YSM Issue 87.1

Yale Scientific

Established in 1894

THE NATION’S OLDEST COLLEGE SCIENCE PUBLICATION

December 2013

Vol. 87 No. 1

Bacterial genomes

present natural drug

libraries

PAGES 16-17

CELL BIOLOGY

Nobel Prize

News

Yale Professor James

Rothman takes the Nobel Prize

in Physiology or Medicine

GENOMICS

Tracing Cancer

Triggers

Investigation of non-coding

regions of DNA uncovers

genetic triggers for cancer

PSYCHOLOGY

Social Media

Psychology

Words used on Facebook and

Twitter reveal personality and

happiness level of users

PAGE 6 PAGES 18-19

PAGE 27

everyday Q&A

Q&A

Ballet dancers can perform multiple pirouettes without feeling dizzy. How do their bodies handle this?

Many are familiar with the not-so-pleasant

feeling that follows a ride on a merry-goround:

Although we are standing still, our

brains still perceive movement. Even just

briefly spinning around in circles can leave

one dizzy and disoriented.

Interestingly enough, ballet dancers can

execute multiple pirouettes without becoming

dizzy. Practice, of course, plays an important

role. Professional dancers train themselves

to focus on one spot in the distance while

performing complex spins, a technique

known as “spotting.” However, researchers

at Imperial College London have also found

a physiological basis for this ability: Their

brains have adapted to become less sensitive

to dizziness.

The culprits responsible for dizziness are

the fluid-filled chambers of the inner ear,

known as vestibular organs. After we stop

Q&A

How Do Dancers Spin Without Becoming Dizzy?

BY CAROLINE AYINON

Conventional wisdom holds that if you want to be socially

successful, you should make eye contact when you speak. With a

quick Google search, shy people can find tips for improving eye

contact, a reputed strategy for boosting likeability, confidence, and

trustworthiness. However, while eye contact may be beneficial in

some cases, a new set of studies in Psychological Science indicates

that when trying to convince someone with an opposing point of

view, eye contact is actually counterproductive.

Researchers at the University of British Columbia and the

Harvard Kennedy School of Government conducted two studies

that led to this unexpected finding. The first found that people

who already agree with a speaker are more likely to look him or

her in the eyes, whereas people who disagree tend to make eye

contact less frequently. The second study found that when people

who disagreed with a speaker were told to look at the speaker’s

eyes, they were less persuaded than those who were told to look

elsewhere.

In adversarial situations, eye contact is a cross-cultural and

even cross-species sign of aggression. Therefore, the researchers

surmised, eye contact from a speaker with an opposing viewpoint

triggers a defensive response in listeners, making them resist

persuasion. On the other hand, when speaking to close friends,

family, and those with shared opinions, eye contact reinforces

interpersonal connections and builds trust. The common belief

IMAGE COURTESY OF LEON NEAL

A ballerina spins rapidly in

her execution of a pirouette.

spinning, the fluid continues moving, sending

signals to the cerebellum and creating the

sense that our bodies are still in motion.

However, MRI scans of ballet dancers’ brains

demonstrate that this signal processing area in

the cerebellum is significantly smaller in their

brains than in brains of individuals from the

general population, suggesting that dancers’

bodies adapt to rely less on information

from their vestibular organs. The study also

found that fewer signals were being sent to

the cerebral cortex, a region of the brain

responsible for the perception of dizziness.

This research, besides demonstrating

the amazing ability of the brain to adapt to

the needs of the body, could be essential

in treating patients suffering from chronic

dizziness. Perhaps in the near future,

that nausea-inducing carnival ride will be

something everyone can safely enjoy.

Does Eye Contact Make a Speaker More Persuasive?

New studies suggest making eye contact is counterproductive when addressing a skeptical audience.

BY SAM MARTIN

IMAGE COURTESY OF WIKIMEDIA COMMONS

The results of the study suggest that eye contact between

opponents, such as these men engaged in a heated discussion,

may foster aggression rather than agreement.

in the persuasive power of eye contact may come from the fact

that those who agree with us are more likely to look us in the

eye. Eye contact itself, however, is not necessarily what causes

that agreement.

2 Yale Scientific Magazine | December 2013 www.yalescientific.org

NEWS

contents

December 2013 / Vol. 87 / Issue No. 1

ON THE COVER

5

6

6

7

7

Letter from the Editor

Michelle Dufault Fund Initiated

James Rothman Wins Nobel Prize

Genes Predict Lung Disease Outcome

Mechanisms of the Dengue Virus

Investigated

8

9

10

11

Dying Dwarf Galaxy Observed

Increased Wood Usage Beneficial

AIDS Disrupts Gut Bacteria

Mara River Sustainability Project

FEATURES

27

28

29

30

31

32

34

35

36

37

38

Psychology

Linking Virtual and Psychological Worlds

Technology & Art

Scientists Investigate Shakespeare's Looks

Bioengineering

Modifying Photosynthesis for Medicines

Social Science

Mythbuster: Were Vikings Savages?

Debunking Science

Food Chemistry

Materials Science

DNA Bridges Computers and Graphene

Undergraduate Profile

Ben Horowitz ES '14

Alumni Profile

Emiko Paul '91

Bioengineering

Engineers Program Chemical Reactions

Using DNA

Trivia

Five Things You Didn't Know about

Forensics Technology

Book Reviews

Einstein and the Quantum:

The Quest of the Valiant Swabian

This is Your Brain on Music

16

12

This past year, the Yale

Scientific has covered breaking

scientific news from across

Yale's campus. From chemical

photosynthesis to "smart

bomb" cancer therapy, 2013

has been a year of great investigation

and achievement.

18

24

Nature's Drugs: The Search for Organic Treatment Products

Bacteria produce bioactive small molecules prolifically. Chemistry

Professor Jason Crawford harnesses rapid sequencing to mine

bacterial genomes in search of products for drug development.

Yale Scientific:

2013 In Review

Less-Explored

Regions of DNA

Code for Cancer

Triggers

Yale researchers Mark

Gerstein and Ekta Khurana

have investigated non-coding

regions of DNA and identified

cancer triggers. Their

process can be used to find

triggers for other diseases —

future targets for therapeutics

and precision medicine.

The Missing

Link in

Alzheimer's

The Strittmatter Lab has

uncovered a protein that

acts as the intermediary in

the downward spiral towards

Alzheimer’s disease.

Domino of Life: Factors in

Maternal-to-Zygotic Transition

14The

20

IMAGE COURTESY OF DIETER SPANNKNEBEL/GETTY

IMAGE COURTESY OF UMASS AMHERST

IMAGE COURTESY OF CRAIG CREWS

The Promising Future of

Biotechnology Startups

More articles available online at www.yalescientific.org

www.yalescientific.org

December 2013 | Yale Scientific Magazine 3

Interfaces

Of Investigation

old DNA, new

tricks

Mankind prides itself on

novelty and invention, yet

we are finding that life’s

oldest code is the key to

programming some of

the trickiest engineering

problems.

pg. 36

“

Alone we can do

so little; together

we can do so

much.

— Hellen Keller

blurring boundaries

”

the circle of

science

Collaboration among many

fields of science is unveiling

the stealthy tendrils of

human diseases — and

innovating better ways to

understand and treat them.

pg. 10

Innovation: the tumbling

and fusing, blending

and blurring of theories

and principles. Only by

doing this can we push

the boundaries of what

is known, answering the

boldest questions and

discovering the most

meaningful answers.

pg. 28

December 2013

CELL BIOLOGY

GENOMICS

PSYCHOLOGY

Vol. 87 No. 1

December 2013 Volume 87 No. 1

Editor-in-Chief

Publishers

Managing Editors

Articles Editors

News Editor

Features Editor

Copy Editors

Online Editor

Production Manager

Layout Editors

Arts Editor

Webmaster

Multimedia Editor

Advertising Manager

Distribution Manager

Subscriptions Manager

Outreach Chair

Staff

Jiahe Gu

Julia Rothchild

Mina Himwich

Andrew Qi

Contributing Writers

William Chang

Stacy Scheuneman

Madeline Popelka

Aparna Nathan

Theresa Steinmeyer

Elena Malloy

Henry Li

Yale Scientific

M A G A Z I N E

Established 1894

Jessica Hahne

Karthikeyan Ardhanareeswaran

Stella Cao

Li Boynton

Renee Wu

Terin Patel-Wilson

John Urwin

Alyssa Picard

Rebecca Su

Grace Cao

Dennis Wang

Walter Hsiang

Chanthia Ma

Carrie Cao

Christina de Fontnouvelle

Nicole Tsai

Jeremy Liu

Seung Yeon Rhee

Aurora Xu

Alex Co

Deeksha Deep

Naaman Mehta

Jake Allen

Emma Graham

Payal Marathe

Ethan France

Claudia Shin

Grace Pan

Stephanie Mao

Kamaria Greenfield

Kevin Wang

Nooreen Raza

Ameya Mahajan

Advisory Board

Sean Barrett, Chair

Physics

Priyamvada Natarajan

Astronomy

Kurt Zilm

Chemistry

Fred Volkmar

Child Study Center

Stanley Eisenstat

Computer Science

James Duncan

Diagnostic Radiology

Melinda Smith

Ecology & Evolutionary Biology

Peter Kindlmann

Electrical Engineering

Werner Wolf

Emeritus

John Wettlaufer

Geology & Geophysics

William Summers History of Science & History of Medicine

Jeremiah Quinlan

Undergraduate Admissions

Carl Seefried Yale Science & Engineering Association

The Yale Scientific Magazine (YSM) is published four times a year by

Yale Scientific Publications, Inc. Third class postage paid in New

Haven, CT 06520. Non-profit postage permit number 01106 paid

for May 19, 1927 under the act of August 1912. ISN:0091-287.

