately four billion years since life

rst appeared on earth, Dawkins quotes J.B.S. Haldane,one of the most important gures in neo-Darwinism:You did it yourself in nine months.

e book is accessible to anyone with an open mindand an interest in the subject. Dawkins knows exactly how long to linger on a par-

ticular subject and how far indepth his audience will care togo into a certain experiment.Plus, the accompanying pic-tures and supplementary colorpages make for an even moreenlightening and enjoyablereading experience.

Now the question remains:if you are a Creationist why would you read this book?

I am reminded of a time when my other roommate,a vegan, attended a debate on vegetarianism. Before theconversation began, the representative from PETA askedthose who were present, How many of you are vegan or vegetarian? More than 90 percent of the audience raisedtheir hands. Is Dawkins merely preaching to the choir?

Despite professing to address his 40-percenters, I can-not say that his book is written for a Creationist audience.His tone o en borders on belligerent and his comparisonof the evolution-denier to the Holocaust-denier couldonly serve to alienate the very people he seems to want toconvince. However, he writes as if trying to engage in thediscussion with the opponent, stating and then refutingeach of the standard arguments against evolution broughtup by Creationists.

e evidence that Dawkins manages to t into a book of easily readable length is vastfrom fossil records toscienti c experiments, from selective breeding by humansto sexual reproduction in shbut evolution-deniersmay be most convinced by the arguments he presents near

the end of his book in his chapter concerning theodicy.eodicy is the attempt to reconcile the goodness of

God with the presence of evil in the world. In evolution-ary terms, one might expect a bene cent creator to reducethe amount of su ering in the world, but that is not thecase. e natural state of the world is one of famine, of

pain and su ering, and of distressall this clearly demon-strated in most predator-prey relationships. e speci cexample that Dawkins chooses to highlight was one thatdisturbed Darwin as wellthe behavior of ichneumonwasps. e females meticulously paralyze and lay eggs inlive caterpillars. eir eggs hatch into larvae that proceedto consume the caterpillar inside out in a manner whichmaximizes su ering by starting with the least importantinnards before consuming the essential onessuch asthe heartto keep the caterpillars alive as long as they

can. is insures that the meat

is fresh for the o spring. Docaterpillars feel pain? Dawkins

hopes not.Even theodicy, however, is

not a compelling argumentfor some. e existence of evilin the world is justi ed easily enough as a result of Adam andEves abuse of free will that led

to their expulsion from Eden. Perhaps, more than any-thing else, this book is a manifestation of the idea that sci-ence and religion simply dont mix. By this, I dont meanto say that one cant be both a scientist and religious, butthat faith-based evidence should not be used to supportor denounce scienti c theory, just as scienti c evidenceis not used to sustain faith. e existence of a place likeEden and the motivations and actions of a divine Creatorare all part of the supernatural, and science does not dealwith the supernatural.

A er reading e Greatest Show on Earth , there is nodoubt that the overwhelming evidence for evolution canbe found in sources as varied as every organism on theplanet. Yet in the face of religion does any of this matter? Itis clearly not lack of evidence that has le so many peopleunconvinced; maybe what Dawkins has shown is that it isimpossible to write a book about evolution for Creation-ists. But this is no fault of the author whose argument isseamless; rather it is a testament to the irreconcilability of science and religion in this debate.

Perhaps, more thananything else, this book is a manifestation of theidea that science and re-ligion simply dont mix.


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like. Reprogramming in general refers to the conceptof changing the wiring, or the global gene expression,of a cell in order to change its identity. In the case of stem cell research, reprogramming refers to the geneticmanipulation of a di erentiated cell a skin broblast, acardiomyocyte, or even a cell of the pancreas to turn

it into a cell that resembles an embryonic stem (ES) cell.e product of successful reprogramming is referred to as

an induced pluripotent (iPS) cell. In 2006, Yamanaka andTakahashi of Japan rst reported the derivation of iPS cellsfrom mouse broblast cells in their seminal paper. Justa year later, various groups had succeeded in generatinghuman iPS cells. Since then,reprogramming has becomeone of the major, if not themain, focus of todays stemcell research.

To the average person,this almost seems like atechnique straight out of asci- movie. By reversingthe time on a di erentiated cell, researchers have beenable to generate iPS cells that exhibit two important char-acteristics of an embryonic stem cell: self-renewal, orthe ability to inde nitely make more copies of itself, andpluripotency, or the capacity to di erentiate into morede ned cell types.

For Dr. Hochedlinger, this phenomenal di erentiationpotential of embryonic stem cells and iPS cells drew himto stem cell research. He found it fascinating that youcan capture in a petri dish undi erentiated cells that canbe coaxed into all cell types of the body.

It is this much talked about concept of pluripotency and iPS cells that has gained the interest of many medicalresearchers who believe that the technique may allow thedevelopment of novel regenerative therapies and treat-ments for degenerative diseases of the human body.

Take, for instance, Parkinsons disease, in which degen-eration of midbrain dopaminergic neurons leads to severeloss of motor skills along with many other debilitatingsymptoms. In the near future, scientists may be able totake the patients skin cells from a simple biopsy andreprogram them into iPS cells. ose iPS cells can thenbe directed to di erentiate into dopaminergic neuronswhich can then be transplanted back into the patient.Not only would this kind of therapy replace cells that arelost during disease, but it would also bypass the problemof immune rejection that always complicates transplantprocedures because the replacement dopaminergic neu-rons would be generated from the patients own skin cells.

Although reprogramming may seem like the perfectsolution for curing various degenerative diseases, thereare still many obstacles to overcome in the original repro-gramming method described by Yamanaka and Takahashibefore they can be used to treat diseases in humans.

First of all, the e ciency of reprogramming remains

very low and the procedure is quite time-consuming.In order for the procedure to be useful for medical pur-poses, it must yield considerable numbers of iPS cellsfor researchers to manipulate in the laboratory. As Dr.Hochedlinger describes, a possible strategy for improvinge ciency is to pick di erent cell types from ones used

today [skin cells, broblasts].Weve shown in the blood systemthat if you start with immaturecells, cells are more e ciently converted to iPS cells. This

approach makes intuitive sense,since less differentiated andyounger cell types are closer inidentity to embryonic stem cells.

ese immature cells would have less distance to travelbefore they are reprogrammed into iPS cells.

Another way to prove e ciency is to inactivatepathways for inducing senescence in cells, as Dr.Hochedlinger explains. Senescence refers to the point atwhich cells have aged so much that they stop dividing.

