brevia fall 2015

BREVIAVo

l. 2

Issu

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A HARVARD COLLEGE UNDERGRADUATE RESEARCH ASSOCIATION PUBLICATION

I M M O R T A L I T Y

FALL 2015

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MASTHEAD

brevia.hcura.org 2 BREVIA Fall 2015

Co-Editors in ChiefJessi Glueck and Amir Bitran

PublisherMolly Zhao

Design EditorSilvia Golumbeanu

Opinions EditorJessi Glueck

Primary Research EditorAtrin Toussi

Features EditorCharissa Iluore

SponsorsBrevia would like to thank the Harvard Undergraduate Council and the Harvard College Office of Undergraduate Research and Fellowships for their generous support of our publication.

Jessi GlueckChristine ZhangAtrin ToussiHannah SmatiLydia GoldbergHa LeSilvia GolumbeanuJaewoo Jang

Alona BachJackson AllenAlan YangAmir BitranSahar Ashrafzadeh

Staff Writers

Thank you to Gregory Llacer for his extensive support of Brevia and HCURA, Jessica Herrmann and Kaitjaveet Chowdhary (co-presidents of HCURA) for their helpful suggestions, and Serena Eggers for providing the cover photo.

Acknowledgements

Matthew AguirreSilvia GolumbeanuAnne ChengDaniel ChenReece Akana

Hannah SmatiAlan YangKeyuree SatamMolly Zhao

Brevia Fall 2015 Masthead

The views expressed in Brevia articles are solely those of the authors. They do not represent the official stance of the magazine or any of its sponsors and affiliates.

Note

Designers

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brevia.hcura.org 3

EDITORS’ NOTES

BREVIA Fall 2015

ImmortalIty Is, fIttIngly, an Immortal concept, present across diverse eras and cultures. In ancient Egypt, people would bury their loved ones with snacks to keep them from getting hungry in the afterlife. The Christian tradition promises resurrection of the dead. For Buddhists, some part of the human being never really dies, but lives on in various incarnations eternally.

And the idea of immortality still moves us, as the themed articles in this issue demonstrate. Whether researchers are attempting to program our brains into computers, make our cells more youthful, or find a way for life to continue on Mars, they join a grand tradition of human struggle against death.

This issue also explores a different kind of immortality: the immortality of ideas. To motivate her discussion of intellectual property, Silvia Golumbeanu uses a centuries-old quotation by Denis Diderot. In my own piece, I write about an ancient Roman play which has outlived its author, Seneca, by nearly 2000 years.

Ovid, another ancient Roman, wrote at the end of the Metamorphoses: “ ... wherever the power of Rome spreads...I shall be on the lips of the people, and through all the ages...I shall live.” Imperial Rome has vanished, but people continue to experience its power anew through Latin literature and history. So in a sense, Ovid does live on.

The struggle against physical death, though it will doubtless yield key medical advancements, may ultimately be futile. But we as a species can take comfort in the fact that we have already achieved this other immortality, this majestic continuum of knowledge and story which inspires us in every generation.

these past few months, it seems like all the craze has been about Pluto. As new images arrive from the New Horizons mission, we are continually shocked to find majestic dunes, craters, and mountain ranges on this remote object (that I insist is a planet). But it is easy to ask, what is the point of spending millions of dollars sending an unmanned spacecraft to a body billions of miles away? In my opinion, the knowledge we have gained about our distant celestial cousin more than justifies all of the mission’s expenses. At Brevia, we believe that pure curiosity is a perfectly valid reason to learn about the world around us.

Of course, directly applicable research is undisputably important as well, and many of our stories highlight such work. But inquiry need not always begin with applications in mind. In fact, one never knows the implications that an abstract idea may ultimately have. An example is the imaginary number “i”, the square root of negative one. Negative one has no “real” square root—that is, we cannot “i” cows. It is hard to believe that an imaginary number, originally devised to solve certain mathematical equations, could have real-world meaning. But today, imaginary numbers are routinely used by quantum physicists, and even electrical engineers. So next time you turn on the light in your room, thank “i”.

I hope this issue of Brevia inspires you to appreciate ideas because they spark your curiosity, regardless of whether or not they seem “real”.

Amir Bitran

Jessi Glueck

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TABLE OF CONTENTS

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primary research

features

opinion

BREVIA Fall 2015

BREVIAfall 2015

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TABLE OF CONTENTS

brevia.hcura.org 5BREVIA Fall 2015

Immortal Stories. Jessi GlueckFamous literary theory sheds light on Roman tragedy.06

0810121416182022242628363840

How to Make a Neuron. Christine ZhangReplacing ALS-damaged neurons using stem cells.

Understanding the Market. Jaewoo JangAssessing public opinion using social media.

Bibles and the Blitz. Alona BachNursing organization’s struggle for autonomy.

Treating MRSA the Old Way. Atrin ToussiMedieval medicine combats lethal bacteria.

Telomerase. Hannah SmatiEnzyme may fight aging.

The Digital Afterlife. Atrin ToussiEmulating brain activity using computers.

Can Eating Less Make You Live Longer? Lydia GoldbergReduced calorie consumption may increase lifespan.

Saving Apes and Sapiens. Jackson AllenTowards an HIV vaccine.

A New Theory for an Age-Old Question. Alan YangA novel, physics-based explanation.

Artificial Photosynthesis. Amir BitranTechnology stores and harnesses solar energy.

NCRC 2015: The winners.Researchers discuss award-winning work.

The Space Columbus. Ha Le We’re not ready for Mars.

The Cost of Creativity. Silvia GolumbeanuThe Internet complicates intellectual property rights.

Precision Medicine. Sahar AshrafzadehObama’s initiative holds promise.

[

[[*

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PRIMARY RESEARCH

Medea, a Roman dRama by Lucius Annaeus Sen-eca based on a tragedy by Euripides, is a play about passions. Intense hatred, love and grief wrack the play’s characters. Yet I argue that the title character, Medea, should not be thought of as a victim of her anguish. Rather, that anguish becomes a source of creative power. Medea engages in a fierce competi-tion with her former self and emerges, violent and victorious, the author of her own immortal story.

Medea has good reason to feel violent. She was the wife of Jason, who had taken her from her homeland after she helped him to obtain the magical golden fleece that was supposed to guar-antee his accession to the throne. When Medea’s father pursued them to prevent Medea from run-ning away, she murdered her own brother in order to distract him. Though she has done so much for Jason, he ultimately spurns her in favor of Cre-usa, princess of the powerful nation of Corinth.

Such is the state of affairs when Medea opens, and Medea spends most of the play in bitter conflict be-

tween her love for Jason and her desire for retribution against him. This conflict can be understood in terms of what critic Harold Bloom has called “the anxiety of influence”. Bloom’s theory posits that authors are forever locked in a battle or “agon” with authors who came before, a “conflict between past genius and pres-ent aspiration, in which the prize is literary survival”.1

Though she is a literary character, Medea herself acts as a kind of author, seeking to craft a narrative of vengeance. But in this case, the precursor author with whom she struggles is her former self. Now that Jason has spurned her, Medea needs to define a story for her life to replace the story she shared with him during their marriage. In one sense, though, the stories will be similar: she wants both narratives to be filled with violence. “Paria narrentur tua / repudia thalamis,” she says; “let the story they tell of your divorce be like the one they tell of your marriage” (trans. Hine).2

But Medea does not merely want her new narrative to be “like” the old story of her murder-stained mar-riage to Jason. She wants to surpass her former self

6 BREVIA Fall 2015 brevia.hcura.org

Immortal Stories: Reading the “Anxiety of Influence” in

Seneca’s Medea by Jessi Glueck

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just as the authors Bloom describes want to surpass their precursors, not by rejecting their work but in-stead by making a key revision in it. Bloom calls this a “corrective movement”.3 Medea hopes to revise her previous narrative by committing new crimes. Speak-ing to herself, she says, “If the Pelasgian cities, if the barbarian ones have known any misdeed of which your hands are ignorant, now that mis-deed needs to be prepared”.2 This is an opportunity to teach her hands, already practiced in murder, some new tricks.

Yet there is more to Medea’s revision than the general desire to create unprecedented evil. The specific “corrective movement” she wants to make in crafting her new narrative is to edit out her love of Jason and of their children. Throughout the play, this love impedes Medea’s autho-rial process, making her hesitant and doubtful. In the past, Medea says, she committed evil acts out of love.2 Her future crimes will be committed out of power-fully creative anguish or “dolor”, and not out of love.

Medea’s ultimate act of revenge is the murder of her two children. In this scene, the conflict be-tween Medea’s love and her strong, creative anguish rages to a climax as she vacillates over shedding the blood of her first son: “Why do tears moisten my cheeks and, as I waver, why does anger now lead me this way, love that way?”2 She kills him, but is filled

with doubt as she does so, and it is unclear whether she will be able to finish the job by murdering her second son as well. Ultimately, her vengeful spirit is victorious, and Medea stands upon the roof of her house and kills her second son coolly while Jason and the townspeople look on. She becomes a powerful

figure, no longer a victim but an icon of villainous splendor.

Why does Medea’s anguished desire for vengeance ultimate-ly conquer her weaker love? Bloom suggests that literary works which win the conflict with their predecessors are more aesthetically powerful than those predecessors.3 This provides a reading for the ulti-mate triumph of Medea’s new, anguish-driven crimes: they simply make a better show. If Medea had mounted the roof only to be subdued by her

timid affection, her story would have been an aesthetic failure. The triumphant avenger, a more aesthetically compelling figure, wins out.

Critics have suggested that Medea is “dom-inate[d],” rendered helpless, by her violent pas-sions.4 But Bloom’s theory reveals that these emotions transform her into a powerful au-thor — whose story, after all, we are still telling.

Image by Biagio d’Antonio via Wikimedia Commons. Creative Commons Attribution.

7BREVIA Fall 2015brevia.hcura.org

Her future crimes will be

committed out of powerfully

creative anguish or “dolor”, and not out of love.

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The golden age of sTem cells is dawning. These cells possess the ability to solve a number of the greatest problems in medicine. Amyotrophic lateral sclerosis (ALS) is one. ALS, commonly known as Lou Gehrig’s disease, causes paralysis as motor neu-rons die and the brain loses control of muscle move-ment. More than 30,000 Americans suffer from ALS at any time and the disease has a low survival rate, with less than 50% of patients living two years or more post-diagnosis. There is no present cure and the only treatment option is Riluzole, a drug that can prolong one’s lifespan by a few months but pro-vides limited relief. We are hoping that stem cells will be able to replace the neurons lost to the disease.

Stem cells have the remarkable ability to transform into many different cell types. Endogenous stem cells, taken from an individual’s own body, hold much promise as a self-repair solution compatible with one’s immune system. The 2012 Nobel Prize in Physiology or Medicine was awarded jointly to Dr. Gurdon and Dr. Yamanaka for their breakthrough on converting adult cells — cells that have developed into specific cell types — back into the embryonic, pre-differen-tiated state. Embryonic cells are pluripotent, able to differentiate into any human body cell type. In con-trast, adult stem cells are multipotent; their differen-tiation is limited to a narrow range of cells. Thus, in-

ducing the embryonic state confers a great advantage.Dr. Yamanaka discovered that through gene reg-

ulation, he could cause adult cells to revert to their embryonic state.1 However, his experimental design involved viruses, a method that would raise health concerns including the destabilization of DNA/RNA and increased likelihood of tumors. In re-sponse, chemical procedures have been created to re-place the need for viruses. From converting adult cells to the embryonic state to differentiating the induced embryonic cells into neurons, the full procedure can span over a month.2 Directly converting adult cells to neurons, bypassing the embryonic state, would provide increased efficiency. However, direct conver-sion through chemicals has not yet been achieved.