We reserve the right to edit any submissions, solicited or unsolicited,

for publication. This magazine is published by Yale College

students, and Yale University is not responsible for its contents.

Perspectives expressed by authors do not necessarily reflect the

opinions of YSM. We retain the right to reprint contributions,

both text and graphics, in future issues as well as a non-exclusive

right to reproduce these in electronic form. The YSM welcomes

comments and feedback. Letters to the editor should be under

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Please send questions and comments to ysm@yale.edu.

F R O M T H E E D I T O R

Interfaces of Investigation

2013 has been an exciting year for the Yale Scientific. As our year-in-review spread on

page 12 of this issue can attest, every corner of Yale’s campus has been stirring with

scientific discoveries, from advancements in drug therapy to astronomical imaging, to

Nobel Prize-winning studies on cell machinery. In the tradition of our publication, each

of our issues this year featured an overarching theme. In March, we wrote about “Limits

and Breakthroughs” in science, followed by “The Human Population Explosion” in April

and “Frontiers of Exploration” in November. For our final issue, this year’s masthead has

gathered one last set of articles under a theme that we hope will bring all the rest of this

year’s news into perspective: “Interfaces of Investigation.”

Welcome to Issue 87.1 of the Yale Scientific. In this issue, we will explore the

growing intersections among fields of science, from joint innovations in biology and

pharmacology under the biotechnology industry (page 20) to the fusion of psychology

and computer science in the analysis of social networks (page 27). Both at Yale and

beyond, researchers from many different fields are now collaborating to bridge the gaps

between different sets of knowledge and build ever more interfaces for new discovery.

This past year at the Yale Scientific, we have seen the power of collaboration even

in the production of our own magazine. Our editorial team expanded the exclusive

online articles section begun last year to include new types of articles, such as Q&Astyle

interviews. Our business team streamlined the advertising process by creating a

media kit and branching out to new businesses in New Haven. Our production team

expanded the number of artists in each issue and filmed our first ever issue-launch video.

Lastly, our outreach team Synapse teamed up with TEDxYale, Splash at Yale, and Yale

College Admissions, to host a conference for high school students. At the first annual

“Resonance” conference, students explored science through interactive classes and heard

from several scientific speakers and student groups at Yale. It was only through the

teamwork of our entire masthead — and in the case of Resonance, collaboration with

other student groups — that any of these accomplishments were made possible.

That being said, credit for our magazine should not go solely to our masthead

members. Every issue is also a collaborative effort of approximately 35 other Yale

undergraduate contributors. And our magazine’s legacy of more than 100 years would

not exist without the continued support of our readers. At the closing of this final letter

from the editor, I would like to say thank you. Thank you to each of our hardworking

masthead members. Thank you to every writer and artist who has made a contribution

this year, whether single or multiple, small or large. Most of all, thank you to all of our

readers and subscribers for your interest, your readership, and your continued support of

the nation’s oldest college science publication.

Yale Scientific

Established in 1894

THE NATION’S OLDEST COLLEGE SCIENCE PUBLICATION

Bacterial genomes

present natural drug

libraries

PAGES 16-17

Nobel Prize

News

Yale Professor James

Rothman takes the Nobel Prize

in Physiology or Medicine

Tracing Cancer

Triggers

Investigation of non-coding

regions of DNA uncovers

genetic triggers for cancer

Social Media

Psychology

Words used on Facebook and

Twitter reveal personality and

happiness level of users

PAGE 6 PAGES 18-19

PAGE 27

Jessica Hahne

Editor-in-Chief

About the Art

The cover, designed by Arts Editor Nicole Tsai, illustrates

this issue's theme "Interfaces of Investigation." A magnifying

glass enlarges the structure of a flower petal, bringing into view

a chemical compound which could be a future drug candidate.

Contributing artists for this issue were Audrey Luo (pages 4,

24), Chanthia Ma (pages 12-13), Annelisa Leinbach (pages 14,

28), Nicole Tsai (page 16), Rachel Lawrence (page 18), Jason

Liu (pages 20-21), and Casey McLaughlin (page 29).

Editorial apology: In Issue 86.4, we attributed "Joan Steitz

Awarded the Grand Médaille" on page 6 incorrectly to Cristal

Suar. This article was written by Jiahe Gu, a staff writer and

seven-time contributor to the Yale Scientific.

WOMEN IN SCIENCE

Michele Dufault Fund Supports Women in STEM

Yale University has established

a $14 million endowment fund to

encourage women’s participation in

the sciences in honor of Michele

Dufault, a senior who was majoring

in Astronomy and Physics when she

died in 2011. This fund will primarily

be used as financial aid to support

women pursuing science, technology,

engineering, and mathematics

(STEM) majors at Yale, with the

remainder to be distributed amongst

summer research fellowships,

undergraduate conferences, and

other events.

“Michele Dufault was a remarkable

student whose enthusiasm and

love of science inspired both her

professors and her fellow students,” Provost Steven

Girvin, ex officio chair of the fund committee stated.

“We felt that establishing a perpetual fund to

provide opportunities for young women who will

become leaders in science, technology, engineering,

BY STEPHANIE MAO

and mathematics to pursue their

dreams would be a fitting tribute to

Michele.”

Although the gender disparity in

STEM majors is now diminishing

(with women now earning about

half of all bachelor’s degrees in

science), women continue to face

job discrimination in STEM fields.

A recent study at Yale showed

that science professors are more

likely to hire a prospective male

employee versus a female with

the same qualifications. With

these setbacks still present, the

endowment may have come at a

particularly apt time.

As women continue to face

roadblocks entering STEM fields, Yale provides

support with programs and groups such as the SUBJEC

IMAGE COURTESY OF NBC CONNECTICUT

Michelle Dufault was a physics

major, passionate student ,

and advocate for women in

science.

Undergraduate Women in Science at Yale. The

Michele Dufault Endowment provides yet another

resource to help women pursue goals in science.

CELL BIOLOGY

Rothman ’71 Wins Nobel Prize in Physiology or Medicine

Over 30 years after first observing

vesicle transport in a crude extract

of cells, James Rothman, Chair of

the Yale Cell Biology Department,

received a call from Stockholm. He

had been awarded the 2013 Nobel

Prize in Physiology or Medicine.

Rothman shares the award with

University of California’s Randy

Schekman and Stanford’s Thomas

Südhof for, according to the Nobel

Prize website, “their discoveries

of machinery regulating vesicle

traffic, a major transport system in

our cells.” During the phone call,

Rothman is quoted to have said,

“you imagine it, but now that it’s

actually happening, it’s an out of

body experience.”

Rothman completed his undergraduate degree

in physics at Yale in 1971. However, a biology

class taught by Fred Richards, founder of the

Yale Cell Biology Department, piqued his interest

in molecular biology. His senior thesis focused

BY EMMA GRAHAM

IMAGE COURTESY OF NOBELPRIZE.ORG

James Rothman, recipient

of the 2013 Nobel Prize in

Physiology or Medicine.

on membrane physiology, at the

time an area full of unanswered

questions.

After Yale, Rothman earned

his doctorate at Harvard Medical

School and later joined the faculty

at Stanford, where he was able

to reconstitute vesicle fusion and

budding in a cell-free environment.

This research would form the

foundation for his discovery of

SNAREs (Soluble NSF Attachment

Protein Receptors), a complex

family of proteins that allow

vesicles to correctly fuse with their

target membranes. As the body of

research on SNAREs expands, the

Rothman lab uses chemical and

physical techniques to further clarify

the machinery behind vesicle transport.

“In that moment of discovery, you have absolute

insight into nature,” said Rothman on receiving the

award. “You know something no one else knows.

Nothing will ever equal that.”


GENOMICS

New Gene Pathway Predicts Outcome of Lung Disease

BY KEVIN WANG

ECT

You have been coughing

for over a month now,

your breathing consistently

shorter every passing day.

Your doctor diagnoses you

with idiopathic pulmonary

fibrosis (IPF), a disease

without known cause or cure.