. . . the e ciency of repro-gramming remains verylow and the procedure isquite time-consuming

A diagram illustrating the goal of using iPS cell technologyto treat various regenerative diseases. A tissue sample can beharvested from a patient, reprogrammed into iPS cells, anddi erentiated into a desired cell type for re-transplantationback into the patient.


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Because the cell types used in reprogramming are o enolder, adult cells and the process takes many days to com-plete, allowing cells to reach an immortal state to allowthem to avoid aging and senescence prior to reprogram-ming may improve the e ciency of the process.

Even if some of these barriers to use of iPS cells in

therapies are overcome, it may be awhile before they canhelp treat numerous degenerative diseases. It is still notknown how to make a variety of true cell types frompluripotent cells, says Dr. Hochedlinger. We know howto make cardiomyocytes and neurons, but thats aboutit. Another problem is how to engra cells. Once youvemade neurons, you have to know how to gra themto make them functional. Yetanother issue lies in the natureof iPS cells speci cally. We dontfully understand if iPS cells are

exactly equivalent to ES cellsif they do everything ES cells do.Despite the seemingly end-

less number of issues withreprogramming that need to beaddressed, researchers are cur-rently trying to solve all of theseproblems in order to perfect the promising technique.

Dr. Hochedlingers lab, for example, seeks to study not the end result of iPS cells, but the actual process of reprogramming. Reprogramming takes about 10 daysto 2 weeks in culture. We have no good understanding of whats going on in those 2 weeks, says Dr. Hochedlinger.Weve isolated cell surface markers that are downregu-lated and upregulated in cells that eventually becomeiPS cells. ese markers allow us to pull out cells [to

study them] at di erent time points when theyre notyet iPS cells. e Hochedlinger lab is also studying theidentity of iPS cells. Were trying to understand if embry-onic stem cells are equivalent to iPS cells, explains Dr.Hochedlinger. Weve developed a system in mice, so wecan compare genetically identical ES and iPS cells. Were

using genome wide technologies to really look at every nucleotide in the genome to gure out what the di erenceis between the two cell types.

With the many stem cell labs working to further re nethe process of nuclear reprogramming, medical therapiesusing reprogrammed cells may not be out of the question.

e original studies of Yamanaka and Takahashi that ledto the derivation of the rst iPScells have led other researchersto develop di erent reprogram-ming methods. For example,

direct lineage reprogramminginvolves the reprogramming of one adult cell type directly intoanother cell type without passingthrough an iPS cell stage.

Although at this point, it is dif-cult to assess how realistic the

expectations of using reprogramming technology fordisease treatments are, iPS cells are already making greatcontributions to researchers understanding of diseases.Deriving iPS cells from diseased cell types give researchers the ability to study diseases in a petri dish as they develop and unfold. By using iPS cells as human diseasemodels, researchers are coming closer to developing newtreatments for many incurable disorders.

We dont fully under-stand if iPS cells are ex-actly equivalent to EScells if they do every-thing ES cells do.


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N F

C C by Patrick Snodgrass 13, THURJ Sta

A lthough not completely acceptedby the public, the idea thathumans can adversely affect

global climate is fast becominga commonplace notion. Yet thesubject of atmospheric chemis-try research addressing climatechange did not even exist justthirty years ago.

Since the 1970s, the toolsavailable to researchers in the

eld have evolved from rudimen-tary weather balloons to complex,infrared satellite instruments. At thesame time, Harvard has emerged as oneof the leading worldwide research centers inatmospheric chemistry and climate change.

Housed in Harvards Department of Earth and Plan-etary Sciences, atmospheric chemists are investigatingeverything from how to model the e ect of pollution onglobal warming to how to develop optical instruments tocreate an accurate climate record. eir research providesinsight into how policy-makers can help mitigate thee ect of human activity on the environment.

Lasers and Satellites

In addition to the continued work on global warming,research is now transitioning toward understanding thebroader e ects that changes in atmospheric compositionhave on the climate. James Anderson, the Philip S. WeldProfessor of Atmospheric Chemistry, recognizes thatresearch in the eld requires more robust as well as moreaccurate climate data. He has witnessed the developmentof the eld and made many of the measurements thatestablished the existence of the Antarctic ozone hole.

Anderson was instrumental in thepassage of the Montreal Protocol,

a document banning the use of

chloro uorocarbons (the mainagents causing depletion of theozone layer). He understandsthat the public remains largely unconvinced that humans havedirectly caused climate changesuch as global warming. How-ever, he stresses that the major-ity of the scienti c community

supports the view that climatechange is primarily caused by

human factors.

However, it is necessary to generate data to demon-strate the connection between human activity and climateto in uence public policy. is is the motivation for many of Andersons current research endeavors.

Setting in place a very high accuracy record of howthe entire coupled climate structure was of paramountimportance, says Anderson. And so, in 1996, we pro-posed to build a highly accurate small satellite that wouldbe in the infrared spectrum.

He understands thatthe public remains largely unconvinced that humanshave directly caused climatechange such as global

warming.


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Although he faced some setbacks along the way,Anderson successfully built this instrument. e devicewill hopefully create a long-term global record of climate,while achieving a new level of accuracy.

is device measures the spectra of infrared radiationemitted by the earth. e data can be used to generate

global temperature distributions, atmospheric composi-tion, and radiative forcing, all of which are necessary tocreate a precise picture of global climate change.

is instrument is meant to help create a climate moni-toring system, key to the development of the eld. iscountry doesnt have a climate observing system, saysAnderson. It only has pieces of what you would call a very rickety system, and its simply not capable of provid-ing hard scienti c evidence for public policy.

e infrared satellite instrument will hopefully provide the data necessary to better understand the earths

dynamic climate structure.

Modeling of Atmospheric Chemicals and Cli-mate

Collecting data with atmospheric instruments is notan end in itself. Rather, atmospheric chemists use climateand chemical models to interpret the raw data suppliedby researchers like Professor Anderson with the intent of understanding the interaction between the atmosphereand climate.

The Harvard Atmospheric Chemistry ModelingGroup, led by Professor DanielJacob and Dr. Jennifer Logan, isat the helm of atmospheric mod-eling with the novel GEOS-Chemchemical transport model. eGEOS-Chem model calculatesthree-dimensional atmosphericcomposition using estimates of emissions of various chemicalsinto the atmosphere. It simulatesthe ow of these chemicals whenthey are blown by winds and when they react with otherchemicals.

Central to this model is the data collected by satellites.Satellites, for a modeler like myself, says Professor Jacob,are very exciting because satellite observations meannothing without a good model.