Dr. Kevin Eggan is co-head of the Stem Cell and Regenerative Biology department at Harvard and his lab specializes in using stem cells to treat neurodegen-erative diseases, particularly ALS. I have been fortunate to work with one of his graduate students, Feng Tian, on novel treatment options. Our experiment consists of using chemicals to discover a pathway of direct conversion to create neurons from other somatic cell types, a technique known as trans-differentiation.

The first stage of the experiment consisted of screening for chemicals that would best stimu-late specialization into neurons. A combination of

PRIMARY RESEARCH


How to Make a Neuron: New Opportunities for ALS Stem Cell Therapy

By Christine Zhang

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chemicals controlling DNA methylation and histone de-acetylation proved to be the most successful. This was followed by the second stage of conver-sion, which promoted neuron maturation and stabi-lization. Afterwards, we established the similarities between the chemically induced neurons and stan-dard neurons by comparing DNA base pairs, elec-trical activities, and expression of neuronal markers.

Using chemicals in place of viruses not only removes the ethical and health concerns that virus-es pose, it also presents its own benefits. The chemical procedure is shorter, more cost-effective, and more adaptable for large-scale processing. Moreover, a tremendous procedural ad-vantage is that directly con-verted neurons possess few-er artifacts than neurons produced from induced embryonic cells. Each time an adult cell transforms identity, it carries over remnants from its past. In this case, neurons could still retain behavioral pat-terns of their previous role, which could interfere with their functionality as neurons. With fewer such artifacts, direct conversion produces neurons that are more stable and viable for long-term use.3

The greatest implication of this discovery is that it provides a powerful tool to combat diseases, in-cluding ALS. A cell sample from a patient with ALS would display a mix of healthy and diseased cells. In our experiments, we were able to cause healthy cells to proliferate and convert into neurons, while

diseased cells did not. We compared chemically in-duced neuron growth in the fibroblasts (cells that are transformed into neurons) derived from mice who had the ALS-related mutation against chemi-cally induced neuron growth in fibroblasts derived from their healthy littermates.4 Consistently, cell lines from mice with the ALS-related mutation expressed significantly lower neuron yields. Furthermore, neu-rons displayed poor survival rates when cultured on

ALS-related mutated glia, cells that support neurons. So when we chemically induce neu-rons, diseased neurons can be distinguished from healthy neurons and only the healthy ones will multiply.

After we collect the patient’s cells and

chemically transform these into neurons, this batch of neurons accumulates and, over time, becomes more robust. These neurons then display greater po-tential for in vivo medicinal applications. For ALS patients who have lost motor neurons, our goal is to have our healthy neurons replace the damaged ones and restore motor movement. We hope this could become a treatment that improves patients’ quality of life and ultimately increases their survival rate.

The greatest implication of this discovery is that it provides a powerful tool to combat diseases, including ALS.

Photo Illustration by Molly Zhao. Modified from “Neurons” by Geralt via Pixabay, Creative Commons Attribution.

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Humans love to recognize patterns. Pattern recognition was a particularly useful skill for traders and financial managers in the past, when finance-re-lated decisions were made solely based on intu-ition and economic theories. But nowadays, traders and bankers must ensure that their decisions are validated by quantitative science. In recent years, many financial institutions and individuals have embarked on a quest to understand the complexity of the financial market by building software algo-rithms to organize and process market information.

As an attempt to quantify the behavior of the market, our software engineering team at Stanford University built a program that assesses the public’s sentiment about a certain company.1 Ashkon Far-hangi, our lead re-searcher, worked along with An-drew

Chen, Jialin Ding, Sid Grover and I in designing this program. Since consumers make the important de-cisions, they drive the market’s movement. Based on this simple principle, our research team developed a software that tracks changes in the market by gather-ing data through Twitter, Facebook, and other major social media outlets and news sources. Specifically, we retrieve media posts to process real-time public sentiments about certain stocks. Though many have attempted this algorithm to determine stock prices, our program does not actually conclude anything about the amount of trading done in the market. Rather, by retrieving a set of relevant posts, we can compute the fluctuations, or “volatility,” of the stock over a certain period of time, which is an integral

component of measuring stock values.The software platform relies on two

key functions: a keyword finder and a machine learning algorithm based on

our analysis of public sentiment. Our technology first uses Google search

statistics in conjunction with a math-ematical model to isolate words that are often present in a company’s so-

cial media posts, known as “keywords.” The program then uses these keywords to

search through prominent social and online me-dia to store posts that are deemed relevant. For

example, if we were to search the relevant key-

PRIMARY RESEARCH

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Understanding the Market By Jaewoo Jang

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PRIMARY RESEARCH


words of the company Apple, our program would extract social media posts by Apple Inc., and scan through all the words in those posts. Then, we apply the Pointwise Mutual Information2 (PMI) statisti-cal modelling, where we only save the most signifi-cant words that are associated with the company as our keywords. So, since the words “Apple” and “iPhone” would be found in the same post more often than “Apple” and “GPS,” a key-word for Apple Inc. would be “iP-hone.” Insignificant words such as “the” are not considered keywords.

After we have determined the keywords that are identified with a company, our technology examines the social media posts of consumers to determine public sentiment towards these keywords. To do so, the technology uses a well-established sentiment analysis from Computational Linguistics & Psycho-linguistics Research Center.3 This library would as-sess the sentence — “I hate this iPhone” — with a negative sentiment value of -0.82. It would ana-lyze the sentence — “I love this iPhone” — with a positive sentiment of 0.82. Also, the sentiment val-ue differs drastically if the post has been made by a

prominent individual -- one with a dominant social media presence. We consider these factors and calcu-late the sentiment values accordingly.3 By aggregat-ing the sentiment values of the posts about a specific company, we can generate a number that is indica-tive of the market’s view of the company. We believe

that applying this technique to all 500 major companies listed in the Standard and Poor market index can provide us with reliable insight into how the public views the market.

The project has yet to finalize its iOS platform — the operat-ing system that makes a software work on Apple computers. The program also needs a test run.

But we are confident that our program will con-tinually provide relevant information, because of its ability to monitor public sentiment in real-time. Though technology cannot prevent us from mak-ing poor financial decisions, it can certainly en-dow us with the tools to make better decisions.

Our technology examines the social media posts of consumers to determine public sentiment.

Left: Image by Robert Scoble via Flickr. Modified by Hannah Smati. Right: Image by mkhmarketing via Flickr. Creative Commons Attribution.

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Bibles and the Blitz: District Nursing in WWII London by Alona Bach

London’s BLoomsBury neighBorhood is full of stately old buildings, but few fascinated me more than the imposing “Nurses’ Home” on Huntley Street. I imagined that it had once housed London district nurses – community-based nurses who pro-vided medical care by visiting the homes of their pa-tients. Cursory research disappointed me: the build-ing on Huntley Street had nothing to do with district nursing (it belonged to University College Hospital). But, as it turned out, Bloomsbury did have an or-ganization which provided district nursing services: the Ranyard Mission, which had been founded in 1857.1 In 1938, the Mission’s move to new headquar-ters on Taviton St. – just three blocks east of the Huntley Street Nurses’ Home – coincided not only with the stirrings of the Second World War, but also with a struggle to retain their institutional identity.

The Ranyard Mission’s century-long history lead-ing up to World War II was already full of institu-tional change. Mrs. Ellen Ranyard had begun the Mission as a way to combine monetary relief with the dissemination of Christian values: she employed “good poor women” of Bloomsbury to sell bibles and give housekeeping advice throughout their com-

munity.1 By 1868, the Ranyard Mission had expanded in both scale and scope and the first Ranyard Nurses had begun their home visits. A century later, in 1965, the Mission was absorbed by other local district nursing services under the National Health Service (NHS), which nationalized health care in the UK.

In the meantime, two world wars shook the world and – on a much smaller scale – the district nursing profession. Much has been written about the role of district nurses during World War I, when district nurses provided care for civilians so that hospitals would have room for wounded soldiers.2 Less, how-ever, has been written about district nursing during World War II. The scholarship which does exist fo-cuses on the unification of the profession: histori-an Brian Abel-Smith argues that the Second World War turned the standardization of nursing into a national issue which required legislative action.3 Government committees began to address chronic problems of low recruitment and varying nursing education standards. Yet while the Ranyard Mission was willing to comply with the initial demands of standardization, such as the new pay scale for nurs-es, they were more troubled by standardization’s

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broader implications. The Mission had always held Christianity as their guiding principle; would the standardization of nursing practices allow the Ran-yard Mission to continue to treat their patients (and train their nurses) both physically and spiritually?

The answer did not come immediately, and throughout the war the Mission wrestled with the question in their annual reports. Changing descrip-tions of the role of a Ranyard Nurse, for example, reflect the growing concern about the presence of Christianity in their work. The 1937 Annual Report states, as the Mis-sion had often written before, that Ranyard Nurses were “fully-trained hospital nurses … working from a sense of Christian vocation”.4 In 1943, though, Ranyard Nurses be-came “state-registered nurses who, after an approved course of district training, engage in domiciliary nurs-ing … They regard their service as the expression of their Christian vocation and it is of the utmost importance that [they] should keep this ideal before [them] in all fu-ture planning of [their] work”.5 The addition of the labels “state-registered” and “approved” in the 1943 report demonstrated adherence to developing stan-dards of nursing practice. Equally notable, though, is that a Christian vocation became embedded not only in the work of each individual nurse, but also in the future planning of the organization’s administration.

Why do these increased references to Christian vocation matter? When the beginnings of standard-

ization made the future of the Mission unclear, refer-ences to Christianity – particularly as the foundation of the Nurses’ successful wartime social work – came to define the individuality of the Mission and became analogous with self-determination. By situating the success of its social work as a product of its Chris-tian ideals, the Mission could show that its religious affiliation had a positive effect on the work of the

Nurses. Arguments to maintain that same religious identity throughout their organization were therefore more compelling. They had to be: the future organizational struc-ture of the Mission was at stake.

Today, those references to Chris-tianity in the Ranyard Mission’s an-nual reports are a striking illustra-tion of how an organization used social practices to advocate for re-taining its autonomy in the chang-ing landscape of public health care legislation. But when the war end-ed in 1945, the heyday of the Ra-

nyard Mission was over too. The Mission’s nursing services, which at the height of the war had served over 40 London neighborhoods, were soon absorbed into secular local organizations. If you stroll through Bloomsbury, the old headquarters of the Ran-yard Mission at 11 Taviton St. are no longer there.

[The] Christian vocation became embedded ... in

the work of each individual nurse

[and] in the future planning of the administration.

Image via Wikimedia Commons, Creative Commons Attribution.