Characterized by scarring and

thickening of the lungs, IPF

proceeds at unpredictable

rates to ultimately suffocate

its victims.

However, a recent study led

by Clinical Fellow Dr. Jose

Herazo-Maya at the Yale School of Medicine has

dragged IPF into the limelight. Hypothesizing that a

peripheral blood mononuclear cell’s gene expression

would predict IPF, just as it does in diseases like lung

cancer, researchers found that under-expression of

45 genes led to lower survival rates among patients

with IPF. These genes are known as “biomarkers,” or

molecules that could be used as indicators of disease

presence or progression. These

biomarkers are correlated

with decreased amounts of

CD4 + CD28 + T cells, which are

critical for immune activation.

Although the study still

provides no cure for IPF, it may

help in determining the optimal

timing for treatment and

avoiding unnecessarily costly

and inaccurate evaluations.

“The suggestion that a gene

expression signature contains

information beyond what

could be gleaned by clinical

testing and imaging is supporting the body of

evidence that personalized medicine is not only for

cancer — but also for chronic lung diseases,” stated

Dr. Naftali Kaminski, senior author of the paper.

However, the study awaits clinical implementation,

a step that “would require at least one additional

replication in a larger cohort and the development

of an assay that is clinically valid,” said Kaminski.

IMAGE COURTESY OF BUZZLE

Lung disease is at the center of much

scientific research today.

Understanding How the Dengue Virus Works

BY HENRY LI

Dengue, a mosquito-borne

virus that infects 100 million

people each year, is becoming a

global health concern. According

to the World Health Organization,

half of the world’s population is

at risk. Marked by high fevers

and vomiting, dengue, though

usually non-life-threatening, can

develop into the deadly dengue

hemorrhagic fever.

The dengue virus belongs

to a genus called Flavivirus. All

flaviviruses have similar infection

pathways. Under the leadership of

Associate Professor of Molecular

Biophysics and Biochemistry Yorgo Modis, Yale

researchers at the Richards Center for Structural

Biology have recently conducted a study on two other

flaviviruses, yellow fever and Japanese encephalitis,

to shed light on the dengue virus’s infection pathway.

“By inhibiting certain steps of the infection

pathway and then testing virus infectivity, we saw how

flaviviruses infected a cell,” Modis said.

VIROLOGY

Researchers previously

knew that flaviviruses

enter the cell through the

endocytic pathway (the

cell’s transport system),

but not how they get

their RNA close to the

nucleus, which is key to

maximizing infectivity.

The new study shows

how this is achieved: The

virus fuses with a vesicle

within the endosome,

releasing its RNA into

it. Then the virus waits

as the endosome follows

regular cell protocol — the endocytic pathway — and

releases its RNA near the center of the cell, next to

the nucleus.

Understanding the virus’s infection pathway is not

necessary for creating a vaccine against dengue. But,

Modis explained, “Vaccines can only be pre-emptive.

Knowing how these viruses work allows us to create

therapeutic drugs for those needing acute treatment.”

IMAGE COURTESY OF YORGO MORDIS

Viral proteins on the surface of the virus

form a fusion loop and pull the viral and

ECV membranes together, releasing the

virus’s genetic material.

www.yalescientific.org December 2013 | Yale Scientific Magazine 7

ASTRONOMY

Yale Astronomers Observe Dying Dwarf Galaxy

BY MINA HIMWICH

Yale astronomers have identified a small dwarf galaxy as the first

observed example of the process of galactic death. “It’s been a mystery

for a long time how small galaxies lose all their gas, or become ‘dead,’”

said Jeffrey Kenney, a professor in Yale’s Astronomy Department and

the principal investigator of the study. “The answer has been suspected

for many years, but we haven’t found a clear, smoking gun example of

the process actually happening. This galaxy is the smoking gun example.”

The galaxy, called IC3418, is part of the Virgo galaxy cluster, the

closest cluster to our own Milky Way galaxy. A galaxy cluster is a group

of galaxies that orbit around each other. Galaxies in the cluster contain

their own gas, and gas is also spread throughout the cluster. As the gas

of the galaxy and the gas of the cluster move relative to each other, a

“ram pressure” — proportional to the density of the cluster gas and the

square of the velocity of relative movement — is exerted by the cluster

gas on the gas in the galaxy. This causes gas to be pushed out of the

galaxy in a process known as “ram pressure stripping.”

There are two different types of dwarf galaxies found in the universe:

dwarf irregular and dwarf elliptical. Dwarf irregular galaxies are characterized

by gas and star formation, while galaxies with no gas and star

formation are called dwarf elliptical. “The dwarf irregular is still turning

gas into stars, and is still alive in that sense,” Kenney explained. “In the

dwarf elliptical, all the stars are older; it’s not making new stars anymore,

so in that sense the galaxy is ‘dead.’” The new research demonstrates the

relationship between the two types: Dwarf irregulars turn into dwarf

elliptical galaxies through the process of ram pressure stripping.

“What’s especially interesting about this galaxy,” Kenney added, “is

that it has a trail of young stars behind it.” As gas is pushed out of the

galaxy, it forms a “tail” of hot gas behind it in the cluster, which can lead

to star formation. In IC3418, the formation of young stars was observed

in the tail extending to one side of the main body of the galaxy, a clear

IMAGE COURTESY OF JEFFREY KENNEY

X-ray image showing hot gas in the Virgo cluster. The center of

the cluster is the white spot in the center of the image, where

the gas density is highest. The small object below the center of

the frame is an ultraviolet image of dwarf galaxy IC3418, showing

recently formed stars. A tail of young stars (blue) extends

to the lower left of the main body of the galaxy (yellow).

IMAGE COURTESY OF NASA

NASA’s GALEX, the first satellite to detect signals from IC3418,

navigates the skies.

signature of ongoing ram pressure.

The star formation in the tail of IC3418 is also an example of what

Kenney calls “fireballs” — balls of gas that are dense enough to form

stars. These “fireballs” in the galaxy’s tail are accelerated out from the

galaxy by ram pressure. However, ram pressure does not affect the

massive, newly formed stars. These stars are gravitationally bound to

the galaxy, and since they have a small surface area, the force from ram

pressure (proportional to pressure times area) leaves them unaffected.

The newly formed stars then decouple from the accelerating fireballs

and get deposited behind them, leaving the tail of young stars that

researchers observe.

Information about was first collected during a survey of the Virgo

cluster conducted by NASA’s Galaxy Evolution Explorer (GALEX)

ultraviolet satellite, which showed the formation of young stars in the

tail. Yale researchers followed up on these observations during their own

survey of the Virgo cluster, comparing images of the galaxy at different

wavelengths, including optical, ultraviolet, X-ray, and H-alpha, a visible

wavelength created by the emission of hydrogen from the galaxy.

The ultraviolet images show star formation that has occured over the

past 100 million years, whereas H-alpha emission shows star formation

from the past 10 million years. “This picture of H-alpha emission shows

you where star formation is happening right now,” Kenney added. The

H-alpha emissions are bright knots showing new stars, while the ultraviolet

images illustrate a fainter tail behind the new star, pointing back

toward the galaxy. This elongation of the ultraviolet images, Kenney

explained, is the “clue that there may be force acting on them in that way.”

“I’m interested in galaxy evolution and formation,” Kenney said,

“and I like to study nearby galaxies because I can get a lot of detailed

information. A lot of astronomers study very distant galaxies, which

are very interesting. But they’re mostly point sources, so you can’t get

much information about each one.” In contrast, galaxies like IC4318 are

interesting and useful for this type of research, as they offer a wealth

of information and data that constrain possible evolutionary scenarios.


BY KAMARIA GREENFIELD

ENVIRONMENT

More Wood Usage: An Environmental Win-Win

IMAGE COURTESY OF DENNA JONES

Cross-laminated timber has properties similar to solid wood

products and is useful for building tall structures.

Contrary to popular belief, the best use of forests is not simply

leaving the vast majority of trees alone. Recent findings suggest that

the best course is more active: harvesting a much higher percentage

of new growth either for raw building materials or for burning as a

source of fuel. In a paper he authored with Yale graduate student

Nedal Nassar and faculty from the University of Washington, Professor

Chadwick Oliver of the Yale School of Forestry & Environmental

Studies analyzed how much carbon dioxide and fossil fuel savings

could be achieved by utilizing solid wood products, wood energy, and

unharvested forests.

The use of wood in new construction prevents decomposition

and therefore sequesters the carbon stored during photosynthesis, a

process termed the storage pathway. However, wood also avoids the

implementation of more fossil fuel-energy intensive processes, such

as the production of steel, concrete, or aluminum. This method is

known as the avoidance pathway. “Some people only calculate the

amount of carbon that’s in the wood, but the real savings is by not

having to burn all of that fossil fuel,” Oliver said. According to his

research, the production of steel, concrete, brick, and aluminum

represented 17 percent of global fossil fuel usage in 2010, not including

transportation and on-site assembly. Replacing the common steel and

concrete building materials with wooden counterparts can save on

average almost four kilograms of carbon dioxide per kilogram of

wood. One mid-rise apartment building in London, completed in 2009,

is built entirely of cross-laminated timber (CLT). CLT is engineered

from layered panels and is similar, in terms of carbon savings, to solid

wood products. For this project, experts estimate that they saved 310

tons of carbon and 23 weeks of labor compared to using conventional

reinforced concrete.