Discrepancies between the measured satellite dataand the data simulated with the GEOS-Chem model arerevealed when the two sets of data are compared. eGEOS-Chem model is subsequently modi ed to reduce

the discrepancy between the measured and simulateddata, and ultimately to improve the models ability toforecast atmospheric composition. is demonstrateswhy the instruments developed by the Anderson Groupare so important to this eld.

Chemical transport models like GEOS-Chem are cru-

cial to an understanding of climate systems since they canreveal how chemicals released into the environment a ectclimate. By pairing these models with climate changemodels, scientists discovered that the release of green-house gasses like CO2 into the atmosphere may be a majorcause of global warming.

Eric Leibensperger, a graduate student in the lab group,recently demonstrated how these chemical transportmodels can be used to understand changes in climate.Leibensperger simulated the changes over time in theatmospheric concentration of aerosols (particles of air

pollution). He then used a global climate model to trans-late these changes into their e ects on global tempera-tures. In the process, Leibensperger showed that if youremove the U.S. sources of aerosols, you actually warmthe United States. He also veri ed that this warminge ect would be felt only locally above the US.

An Interconnected Climate System

Despite improvements in modeling technology anddata collection, climate and chemical models still struggleto replicate the complex climate structure. Professor Ste-

ven Wofsy, who studies sources andsinks of CO2 and other chemicals inthe atmosphere, is well acquaintedwith the challenges of climate models.

What I think is the most impor-tant scienti c issue that slops overto the policy and social realms isthat the [climate] system is highly interactive and nonlinear and thatthe one thing we really know aboutthese systems is that they are hard to

predict, says Wofsy. In fact, they are generally thoughtof as being unpredictable.

e reason that these complex models o en break down is that the atmosphere is intricately connected tothe environment in ways we do not yet understand. eatmospheric changes caused by chemical emissions donot stop with changes in global temperatures.

Professor Anderson explains this phenomenon: I liketo make the analogy that a 1C increase in global meantemperature, global warming, is to the climate as a 2%

Chemical transportmodels like GEOS-Chem are crucial toan understanding of climate systems


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default rate on a mortgage is to the nancial structure. Ittriggered a sequence of events in the climate and nan-cial structures that led to collapse, but the feedbacks inthe nancial system are what really caused the systemto implode.

e new frontier of climate change research is shi ing

toward understanding these climate feedbacks. Althoughthe Anderson Group is continuing to work on their infra-red satellite instrument, the group is now also exploringthese feedbacks.

Two main focuses of the Anderson Groups newresearch are the Arctic ice caps and the glaciers onGreenland. e melting and collapse of these systemshave the potential to exacerbate climate change and globalwarming.

To better forecast the futureof the Greenland glaciers, the

Anderson Group is developinginstruments to map the topog-raphy and three-dimensionalstructure of the glaciers. Inaddition, the group is develop-ing underwater instruments togather information about the Arctic ice caps.

e endeavors of Professor Wofsy and the AndersonGroup are providing the eld with much-needed infor-mation on the interaction between the climate and envi-ronment. is information is critical to the developmentof the eld since it is necessary to develop more accu-rate models and to understand the mechanisms throughwhich human activity a ects the environment.

What Now?

Although there are already noticeable consequencesdue to climate change, its future e ects promise to befar worse than any observed to date. Something bad isgoing to happen, says Wofsy. What, I dont know, but I

do know that it is going to be sudden.Both Wofsy and Anderson agree that establishing pub-

lic policy sooner rather than later is necessary to curb thee ect of human activity on climate. e role of govern-ment here is unprecedented, says Anderson. For eco-nomic competitiveness, for national security, we have tomove very quickly to renewable energy and fortunately,we have it. e United States has the resources to power

two thirds of its energy withsolar and wind power. It justrequires time to develop.

However, with climateresearch in an early stageof development, it seemsunlikely that politicianswould support changes inenvironmental public policy

based on current ndings. Establishing unequivocal evi-dence is a huge feat, let alone dra ing legislation with aprice tag that taxpayers would approve.

Yet Anderson is optimistic about the future: I have nodoubt that we can do it. But the government has got tostep in and develop the economic infrastructure.

But Anderson is not the only one with this positive atti-tude. Rather, it pervades Harvards atmospheric chemistry and climate change research groups. ese researchers aredetermined to not only understand the complex climatesystem but also to ght for its preservation.

The United States has the

resources to power two-thirds of its energy withsolar and wind power.


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Collaborative e orts between the Harvard Medi-cal School, Beth Israel Deaconess Medical Center(BIDMC), and Partners HealthCare founded the non-pro t institution, the Harvard Clinical Research Institute(HCRI). In this joint venture headquartered near theBoston University campus, industry meets academia toadvance clinical research in multiple areas, from medicaldevice trials to quality of life assessments.

The OriginsHCRI was founded with much of the same collabora-

tive zeal and academic focus that the institute continuesto emphasize today. At the Harvard Medical School abouta decade ago, Dr. Eugene Braunwald, Dr. Joseph Martin,Dr. Victor Dzau, and Dr. Ray Dolin shared the vision of aunion between academia and industry to create a clinicalresearch organization that would contribute to the eldin a productive and responsible way. eir brainchildcame to life with the launch of HCRI in 2000.

e institute also involved entities from BIDMC andPartners Healthcare. For instance, the then Cardiovascu-lar Data Analysis Center (CDAC) at BIDMC became animportant part of HCRI. Dr. Je rey Popma, a founder of CDAC, recalls the inspiration behind the beginning of thecenter. At the time, he says, the databases to house thedata were not very sophisticated. So, CDAC was foundedto assist in the generation of reliable data and to facilitatean interface with industry. In the mid-1990s, CDAC car-ried out many clinical trials that would come to transformthe eld of coronary stenting. A er the founding of HCRI

in 2000, CDAC became a part of the institute formed tofacilitate collaboration between BIDMC, MassachusettsGeneral Hospital, and Brigham and Womens Hospital.

The Mission of the InstituteCurrently, HCRI continues to provide full-service clini-

cal trials and is regarded as one of the premier institutionsof its eld. HCRI is a liated with Harvard and consistsof professionals involved with the institute at a formal orinformal level. However, it also has characteristics thatset it apart from other clinical research organizations.For one, Executive Director of Clinical InvestigationsDr. Donald Cutlip says that what makes HCRI uniqueis the availability of typical commercial services withina world-class academic environment. at is, academicphysicians and scientists are involved throughout eachstage of a trial, and the institute is supervised by a Boardof Directors composed of academic professionals. Fur-thermore, HCRI upholds a strict con ict of interest policy.As Dr. Cutlip notes, this adds a level of independentoversight that is not seen in most commercial clinicalresearch organizations or certainly when individualindustry sponsors oversee their own trials.