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FEATURES


The producTion of new medicine is one of the fastest-changing areas of healthcare. But even these days, some drugs seem to have an immortal life span: after centuries, they’re still being used! The most recent example of such a time-tested drug comes from a recipe found in Bald’s Leechbook, one of the earliest known medical textbooks dating back to the ninth century. In it, scientists found a recipe for “eye-salve” (eye ointment) that had to be translated from Old English by Dr. Christina Lee, an expert in An-glo-Saxon societies at the University of Nottingham.1

This 1,000 year old recipe called for precise ra-tios of garlic, onion (or leek), wine and bile from a cow’s stomach to be prepared in a brass vessel, left to brew for nine days, and then strained.1 Fol-lowing the recipe as closely as they could, micro-biologists at the University of Nottingham rec-reated the medicine. To their surprise, the recipe was found to fight against an antibiotic resistant strain of the staph bacteria known as methicil-lin resistant staphylococcus aureus, or MRSA.1,2

As an antibiotic resistant strain of bacteria, MRSA is difficult to treat with the same anti-bacterials com-monly used to treat a staph infection. The infection and its symptoms are caused by the staphylococcus bacterium, which is present in the nose or on the skin of healthy individuals, but can turn deadly if it enters the bloodstream, joints, bones, lungs or heart. Typical treatment of a staph infection is through drainage of

Fighting MRSA the Old Wayby Atrin Toussi

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FEATURES


the infected area or with antibiotics.3 However, in the case where neither of these treatments work very well – as for some infected by MRSA – now there is hope.

Researchers claim the eye salve recipe took an MRSA cell population of approximately a few billion cells down to only a few thousand cells. The real test, however, was whether these results could be replicated in living animals infected with MRSA. As they later found, the eyesalve recipe killed up to 90% of the MRSA cells in the MRSA infected wound area of the mice.1

Though the scientists are still unsure exactly what mechanism is responsible for the potency of the concoction, they’re speculating that the diverse ar-ray of ingredients may be attacking MRSA from a variety of different angles. For example, the ancient recipe seems to penetrate MRSA’s biofilm – the ad-

hesive coating that typically covers populations of bacteria. This biofilm makes bacteria stick together and provides a tough barrier for antibiotics.1,4 Anoth-er idea is that leaving the materials in alcohol1 (the

wine mentioned in the recipe) could potentially transform the active ingredients of the recipe, creating another, more effec-tive molecule that has enhanced fighting power against MRSA.

Though this millennium- old recipe has many more steps to take before it can be thought of as an antibac-terial by today’s standards, it proves that not all good

things must be new: old medical instructions may have the potential to fight against a bacteria that sometimes has our “new” medicines stumped.

The eye salve recipe took an MRSA

cell population of approximately a few billion cells down to only a few thousand.

Images by Janice Haney Carr via Wikimedia Commons. Creative Commons Attribution.

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Fountain of Youth?

FEATURES

By Hannah Smati

Telomerase:

Telomeres, The shorT pieces of DNA at the ends of our chromosomes, do more than just protect our genetic information — they control the inter-nal clock within each of our cells and may hold the secret to slowing aging and prolonging human life.

The discovery of telomerase, the enzyme re-sponsible for telomere formation and its protective mechanisms came in the 1980’s. These discoveries were made through a collaboration between Profes-sors Elizabeth Blackburn at UC San Francisco, Carol Greider at Johns Hopkins University School of Med-icine, and Jack Szostak at Harvard Medical School.1

Though the three later commented that “[t]he dis-covery … was pure curiosity-driven research, with no obvious medical impact,” their work won them the 2009 Nobel Prize in Physiology or Medicine.2

Before a cell divides, its DNA is copied by DNA polymerase enzymes in the nucleus, which bind to the DNA and copy it nucleotide by nucleotide. However, polymerase enzymes do not bind at the very end of

the strand, and so the ends of the DNA strand are not copied. Over the course of several replications, the DNA would surely shorten and degenerate with each cell division — and yet scientists have observed that no genes are lost during division.3 Instead, with each cell division, telomeres shorten, protecting the main part of the DNA that makes up the chromosome.

When the telomeres become too short, which typically happens after a cell has divided around 75 to 100 times, cells can no longer undergo division. Newborns have telomeres that can be around 15,000 base pairs long. Once the biological clock starts tick-ing, the telomeres shorten by about 100 bases with each cell division.4 There is a clear link between telo-mere shortening and cellular degeneration as people age, so one wonders whether the body can do any-thing to counteract this process. Enter telomerase.

Telomerase adds bases to telomeres, prevent-ing excessive shortening. However, the majority of cells in the body have very little telomerase ac-

A

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tivity, and as cells continue to divide, it is not pres-ent at high enough levels to continue to length-en the telomeres.5 If there was some way to turn telomerase back on in older cells, new telomeres could be produced and the cell could continue di-viding indefinitely: a sort of cellular immortality.

The scientific community, interested in aging re-search, is seeking ways to increase telomerase activity in cells. Already, advances in the field have allowed telomeres to be extracted from cells and new telo-merase to be introduced into cultured cells in a lab dish, prolonging cell life.4 Dr. Helen Blau and her colleagues at Stanford Medical School have developed a modified RNA that codes for TERT, a subunit of the telomerase enzyme. Using the TERT they had designed, they extended human cell telomeres by a thousand nucleotides. Accord-ing to their study, the group of treat-ed cells divided and functioned like much younger cells, in comparison to the untreated group.6 Other researchers have al-ready moved on to creating remedies that can be used on humans — TA-65 is a patented nutritional supplement, marketed as an anti-aging remedy, that contains small molecules that activate telomerase.7 While its potential for slowing aging is still under debate, one study found that TA-65 had increased the years of healthy life in old mice, and another found that it had lengthened telomeres in 125 hu-mans, who also had improved levels of fasting glu-cose, insulin, LDL-cholesterol, and blood pressure.8

Despite ongoing research, there could be risks

associated with increasing telomerase activity. Ac-cording to Szostak, who used cultivated yeast cells to discover that a shortening of telomeres led to short-er cellular lifespan, telomerase exists in such small amounts in each person for a good reason. “In nor-mal cells, you don’t want to have a lot of telomer-ase because presumably if you did, the cells could keep dividing forever because their telomeres would be maintained at the proper length. That’s what hap-pens in tumor cells,” he said, alluding to the fact that uncontrolled telomerase activity is one of the main

factors in cancerous cell growth. Despite the risks associated

with reversing telomere shorten-ing, there are studies that show that longer telomeres are correlated with longer life. In a experiment by Uni-versity of Utah School of Medicine professor Richard Cawthon and his colleagues, people with short-er telomeres in their blood DNA died around five years earlier than

the subjects with longer telomeres. Cawthon’s paper suggested that increasing telomere length could sig-nificantly increase life span.9 While there are many other natural processes that contribute to human cellular aging, telomere shortening may be one cause that has potential to be reversed in the near future. “If we turned on telomerase in just the right way in just the right cell,” Szostak said, “then it could be quite beneficial for certain diseases of aging.”

The cell could continue dividing indefinitely: a sort of cellular immortality.

Image by Stuart Caie via Flickr. Creative Commons Attribution.

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Some people juSt Seem to have everything. There is, however, one thing that eludes us all: immortality. Over time, theories have been forged, minds have col-laborated, and money has been spent in pursuit of this unattainable ideal. But are we any closer to achieving it?

A few believe we are. The answer lies not in bi-ology, but in mathematics and computer science; the way to beat an organic death is through inor-ganic living. To live beyond the finite years, we need to upload digitized blueprints of our brains into a computer,1 which will then have our personalities operating inside. Never mind the fact that we don’t know what consciousness is, how it arises, or even how an algorithm could model – and then replicate – the individualized, and constantly changing, nature of our neural circuits. For now, let’s suspend our disbelief and examine the kinds of progress being made to create these inorganic vessels for thought.

The best known and most focused effort to devel-op such a technology is the 2045 Initiative founded by Russian billionaire Dmitry Itskov.2 His initiative’s website, 2045.com, outlines the most recent advanc-es in the field and highlights Itskov’s goals: “to cre-ate technologies enabling the transfer of an individ-ual’s personality to a more advanced non-biological carrier, and extending life, including to the point of immortality”.3 The website even features a timeline of the project, whose overlying theme (and title) is the Avatar Project. By 2035, for example, we should be at “Avatar C”: a synthetic carrier of personality and consciousness that results from brain transfer to a machine at the end of life.3 Itskov’s Avatar Project has even received the support of the Dalai Lama (for

The Digital Afterlife:Using Technology to Conquer Death

By Atrin Toussi

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more information, visit the 2045 Initiative website). Such a grand scheme must begin in small steps.

Evidence supporting the project comes in the form of recent advancements in brain-computer interfac-es (BCIs). In 2011, researchers at the University of Southern California and Wake Forest University suc-cessfully created the world’s first neural implant.4 Re-searchers deciphered the pattern of neuronal firing that gives rise to specific aspects of mouse learning and memory and from it, fashioned a neural implant that emulated the original firing patterns.4 Then, they obliterated a portion of the real region responsible for memory in mice and saw that those mice outfitted with the neural implant retained their ability to learn and remember, while the other non-engineered mice did not.3 This discovery has profound implications for victims of epilepsy or other diseases who’ve had brain regions removed as part of their treatment. With the advent of this technology, the removed structure’s function could be retained through a neural implant.

Another, more direct step toward replication and transfer of neural circuitry to a synthetic carrier is the worm robot. Caenorhabditis elegans (C. elegans) is a tiny worm well-studied in neuroscience. It is known to have 302 neurons whose connections have all been meticulously mapped out in a “connectome” by researchers.5 OpenWorm, the organization that pio-neered the study, seems to have effectively created the world’s first computer organism: the C. elegans ner-vous system was uploaded into a Lego Mindstorms

EV3 robot, and it was found to respond to stimuli just as biological C. elegans would.5 This was done without any programming. The researchers simply imported the worm’s neural circuitry in the form of software into the robot, and observed its C. elegans-like behav-iors such as moving forward when its food sensor was touched or stopping when its nose was stimulated.5

Aside from such physical progress, the next step these researchers (and Itskov) might take is to con-vince their skeptical peers. Many neuroscientists staunchly believe that the brain is irreducible to the circuits reconstructed by mathematicians and computer scientists. Others, like Roger Penrose of Oxford University, believe that consciousness is a quantum phenomenon – a phenomenon that emerges from the properties and interactions of tiny particles at nanoscopic scales.6,7 In his view, quantum computers need to exist before we can tackle the re-creation of human consciousness in a computer.6 Regardless, there’s still a long way to go before any of these ventures are translatable to humans and their brains. These studies and their ideas, however, provide evidence for the leaps man-kind is making toward an inorganic immortality.

Photo Illustration by Molly Zhao. Modified from “Digital Design” by Geralt via Pixabay, Creative Commons Attribution.

These studies and their ideas, however, provide evidence for the leaps mankind is making toward an inorganic immortality.

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Human life expectancy Has increased over the last century and a half by an impressive average of three months per year,1 and yet we continue to search for more ways to increase our longevity. Some scientists suggest that there may be a very simple solution: eat less.

Calorie restriction refers to cutting caloric intake by 10 - 40% of the standard recommended value,2

and its potential benefits have been examined by the scientific community for the better part of a century. Back in 1935, C.M. McCay and colleagues at Cornell University published one of the first studies providing evidence that calorie restriction could lead to a longer lifespan in animals. They found that rats on a reduced calorie diet lived significantly longer than a control

group of rats that were allowed to eat as much as they wanted.3 Research over the subsequent decades con-firmed similar results for other animals such as yeast and fruit flies.4 More recently, scientists have sought to discover the exact mechanisms by which caloric restriction improves health and increases lifespan.