However, misconceptions about wood, especially as a primary loadbearing

structure, abound. The association betwen wood and fire is a

strong one, but dense, solid wood is surprisingly flame-resistant. When

a beam is thick enough, fire will char the outside, case-hardening it

and preventing further damage to the core. In fact, a wood beam will

retain structural integrity at temperatures capable of melting steel.

When properly treated, wood buildings can have a lifespan comparable

to those made from other materials, although buildings in the tropics

need to have their first stories made from concrete to prevent rot and

termites. “The issue that it is a short-term product or a dangerous

product ... is a myth,” Oliver concluded.

Burning wood as an alternative to fossil fuel saves slightly less than

the combined avoidance and storage pathways of using wood as a

construction material. It is useful in conjunction with the first strategy

because parts of trees that are unsuitable for building can be burned,

keeping them from rotting and releasing both carbon dioxide and

potential energy. With the increase in wood harvesting proposed by

Oliver and his co-authors, the use of scrap wood and un-merchantable

logs would raise the total global fossil fuel savings by at least 10 percent,

and by up to 15 percent if waste wood were used for energy.

Removing wood becomes even more beneficial where there is a

significant acreage vulnerable to wildfires. “If you have an overly thick

forest over a large area, it is highly susceptible to one big catastrophic

fire,” Oliver explained. Naturally occurring variations in a forest’s age

and density, called a mosaic, make forests more resistant to a single

massive fire. A renewed interest in sustainable tree harvesting would

work to preserve this mosaic, whose patchwork of dense and sparse

growth also encourages animal biodiversity. This active management

could restore the mosaic in places compromised by cropland

development and other human activity.

Around 20 percent of wood growth — the amount of new growth

that occurs on top of existing mass — is currently being harvested

globally. In the U.S., this number is higher, with around half of new

growth being felled. About 41 percent of the current harvest comes

from planted forests. With a dramatic increase in the amount of wood

sustainably harvested, up to 31 percent of carbon dioxide emissions

and 19 percent of fossil fuel consumption could be avoided, an

undertaking producing benefits across a number of spheres. Oliver

thinks that the focus in construction should be on mid-rise buildings

and infrastructure. “If we build it out of wood, we can have both

better forests in terms of biodiversity ... and save a lot of carbon

dioxide and a lot of fossil fuel,” he said. In other words, as scientists

and environmentalists study ways to reduce detrimental emissions,

IMAGE COURTESY OF FLICKR CREATIVE COMMONS

Most construction wood is harvested from conifers like these.


MICROBIOLOGY

A study done in the lab of Howard Ochman, a former Yale Professor

of Ecology and Evolutionary Biology starting a position this year at

the University of Texas at Austin, shows that chimpanzees infected

with SIV lose the immune capability to maintain stable gut microbial

composition. SIVcpz, the chimpanzee simian immunodeficiency

virus, is closely related to HIV-1, human immunodeficiency virus, and

is the direct ancestor of the latter.

Although many forms of SIV are

non-lethal, SIVcpz can cause AIDS

in chimpanzees which, as in humans,

depletes host CD4+ T cells. These

cells play a role in regulating the

growth of bacteria in the gut. One

of the hallmarks of AIDS is the

opportunistic growth of bacteria,

unimpeded by the immune system.

In order to further investigate

the connection between SIV

infection and the gut microbiome,

the researchers looked at the

composition of gut microbiomes in

chimpanzees pre-SIV infection and

post-infection. The analyzed fecal

samples were collected between

2001 and 2010 under Jane Goodall,

a leading expert and pioneer in

chimpanzee behavioral research.

Lead author Andrew Moeller, a PhD

student in Ecology and Evolutionary

Biology at Yale, sequenced the

bacteria present in the fecal samples

and was in charge of bioinformatic

and statistical analysis.

Although the link between

gastrointestinal dysfunction and

HIV has been observed, insight into the correlation has been limited

because of the significant variance between individual gut microbiome

compositions. The importance of comparing individual microbiomes

pre- and post-infection is therefore paramount. However, doing

so in humans with HIV is difficult due to the unpredictability of

transmission. Studying chimpanzees offers a solution to the problem.

The chimpanzees in question live in Gombe National Park in

Tanzania. “Chimpanzees in Gombe have been studied and sampled for

decades, and they are naturally infected by SIV, the ancestor of HIV,”

Moeller explained, “and so they represent the ideal system for revealing

potential links between the gut microbiota and the progression of

AIDS.” Samples from six chimpanzees over a span of nine years were

used, all of which contracted SIV infection during collection.

From the six chimpanzees studied, a total of 49 fecal samples were

analyzed. DNA from the samples was extracted, purified, amplified,

and sequenced. Bray-Curtis dissimilarities and Euclidean distances

Gut Bacteria Disruption in AIDS:

Strong Links to Lethal Bacterial Infections

BY STACY SCHEUNEMAN

(indicating compositional differences), as well as UniFrac distances

(indicating phylogenetic relatedness), were calculated for 7,000

randomly sampled sequences per sample.

The results show that SIV infection distorts the composition of the

gut bacterial communities. After SIV infection, individuals had a much

greater variance in the relative abundance of different types of bacteria.

Additionally, results support the

conclusion that this disruption

of the bacterial composition of

the gut is a result of long-term

instability in the gut microbiome

rather than a single shift at the

point of infection. The elevated

rate of change in gut microbiota

composition did not stop or slow

down after the initial infection.

This was found by measuring

the degree of change between

consecutive samples taken before

and after infection.

In addition to these general

changes discovered in the gut

communities, the group also

found that SIV infection led

to an increase in the relative

abundance of pathogenic

bacterial genera, including

Sarcina, Staphylococcus, and

Selenomonas. They also found

that Tetragenococcus, which

was virtually absent in all of the

samples before infection, had

increased in relative abundance

in half of the chimps after

infection. Tetragenococcus is a

genus of bacteria that promotes T cell immunity. However, although

significant differences between composition and abundance exist on

the level of bacterial genera, the study revealed stability in composition

at the phylum level. Furthermore, no single species of bacteria was

determined to be associated with SIV.

How can these findings be applied to HIV and AIDS in humans?

Moeller said that this research may open avenues for monitoring the

lethal opportunistic bacterial infections that have a high chance of

originating from the gut microbiome. “By monitoring gut microbiomes,

it may be possible to identify rises in the abundances of potential

pathogens in the gut before the pathogens spread to the rest of the

body and cause disease — allowing doctors to begin treatment for the

infections early,” said Moeller.

The lab is now continuing their investigation of gut microbiome

disruption by conducting a study on gorilla gut microbiomes before

and after infection.

IMAGE COURTESY OF THE NATIONAL INSTITUTES OF HEALTH

A new study links infection by SIV, a direct ancestor of HIV,

to distortions of gut bacteria composition in chimpanzees.


Graduate students working towards improved water quality in the

Mara River Basin have formed a partnership with undergraduates

to implement new monitoring technology. Amanda Subalusky, a

member of the David Post Lab in the Deparment of Ecology and

Evolutionary Biology, and Chris Dutton of

the Shimon Anisfeld Lab at the Yale School

of Forestry & Environmental Studies, focus

on the Mara as one of the only permanent

sources of water for millions inhabiting the

region. The river passes through Kenya and

Tanzania before flowing into Lake Victoria.

Not only does it provide water to the many

people living there, but it also sustains

millions of animals, including zebras,

gazelles, and migrating wildebeest in the

Serengeti National Park and Maasai Mara

National Reserve.

Dutton and Subalusky have explored

the determinants of water quality and

its variability in the Mara

River. There is a “master

variable” that researchers

refer to when studying water

quantity and quality called

the discharge level, a measure

of the flow level in a river.

“It determines everything,

from water quality, to aquatic

biodiversity, to bacterial and

sediment loads in the river,”

Subalusky said. Discharge

can interact with a number

of factors to affect water

quality. For example, when

large animals migrate across

ENVIRONMENT

Yale Students Collaborate on Serengeti

Water Sustainability

BY NOOREEN RAZA

IMAGE COURTESY OF CHRISTINA HOFFMAN

The Mara River is an important water

source for millions of people and animals.

the river, they bring in organic materials from the land, while aquatic

animals like hippos deposit their feces in the river. Moreover, there

are humans who take water from the river for their livelihoods and

deposit materials such as pesticides and wastewaters. These inputs

may be more concentrated under low discharge levels, with larger

resulting effects on river health.