HCRIs emphasis on academics does not go unno-ticed. Dr. Cutlip accredits HCRIs academic reputa-tion and ability to work with industry without the usualcon icts as crucial in their winning a proposal for animportant research project called Dual Anti-Platelet

erapy (DAPT). e project, which just started thispast fall, aims to design and manage a large public health

The Synergistic Combination of

&

at the H ARVARD C LINICAL R ESEARCH INSTITUTE

By Yi Cai 11, THURJ Sta


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trial for the study of appropriate clot prevention therapy for patients who receive coronary stents (small tubesplaced in coronary arteries that are blocked in orderto treat coronary heart disease). is study was man-dated by the Food and Drug Administration (FDA), issponsored by four large stent manufacturers and four

large drug companies, and is projected to involve over20,000 patients. Indeed, it is a high-pro le study and theproposal was won during a very competitive process.

Facing the Future

HCRI faces many challenges moving forward, espe-cially in the current economic climate. Inevitably, inno- vation in the eld has slowed as a result of clinical trialsmoving along longer timelines than in the years before.

Consequently, the economic side of clinical researchhas become increasingly signi cant. Dr. Matthew Reyn-olds, Director of HCRIs Economics and Quality of LifeResearch Center, says that it is now more important fordevelopers of new technologies, such as our sponsors,to demonstrate not only the clinical value, but also theeconomic value of their techniques.

However, HCRI has been pleasantly surprised by theirperformance in the dire economic climate. Last year,HCRI overcame economic challenges by sound businesspractices and careful economic planning, says SpencerGoldsmith, President of HCRI. Dr. Reynolds also creditsthe federal stimulus package with creating many newopportunities for comparative e ectiveness research. Cur-rently, HCRI is undertaking two NIH-funded compara-tive e ectiveness projects and in the process of designingmore. Dr. Cutlip explains that some prospective studiesplan to compare non-surgical heart valve replacementwith open heart surgery in patients who are at higherrisk for open heart surgery. is is a very novel therapy that is in its infancy but could have major impact onfuture treatments. us, despite economic challenges,

HCRI still seems to be steadily making progress towardits original mission each day.

One new goal for the future of HCRI, according toDr. Cutlip, is to reach out as an academic leader tohelp improve clinical research methods, which includesdevelopment of industry models for adjudication of

clinical events within clinical trials, an area in which wehave become recognized as a leader. HCRI has recently founded the Academic Research Consortium, a collabora-tion of other academic research organizations, industry,and the FDA that aims to standardize clinical trial designsand endpoint de nitions for clinical trials of coronary

stents and heart valves. In its collaborations with the gov-ernment, HCRI has had a powerful impact on the produc-tion of biomedical products and on their implementation.HCRI also hopes to play a role within Academic ResearchConsortium to help improve the con ict disclosure andmanagement process. Dr. Cutlip says that clari cationof these policies within Harvard institutions has been amajor development, and extending such developmentsto the rest of the eld is an important issue.

HCRI has clearly made great contributions to theeld of clinical research, due in part to its academically-

oriented mindset. As Dr. Popma re ects, without thecollaboration between academics and industry, I am notsure that the advances that have happened over the pastdecade could have been achieved. As HCRI celebratesits decade anniversary, it has not only many accomplish-ments to commemorate, but also many more to expect.

HCRI continues to providefull-service clinical trialsand is regarded as one of the premier institutions of its eld.


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One night in the spring of 2007, in the uorescent white con nes of Cabot Library, two freshmen labored on their problem set for PhysicalSciences 1. Talk of p-orbitals and reaction rates turned to talk of under-graduate research. Other top schools had research journals, reasonedJohn Zhou 10 and Shoshana Tell 10, so why doesnt Harvard have one?From this discussion arose what would become The Harvard Under-graduate Research Journal, Harvards only undergraduate journal thatpeer reviews and publishes original undergraduate research.

John and Shoshana spent an entire semester laying out the ground-

work for the journal before beginning to recruit members and acceptsubmissions; they looked for potential executive board members,talked with professors and deans, and established nancial support fora journal whose rst issue would be door dropped to every undergrad-uate on campus and distributed among graduate students and faculty.

This issue, the rst of the third volume, marks the last issue that Johnand Shoshana will see as undergraduates, before they pursue granderendeavors outside of the College. Despite their emeritus status, thetwo co-founders have inevitably lent a helping hand to their successorsas best they could; for THURJ, their graduation will be bittersweet.

For those of us who have been lucky enough to work with John and

Shoshana personally, we will remember their academic brilliance, senseof institutional development, political acumen, energy, and persever-ance. And for those of us to whom John Zhou and Shoshana Tell are just legendary names, we unequivocally see their legacy from cover tocover. Today, THURJ retains the ow of writing, reviewing, and editingthat it has had since its inception. We retain the regular sta meetings,speaker events, and celebration of our passion for original research.We continue their mission to provide undergraduates not only with aforum for scienti c discovery but also with exposure to the process bywhich high quality, peer reviewed science is produced.

To the co-founders of The Harvard Undergraduate Research Journal,we wish you both the best and that you continue to use your creative

talents in extraordinary pursuits.

Sincerely,!"#$%&'(($)($!"#$*'+,'+-$./-#+0+'-1'$2#3#'+4"$5)1+/'6

!"#$%&'"())*"!+ !"#$%&

THURJ Co-FoundersJohn Zhou 10 (top), Shoshana Tell 10 (bottom)


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2007 2008 2009

Fall 2007John Zhou and Shoshana Tell co-founded The Harvard Undergrad-uate Research Journal and spenta semester garnering supportfrom departments and faculty.

Spring 2008Volume 1, Issue 1For our inaugural issue, we spotlighted Biological,socioeconomic, and political aspects of the Nassaugrouper ( Epinephelus striatus ) shery in the Turks andCaicos Islands by Anh-Thu E. Vo. Vos study determinedthat the increasing shing intensity will eventuallycompromise the reproductive potential of the naturalstock without a government regulation to curtail it.

Fall 2008Volume 1, Issue 2The impacts of stricter high school graduation requirementson youth crime by Alice Chen won the manuscript prize for Fall2008 issue. Her work examined the association between statehigh school exit examinations and course graduation require-ments and youth crime.

Spring 2009Volume 2, Issue 1 The best manuscript for Spring 2009 issue went toElasticity in ionically cross-linked neuro lamentnetworks by Norman Yao. Neuro lament networksprotect the neuron from external physical stress. Yaoswork examined problems associated with neuro la-ments, ranging from polymer elasticity to nonequilib-rium statistical mechanics.

!"#$%&'"())*"!