Further research on caloric restriction has sug-gested that it could have multiple health benefits, including a reduction in incidences of life-threat-ening diseases like cancer. Studies on the effects of caloric restriction in rodents suggest a few dif-ferent possible mechanisms that might account for how caloric restriction prevents cancer. A hormone called insulin-like growth factor 1 (IGF-1) is a risk

Can Eating Less Make You Live Longer?

by Lydia Goldberg

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factor for a number of types of cancer, but its pro-duction can be decreased by calorie restriction.5 In addition, caloric restriction turns on the AMP-ac-tivated protein kinase pathway, which can suppress tumors (Meynet and Ricci). While these findings indicate useful progress, scientists have yet to con-clusively identify how caloric restriction affects life span, and one major question remains: can ca-loric restriction increase longevity in humans?

In the late 1980s, two ma-jor longitudinal studies were launched in order to explore this question, one by a team of researchers at the University of Wisconsin and the other by a team at the National Institute of Aging in Baltimore. Both studies used rhesus monkeys, which make excellent subjects because they show many of the same signs of aging as humans, such as redistribution of body fat, graying and thinning hair, loss of muscle and skin tone, loss of bone mass, and an in-crease in diseases like diabetes.6 After over 25 years, these studies have only recently published results.

The 2009 study “Caloric Restriction Delays Dis-ease Onset and Mortality in Rhesus Monkeys” con-ducted by Ricki J. Colman and colleagues at the University of Wisconsin uncovered some exciting findings: monkeys that had been fed a calorically restricted diet showed decreased incidence of dia-betes, cancer, cardiovascular disease, brain atrophy,

and most importantly, decreased mortality during the period of the study, when compared to a control group.7 Unfortunately, the 2012 National Institute of Aging study, “Impact of caloric restriction on health and survival in rhesus monkeys”, conducted by Julie A. Mattison and colleagues, showed different results: there was no statistically significant differ-ence in survival of calorically restricted and control monkeys (Mattison et al.). Later comparisons of the

methodologies of the two stud-ies showed that one significant difference between the studies was the control group. The Wis-consin study allowed its control group to eat as much as it wanted, while the NIA control monkeys were given limited amount of food to prevent obesity, so that they weighed less and lived lon-ger than the Wisconsin controls.8

With the differing results of these two studies, scientists can-not yet decisively support or refute the idea that caloric re-striction lengthens the human

lifespan, so no need to start cutting calories. While researchers continue to gather more data on calorie restriction, perhaps we can all aim for a well-bal-anced, nutritious diet, rather than a smaller one.

Left: Image by Steven via GoodStockPhotos.Right: Image via Wikimedia Commons. Creative Commons Attribution.

Scientists have sought to discover

the exact mechanisms by

which caloric restriction

improves health and increases

lifespan.

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This February, in a remarkable sTep Forward for HIV/AIDS research, scientists announced a novel anti-HIV agent so effective at targeting the virus that it provides protection years after a single injection.

The study, published in the scientific journal Na-ture, was led by Dr. Michael Farzan of the Scripps Research Institute and researchers at Harvard Med-ical School’s New England Primate Research Center (NEPRC). The study showed that eCD4-Ig, a mole-cule engineered by the scientists, can inactivate even the most resistant HIV strains. It tightly binds two sites on the glycoprotein that sits on the viral enve-lope of every strain of HIV and SIV, the Simian Im-munodeficiency Virus found in primates.1 The gene for eCD4-Ig was inserted into the DNA of an Ade-no-associated Virus (AAV), and the AAV was injected into muscle cells. AAV can then hijack muscle cells and use their protein synthesis machinery to produce copies of itself and the eCD4-Ig molecule. Because eCD4-Ig is so similar to native human proteins, it can neutralize HIV particles without eliciting a reac-tion from the body’s defenses.1 Using an AAV virus comes with some risks, such as the possibility of ge-netic mutations (due to imprecise integration of AAV

DNA into muscle cells) or immune responses. As a result, Farzan suggested that the molecule may have a better chance of reaching paatients as a therapy than as a preventative vaccine, at least in its initial stages.

“[A therapy] is a very attractive possibility for two reasons,” Farzan said. “The risks versus re-wards shift in the case of an infected individual. If he or she is given an opportunity to get off two or three [anti-HIV] drugs, he or she may be more in-terested in taking on the risk associated with AAV expression. The second reason has to do with trans-mission. There are very good theoretical reasons to believe that the HIV virus may be less transmissible after treatments with eCD4-Ig and other therapies.”

Dr. Lisa Kattenhorn, a veterinary pathologist at the NEPRC, also emphasized that this therapy can reduce the amount of HIV in the body while avoiding side effects induced by other drugs. Kat-tenhorn joined the project to design and conduct experiments with eCD4-Ig in rhesus macaques, a type of monkey widely used for animal research due to similarities to human anatomy and physiology. When these animals were inoculated with eCD4-Ig, they were protected against infection by HIV-1,

Saving Apes and Sapiens: How the New HIV Vaccine Inspires Hope

By Jackson Allen

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HIV-2, and SIV, even when the researchers direct-ly injected high levels of live virus into their blood.

Katterhorn and Farzan both said that their meth-odology could have applications beyond the treat-ment of HIV. “We could do a lot of things that were not previously available. HIV is the leading edge, paving the way, but there is a lot that will follow,” said Farzan. Influenza and ma-laria are promising applications for the use of AAV-delivered medicines, because this meth-od could provide protection for years.2,3 Some vaccines for the Ebola virus, said Kattenhorn, could rely on this system as well.

Though many HIV trans-missions in people occur at the mucous membranes, the animals used in this study were infected intravenously.1,4 “This is a stricter method for looking at the effec-tiveness of our molecule,” said Kattenhorn, because intravenous injection guarantees that the animals con-tract HIV, whereas infection at mucous membranes creates no such guarantee. The next step, Kattenhorn and Farzan agreed, is to determine if eCD4-Ig pro-tects against HIV entering at the mucous membranes.

In addition to providing a potential treatment for human patients, this research may benefit laboratory animals as well. Laboratory chimpanzees are often infected with HIV or SIV to test new treatments against AIDS. Recent studies indicate that these

animals often develop reproductive problems later in life, including increased infant mortality and an AIDS-like syndrome.4,5 It is impractical, in terms of both time and money, to give daily anti-HIV drugs

to laboratory animals once they have played their part in scien-tific research. But Kattenhorn explained that since a single in-jection of eCD4-Ig lasts for months or years, this treatment could allow scientists to cure these apes with little difficulty. Kattenhorn stressed the excit-ing nature of such cross-species applications: after all, humans and monkeys are part of one big primate family. “This re-search is truly about monkeys helping monkeys,” she said.

But the future of this research will have to continue elsewhere. Harvard Medical School will be closing the doors of NEPRC on

May 31, 2015, citing funding pressures.6 This will leave only seven NIH-funded primate research centers in the country. “This particular study is an example of some of the amazing work that has been done here at the Center,” said Kattenhorn. “There aren’t many of these centers left, and this was one of the best.”

Scientists announced a novel anti-HIV agent

so effective at targeting the virus that it provides protection years after a

single injection.

Left: Image by PhotoLizM via Pixabay.Right: Image by J. Roberto Trujillo via Wikimedia Commons. Creative Commons Attribution.

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A New Theory for an Age-Old

Question By Alan Yang

ScientiStS have long been trying to understand how life on earth originated. Perhaps the most wide-ly accepted theory of the origin of life is that a “pri-mordial soup” of inorganic chemicals was subjected to intense jolts of energy from lightning strikes and solar radiation, which gave rise to organic molecules such as amino acids and RNAs. Some of these mol-ecules eventually developed self-replicating abilities, compartmentalized inside lipid membranes and be-came the world’s first cells. From there, organisms un-derwent Darwinian natural selection, whereby those organisms more well-adapted to their environments transmit their genes to the next generation at a higher rate than those less well-adapted. This process gradu-ally produced the different forms of life we see today.

Given that life has developed and evolved in a world driven by physical laws, we can expand our perspective by investigating how physics accounts for evolution. Recently, a 31-year-old assistant pro-fessor of physics at MIT, Jeremy England, has put forth a new theory that seeks to accomplish this.1 England’s theory explains the physics behind or-ganisms’ ability to replicate themselves. This self-replication is a key component of evolution.2

His theory relies on the second law of ther-modynamics. According to this law, any process that occurs must increase the entropy of the uni-verse. Entropy is a quantification of the number

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Image via Pixgood.com. Creative Commons Attribution.

of ways in which a system can exist under a giv-en set of conditions. Specifically, England’s theo-ry is based on the fact that biological replication dissipates waste heat. This is true for all types of replication ranging from the reproduction of or-ganisms to the copying of DNA molecules. This heat increases the entropy of the universe3 because heated molecules can move around randomly in more ways than molecules at a lower temperature.4

Indeed, England found that in order for a repli-cator to replicate at a given rate, a minimum amount of heat must be dissipated by the replicator. And the more heat a system releases while replicating, the more likely it is to replicate. So systems that re-lease more heat while replicating are more capable of producing offspring or copies of themselves and enduring across generations. Interestingly, RNA has physical properties that make its self-replication better at dissipating heat than DNA’s, and therefore more spontaneous. This finding provides further support for the theory that RNA was the first he-reditary molecule, known as the RNA world theo-

ry. In this way, England’s paper provides a quantified description of the physical driving forces behind the abstract concepts of evolution and natural selection. The rule of “survival of the fittest” operates through a mechanism of heat dissipation and entropy.

Controversy rages on about England’s entropic explanation of life, but even if validated, England’s theory would not supplant current theories. It would instead provide scientists with a more complete view of life than the current primordial-soup-Darwinian theory. “I am certainly not saying that Darwinian ideas are wrong,” England notes. “On the contrary, I am just saying that from the perspective of the physics, you might call Darwinian evolution a spe-cial case of a more general phenomenon”.2 Rather than explaining all of natural selection strictly in terms of genetic fitness, scientists could alternative-ly view evolution as a spontaneous process that fa-vored replicators that are more “thermodynamically fit”. In particular, the driving force for evolution no longer has to be adaptability to the environment; it can also be described as obedience to physical laws.2

England’s paper provides a quantified description of the physical driving forces behind the abstract concepts of evolution and natural selection.

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Artifical Photosynthesis: An Interview with Daniel NoceraBy Amir Bitran

Daniel nocera is the Patterson rockwooD Professor of Energy at Harvard’s Department of Chemistry and Chemical Biology. Nocera has achieved worldwide acclaim in renewable energy circles for his work on artificial photosynthesis, a biologically inspired method of harnessing solar energy to produce renewable fuels. Nocera’s take on photosynthesis incorporates an “artificial leaf ”, which uses energy from sunlight to split water into hydrogen and oxygen, much like real leaves. The hydrogen is subsequently fed into specialized hy-drogen fuel cells1 to produce electricity. Excess hydrogen can be used in fuel cells even while the sun isn’t shining, solving a major weakness of tra-ditional solar methods. In this interview with Bre-via, Nocera expresses his hopes and concerns for this technology, as well as the global energy future.

AMIR BITRAN: What made you look towards plants as a source of inspiration for renewable energy?

DANIEL NOCERA: So photosynthesis is ac-tually lousy at storing energy. But plants are really good at using energy efficiently. So what we did is, we looked at photosynthesis and asked, how can we take all the functional steps and put them together

to make a good storage machine? And there were real lessons to be learned there. Plants are really good at taking sunlight and using that energy to create an electric current. The current splits water into oxy-gen and hydrogen. … [W]hat we decided to do is, stop there. Once you have hydrogen, you can make any fuel subsequently. [This is in contrast to plants, which use their excess hydrogen to make glucose.]