The Kenyan and Tanzanian governments have passed laws

establishing a minimum discharge level, called the “reserve level,”

that must be protected to ensure that the ecosystem can survive.

However, with a river as vast as the Mara, it is not easy to measure the

discharge level on a consistent basis. The commercial tools available

to measure discharge and water quality along the Mara’s route are

both very expensive and unreliable in that setting, where they could

easily be damaged by frequent floods, large animals, or clogging from

sediment and nutrient deposits.

Subalusky and Dutton presented these challenges to groups of

undergraduate students in an introductory engineering course taught

by Eric Dufresne at the Yale Center for Engineering, Innovation, and

Design. They worked together to design new technologies that could

accomplish the same tasks of monitoring the discharge and water

quality that the commercial equipment could

— but without having to worry about Mother

Nature, errant hippos, or the monetary costs.

The students designed two technologies. The

first was a protective housing for underwater

water quality meters made out of aircraft

aluminum and heavy plastic. This design is

lightweight and portable but strong enough to

shield the meters while they are submerged.

The housing includes a funnel-shaped guard to

prevent the meter from getting clogged by hippo

feces, a modification that is incredibly helpful

for Mara River research, but understandably not

IMAGE COURTESY OF CHRIS DUTTON

Massive herds of wildebeest, zebra, and gazelles migrate across the

Mara River every year.

a common feature of the commercial meters.

The second tool was a water level logger

that provides easily understood

measures of discharge. It is

especially useful as it can be

installed above the river rather

than under it. This is because the

logger uses ultrasonic sensors

to measure the water level,

allowing Dutton and Subalusky

to place it under a bridge

crossing over the river, away

from the dangers of floods and

animals. In addition, Dutton

made technical modifications

that allowed them to upload

the data to the Internet every 15

minutes, an improvement from

the infrequent measures given by conventional equipment. “We now

have real-time data uplinked to our website from one of the loggers

in Kenya. When the gauge hits yellow, you know the water quality

is deteriorating ... when it hits red, it’s not good,” Dutton explained.

The real-time measurements are open to the public on their online

blogsite, www.marariverresearch.org.

Subalusky and Dutton are excited about the new technologies

and believe they could make a significant impact on their work.

Importantly, their team can troubleshoot the equipment themselves

if anything goes wrong, rather than relying on commercial meters

with no “customer support” in the middle of the basin. The cheap,

sturdy, user-friendly designs the students created could have positive

effects for other researchers, residents, and even governments in the

region. “I think creative, low-cost solutions like the ones designed by

the students in the CEID class are really the key to improved water

resources management in developing countries,” Subalusky said.


The Domino of Life

identifying factors regulating the

maternal-to-zygotic transition

by grace cao

Over a nine-month period, a human

baby develops from a single-celled

zygote into a fully-formed infant

capable of seeing, crying, and eating. This

carefully coordinated process requires a

tightly regulated genetic program controlling

the proper differentiation of each cell at every

stage along the way. Although the process is

initiated by maternal instructions, the newly

formed zygote quickly takes over, activating

its genome to begin dictating its own

fate. The way by which this zygotic genome

activation, a critical part of the maternal-tozygotic

transition, occurs is not currently

well-understood. However, a recent study led

by Antonio Giraldez, Yale Associate Professor

of Genetics, has begun to shed light on

this fundamental process by identifying the

necessary maternal proteins.

Development of the Embryo

Development begins with fertilization,

when a sperm enters the egg and forms

the zygote. Following fertilization, cleavage

occurs, during which a series of rapid cell divisions

forms a bundle of small cells known as

the blastula. During these divisions, the single

cell multiplies into 32 cells without increasing

in size. Up to this point, the zygotic genome is

still inactive and no genes are expressed. The

developing embryo is completely reliant on

maternal proteins and genes to direct these

early steps.

Once a sphere of cells called the blastula

is formed, cell divisions change from cleavage

to normal mitosis, which includes the

gap phases in the cell cycle that allow the

cells to grow. In order for this switch to

occur, the maternal-to-zygotic transition is

required. This is “a transition point when the

maternal instructions are no longer enough

for development, when the embryo starts to

follow some of its own instructions,” said

post-doctoral researcher Dr. Miler Lee, cofirst

author of the paper.

The shift involves activation

of the zygotic genome and

clearance of maternal products,

marking a turning point

in the independence of the

embryo. While many of the

mechanisms involved have

been studied, the specific

maternal proteins responsible

for initiating the transition

are not yet known.

Identifying these protein

factors was the goal of

the Giraldez Lab’s study.

The study used zebrafish, a

model organism favored in

developmental biology for

its transparent embryos that

develop outside the mother’s

body. The research team

began by sequencing all of

the RNA within the embryo

to determine which zygotic

genes were the first to be

activated, or transcribed.

By pinpointing these genes,

the researchers defined potential targets for

maternal factors involved in zygotic genome

activation. Graduate student and co-first

author Ashley Bonneau explained that,

because maternal messenger RNA (mRNA)

should be fully processed, or spliced, into

its mature form, if “we look for sequences

that should already be processed out, we

can hypothesize that transcripts with these

IMAGE COURTESY OF MILER LEE

Gene expression dynamics during early embryogenesis.

On top, zebrafish embryos are shown just after fertilization,

just after zygotic genome activation, and at approximately

21 hours after fertilization. The maternal gene

products Nanog, Pou5f1, and SoxB1 induce expression

of zygotic genes, and subsequently one of those zygotic

genes, miR-430, represses the activity of maternal genes.


DEVELOPMENTAL BIOLOGY

128-cell 256-cell 512-cell 1K-cell 2K-cell oblong

IMAGE COURTESY OF NEW SOUTH WALES EMBRYOLOGY

The blastula period of zebrafish embryonic development. It is during this period that the maternal-to-zygotic transition begins.

sequences are the zygotic transcripts.”

This analysis resulted in the identification

of over 5,000 genes that had been transcribed

within four hours post-fertilization.

To narrow this field down to genes whose

expression is actually activated by maternal

as opposed to zygotic factors, the scientists

specifically blocked splicing of zygotic

mRNA, thereby preventing their translation

into proteins. When only the maternal factors

were able to act, transcription of 269 genes

was still detected, representing the “first

wave” of zygotic gene expression.

Activating the First Wave

Once the team had identified the genes

activated by maternal products, the question

became which products were responsible

for their activation. To this end, ribosome

profiling, which sequences mRNAs bound

to cellular units responsible for producing

proteins, was used to determine which

maternal mRNAs for transcription factors

were being translated most frequently into

proteins. Transcription factors are proteins

that regulate the expression of other genes

and are likely to be important players in activating

the zygotic genome.

The profiling identified three frequently

translated transcription factors: Nanog,

Sox19b, and Pou5f1. 86 percent of zygotic

genes showed reduced expression levels when

the researchers blocked the production of

these factors. Even more significantly, more

than 95 percent of treated embryos reached

complete developmental arrest. However,

although these factors are crucial, they do

not account for all gene activation according

to the team’s analysis. Bonneau believes that

the remaining 14 percent may not have shown

reduced activation due to a combination of

reasons. “It may be that there was only a

partial loss of function [of Nanog, Sox19b,

and Pou5f1], that other transcription factors

are also essential for this process to occur,

and that the landscape that this event is taking

place in is important. It’s not just that the


factors have to be present, but the chromatin

— how the DNA is actually packaged — has

to be in a proper state for the activation to

occur,” she said.

One gene that was markedly reduced in the

absence of Nanog, Sox19b, and Pou5f1 was

the microRNA (miRNA) miR-430. miRNAs

are small, noncoding RNAs that function

to silence other gene products. miR-430 in

particular binds to many maternal RNAs

in the zygote, resulting in their degradation

and the clearance of the maternal genetic

program. “Maternal instructions in the form

of mRNAs are very important for the early

stages of embryogenesis, but as [the embryo]

transitions towards differentiation, a lot of

those RNAs become unnecessary,” said Lee.

“miR-430 hastens this process of getting rid

of these unnecessary products … so that

cellular resources are focused more on things

that are necessary moving forward.” Therefore,

regulating miR-430 expression is a key

part of Nanog, Sox19b, and Pou5f1’s roles

in setting embryonic development in motion.

Cleaning the Slate

Interestingly, the same factors Nanog,

Sox19b, and Pou5f1 have been identified by

previous studies as the main regulators of

pluripotency, or the ability to differentiate into

many different cell types, in stem cells. This

link may provide deeper insight into what

is occurring during the maternal to zygotic

transition. According to Bonneau, “with

iPS (induced pluripotent stem) cells, you’re

taking a differentiated cell, clearing away [its]

instructions … and reprogramming it into

an iPS cell that has a different transcriptional

landscape. That’s what we think is occurring

at [the transition] — it’s a reprogramming of

the embryo from one state to another to allow

development to proceed.” The connection

between embryonic development and stem

cell pluripotency suggests that the three factors

may represent a fundamental pathway to

“clean the slate” of a cell and allow it to take

on a new genetic program.