!"#$%+,$)-.,"+,&"/&!$0


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2010


25www.thurj.org

September 2009Cambrian Explosion THURJ began the year with a jointevent with various science groups atthe Queens Head Pub. We hosted sci-ence bands like Thousand Bands andGertlers Law and invited Dr. AndrewBerry to host for the night. The eventprovided a fun place for freshmen andreturning members alike to mingle andsocialize.

October 2009Halloween Talk with Dr. An-drew BerryOn Halloween, Dr. Andrew Berrycame to speak about a fascinatingstudy of evolution in beetles.

November 2009A Talk on Healthcare Reformby Dr. Arnold RelmanDr. Relman, Professor of Medicine andSocial Medicine at Harvard MedicalSchool came and discussed alternativeways of thinking about the healthcarereform. With the recent election of President Obama, healthcare was aheated topic on campus and manyinterested students attended.

February 2010A Talk on Linguistics with NoamChomsky THURJ was honored to host Noam Chom-sky of MIT to discuss some of his views onlinguistics. As a part of THURJs continued

e ort to outreach into social sciences aswell as the basic sciences and engineering,Dr. Chomsky wasa great speakerwho enlighteneda packed houseabout theories likegenerative gram-mar.

Fall 2009Volume 2, Issue 2Our prize winning manuscript was Still images of motionpicture: Using static crystal structures to understand thebehavior of a DNA glycosylase by Kimberly Oo. DNA glyco-sylase is a DNA repair enzyme that removes damaged bases. The article revealed the structure of a catalytic intermediateduring the excision of the damaged base via crystallizationdata.

April 2010A Talk on Snowball Earth Theory with Francis MacDon-aldProfessor Francis MacDonald from theDepartment of Earth and Planetary Sci-ences came to speak about the Snow-ball Earth Theory, which hypothesizesthat the earth was entirely covered inice at one point. He discussed someof the perspectives on this theory andimplications of such a theory.

Spring 2010Volume 3, Issue 1


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RESEARCHVolume 3 Issue 1 | Spring 2010

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Social stress and scapegoatism:An economic model

David Joosten 11

Harvard College

IntroductionYou didnt want to come. e average man dont like

trouble and danger. You dont like trouble and danger.But if only half a man like Buck Harkness, there shouts Lynch him! Lynch him! youre afraid to backdown afraid youll be found out to be what you are cowards and so you raise a yell, and hang yourselvesonto that half-a-mans coat-tail, and come raging uphere, swearing what big things youre going to do. e

pitifulest thing out is a mob; thats what an army is amob; they dont ght with courage thats born in them,but with courage thats borrowed from their mass.

Colonel Sherburn, e Adventures of Huckleberry Finn by Mark Twain 1

e term scapegoat originated from a Jewish practice describedin Leviticus XVI in which a townspeople would confess their trans-gressions over a sacri cial goat on Yom Kippur and subsequently cast the goat out into the dessert to die, thereby purifying the townof its sins.2 Today, the term is applied freely to a variety of situationsin which a collective fault or social stress is blamed on a particu-lar minority. 3 Modern historians have used the term to describe

political developments, from protectionist tax policies to the Jew-ish Holocaust itself. 4 In economics, the term has been applied toa variety of situations, such as to describe those a ected by laborpolicies or the focus of investors attention in the currency mar-kets.5 Psychologists, particular social psychologists, have conductedexperiments and described the dynamic features of scapegoatism. 6 Although the original, ritual meaning of scapegoat is no longerpracticed today, the term has come to describe a dynamic socialprocess witnessed in a variety of elds.

1 Mark Twain. e Adventures of Huckleberry Finn, (New York: Harper andBrother Publishers, 1912), 203.

2 Calum Carmichael, e Origin of t he Scapegoat Ritual, Vetus Testamen-tum , Vol. 50, Fasc. 2 (Apr., 2000), pp. 167-182.

3 Labour: e Scapegoat, Economic and Political Weekly, Vol. 9, No. 26(June 29, 1974), p. 995.

4 Claude R. Foster, Jr, Historical Antecedents: Why the Holocaust, Annalsof the American Academy of Political and Social Science, Vol. 450, (July, 1980),pp. 1-19.

Edson W. Spencer, Japan: Stimulus or Scapegoat? Foreign A airs , Vol. 62,No. 1 (Fal l, 1983), pp. 123-137.

5 Labour: e Scapegoat, Economic and Political Weekly, Vol. 9, No. 26(June 29, 1974), p. 995.

Philippe Bacchetta and Eric van Wincoop, A Scapegoat Model of Exchange-Rate F luctuations, e American Economic Review, Vol. 94, No. 2 (May, 2004),pp. 114-118.

6 Louis A. Zurcher and Kenneth L. Wilson, Role Satisfaction, SituationalAssesment, and Scapegoating, Social Psychology Quarterly, Vol. 44, No. 3 (Sep.,1981), pp. 264-271.

is paper analyzes scapegoatism from the perspective of theindividual members of a social network, their social utilities, andthe decisions that result. Using basic psychological descriptions of the e ects of a scapegoat event 7 on the members of a social group,this paper formalizes an economic model to describe this dynamicsocial process. Furthermore, the models results lead to severalgeneral conclusions about the factors that increase the likelihoodof scapegoat events.

Scapegoat eventslargely occur because a particular stress dam-ages a groups solidarity or the strength of its social connections. To

alleviate some of the social repercussions of this stress, the groupmembers can choose to blame an individual within the group,thereby sacri cing that individual for the good of the remaininggroup members social connections. In other words, scapegoat-ing relieves the social impact of the stress, or the social stress, andenables the group as a whole to regain solidarity. 8

e decision to pursue scapegoatism or not is an individual deci-sion on the part of each group member that depends on the relative values of various factors. Generally, the social utility each membercould regain by scapegoating must be compared to the social util-ity lost if a particular member were excluded from the group dueto the occurrence of a scapegoat event. Since di erent membersof the group are more or less valuable to the group as a whole, the

comparison between the relative social utilities of scapegoating ornot may be di erent for each group member. erefore, the decisioneach group member makes depends on his particular circumstanceswithin the group and the resulting group decision is dependent ongroup composition as well as the social stressinhibiting solidarity.