AB: How does your artificial leaf work? How is it different from your average rooftop solar panel?

DN: The artificial leaf is an energy storage tech-nology; this is totally different from solar panels, which are energy generating. [Our] technology has sunlight go to a fuel, which you can then use any time you want. Our technology is called a buried junction – you use the silicon of a solar panel to make a wire-less current, and bury it between two conducting surfaces. Then you [place] catalysts, or compounds that can collect that charge and do the fuels trans-formation [i.e. split water into hydrogen and oxygen].

AB: Storing solar energy in the form of hy-drogen seems like a great solution to perhaps the biggest hurdle of solar power: the sun doesn’t shine when it’s dark or cloudy. So why hasn’t

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hydrogen-based energy storage taken off yet? DN: The problem there is, there is no infrastruc-

ture for you to use the hydrogen. And there’s nothing you’re going to make that, at the snap at the finger, will replace trillions and trillions and trillions of dollars of investment that have already been paid out building our current energy system. But in the developing world, they haven’t made that decision. Instead, they’re going to a decentralized energy system2, where you might have one hut generating the energy for a little village.

AB: So if developing nations suc-cessfully adopted decentralized ener-gy, would developed nations follow suit and decentralize, potentially mak-ing room for hydrogen infrastructure?

DN: Yeah, we’re going to get re-ally jealous when we see a bunch of people we consider in the devel-oping world living better than us.

AB: A key feature of your artificial leaf is that it splits water into hydrogen. But if clean water is scarce in devel-oping nations, does dirty water damage your technology?

DN: That, we’ve solved. We really listen to plants – plants use kind of dirty water. And they can [do this] because they’re self-healing; they fix themselves [in case of damage]. So part of our invention was, could we make a self-healing technology? And we’ve devel-oped a huge scientific ruleset for self-healing, and it’s now very predictable, and you can design self-heal-ing. Because we made a self-healing system, our tech-nology can literally take a puddle off the ground.

AB: As a source of energy, where does artificial photosynthesis stand in terms of efficiency? Carbon neutrality?

DN: The latest thing we came up makes hydro-gen and oxygen at 10% efficiency [10% of the solar energy that strikes the artificial leaf is successfully converted into fuel]. But we’re continuing to improve it. We’re also exploring how we can combine hydrogen with other sources, such as CO2, to make different fuels. Say I’ve split water to hydrogen and oxygen. In a fuel cell, I can recombine these to produce electricity. But we don’t even deal with carbon. In the second scenario, I take the hydrogen and combine it with car-

bon dioxide from the atmosphere, and I make a fuel. But then you’re going to burn it, and the CO2 is going to go back in. So it’s carbon neutral [the net amount of CO2 in the atmosphere doesn’t change].

AB: What advice do you have for our readers who are interest-ed in tackling the energy crisis?

DN: So first, scientifically, you should join labs. And then, my other advice, which I feel pretty strongly about, is to get really good at something. So one dan-ger of this area is, “oh, energy is really complicated, so there is science, and technology, and invention, but then there’s policy, government,” and that all might be true, but when you’re a student, you shouldn’t be trying to do all forty things at one time. The energy landscape is so broad, if you think of a funnel. But it is good to start at the bottom of the funnel, and then give yourself time in your own life, and let it open up. And the way that happens is being a good listener.

Image by Takashi Hososhima via Flickr. Creative Commons Attribution.

“We really listen to plants.”

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PRIMARY RESEARCH


NCRC: Top 6 Research Endeavors

The annual National Collegiate Research Conference concludes with a competitive poster session. Participants display their work as an elite panel of researchers, leaders, and entrepreneurs evaluates their projects based on a number of selective criteria. The following research experiments represent the high caliber of all submitted projects.

Here are this year’s winners.

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PRIMARY RESEARCH


Social and Behavioral Sciences

It remains unclear exactly which neural pathways lead to the onset of dyslexia. This is partly because functional MRI (fMRI), a standard brain imaging technique, requires the subject to perform a task in order to observe brain structure activation. Brain im-pairments caused by dyslexia vary so much that it can be difficult to develop a task that will reveal popula-tion-wide deficits in brain activation. To overcome this difficulty, Isobel Green ’17 examined dyslexic children’s brains at “rest;” fMRI was done on pa-tients not performing any specific task. At the Psy-chiatric Neuroimaging Laboratory at Brigham and Women’s Hospital, she studied brain scans of dyslex-ic boys and healthy controls from Munich, Germany.

Green studied the correlation between two parts of the brain that are thought to play a crucial role in reading: the supramarginal gyrus (SMG) and the infe-rior frontal gyrus (IFG). When individuals read, they must be able to associate written language with sounds. The SMG, located in the posterior brain, is believed to process these sounds. These processed sounds are then sent to the IFG, which associates them with words from the individual’s memory. Green observed that the correlation in neuronal activity between the SMG and the IFG was much lower for dyslexic sub-jects than control subjects. The SMG’s transmission of sounds to the IFG may be impaired in the dyslex-ic group, hindering associations between sounds and words. According to Green, this decreased correla-tion could be identified before reading age in dys-

lexic children, which may allow for early diagnosis.Green’s next goal is to look for evidence of a phys-

ical impairment in the connection between the SMG and the IFG using a technique called diffusion tensor imaging. If she finds such evidence, Green may ex-plore treatments to compensate for the deficiency of this connection. Green believes this research could provide “exciting implications for remediation work.”

— Hannah Smati

Photographs by Arthur Nguyen.

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There’s an old saying that the eyes are windows to the soul. In a similar way, we might think of the cornea as the window to the eye: it is the clear, dome-shaped surface that forms the eye’s outermost layer.1 But as scratches and cracks can form in the glass of a window, so too abrasions and wounds can occur in the cornea. These wounds were the subject of Jacqueline Masehi-lano’s award-winning research for NCRC. Masehi-Lano, Caltech ‘15, wrote in her abstract that the natural healing process of corneal injuries can create problems in vision. Following a corneal injury, normal corneal cells called keratocytes differentiate into myofibroblasts, which are cells in-volved in tissue repair.2 But these myofibroblasts also cause negative side effects. Masehi-Lano wrote,

Engineering, Math, and Computer Science

Government, Policy, and Economics

Many of us take for granted the fact that we get unlimited, clean water at the turn of a tap. But Har-vard junior JaMes Golden knows better than most how rare this phenomenon is. Golden’s research project for NCRC was conducted as part of his work with a nonprofit organization called Water Ecuador, which was founded in response to the prevalence of diarrheal illnesses in Ecuador due to lack of quality drinking water. The company’s original purpose was to operate its own water treatment centers in order to distribute large, reusable plastic water bottles in rural areas that can’t support a piped water system. But the rise of a private, for-profit water bottling industry in the region has necessitated a change in focus. Now, the company is emphasizing research on the bottled water landscape that already exists. “We realized that we can impact a whole lot more people if we make sure that the bottled water that’s being distributed is actually clean,” Golden said.

His project investigated the bacterial contamina-tion of water from rural Ecuadorian treatment cen-ters both before bottling and over a period of a month after bottling. His results, though, suggest that bacte-rial contamination does not occur before the water is bottled or increase over time: instead, it happens im-mediately when the water is bottled. “The US EPA and Ecuadorian regulations state that there should be zero coliforms and E. coli bacteria in [a given vol-ume of] water,” Golden said. “There were thousands of coliforms and E. coli found [in these bottles].” Since the bottles are reusable, families return their

bottles to treatment centers for refilling. But it seems that the cleaning processes for these used bottles are severely inadequate, so water that is initially clean be-comes contaminated in the bottles. Water Ecuador is now exploring more effective sanitation methods that are scalable in terms of both cost and time efficiency.

Golden himself has experienced the effects of contaminated water, becoming very ill on his most recent trip to Ecuador. “There was this realization that getting sick doesn’t necessarily translate in the same way in a developed country and in rural Ec-uador,” Golden said. “It’s challenging, understanding the implications of these health concerns … But that also makes it worthwhile working toward solutions.”

— Jessi Glueck

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“Myofibroblasts deposit disorganized protein and contain … fibers that distort the cornea’s refracting surface,” making it harder to see. In fact, said Mase-hi-Lano in an interview, “Corneal injuries impact millions of children in third-world countries and are the cause of 30% of all blindness cases there.”

Under the guidance of graduate student Amy Fu, Masehi-Lano set out to create a substance that could allow corneal wounds to heal while suppressing the negative effects of myofibroblast activity. She calls it a “3D eye bandage.” Masehi-Lano tested the abil-ity of three growth factors to act as chemical cues, suppressing myofibroblasts’ expression of the pro-teins that cloud vision. Though her results are pre-liminary and will require more testing, they currently suggest that all three growth factors are effective for this purpose. These growth factors are special pro-teins that can be added to a gel-like substance and injected into the eye. The transparent gel could “pro-mote orderly wound healing and salvage the vision of millions of people,” Masehi-Lano wrote. After all, we should gaze into one another’s eyes — and look upon the outside world — through pristine windows.

— Jessi Glueck, with assistance from Erica Budina

BiologyTomatoes may seem like mere salad ingredients,

but they raise complex scientific questions. For NCRC, Wake Forest University student Kathleen dinapoli researched the genetic and biochemical controls of lateral root growth in tomato plants. Lateral roots grow sideways off a vertical primary root. “[They] increase the plant’s surface area and so increase its ability to pick up water and nutrients,”

DiNapoli said. An understanding of factors that are conducive to better lateral root growth could al-low us to breed for tomato plants with those traits.

DiNapoli first examined the effects of flavonoids on lateral root growth in a tomato mutant called an-thocyanin reduced (are). Flavonoids are substances produced by the plants’ metabolisms that regulate de-velopment and reproduction. In are, though, there is a mutation in the gene that codes for an enzyme cru-cial to flavonoid synthesis. Flavonoid production in are decreases and lateral root growth suffers. Lateral root growth in these mutants was returned to normal when a functional copy of the mutated gene was sup-plied. Therefore, flavonoid synthesis may play a crit-ical role in the lateral root growth of tomato plants.

DiNapoli also studied introgression lines, mod-ern tomato plants that have some DNA from an older, ancestral tomato plant embedded in a small area of their genome. DiNapoli observed that one introgression line, IL 2-5, had more lateral roots than normal tomato plants. She found that IL 2-5 contained ancestral DNA that codes for enzymes needed in flavonoid synthesis. This finding sug-gests a relationship between flavonoid production and lateral root growth. Additionally, the ancestral tomato plant was more drought-resistant than mod-ern tomato plants. So DiNapoli’s work may ulti-mately provide insight into the relationship among lateral root growth, flavonoids and drought resis-tance. “I think this research is … pertinent … [to] all the conversations about feeding the [growing] population,” DiNapoli said. “We’re helping [solve] some of the most pressing problems of our time.”

— Jessi Glueck

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Deep in the misty, verdant slopes of the Ecua-dorian cloud forest, NNeoma adaku has discov-ered a promising weapon in the fight against cancer. Adaku, a 2015 NCRC winner, helped to identify a new species of fungus from the region which could be useful in the development of cancer treatment. The fungus synthesizes an extract that could pre-vent tumor cell resistance to chemotherapy and ra-diation therapy. Because of their ability to develop resistance, some cancers, such as lung cancer, defy virtually every existing form of treatment.1 Existing treatments often work by inducing double-strand

breaks (DSB’s), or fractures in both of the paired DNA strands comprising a tumor cell’s genome. But this doesn’t always work. As Adaku explained, “some tumors become resistant to radiation therapy [and chemotherapy] when they acquire mutations that enable them to better repair double-strand breaks”.