In the future, Lee and Bonneau plan to

investigate the role of Nanog, Sox19b, and

Pou5f1 on a molecular level to see how they

interact with other proteins to activate the

first wave of zygotic transcription. They are

also examining the timing of the recruitment

of factors to determine if one needs to arrive

before the others to facilitate an interaction.

By completing these further studies, they

hope to gain a more detailed understanding of

how Nanog, Sox19b, and Pou5f1 orchestrate

the first steps in the development of life.

About the Author

Grace Cao is a sophomore Molecular, Cellular, and Developmental Biology

major in Timothy Dwight College. She is a copy editor for the Yale Scientific Magazine

and works in Professor Carla Rothlin’s lab in the Immunobiology Department.

Acknowledgements

The author would like to thank Antonio Giraldez, Miler Lee, and Ashley Bonneau for

their time and clear explanations of their research on the maternal-to-zygotic transition.

Further Reading

• Lee, Miler T et al. (2013)“Nanog, Pou5f1 and SoxB1 Activate Zygotic Gene

Expression During the Maternal-to-Zygotic Transition.” Nature. doi:10.1038/

nature12632.


the search for

ORGANIC

treatment products

Drugs

Nature’s Drugs

Nature’s

preserving insulin production in type 1 diabetes

by jake allen

Human health and disease are

intimately connected to the bacteria

around us. Throughout history,

bacteria have afflicted the human race with

infections ranging from minor food poisoning

to massive epidemics of cholera and bubonic

plague. On the other hand, a whole host of

beneficial bacteria are carried around in the

human gastrointestinal tract, helping us to

thrive. With such diverse biological effects,

bacteria hold the key to uncovering the drugs

of tomorrow.

The Crawford Laboratory, located on Yale’s

West Campus, is especially aware of bacterial

diversity and the potential biomedical

IMAGE COURTESY OF JASON CRAWFORD

The Crawford Lab’s gene-to-molecule approach

for discovering novel natural products. Symbiotic

or parasitic bacteria are selected for their unique

functions in hosts. Bacterial gene clusters without

known function are then probed for their ability to

encode biocatalysts responsible for synthesizing

these small molecules.

22 Yale Scientific Magazine | December 2013

relevance of how bacteria interact with their

hosts. The lab’s principal investigator, Dr.

Jason Crawford, strategically mines bacterial

genomes in search of the biologically active

small molecules these microorganisms use to

fulfill their unique roles throughout nature.

To this end, the lab takes advantage of the

readily accessible genomic data available

through modern sequencing technology and

locates orphan gene clusters — those without

any assigned function. Such gene clusters are

often acquired in the gain of an evolutionarily

advantageous trait, making them ripe for the

discovery of novel bioactive compounds.

Beginnings of a Search

Though Crawford’s genome

screens and orphan gene clusters

are new, the search for medicines

from bacteria is not. Ever since

Alexander Fleming’s isolation of

penicillin from a fungus in 1928,

scientists have been intrigued

by natural treatment products

derived from microorganisms.

Investigation of the bacteria

behind diseases like cholera has

revealed that some pathogenic

and mutualistic bacteria interact

with humans and other host

organisms using secondary

metabolites, or small molecules that have

evolutionary purposes beyond normal

growth and reproduction. Bacteria produce

these metabolites as a way of surviving

within a host and use them to affect cellular

machinery, elude the immune system, and

outcompete other bacteria.

The ability of such compounds to target

proteins with high specificity has made

natural products ubiquitous in drug discovery

and pharmaceutical development. According

to David Newman at the National Cancer

Institute, just over half of the small molecule

drugs today are natural products or derivatives

of natural products. Several antibiotics,

including the widely used tetracycline class

first isolated from Actinobacteria, are derived

from natural products that exist as secondary

metabolites in bacteria. In addition, natural

product discovery in plants and fungi has led

to drugs ranging from Fleming’s penicillin to

the anticancer agent Taxol.

The advantage of natural products

over human-designed drugs lies in their

evolutionary optimization. Designed drugs

may result in unintended, deleterious

interactions with other body systems or

proteins that outweigh their benefits. “If

you want to design a molecule, there’s no

evolutionary selection in that process,” said

Crawford, “which means that the chances of

a molecule from a synthetic library having a


MEDICINE

pharmacologically relevant or functional role

is actually quite low.” Natural products, on the

other hand, have been sculpted by evolution

to affect specific proteins or processes in

hosts or competing microorganisms.

Mining for Natural Products

Crawford and other researchers who seek

to isolate the products of evolution have long

realized their potential. However, the high

costs — even just five years ago — associated

with genomic sequencing and the relative

lack of sequence information at that time

traditionally limited research like Crawford’s.

The search for natural products has instead

relied more commonly upon finding novel

bacterial and fungal species in soil and

vegetation samples from around the world.

Extracts from these species can be screened

for therapeutic or anti-bacterial functions in

eukaryotic and other bacterial cells.

“Genomics-guided approaches are newer,”

said Crawford. “The whole field is only about

10 years old, but the explosion in genomic

sequencing over the past five years is what

has really catapulted it forward.” Now,

comparing bacterial genomes before and

after the acquisition of new traits allows

Crawford to identify gene clusters that

encode small molecules responsible for what

he calls “evolutionary leaps.” For example, a

bacterium that makes the leap from the insect

gut to infecting humans must gain new traits

in order to survive and compete. If these

traits can be pinned to an orphan gene cluster

acquired in the leap, it is likely that the gene

cluster codes for useful metabolites with these

exact functions. The same compound the

bacterium uses to fight off other pathogenic

bacteria can be isolated and developed into a

novel, potent antibiotic.

The orphan clusters that Crawford

identifies do not necessarily code directly

for small molecules. Bacteria often make

use of enzymes like polyketide synthases

and nonribosomal peptide synthetases,

complexes of several proteins that piece

together natural products in assembly line

sequences. Tetracyclines and other antibiotics,

immunosuppressants, and anticancer drugs

are all synthesized by these enzymes. Other

biocatalysts and machinery for exporting or

processing small molecules could also be

found nearby in gene clusters. “There was a

point in time long ago when nobody knew

what a polyketide synthase was,” Crawford

explained. “So the question is: What other

enzyme systems are left that we haven’t yet

discovered?” In a recently published review,

Crawford discussed one system in particular

he has worked with, in which such enzymes

are coming to light. His work involves two

bacteria, Xenorhabdus and Photorhabdus, found

in the gut of nematodes. The nematodes,

which act as insect parasites, have a

developmental response that causes them to

regurgitate the bacteria when inside a host. The

bacteria respond by producing insecticides to

kill the insect and antibiotics to outcompete

competitors. These responses are exactly

what Crawford looks for in his search for

natural products. “A developmental biologist

would say the developmental response is

regurgitation and then look for the genes that

cause this response, but a chemist focuses

on the small molecules controlling this

response,” he said. Not only do the bacteria

produce molecules capable of inducing

regurgitation in nematodes, they must

also work to suppress the insect’s immune

system, kill the insect, and then outcompete

other bacteria or fungi. “Just there, there are

about five biomedically relevant objectives

in this simple life cycle: developmental

modulators, immunomodulators, insecticides,

antibacterials and antifungals,” said

Crawford. Even the most basic bacteria-host

interactions are rich sources of potential

drugs, making research like Crawford’s

particularly exciting for the pharmaceutical

industry.

Looking to the Future

Though they are still somewhat new

at Yale, the Crawford group has several

About the Author

projects in the works. Studying bacteria like

Xenorhabdus or Photorhabdus, they are focusing

on identifying enzymes in gene clusters

that can catalyze the synthesis of novel

small molecule structures. “If you find new

structural features the chance of finding new

function is also higher,” Crawford explained.

“Our version of a grand slam is identifying

new biocatalysts that are involved in the

synthesis of new structural features that then

lead to new biology through the functions

they encode.” This “grand slam” may not be

so far off. Members have already functionally

identified an enzyme in Photorhabdus with no

known homologues and a separate novel

small molecule class characterized by an

unusual carbon-nitrogen bond linkage. In

addition, the lab recently received a grant

to investigate and isolate small molecules

involved in bacterial ability to both suppress

inflammatory bowel diseases and drive

colorectal cancer in humans. Given the

incredible diversity of bacterial systems in

nature, the possibilities for research seem

endless. Whether applied to colorectal cancer

in humans or the modulation of the immune

system by nematode bacteria, the Crawford

lab’s gene-to-molecule approaches have great

potential for natural product discovery. A

future in which genomic screening allows

for the development of potent anticancer

agents from even the most unlikely, gutresiding

bacteria may be closer than we think.

“A lot of researchers want to be a part of

an already-developed history and fine-tune

some of the pages in that history,” Crawford

said. “We would like to see if we can start our

own little chapter.”