However, although group members individual decisions may be di erent, they are subject to many of the same factors and so aresigni cantly correlated. e social stressdiscounts all of the linksbetween the members in a group universally, so that a larger social stress will compel every member to increase the opportunity costof not scapegoating in his decision on whether to scapegoat or not.Additionally, the value of the weakest member of the group, thewould-be target of a scapegoat event, factors into every members

decision through the cost incurred if he chooses to scapegoat.Overall, the group as a whole is more likely to scapegoat itsweakest member when the social stress inhibiting all group con-nections is high relative to the value of the weakest member. isresult helps explain the prevalence of scapegoat events in the fol-lowing situations:

When a group is large and the weakest members valuecomprises only a small fraction of the group members

7 e concentrated casting of blame for a collective socia l stress on a part icu-lar individual

8 Kenneth Westhues, At the Mercy of the Mob, OHS Canada , Vol. 18, No. 8(Dec., 2002), pp. 30-36.


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Economics

valuesWhen a group experiences a high level of variation insocial stressWhen group member values are right-skewedWhen group leaders support a scapegoat event

Previous studies of historical scapegoat events con rm thesedriving factors. In the most extreme cases of historical scapegoatevents, all of the above factors are present at the time of the scape-goat event. Whether one considers the post-WWI Red Scare, thescapegoat Charles Mitchell at the time of the 1929 Stock MarketCrash, or the rise of anti-Semitism during the ird Reich in Ger-many, a great social stress coupled with a belief that the minority held weak social values is present in all of them.9

Although there has been a great focus on scapegoatism in his-torical literature and in the eld of social psychology (particularly in organizational behavior), economic literature has not exploredthe topic in-depth. 10 Bandiera, Barankay, and Rasul (2007) discussthe e ects of manager favoritism and subsequently the incentivesystems that can remove favoritism in the workplace. 11 However,their paper does not focus on the opposite of favoritism scape-goatism, in which a member in the workplace is isolated from his

peers and deliberately excluded socially. Additionally, Chwe (2000)focuses on the integration of social network theory and game theory by exploring social coordination and the requirements necessary for coordination. 12 In essence, his paper helps fuel the concepts of link variation and social valuesfound in this paper, and speci cally the barriers to achieving a scapegoat event. While Chwe discussesthese dynamics generally, this paper focuses on the speci c char-acteristics of coordination as they relate solely to the occurrenceof scapegoat events.

e rest of the paper is structured as follows: the rst sectionsets up the model of the social group, including a few stochastic variables and underlying assumptions. e second section analyzesthe results of various simulations. e last section analyzes some

examples from two papers on organizational behavior within theframework of model. e conclusion discusses the implications of these results and potential areas of further research in the area of scapegoatism.

9 Claude R. Foster, Jr, Historical Antecedents: Why the Holocaust, Annalsof the American Academy of Political and Social Science, Vol. 450, (July, 1980),pp. 1-19.

David R. Colburn, Governor Alfred E. Smith and the Red Scare, 1919-20,Political Science Quarterly, Vol. 88, No. 3 (Sep., 1973), pp. 423-444. PoliticalScientist Colburn characterizes the rise of Gov. Alfred E. Smith and the socialtensions that brought about the post-WWI Red Scare in the United States.

omas F. Huertas and Joan L. Silverman, Charles E. Mitchell: Scapegoatof the Crash? e Business History Review, Vol. 60, No. 1 (Spring, 1986), pp. 81-103. Historians omas Huertas and Joan Silverman discuss Charles Mitchell srole in the 1929 Stock Market Crash and his subsequent role as scapegoat duringthe Depression.

10 Such as in: Zurcher and Wilson, Role Satisfaction, Situational Assesment,and Scapegoating, Social Psychology Quarterly, Vol. 44, No. 3 (Sep., 1981), pp.264-271.

11 Oriana Bandiera, Iwan Barankay, and Imran Rasul, Social Connectionsand Incentives in t he Workplace: Evidence from Personnel Data, (revisions re-quested, Econometrica).

12 Michael Suk-Young Chwe, Communication and Coordination in SocialNetworks, Review of Economic Studies, Vol. 67, (2000), pp. 1-16.

Scapegoat Model

Network structure

e social group is comprised of k members, or nodes, thatare connected to all other members of the group. e completeinter-connection of the group serves as the most socially cohesivecon guration of the groups social network, and so it acts as an e ec-tive baseline from which to draw conclusions about the prevalenceof scapegoatism. Furthermore, a completely inter-connected network accurately describes many real-world social groups such as thosethat are found in corporations, on athletic teams, and in families.

Connection structure

As a result of the complete inter-connection of the group, thereis the following composition of network connections:

ii

k

=

11

total connections (of which k1 connect to thewould-be scapegoat)

Each member of the group (excluding the would-be scapegoat)faces the following:

k2 non-scapegoat connections

1 scapegoat connection

Social values

Each of the k group members is assigned a social value(denotedby V i) drawn from a random, normal distribution centered so that5% of the social valuesare negative. is social value is exogenous tothe model and is meant to describe the value of each member of thegroup to the group as a whole. One could imagine a particular teamworking on a project requiring physical strength and certain teammembers being inherently stronger than others. In this model, thestronger team members are denoted as having higher social values than the rest of their team. Furthermore, one could imagine thatsome team members are so weak that they actually detract from

the groups e orts, which would result in a negative social value .Note that these social valuesare di erent from the link values thatare discussed subsequently.

Links and social stress

e social stress (denoted by ) is the discount factor applieduniversally to all links within the social network of the group. Alllinks are assumed to have a value of 1 that is subsequently multi-plied by (1 ) to arrive at the current value of the social link. eassumption that links have a base value of 1 is made to simplify the model the social values discussed above have been choseninstead to represent the diversity of group members. One couldalso potentially vary the link values in this model to di erentiate

group members individual links with one another in addition totheir social values, but the conclusions of this paper are una ectedby assuming their base value of 1.

e social stressis perhaps the key ingredient into the model, andso it deserves particular attention. e social stress is consideredexogenous to the model it represents the combined e ect of allexternal factors on the social network and the l inks therein. ismodel targets the following characteristics for the social stress:

It is centered around zero so that it has a 50% probability of inhibiting link valuesIt is derived from a distribution which makes extremeoutcomes unlikely


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It is boundedIt cannot increase the link values beyond their base valueof 1

Overall, to achieve these characteristics, the social stress is drawnat random from a normal distribution, its cumulative probability iscalculated, and then centered at zero (by subtracting 0.5 from it).Additionally, any negative values are set to zero to ensure that link values are never greater than 1. 13 ese modi cations ensure that allthe targeted characteristics listed above are satis ed in the model.