In the most common repair mechanism — known as canonical non-homologous end-joining (C-NHEJ) — the damaged DNA molecules are simply ligated back together.2 Less prominent path-ways include mutagenic non-homologous end-join-ing (M-NHEJ, which is similar to C-NHEJ except that damaged DNA molecules are processed before ligation) and homologous recombination (HR, in which a damaged sequence uses an identical, intact sequence as a repair template).3 Adaku devised an assay that uses fluorescence to measure the rates of M-NHEJ and HR in cells. She found that, fol-lowing incubation with her fungal extract, HR and M-NHEJ activity significantly increased with-in treated cells. This result suggests that C-NHEJ was being inhibited, because M-NHEJ and HR often compensate for decreased C-NHEJ activity.

This finding is key because, according to Adaku, “the [C-NHEJ pathway] is the main pathway of dou-ble strand-break repair.” Thus, the compound may heighten tumor cells’ sensitivity to therapies and sup-press resistance. One of Adaku’s next steps is to test this hypothesis. If confirmed, Adaku’s discovery could mark the beginning of a new era in cancer treatment.

— Amir Bitran

Chemistry

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PRIMARY RESEARCH


Every surfer who has spent sweltering summer days gliding over the ocean knows a key fact about waves — they carry energy. This is true not only of water waves, but also of electromagnetic waves, sound waves, and a more abstract waveform known as a quantum mechanical wave. Quantum mechanical waves and their energetic properties, were the subject of MIT junior Nicholas RiveRa’s NCRC award winning research project. But what exactly is a quantum wave? Quantum mechanics states that we cannot pinpoint the exact position of a small particle, such as an electron. We can, however, describe the probability that it will be found within a range of locations using a mathematical descriptor called a “wave function”. In a sense, the particle can be treated as a wave that is spread out in space, rather than as a discrete point.1

When a quantum mechanical wave is low in energy, it is confined within a certain length, just as a vibrations on a guitar string are trapped between its ends. Meanwhile, high energy quantum mechanical waves are generally thought to travel, resembling ocean waves that move past a surfer.2 But could these high energy quantum waves be captured as well? Rivera, building on previous theoretical work, has shown that this may be possible. Rivera’s theory predicts that these trapped high energy waves, known as “bound states in the continuum”, could manifest themselves in real-world systems with

particular energetic properties. These systems may include gases at temperatures close to absolute zero. Rivera’s predictions may guide experimentalists in their search for bound states in the continuum. If confirmed, this concept of bound waves may apply beyond just quantum mechanical waves. For instance, Rivera envisions an technology that traps solar radiation as a bound wave. The energy could then be released even when the sun isn’t shining.

— Amir Bitran

Physical Sciences

Photographs by Arthur Nguyen.

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PRIMARY RESEARCH


Grand Prize: Mahima Sukumar

The social issues pertaining to mental health reach newspaper headlines daily, but National Collegiate Research Conference grand prize winner MahiMa SukuMar ’16 has dedicated her work to the science behind this complex topic. An undergraduate at Johns Hopkins University, Sukumar works at the Lieber Institute for Brain Development, which, she said, “explore[s] the neurodevelopmental basis of psychiatric disorders.” Her prize winning project specifically focused on electroconvulsive seizure therapy (ECT), or electrically induced seizures, and the biological reason behind its efficiency in treating patients with depression. “For a small population of patients, who don’t respond to … traditional oral chemical methods, ECT is one of the most effective treatments,” she said. “The effects come … a lot sooner than normal medications.” According to Sukumar, researchers do not know exactly why ECT works the way it does. This gap in understanding drove her research.

While the scientific basis of depression is only partially understood, there is some evidence of depression’s effects on the brain. The brain can be thought of as a circuit. It is a network of neurons, specialized cells that transmit nerve impulses. The

neurons’ structure includes a cell body that processes the signals the neuron receives, an axon to transmit the signal after processing, and dendrites — branchlike extensions that increase the neuron’s surface area. Sukumar said that, in a depressed person, these dendrites shrink.This may drastically affect the transmission of signals within in the brain and lead to changes in behavior. A way to alleviate the situation, however, is through neurogenesis, the production of new neurons. “Neurogenesis means new neurons are being added to the circuits,” Sukumar says. “Adding any sort of new neuron is changing the way the circuit is able to communicate within each of its components.”

How does electroconvulsive therapy play into this?Neurogenesis occurs in only two parts of the

brain, one of them being the dentate gyrus of the hippocampus — the area of the brain in charge of memory and the focus of Sukumar’s research. Interestingly enough, ECT induces neurogenesis in this region of the brain, likely producing the behavioral effects witnessed in patients with depression. This foundational idea guided Sukumar’s work. “We were interested in the role that neurogenesis plays specifically for electroconvulsive seizure therapy,” she said. “And this entire experiment

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PRIMARY RESEARCH


1. Willers, Henning, Christopher G. Azzoli, Wil L. Santivasi, and Fen Xia. “Basic Mechanisms of Therapeutic Resistance to Radiation and Chemotherapy in Lung Cancer.” The Cancer Journal 19.3 (2013): 20007. Web. 2. Mahaney, Brandi L., Katheryn Meek, and Susan P. LeesMiller. “Repair of Ionizing Radiationinduced DNA Doublestrand Breaks by Nonhomologous Endjoining.” Biochemical Journal 417.3 (2009): 639. Web. 3. Bindra, R. S., A. G. Goglia, M. Jasin, and S. N. Powell. “Development of an Assay to Measure Mutagenic Nonhomologous Endjoining Repair Activity in Mammalian Cells.” Nucleic Acids Research 41.11 (2013): E115. Web. 12 Apr. 2015.

ReferencesJacqueline Masehi-Lano1. “Facts about the cornea and corneal disease.” National Eye Institute. National Institutes of Health, Web. 26 May 2015. 2. Myrna, Kathern et al. “Meet the Corneal Myofibroblast: the role of myofibroblast transformation in corneal wound healing and pathology.” Veterinary Ophthalmology 12.1 (2009): 2527. Web.

Nneoma Adaku

Nicholas Rivera1. “Varieties of Wave Equations.” HyperPhysics. Web. 20 Mar. 2015. 2. “Particle in a Box.” Schrodinger Equation. Web. 12 Apr. 2015.

was to illuminate why the therapy works and how we can perhaps make it more accessible for patients.”

To do this, Sukumar conducted studies on two sets of mice. Both sets were administered corticosterone, a hormone involved with stress, to induce symptoms of depression in the mice and create a working model. One group, however, was neurogenesisablated, which means that their capacity to increase nerve cell production was impaired. The other group did not undergo this procedure. Sukumar said she created these two groups of mice because she hypothesized “that neurogenesis plays a really large role in creating this antidepressant treatment” for ECT; thus, she needed to test whether ECT still works when neurogenesis cannot occur. She then gave all of the mice ECT for two weeks and conducted behavioral tests and scans of their brains.

Sukumar’s project revealed that the mice who were neurogenesis ablated could not recover from their depression despite the electroconvulsive therapy. Mice with normal circuitry — in other words, no change in their ability to produce new cells — improved behaviorally, however, and showed signs of recovery. “It goes to show that the therapy is based on the upregulation of neurogenesis,” she said.

The conclusions drawn from the research have many implications for future scientific work on depression and its treatment. ECT currently has various side effects, including memory loss, and Sukumar hopes that by understanding why ECT is effective, researchers can develop safer and less stigmatized alternatives to ECT. She also sees the results as a step toward comprehending the brain and its relationship with depression. “This is a great

insight into how antidepressants actually work and what type of changes go on molecularly in the brain that could really help in terms of diagnosis or... even creating novel methods [of treatment],” Sukumar said.

— Ha Le

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OPINION


Centuries ago, the Americas were the New World. These days, our frontiers have stretched be-yond the earth. Instead the night sky offers myriad possibilities for exploration and colonization. And one venture capitalizing on this dream is Mars One, a not-for-profit foundation planning to establish permanent human settlement on Mars.1 The Mars One itinerary appears reasonable, and the compa-ny seems to have the machinery, the funding, and the attention to make its mission — however crazy it may appear — work. Yet while the project pres-ents a glorious future, the reality might not be as pretty. The unfortunate fact is that Mars One is a game of Russian Roulette. And while every space mission might carry risks, Mars One is pursuing a venture that might be too perilous for comfort.

The desire to colonize space is a legitimate one, in large part because our own planet is mortal. There is much discussion of the short-term dangers to hu-manity’s existence — massive nuclear conflict and global warming, for example. But massive and per-haps inevitable causes of destruction loom in the more distant future. The sun is becoming progres-sively hotter and may one day evaporate all of earth’s oceans, resulting in a greenhouse effect that would

cause temperatures to soar. These elevated tempera-tures could kill all living beings through heat stroke. Furthermore, scientists believe that this increasing warmth can catalyze quicker reactions between car-bon dioxide and rocks. Such reactions would deplete atmospheric carbon dioxide, eliminating plants and soon after, animals.2 While these doomsday scenar-ios will likely not occur for a few hundred millions of years, they suggest that humanity’s only chance at ultimate survival is to branch out. As SpaceX CEO Elon Musk succinctly puts it: “[T]here is a strong hu-manitarian argument for making life multi-planetary in order to safeguard the existence of humanity in the event that something catastrophic were to happen”.3 Colonizing Mars is an insurance against extinction.

Mars One is committed to colonizing the red planet within the century. The company’s mission has several phases: a Mars surface lander will be de-ployed in 2018 — the first in a cascade of technolo-gy being slowly sent to Mars each year until the first colonists, four astronauts, land in 2026.1 This cascade will include modified space technology such as a life support unit — a Lander that can generate solar en-ergy through photovoltaic panels and create potable water through the heating of water ice in the local

The Space Columbus: Mars One and the Quest to

Colonize the Red PlanetBy Ha D.H. Le

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OPINION


ground soil — and rovers equipped to perform func-tions like measure the amount of water in ground soil or remove protective panels from the landers.1

So is Mars One the solution?If the mission had minimal risk, the answer would

be ‘yes.’ But researchers at MIT recently published a report with a macabre assessment of the mission. For instance, the study points out that, to nourish themselves, the crew would have to cultivate so many crops that the plants would produce levels of oxy-gen passing safe thresholds in the confined spaces where they would be living.4 Thus, the crew’s safety would require “some form of oxy-gen removal system … a technolo-gy that has not yet been developed for spaceflight”.4 Furthermore, the study concludes that Mars One’s purported six launches for each crew expansion mission would be insuffi-cient. To carry all the necessary sup-plies before and during the coloni-zation mission, the required number of launches per mission would exceed 30.4 For these reasons, with its current layout, the Mars One mission is unfeasible.

Mars One CEO Bas Lansdorp refutes the study, however. He points out that the MIT study assumes that the technology aboard Mars One will resemble that of the International Space Station. But accord-ing to him, the Mars One technology is far more advanced.5 For instance, Mars One’s space technol-ogy will include improvements and modifications

by Paragon Space Systems Corp. (an environmen-tal control firm for extreme environments),6 which produces life support systems that exceed NASA standards for oxygen and carbon dioxide control.5

This would ultimately make Mars One’s technol-ogy more advanced and capable of sustaining life.