Jake Allen is a junior Molecular, Cellular, and Developmental Biology major in

Ezra Stiles College. His past research has focused on the pathogenesis of Alzheimer’s

disease and the effects of ketamine on signal transduction in depression.

Acknowledgements

The author would like to thank Professor Jason Crawford for his time and guidance

and for his work bridging the gap between chemistry and biology.

Further Reading

• Vizcaino, Maria I., Xun Guo, Jason M. Crawford. 2013. “Merging chemical ecology

with bacterial genome mining for secondary metabolite discovery.” Journal of Industrial

Microbiology and Biotechnology. doi:10.1016/S0140-6736(06)68341-4.

• Newman, David J. 2008. “Natural Products as Leads to Potential Drugs: An Old

Process or the New Hope for Drug Discovery?” Journal of Medicinal Chemistry (51):

2589-2599.


from

TRIGGERS

to

TARGETS

LESS-EXPLORED REGIONS

OF DNA CODE FOR CANCER

TRIGGERS

By Deeksha Deep

DNA, the key to our individuality

and the unique traits that make us

who we are, is also the key to many

of our medical problems. However, due to

technological limitations we have not been

able to fully utilize the information stored in

DNA until recently. Advancements in technology

have made full genome sequencing

faster and cheaper, making its information

accessible to researchers across the nation.

One such research team under Professor Mark

Gerstein’s lab recently made a breakthrough by

collaborating with groups that have extensive

databases of human genomes. The joint teams

discovered specific regions of the genome

which may act as signals for particular types

of cancer. These regions are termed “sensitive

regions.”

The Target of the Project

In 2003, a partnership between the National

Institutes of Health and the Department

of Energy succeeded in fully sequencing

the first human genome after thirteen years

of research. Now, the human genome is no

longer an end goal in genetic research, but a

means to an end. The advent of new projects

such as ENCODE, which aims to characterize

functional elements of the genome; 1000

Genomes, which aims to create a deep catalogue

of human genetic variation; and TCGA,

the cancer genome atlas, provide extensive

databases of human genomes. These projects

were also the resource for the raw data used

by Gerstein and Dr. Ekta Khurana’s team to

determine specific cancer trigger mutations in

the human genome.

The human genome contains over three

billion base pairs, about one percent of which

code for genes. Although 99 percent of the

human genome is non-coding, these regions

are still important. Non-coding regions actually

form the primary focus of study for many

bioinformatics projects, because gene regulation

occurs within these segments. According

to Gerstein, “the genes may be like light bulbs

— where one can actually

see the light — but

the non-coding region

is like the wire with all

the essential controls

and switches, and that

is where the regulatory

apparatus is located.”

But how do you find

the regions in non-coding

segments of DNA

that are pertinent to

essential genes? The

answer lies with evolution:

the most important

sections of DNA

have been conserved

in living organisms

because their functions

are vital for survival.

Out of the three bil-

lion base pairs, there are about three million

positions that differ from one person to the

next, and another set of roughly thousands of

positions are mutated in cancer. However, not

all of them are important in gene regulation

or determining disease. Historically, the important

variations were identified as those within

actual genes, but because some non-coding

segments influence the regulation of genes, we

now recognize the importance of investigating

other variations further. The first goal in this

project was to find the variants that overlap

with the conserved and functional regions of

IMAGE COURTESY OF MARK GERSTEIN

The prioritization and categorization of each variant is shown.

This is used to determine functional connectivity and whether

the variant is common in the same region for the same cancer.


GENOMICS

the non-coding DNA, and then to mark those

regions for further study.

The “Elaborate Filter” for the Triggers

The sequencing and data collection for the

project necessitated collaboration between

many institutes and universities, but Khurana’s

team lead the primary analysis. In order to

narrow down thousands of somatic variants

in cancer genomes to less than ten important

mutations, the researchers needed an elaborate

filtration system. By cross-referencing

about 1000 human genomes from the 1000

Genomes project with the noncoding elements

from ENCODE, the truly conserved regions

were first determined. Then these regions

were ordered according to their functional

annotation, specifically with regards to the

importance of each region in gene regulation.

Finally, the approximately 5,000 variations

(excluding those within genes) were overlapped

and ranked according to their occurrence

in a prioritized region of the non-coding

genome. Genomes from TCGA were then

used to identify specific cancer variations that

occur in conserved regions. Once the variants

were narrowed down, they were further

ranked based on their central roles in biological

networks. Finally, the variants were further

prioritized by recurrence in the same region

for multiple cancer genomes. Experimental

validations showed the identified candidate

cancer-driving mutations to be significant.

By applying this filter and creating “decision

trees” for about 90 prostate, breast, and

medulloblastoma cancer genomes, Khurana

and her team identified around 100 candidate

cancer-driving mutations.

Challenges in Identifying the Triggers

When someone mentions biology research,

the first things that come to mind are usually

Petri dishes and mice, but Khurana’s project

was conducted on computers. It may seem

that technology would eliminate many processrelated

issues. However, the real challenge

of this project did not lie in its execution,

but rather in conceptualizing the biological

framework of the problem as a measurable

test. For such a bioinformatics project, this

proved quite challenging. There are over three

billion base pairs in the genome, and this study

utilized thousands of genomes, which involved

trillions of data points. Experimental testing

necessitates careful accounting of technical

artifacts, and with thousands of genomes the


required controls can become complicated.

The grand scale at which it is now possible to

analyze biological systems means that scientists

are now limited less by the technology and

more by the boundaries of their own creativity.

Triggers as Potential “Targets”

The scientific world has known of the

genome’s power since Watson and Crick

described the double-helix model for DNA

in 1953; however, the vast amount of information

stored in the genome has been largely

inaccessible until recent

years. With the invention

of better DNA sequencing

machines as well

as improved computer

power, the determination

and analysis of the

genome was made possible,

and since 2003 the

application of scientific

investigation upon that

information has led to

the discovery of almost

2,000 genes linked to

diseases. Gerstein’s lab

and collaborators have

ventured into a relatively

unmapped region of

DNA: the non-coding area. If the past is any

indicator, further research in these regions will

provide rapidly increasing insight to our inner

genetic workings and reveal more targets to

control disease. This path of progress regarding

insights into the genome is a common

theme in science. First, the sequencing of the

genome was the target; then it became the tool

or the “trigger” for new discoveries. These

new discoveries can be specifically “targeted”

in further investigations.

The identified triggers are now potential

candidates for study by cancer biologists.

Results of mass scale experiments tend to

provide direction for many in-depth experiments,

as is the case here. “Most people don’t

know what to do with noncoding variants,”

said Khurana. “Our tool can be used to prioritize

these variants for further follow up.”

Indeed, the higher priority trigger points will

be extensively characterized to confirm that

they are, in fact, cancer drivers and to further

examine how exactly each one is involved in

the development of a particular cancer. Only

then does the possibility of personalized

therapeutic approaches come into consideration.

Moreover, this approach of determining

cancer triggers can be applied more generally

to determine countless other disease triggers,

truly setting the foundation for further progress

in fighting disease.

About the Author

IMAGE COURTESY OF MARK GERSTEIN

The cancer genome is distorted by mutations during

replication. The goal is to find out which key mutations lead

to the development of tumor cells with distorted genomes.

Deeksha Deep is a sophomore Molecular Biophysics & Biochemistry major in

Morse College. She is on the business team for the Yale Scientific Magazine and the

beat editor for the Yale Journal of Public Health. She works in Professor Spiegel’s lab

studying cell surface reconstruction in bacteria and vaccine design.

Acknowledgements

The author would like to thank Professor Mark Gerstein and Dr. Ekta Khurana for

their time and enthusiasm about their research.

Further Reading

• Khurana, E. et. al, “Integrative Annotation of Variants from 1092 Humans: Application

to Cancer Genomics,” Science 342 (2013), DOI: 10.1126/science.1235587


THE PROMISING FUTURE OF

BIOTECH

AN INVESTIGATION INTO THE ROLE OF BIOTECHNOLOGY START-UPS

AS THE BRIDGE BETWEEN YALE RESEARCHERS AND BIG PHARMA

BY JULIA ROTHCHILD

20 Yale Scientific Magazine | December 2013


In the movies, scientists wear white lab coats and bend over toxic

liquids in windowless laboratories. An older man with white

Einsteinian hair has an epiphany one day, shouts “Eureka!,”

victoriously holds up a test tube, and his discovery cures thousands

of people.

It is easy to forget how much this storyline skips. But outside the

movie theater, a wide gulf stretches between the Eureka moment and

a cure. Filling this gulf are long periods of additional research and

extensive drug testing. These periods are unavoidably infused with

high amounts of both money and risk. The entity capable of spanning

the gulf, guiding the often-twisted path of a scientific discovery to

its new life as a drug, is the biotechnology company.