Voting When a social stress is imposed on the social network, each

group member must decide whether he will attempt to scape-goat the stress or not. is is a personal decision that may vary from member to member depending on group composition. Incomparing the opportunity to regain social utility by scapegoat-ing versus the cost of excluding the weakest group member, themodel applies the following condition 14 for a particular member(member X) of the group choosing to vote for a scapegoat event:

> =[ ( ) ] ( ) i

k

i X weakest weakest V V V V

1 1

A er each member evaluates his situation and votes whether toscapegoat or not, there is a scapegoat event if and only if all membersbut one (the weakest member) vote in favor of scapegoating. 15 In thismodel, the weakest member will never vote in favor of scapegoat-ing because he would never bene t from the solidarity a scapegoatevent would bring about, but would rather lose all social utility by his exclusion from the group.

Trials 16

Each trial represents the introduction of a particular social stress on the social network of the group, each group members evalua-tion of the comparison discussed previously and vote, and nally the aggregate result of the individual group members votes. Each

trial is independent of all other trials. e procedure of each trialis detailed as follows:

1. For each member of the group (not including weakest):a. Calculate the social utility lost due to the social stress.b. Calculate the social utility of the weakest member.c. Vote in favor of scapegoating if L > W , against scape-goating otherwise.

2. Tally the votes and perform a scapegoat event if the votesin favor of scapegoating sum to k - 1 (i.e. unanimousdecision of all members not including the vote of theweakest member).

3. Repeat, drawing new social valuesand a new social stress.17

13 is is a simpli cation made to avoid issues with members whose social values are negative, which when multiplied by a link value greater than 1 (a nega-tive social stress) would actually yield a more negative social utility, an illogicalresult considering there is a negative social stress, or positive e ect on the social network.

14 Note that if the social stress is equal to 0.0, there is a scapegoat event i V weakest < 0.0. In other words, when there is no social stress, only members thatdetract from the group can be scapegoated.

15 One could use di erent voting systems, such as simple majority, but theimplications of voting by unanimous decision lead to conclusions supported by models of leadership, discussed i n the simulation results under Leadership.

16 For the actual PHP program used to produce the data, refer to Appendix B[editors note: published online].

17 Note that we still have the original total number of members, so that we

Simulation Results and Analysis

Group sizeTo gauge the e ects of varying group size, this paper presents

the results of a simulation with a group size of 3 and compares it toa simulation with a group size of 10 each run for 1,000 trials. esample proportion of the frequency of scapegoat events for eachsimulation is shown in the following table:

Group Size p^

n

3 29.8% 100010 68.1% 1000

Running a statistical test to compare the proportion means yieldsa highly statistically signi cant result at the 5% signi cance level18 in which the frequency of scapegoat events for the group of size 10is greater than that for the group of size 3. e simulation resultscon rm the reasoning that the greater the number of members inthe group, the greater the opportunity cost of not scapegoatingis for each member relative to the value of the member with theweakest social value.

If the situation from the perspective of member X in Figure 1and Figure 2 above is compared, the increase in opportunity costfor larger groups is made apparent. While member X in Figure 1must sacri ce 50% of his links to gain a proportion on 50% of hislinks, member X in Figure 2 must sacri ce only 25% of his linksto gain a proportion on 75% of his links. Although this need notalways be the case19, member X in Figure 2 on expectation wouldbe more likely to pursue a scapegoat event than member X in Fig-ure 1 because less of a sacri ce is required proportionally to theexpected gain.

Variance of social stressIn analyzing the e ect of the social stress on the frequency of

scapegoat events, this paper presents the results of a simulationin which the social stressis that which is described in the originalmodel speci cations and compares it to the results of a simulationin which the social stresss variance is subsequently quadrupled,each run for 1,000 trials. e sample proportion of the frequency of scapegoat events for each simulation is shown in the following table:

are essentially running the same simulation but with di erent random values.18 See Appendix A for the full statistical test [editors note: published online].19 If social values are negative, then member X in Figure 2 would be more

likely to want a scapegoat event.

Figure 1. Figure 2.


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a scapegoat event may decrease social valueof the group as a whole,each individual member gains in terms of social utility, and it is thisthat drives a group to perform a scapegoat event even in situationswhen the weakest member still has a positive social value.

Social role and scapegoatismZurcher and Wilson (1981) nd that ones ability to ful ll a

particular role in a group setting is highly correlated with groupsatisfaction and individual performance through a Marine eldexercise done with Naval Reservists.31 Based on a previous eld exer-cise, subjects were told to choose whether they had more satisfactionwith a Naval role, a civilian occupational role, or anywhere inbetween on a gradient scale. All subjects were then put in groupsto complete assignments that strongly favored one role and thenthe other. Zurcher and Wilson nd that those subjects who iden-ti ed with neither role rated the assignments the most negatively,followed by those subjects who participated in an assignment con-trary to their chosen role. is result can be explained throughthe framework of the scapegoat model developed in this paper inthe following manner: ose who participated in an assignmentcontrary to their chosen role gained from their social network themost since they were able to rely on their fellow members whoseself-described role related to the assignment. ose members whoidenti ed with neither role did not gain as much from their social network since they were more like their fellow members whosechosen eld related to the assignment.

In fact, the study nds that those who identi ed with neither theNaval role nor the civilian occupational role were actually likelyto scapegoat someone within the setting 32. Since these subjectswere neither di erentiated from the Naval role group membersnor the civilian occupational role group members, they stood togain the least from their social network, and therefore would havehad the lowest overall social utility. As a result, these subjects dis-satisfaction with the assignment reached the critical level required

to choose a scapegoat event.

Conclusionis paper develops a model for scapegoatism and examines the

factors that lead to higher probabilities of scapegoat events throughcontrolled simulations. First, the paper nds that larger group sizes(or more speci cally, group sizes in which the minority is small)lead to higher incidence rates of scapegoatism on expectation. isoccurs as a result of the low marginal social utility the weakestgroup member provides the rest of the group members relative to

their total social utility. Second, environments in which a social network experiences highly variant levels of social stress( ) tend tohave higher rates of scapegoatism. As the probability that a social stress is greater than the critical point required for a scapegoatevent increases, the probability that a scapegoat event occurs alsoincreases. ird, certain types of social valuedistributions, namely right-skewed distributions, are more likely to lead to higher ratesof scapegoatism. is occurs as a result of the greater probability that a given group has a member whose social value is low enough

31 Zurcher and Wilson32 Zurcher and Wilson, pg. 270.

presents the same social group in the Leader Model. In either Fig-ure 4 or 5, the social utility the strongest member receives from hissocial network is the same. erefore, the decision of the strongestmember is le una ected by his own social value. However, thesame is not true for the other members of the group. While themembers whose social values are 2, 2 and 3 in Figure 4 lose 4 asa result of the social stress imposed on the social network, thosemembers in Figure 5 lose 8 . ese members from Figure 5 have ahigher opportunity cost for choosing not to scapegoat relative totheir counterparts in Figure 4, and subsequently are more likely tochoose to scapegoat. As a result, it is the strongest members votethat is both the limiting factor and the deciding factor to achievinga scapegoat event, and this result is borne out in the data under theLeadership Model.