But even if the MIT study’s assumptions were in-valid, the concern remains that the mission’s tech-nology has hardly been studied. The study notes that “very little has been published in the technical

literature on this mission ar-chitecture”,4 and that makes it difficult to completely discount the study’s concerns. Transpar-ency is paramount. We need reports concerning the tests Mars One has done with their technology. We need evidence from other scientists about the project’s feasibility and sustain-ability. Mars One, though or-chestrated by a private compa-

ny, represents a future for humanity. Yes, Columbus discovered the Americas by accident, but do we want to rely on pure chance for such a profound and im-portant mission? If the human race’s future is truly at stake here, then more rigorous inspection is required.

The desire to colonize space is a legitimate

one, in large part because our own planet is mortal.

Image by Kommesser via Google Images. Creative Commons Attribution.

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OPINION


The Cost of Creativity:Intellectual Property and the Internet

By Silvia Golumbeanu

Denis DiDerot writes, “What form of wealth could belong to a man, if not the work of the mind … if not his own thoughts … the most precious part of himself, that will never perish, that will immortalize him?”1

This “wealth”, what we might now call our in-tellectual property, has acquired a new dimen-sion with the advent of the Internet. Instan-taneous publication and viewership allows us to discover, cite, and be inspired by other people’s thoughts almost effortlessly. But it also presents unprecedented opportunities for piracy, or the theft and illegal distribu-tion of another person’s intellectual property.

Piracy has always plagued print media. Yet the Internet is a new playing field, allowing pi-racy to change forms and elude definition as well as detection. This is of course due to the fact that the Internet makes it easier to share material anonymously. But we could also think about the distinction between piracy in print

and piracy online in terms of commercial and noncommercial information. Commercial in-formation is information that has immediate market relevance, in that it is explicitly pro-duced to be sold: publication houses that sup-ply bookstores specialize in the distribution of this kind of information. Noncommercial information, by contrast, consists of ideas that are not meant to be sold: for example, the ideas contained in a conversation with a friend or a series of letters. In the 16th through early 20th centuries, when the transfer of ideas was dominated by print circulation, it was fairly easy to differentiate a grocery store conversa-tion from a published essay. The essay would have a name, and likely a price, on it. The streetside conversation would be what Law-rence Lessig calls “noncommercial culture”. Lessig writes, “At the beginning of our his-tory, and for just about the whole of our tra-dition, noncommercial culture was essentially

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OPINION


unregulated”.2 Without direct commercial relevance, there was no need to stamp copy-rights on anything that constituted the casu-al sharing of an idea. On the Internet, the distinction between the commercial and the noncommercial is not so clear. A blog post is free to distribute and read, but the author has as much of a claim on the ideas within it as the author of a pub-lished print book. This has problematic im-plications, particularly for those who hope to use the Internet for commercial means.

Because the Inter-net has flattened the commercial and the non-commercial onto the same plane, the things we might actually want to sell — original mu-sic, writing, artwork, etc — become easy prey to online pirates. It is as easy to share free, il-legal music as it is to share blog posts. Piracy is facilitated by the Internet because we have become desensitized to the distinction be-tween the commercial and the noncommer-

cial. Downloading an illegal copy of your textbook seems very different from pluck-ing it off the shelf and running out of the bookstore. All it takes is the click of a button in the privacy of a dorm — which feels ex-

actly like it would if the textbook didn’t cost money at all.

As Diderot wrote in the 18th cen-tury, our ideas are an incredibly valu-able part of our-selves. They are our “wealth”. They can even “immortal-ize” us. Now, in the 21st century, our ideas can be trans-

ferred, shared, and monetized with un-precedented ease across a vast network of contributors and consumers. But with the consequent rise in regulation of this con-tent, sharing also creates a growing legal and commercial responsibility. In cyber-space, the question of the future will be how to reconcile the free exchange of ideas with the protection of intellectual property.

A blog post is free to distribute and read, but the author has as much of a claim on the ideas within it as the author of a published print book.

Image by Jared Zammit via Flickr. Modified by Silvia Golumbeanu. Creative

Commons Attribution.

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OPINION


Precision Medicine: Using Genomic Data to Treat Disease

By Sahar Ashrafzadeh

During his state of the Union address on Jan-uary 20th, 2015, President Obama presented the nation with his vision for “a new era of medicine.” As a growing number of researchers study the se-quenced human genome to learn about mutations that cause diseases, precision medicine – medicine that is prescribed to patients based on genetic in-formation from their DNA sequences – seems in-creasingly promising. Obama portrayed his new precision medicine initiative as an endeavor that will improve our ability to treat and cure diseases. This sounds encouraging, but is developing personalized medicine for such a broad range of genetic disor-ders a realistic goal for the scientific community? Precision medicine exhibits great potential to im-prove disease treatment; we just need more time.

Therapies based on personal genetics hold much promise. But before we implement them, we must better understand how the human genome works. Despite the impressive achievements that genomics research has seen in recent years, it is still difficult to reliably predict whether specific genes are impli-cated in diseases. The excitement surrounding ge-nomics has understandably led to a vast number of scientific publications that claim to have identified DNA mutations that cause genetic disorders. But many claims, especially those published during the

early years of genomics research, are based on limit-ed scientific evidence. For example, a study on severe recessive childhood diseases found that 27% of pub-lications that claimed to have identified disease-caus-ing DNA mutations in fact lacked sufficient evidence to make their claims.1 If treatments are developed to target DNA mutations and genes that have been falsely associated with disease, they may be a waste of valuable time and resources and cause negative effects on the patients to whom they are prescribed.2

Not only is our understanding of the human ge-nome lacking, but our very ability to sequence DNA and identify mutations leaves room for improve-ment. The human genome consists of approximate-ly three billion base pairs, and a single nucleotide change in a person’s DNA sequence can have vast impacts.3 This means that it is critical that DNA se-quencing information be accurate down to every nu-cleotide. However, some regions of an individual’s genome produce low-quality sequencing data or are altogether missed in the DNA sequencing process, preventing us from being able to study the effects of mutations in these regions on the individual.4

Furthermore, due to a lack of understanding in the scientific community regarding the role of non-pro-tein-coding DNA, most genomic research focuses only on the protein-coding portion of the genome.

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OPINION


These regions, which are collectively referred to as the “exome,” account for only 1.5% of the human genome.3 While our current understanding of ge-netics suggests that mutations in non-protein-cod-ing DNA are unlikely to be pathogenic, it is possible that we are in fact missing out on countless DNA mutations that have implications for human disease.

Each year brings significant improvements in the quality of DNA sequencing information and vari-ant identification, but the technology and scientific knowledge required to thoroughly analyze the en-tire genome is beyond what is currently available. Eric Lander, founder and director of the world-re-nowned Broad Institute of Harvard and MIT, a genomics research center, weighed in on this is-sue during a recent talk entitled “The Past, Present and Future of Genomic Medicine.” Lander admit-ted, “There exists a gap between what the public thinks we can give them and what we actually can.”

Despite these limitations, precision medicine has made great strides in a number of well-studied ge-netic disorders.5,6,7 With the growing wealth of ge-nomic research studies, powerful drugs have been developed to target identified disease predisposi-tion markers in the genome.5 One recent example is Kalydeco, a drug that targets a gene involved in the transport of water and sodium throughout

the body.8 This drug is highly effective in improv-ing the lung function and overall health of patients with cystic fibrosis who carry the targeted genetic mutation. Successful personalized medicine treat-ments also exist for some individuals with cancer.8 Patients can now have simple genetic tests that de-termine whether an appropriate personalized treat-ment exists for their conditions. For those who are fortunate, precision medicine can make remarkable improvements in their health. These drugs offer in-dividuals a greater life expectancy, better quality of life and, sometimes, even a cure from their illnesses.5

Promising drug discoveries like these motivate us to strive for an era in which personalized medicine will be the standard for patient treatment. Will we reach that era within the next few years? Probably not. But are the time, energy, and financial resources invested in genomics and precision medicine research worth it? I, with President Obama, say yes. Despite the long road of scientific discovery ahead, genome sequencing offers an entirely new perspective on hu-man disease. And that perspective could lead to cures.

Precision medicine exhibits great potential to improve disease treatment; we just need more time.

Image by Micah Baldwin via Flickr, Creative Commons Attribution.

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REFERENCES


PRIMARY RESEARCH

18 Inorganic Immortality1. Dvorsky, George. “You Might Never Upload Your Brain Into a Computer.” Io9. Gawker Media, 17 Apr. 2013. Web. 28 Mar. 2015. 2. Wu, Tim. “How to Live Forever.” The New Yorker. Conde Nast, 21 Feb. 2015. Web. 21 Mar. 2015. 3. Itskov, Dmitry. “2045 Initiative.” 2045 Foundation. Web. 21 Mar. 2015. 4. Piore, Adam. “The Neuroscientist Who Wants to Upload Humanity to a Computer.” Popular Science. Bonnier Corporation Company, 16 May 2014. Web. 21 Mar. 2015. 5. Hamilton, Kristy. “Scientists Put A Worm’s Mind Into A Robot’s Body.” IFLScience. 14 Dec. 2014. Web. 21 Mar. 2015. 6. Lewis, Tanya. “The Singularity Is Near: Mind Uploading by 2045?” LiveScience. TechMedia Network, 17 June 2013. Web. 21 Mar. 2015. 7. Atmanspacher, Harald. “Quantum Approaches to Consciousness.” Stanford University. 30 Nov. 2004. Web. 12 Apr. 2015.

14 Fighting MRSA the Old Way1. Thompson, Nick, and Smith-Spark, Laura. “Thousand-year-old Anglo-Saxon Potion Kills MRSA Superbug.” CNN. 31 Mar. 2015. Web. 04 Apr. 2015. 2. Feilden, Tom. “1,000-year-old Onion and Garlic Eye Remedy Kills MRSA.” BBC News. 30 Mar. 2015. Web. 04 Apr. 2015. 3. “Staph Infections.” Mayo Clinic. Mayo Foundation for Medical Education and Research, 11 June 2014. Web. 04 Apr. 2015.. 4. Axelson, Ben. “1000-year-old Anglo Saxon Remedy Kills MRSA Superbug That Resists Modern Medicine.” Syracuse.com. Syracuse Media Group, 31 Mar. 2015. Web. 09 Apr. 2015.

12 Bibles and the Blitz1. Platt, Elspeth. The Story of the Ranyard Mission, 1857-1937. London: Hodder and Stoughton, Limited, 1937. 2. Dingwall, Robert, Anne Marie Rafferty, and Charles Webster. An Introduction to the Social History of Nursing. London: Routledge, 1988. 72, 197. 3. Abel-Smith, Brian. A History of the Nursing Profession. London: Heinemann, 1960. 161.4. “The Ranyard Nurses Report for 1937.” The British Journal of Nursing, April 1938. 104. Royal College of Nursing Archives. Web. 5. The Ranyard Mission. Annual Report for 1943. 24. Ranyard Mission and Ranyard Nurses, London Metropolitan Archives: City of London.

06 How to Make a Neuron

1. Bloom, Harold. The Western Canon: The Books and School of the Ages. Orlando: Harcourt Brace & Company, 1994. Print.2. Seneca, Lucius Anneus. Medea. Trans. and ed. H.M. Hine. Eastbourne: Aris & Phillips Classical Texts, 2007. Print.3. Bloom, Harold. The Anxiety of Influence. New York: Oxford University Press, 1973. Print. 4. Lefèvre, Eckard. “A Cult without God or the Unfreedom of Freedom in Seneca Tragicus.” The Classical Journal 77.1 (1981): 32-36. Web.

16 Telomerase1. Blackburn, Elizabeth H., and Joseph G. Gall. “A Tandemly Repeated Sequence at the Termini of the Extrachromosomal Ribosomal RNA Genes in Tetrahymena.” Journal of Molecular Biology 120.1 (1978): 33-53. 2. Blackburn, Elizabeth H., Carol W. Greider, and Jack W. Szostak. “Telomeres and Telomerase: The Path from Maize, Tetrahymena and Yeast to Human Cancer and Aging.” Nature Medicine 12.10 (2006): 1133-138. 3. “The 2009 Nobel Prize in Physiology or Medicine - Press Release.” Nobelprize.org. Web. 25 March 2015. 4. Andrews, William, and Michael West. “Turning on Immortality: The Debate Over Telomerase Activation.” Life Extension Magazine Aug. 2009. Web. 25 March 2015. 5. “Are Telomeres The Key To Aging And Cancer?” Genetic Science Learning Center. University of Utah Health Sciences. Web. 25 March 2015. 6. Ramunas, J., E. Yakubov, J. J. Brady, S. Y. Corbel, C. Holbrook, M. Brandt, J. Stein, J. G. Santiago, J. P. Cooke, and H. M. Blau. “Transient Delivery of Modified MRNA Encoding TERT Rapidly Extends Telomeres in Human Cells.” The FASEB Journal 29.5 (2015): 1930-939. 7. “Dr. Bill Andrews on the Aging Process.” YouTube, 15 May 2013. Web. 25 March 2015. 8. “Recent TA-65 Studies.” RevGenetics, 27 Sept. 2014. Web. 25 March 2015. 9. Cawthon, Richard M., Ken R. Smith, Elizabeth O’Brien, Anna Sivatchenko, and Richard A. Kerber. “Association between Telomere Length in Blood and Mortality in People Aged 60 Years or Older.” The Lancet 361.9355 (2003): 393-95.

10 Understanding the Market

1. Farhangi A., Chen A., Jang Jw., Ding J.L., Grover S. Optima Technology Research Team, Blyth Fund Strategic Research Development Team, Stanford University. 2. Rogeli P., Stanislav K. “Point similarity measure based on mutual information.” University of Ljubljana, Faculty of Electrical Engineering. pp. 9. 3. Domingos P. “A Few Useful Things to Know About Machine Learning.” University of Washington, Department of Computer Science and Engineering. pp. 3-4.

08 Immortal Stories

1. Yamanaka, S., and Takahashi, K. (2006). “Induction of pluripotent stem cells from mouse fibroblast cultures.” Tanpakushitsu kakusan koso Protein, nucleic acid, enzyme 51, 2346-2351. 2. Hou, P., Li, Y., Zhang, X., Liu, C., Guan, J., Li, H., Zhao, T., Ye, J., Yang, W., Liu, K., et al. (2013). “Pluripotent stem cells induced from mouse somatic cells by small-molecule compounds.” Science. New York, NY 341, 651-654. 3. Dimos, J.T., Rodolfa, K.T., Niakan, K.K., Weisenthal, L.M., Mitsumoto, H., Chung, W., Croft, G.F., Saphier, G., Leibel, R., Goland, R., et al. (2008). “Induced pluripotent stem cells generated from patients with ALS can be differentiated into motor neurons.” Science. New York, NY 321, 1218-1221. 4. Di Giorgio, F.P., Carrasco, M.A., Siao, M.C., Maniatis, T., and Eggan, K. (2007). “Non-cell autonomous effect of glia on motor neurons in an embryonic stem cell-based ALS model.” Nature neuroscience 10, 608-614.

FEATURES

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REFERENCES


22 Saving Apes and Sapiens1. Gardener, M. R., L. M. Kattenhorn, et al. 5 Mar. 2015. “AAV-expressed ECD4-Ig Provides Durable Protection from Multiple SHIV Challenges.” Nature 519: 87-91. 2. Farzan, Michael. “A New HIV Vaccine with Dr. Michael Farzan.” Telephone interview. 20 Mar. 2015. 3. Nieto K., Salvetti A. 21 Jan. 2014. “AAV vectors vaccines against infectious diseases.” Front Immunol 5: 5.4. Kattenhorn, Lisa. “A New HIV Vaccine with Dr. Lisa Kattenhorn.” Telephone interview. 13 Mar. 2015. 5. Keele BF, et al. 23 Jun. 2009. Increased mortality and AIDS-like immunopathology in wild chimpanzees infected with SIVcpz.” Nature 460(7254): 515–519. 6. “HMS to Wind Down Operations at Primate Research Center.” HMS News. Harvard University, 23 Apr. 2013.

20 Can Eating Less Make You Live Longer?1. “Global Health and Aging: Living Longer.” National Institute on Aging. U.S. Department of Health and Human Services, Oct. 2011. Web. 19 Mar. 2015. 2. Mattison, Julie A., et al. “Impact of Caloric Restriction on Health and Survival in Rhesus Monkeys from the NIA Study.” Nature 489 (2012): 318-21. 29 Aug. 2012. Web. 19 Mar. 2015. 3. McCay, C. M., Mary F. Crowell, and L. A. Maynard. “The Effect of Retarded Growth Upon the Length of Life Span and Upon the Ultimate Body Size.” Journal of Nutrition 10.1 (1935): 63-79. Web. 19 Mar. 2015.4. Weindruch, Richard, and Roy L. Walford. The Retardation of Aging and Disease by Dietary Restriction. Springfield, IL: Charles C. Thomas, 1988. Print. 5. Meynet, Ophélie and Jean-Ehrland Ricci. “Caloric Restriction and Cancer: Molecular Mechanisms and Clinical Implications.” Trends in Molecular Medicine 20.8 (2014): 419-27. Web. 19 Mar. 2015. 6. Colman, Ricki J., T. Mark Beasley, Joseph W. Kemnitz, Sterling C. Johnson, Richard Weindruch, and Rozalyn M. Anderson. “Caloric Restriction Reduces Age-related and All-cause Mortality in Rhesus Monkeys.” Nature Communications 5 (2014). Web. 19 Mar. 2015. 7. Colman, Ricki J. “Caloric Restriction Delays Disease Onset and Mortality in Rhesus Monkeys.” Science 325.5937 (2009): 201-04. Web. 19 Mar. 2015. 8. Austad, Steven N. “Ageing: Mixed results for dieting monkeys.” Nature 489 (2012): 210-211. Web. 19 Mar. 2015.

36 The Space Columbus1. “Mars One.” Mars One. Web. 20 Mar. 2015. 2. Barras, Colin. “How long will life survive on planet Earth?” BBC Earth. Web. 23 Mar. 2015. 3. Andersen, Ross. “Exodus.” Aeon Magazine. 30 Sept. 2014. Web. 20 Mar. 2015. 4. Do, Sydney et al. “An Independent Assessment of the Technical Feasibility of the Mars One Mission Plan.” 65th International Astronautical Congress, Toronto, Canada. 5. Howell, Elizabeth. “Mars One Dustup: Founder Says Mission Won’t Fail As MIT Study Predicts.” Universe Today. 15 Oct. 2014. Web. 20 Mar. 2015. 6. Paragon: Space Development Corporation. 2015. Web. 20 Mar. 2015.

24 A New Theory for an Age-Old Question1. England, Jeremy L. “Statistical Physics of Self-replication.” The Journal of Chemical Physics 139.12 (2013): 121923. Print.2. Wolchover, Natalie. “A New Physics Theory of Life.” Quanta Magazine. Simons Foundation, 22 Jan. 2014. Web. 20 Mar. 2015. 3. Loren, Williams. “Why Things Happen (or Not).” Macromolecular Structure Proteins and Nucleic Acids. Georgia Tech Chemistry and Biochemistry. Web. 28 May 2015. 4. “What Is Entropy.” New Mexico Solar Energy Association Energy Concepts Primer. New England Solar Energy Association. Web. 28 May 2015.

40 Precision Medicine1. Bell, Callum J., et al. “Carrier testing for severe childhood recessive diseases by next-generation sequencing.” Science translational medicine 3.65 (2011): 65ra4-65ra4. 2. MacArthur, D. G., et al. “Guidelines for investigating causality of sequence variants in human disease.” Nature 508.7497 (2014): 469-476. 3. Eisenstadt, Leah. “What Is Exome Sequencing?” Broad Institute. 15 Oct. 2010. Web. 20 Mar. 20154. Kircher, Martin, and Janet Kelso. “High-throughput DNA sequencing–concepts and limitations.” Bioessays 32.6 (2010): 524-536. 5. Lee, Moo-Sik, et al. “Personalized medicine in cardiovascular diseases.” Korean circulation journal 42.9 (2012): 583-591. 6. “President Obama Highlights Advances in Cystic Fibrosis Research as Model for Precision Medicine Initiative.” Cystic Fibrosis Foundation. 30 Jan. 2015. Web. 20 Mar. 2015. 7. “Impact of Cancer Genomics on Precision Medicine for the Treatment of Cancer.” The Cancer Genome Atlas. National Cancer Institute. Web. 20 Mar. 2015. 8. “Paving the Way for Personalized Medicine.” FDA. 1 Oct. 2013. Web. 9 Apr. 2015.

38 The Cost of Creativity1. Diderot, Denis. trans. Hesse, Carla. “The rise of intellectual property, 700 B.C. - A.D. 2000: an idea in the balance.” Daedalus, Spring 2002: 26-45. Web.2. Lessig, Lawrence. “Introduction.” Free Culture: How Big Media Uses Technology and the Law to Lock Down Culture and Control Creativity. 2004. Web. 2 April 2015.

26 Artificial Photosynthesis1. “Hydrogen Energy.” Hydrogen Power and Fuel Cells. RenewableEnergyWorld. Web. 22 Jan. 2015. 2. “How Microgrids Can Help Developing Nations Leapfrog the Landline.” GreenBiz. 1 Aug. 2013. Web. 22 Jan. 2015.

OPINION

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on the cover

— Serena Eggers

Man: Attributed to the little-known 14th century French sculptor Guillaume de Nourriche, this limestone bust sits in the Fogg museum without a title, listed merely as “Male Head.” It is thought to be one of two apostle figures crafted for a Paris hospital. Though the sculptor once carved a face out of this block of stone, time seems now to be slowly transforming it back into featureless rock.

BREVIA is a forum for science, culture, and other big ideas. We are committed to bringing all disciplines of research out of the ivory tower and into the discourse of the interested public. Through our opinion, features, and primary research articles, we explore the myriad connections in the world of intellectual endeavor. Our stories are brief because we want to make knowledge accessible and interesting, providing a palette of perspectives on the world around us.

BreviaVolume 3 • Issue 1 • Fall 2015

brevia.hcura.org

table of contentsangels: These angel figures are not full sculptures, but rather bozzetti, clay sketches by the famous baroque sculptor Bernini. As such, they bear the direct marks of his hands, and are shaped with a roughness and movement absent in large-scale marble or bronze works.In the Fogg, Harvard’s art museum, the figures perch on simple white pedestals in a bright, open room. In a space filled with air and light, the angels are somehow the earthiest part.

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brevia fall 2015

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