Examples

Mobbing

According to Westhues (2003), the term mobbing is de nedas a collective campaign by co-workers to exclude, punish, andhumiliate a targeted worker. 29 Mobbing is a speci c example of the scapegoatism, and there are two characteristics of mobbing asdescribed by Westhues that relate to the conclusions of the modeldeveloped in this paper. Firstly, Westhues characterizes mobbing asan act that is initiated most o en by a person in a position of poweror in uence.30 In most cases of documented mobbing , workplacetensions are only released through the form of mobbing when it islegitimized by a manager. is feature of mobbing can be explainedin the model by the critical importance of the strongest memberin determining whether a scapegoat event is successful or not (asshown through the Leadership Model in the simulation results).

Since the strongest member of a group has the least to gain by scapegoating in terms of social utility, it is this member who acts asthe barrier to a successful scapegoat event in borderline situations.

Secondly, Westhues describes scapegoating as an e ective if temporary means of achieving group solidarity, when it cannot beachieved in a more constructive way. In terms of the scapegoatmodel, this gain in solidarity is captured by the opportunity cost of choosing not to scapegoat, or =[ ( ) ] ik i X weakest V V V 1 . Although

29 Westhues... See also Noa Davenport, Ruth Schwartz, and Gail Elliott,Mobbing: Emotional Abuse in the American Workplace (Ames, Iowa: Civil So-ciety Publishing, 1999)

30 Westhues, paragraph 9.

Figure 4. Figure 5.


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Economics

to merit a scapegoat event. Lastly, leaders emerge as the deciding vote in thwarting scapegoat events as a result of their low relianceon the social network relative to the rest of the group members.

is conclusion results from the unanimous voting structure themodel utilizes as its framework for determining when scapegoatevents occur and the independence a group leaders vote has fromhis own social value.

ese scapegoat factors have implications that reach a variety of elds: sociology, history, economics, and particularly organizational

behavior. e model recommends that to achieve solidarity, groupsshould be relatively small, should avoid having critically high levelsof social stress imposed upon them, should have members whosesocial valuesare not skewed-right, and should have clearly de nedgroup leaders. ese group characteristics lead to the highest levelsof social utility for each of the group members, and can help detergroup dynamics from negatively impacting group objectives.

ReferencesBacchetta, P. and Wincoop, E. (2004) A Scapegoat Model of Exchange-Rate

Fluctuations, e American Economic Review 94: 2-114.Bandiera, O., Barankay, I., and Rasul, I. (2008) Social Connections and Incen-

tives in the Workplace: Evidence from Personnel Data, (revisions requested,Econometrica ).

Charmichael, C. (2000) e Origin of the Scapegoat Ritual, Vetus Testa-

mentum 50: 2-167.Chwe, M. S.-Y. (2000) Communication and Coordination in Social Networks,

Review of Economic Studies 67: 1.Colburn, D.R. Governor Alfred E. Smith and the Red Scare, 1919-20, Political

Science Quarterly 88: 3-423.Davenport, N., Schwartz, R., and Ell iott, G. (1999) Mobbing: Emotional Abuse

in the American Workplace, Ames, Iowa: Civil Society Publishing.Foster, C.R. (1980) Historical Antecedents: Why the Holocaust, Annals of the

American Academy of Political and Social Science 450: July-1.Huertas, T.F. and Silverman, J.L. (1986) Charles E. Mitchell : Scapegoat of the

Crash? e Business History Review 60: 1-81.Spencer, E.W. (1983) Japan: Stimulus or Scapegoat?, Foreign A airs 62: 1-123.Twain, M. (1912) e Adventures of Huckleberry Finn , New York: Harper a nd

Brother Publishers.Unknown (1974) Labour: e Scapegoat, Economic and Political Weekly 9:

26-995.Westhues, K. (2002) At the Mercy of the Mob, OHS Canada 18: 8-30.Zurcher, L.A. And Wilson, K.L. (1981) Role Satisfaction, Situational Assesment,

and Scapegoating, Social Psychology Quarterly 44: 3-264.


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Circulating hormone adrenomedullin andits binding protein protect neural cells from

hypoxia-induced apoptosisStephanie M. Wang 13 and Weng-Lang Yang

The Feinstein Institute for Medical Research, Manhasset, NY 11030, USA

Brain ischemia is the underlying cause of neuron death during stroke and brain trauma. In addition to necrosis,neural cells exposed to the condition of oxygen depletion during ischemia can also undergo apoptosis, whichsigni cantly contributes to brain injury. Adrenomedullin (AM), a multifunctional hormone, in combination withits enhancing binding protein, AMBP-1, has been shown to e ectively reduce tissue damage under hemorrhageand ischemia/reperfusion in animal models. To evaluate a bene cial e ect of AM/AMBP-1 administration inbrain ischemia, we employed an in vitro model of neuronal hypoxia using di erentiated human neuroblastomaSH-SY5Y cells. A er exposure to 1% O 2 for 20 h, the neural cells were injury with a reduction of the cellular ATPlevels and an increase of lactate dehydrogenase released in culture medium. Pre-administration of AM/AMBP-1

signi cantly reduced the hypoxia-induced cell injury. Moreover, AM/AMBP-1 treatment reduced the number of TUNEL-positive cells and activation of caspase-3 in comparison to those cells exposed to hypoxia alone. AM/AMBP-1 prevented a reduction of cAMP levels and protein kinase A (PKA) activity in neural cel ls a er hypoxiaexposure. Correspondingly, treatment of forskolin, a stimulator of cAMP production, also protected neural cellsfrom hypoxia-induced injury. Inhibition of PKA, a downstream target of cAMP, by KT5720 abolished the protec-tive e ect of AM/AMBP-1 on hypoxia-induced apoptosis. ese results indicate that AM/AMBP-1 elevates cAMPlevels, followed by activating PKA activity, to protect neural cells from the injury caused by hypoxia. is study suggests that AM/AMBP-1 may be used as therapeutic agents to prevent neuron damage from brain ischemia.

Introduction

Cerebral ischemia results from an insu cient supply of bloodand oxygen to the brain a er injuries. It is the underlying causeof neuron death during stroke and brain trauma, two leadingperpetrators of death in the United States [1]. According to theNational Center of Injury Prevention and Control, about 1.4 millionAmericans sustain traumatic and ischemic brain injuries annually.

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