Before 1980, the federal government owned the intellectual

property produced with research funded by the government. It

was therefore up to the federal government to commercialize and

develop discoveries made at an institution like Yale. But often the

government retained patents without licensing them, so discoveries

sat in laboratories, unused. With the 1980 Bayh-Dole Act, the

university was allowed to take charge of privatizing its own research

discoveries. Yale took little advantage of the policy change, compared

to other universities like MIT and UCSF, until Richard Levin became

the university’s president in 1993. As an economist especially attuned

to the drug field — his PhD thesis was entitled “Intellectual Capital

in the Pharmaceutical Industry” — Levin and his administration put

structures in place that would encourage the creation of companies

based in New Haven. During the course of Levin’s tenure, several

dozen different biotechnology companies arose as direct outgrowths

of Yale professors’ intellectual achievements.

Yale’s Newest Biotech: Arvinas

The newest biotech to grow out of Yale research is called Arvinas.

In just the last few months it has budded out of the research of

Craig Crews, the L.B. Cullman Professor of Molecular, Cellular, and

Developmental Biology, Chemistry, and Pharmacology, and Director

of the Yale Center for Molecular Discovery. The company has

fourteen employees so far and hopes to have twenty-five by the spring.

Arvinas is investigating ways to induce the degradation of certain

harmful proteins implicated in cancer and other serious illnesses.

This is a novel approach to curing disease: most drugs use small

molecules to block harmful proteins but do not actually remove

them from the system. Because some proteins cannot be blocked

using current methods, Crews’s new approach has the potential to

eliminate proteins that currently lie outside our medicinal control.

Crews did not invent the concept of protein degradation. Scientists

have known for years that every protein in the body is broken down

when it shows signs of tiredness. Cells recognize when it is time

to degrade proteins by monitoring their structures and sensing

when they are altered. Healthy proteins have stable, organized,

three-dimensional structures. Certain specific amino acids line

their surfaces, while different amino acids remain hidden inside the

molecule, like internal organs that are never revealed. But after too

many uses, a protein begins to wilt. Bonds become unbound and the

molecule’s organs spill outwards. A cell detects the exposed innards,

determines that the protein is nearing its demise, and marks it for

destruction.

This built-in cellular ability to degrade its own proteins is what


BIOTECHNOLOGY

left: Before a biotechnology

company forms, years of research

in a laboratory must

be completed. A tremendous

amount of money and resources

is needed to conduct effective

research. right: Craig Crews is

a Yale Professor of Molecular,

Cellular, and Developmental

Biology; Chemistry; and Pharmacology

whose research is

being developed by Arvinas.

IMAGES COURTESY OF CRAIG CREWS

Arvinas hopes to manipulate. Crews has

found a way to tag perfectly healthy proteins

with compounds that resemble the protein’s

normally hidden internal structures. The tags

make the cell think the protein is wearing out.

As a result, the cell is tricked into destroying

the proteins that are harmful to the body. One

of Arvinas’s goals is to create a tag that can

target proteins responsible for maladies like

cancer and autoimmune diseases, destroying

their proteins and therefore halting their

progress.

Investors Get Interested

Because of its promise as a drug, groups

have jumped at the opportunity to invest in the

research and in Arvinas: As of late September,

in the very early stages of its creation, the

company had raised a little over $18 million.

Crews recognizes why investors are highly

interested in Arvinas. “I was fortunate in a

combination of things,” he said. “The science

is very attractive — it’s an innovative approach

that others haven’t tried — and I was able to

demonstrate previously a successful startup

in Proteolix. And so there are multiple factors

that allowed this to come together nicely.”

Proteolix is the company Crews’s research

inspired ten years ago. It was extremely

successful: the drug it yielded, Kyprolis, is now

approved for patients suffering from multiple

myeloma, a cancer of white blood cells. Then

in 2009, Onyx Pharmaceuticals acquired

Proteolix for over $810 million. A success

like that under Crews’s belt no

doubt helped persuade investors

considering contributing to

Arvinas.

The second reason Crews gives

for investors’ interest — that the

science behind the company is

innovative and attractive — is

also an important factor. But

many biotech companies, even

ones investigating science just

as innovative and attractive as

this one, fail to garner support.

This is because the science and

the researcher’s past experience

are not the only criteria holding

sway over investors.

Why Some Biotechs Fail

Investors must contend

with other forces at play

when deciding how to allocate

their funds: pharmaceutical

companies. Biotech ventures

must cater to these giant companies’ interests

in order to be successful, as they choose which

drugs to manufacture and which to reject.

Ronald Breaker, Yale Professor of Molecular,

Cellular, and Developmental Biology, has

IMAGE COURTESY OF THE SPECMETCRIME WEBSITE

An example of a protein’s three-dimensional folded

structure. Many amino acids inside the complex are

not exposed to the outside environment until the

protein is ready to undergo degradation.


BIOTECHNOLOGY

IMAGE COURTESY OF THE CREWS LAB

Adding a special tag can make a protein a target of the proteasome, which is responsible for its

degradation. This invention formed the basis for one of Arvinas’s goals: novel drugs that can tag

and destroy harmful proteins in cancer and other diseases.

experience with a failure of interest on the part

of pharmaceutical companies. Over ten years

ago, Breaker discovered a new class of RNA

molecules that act as switches, primarily in

bacteria. Flipping one of these switches turns

the gene attached to it on or off. This is a huge

discovery for basic science and for medicine:

Using molecules to bind to the switches, we

could make drugs to turn off genes in bacteria

in order to eliminate them and cure people.

Like Crews’s idea, Breaker’s had piqued the

interests of investors. He started a company

called BioRelix in the early 2000s, founded

officially around 2005. In 2010, BioRelix

partnered with a subsidiary of Merck, one of

the largest pharmaceutical companies in the

world. Merck paid for some of the research

for a few years. But ultimately, pharmaceutical

companies were not interested in the BioRelix

antibiotic. The company closed its Research

and Development branch in the past year,

and with its closure the development of

riboswitches has come to a halt.

Why didn’t Breaker’s company thrive,

given the significant potential of riboswitches

to cure bacterial infections? The answers

revolve around the inability of antibiotic

sales to make up for the cost of developing

them. One problem is that antibiotics are by

nature short-term drugs; after a few weeks

on the medication, the patient is cured

and they stop paying for treatment. So,

unlike Advil or another daily-use drug, most

antibiotics, because of their nature as shortterm

medications, are not good money-making

drugs for manufacturers.

A second problem is that patients are

accustomed to paying low amounts of money

for antibiotic treatments. Drug companies

cannot charge thousands of dollars for a

course of antibiotics, as they can (and do)

for a course of chemotherapy. Yet another

issue is that antibiotics are working against

the bacterial evolutionary clock, which runs

quickly: Bacteria mutate and evolve in months

or weeks. This quick evolution can mean that

an antibiotic, which takes a decade or more

to create, could be obsolete in a few years.

Companies want drugs that will last, not those

that will quickly become useless.

All these problems compounded with the

high costs of developing a drug, a process

that requires a lengthy testing and approval

process to comply with FDA regulations,

make it difficult for pharmaceutical companies

About the Author

to break even on their

investments in antibiotics.

Therefore, despite the science’s

validity and the pressing need

for new antibiotics in a world

of quickly evolving bacteria,

biotech companies making

antibiotics are impossibly risky

enterprises.

The underlying problem in

this case is not the quality or

innovation of the reseaerch,

but a misalignment of financial

incentives for pharmaceutical

companies with medical

need. And so starting a

biotech company, even with

the intellectual might of Yale

and top scientists like Breaker

behind the research, is risky.

“There’s a lot of excellent

research here that goes on at

Yale; there’s a lot of innovation,” said Bill

Wiesler, Director of New Ventures at the

Yale Office for Cooperative Research. “But

only some portion of that is something that

some business could figure out how to make

money on in some reasonable period of time.”

In the meantime, though, private investments

in Yale-founded biotechs located in New

Haven are booming. These companies bring

jobs and investment into the area, and, when

they are successful, they share their profits

with the university. A pamphlet on the City of

New Haven’s website terms the place “A City

of Innovation,” and boasts that 39 of the 52

biotech firms in Connecticut are in the Greater

New Haven area. Biotechnology companies

are aiding not just sick people in need of drugs,

but the whole city as well.

Julia Rothchild is a sophomore in Timothy Dwight College from Ann Arbor,

Michigan.

Acknowledgements

The author would like to thank Professor Craig Crews and Bill Wiesler for their

time.

Further Reading

• Golec, Joseph and John A. Vernon. “Financial Risk of the Biotech Industry

Versus the Pharmaceutical Industry.” Applied Health Economics and Health Policy. 7,

no.3 (2009):155-165


THE

MISSING

AND ITS LINK TO

LINK

IN

ALZHEIMER’S

BY NAAMAN MEHTA

In the early 1900s, German physician

Alois Alzheimer analyzed the nervous

tissue of his now most-famous patient:

a woman who had experienced significant

memory loss. Upon meeting her, Alzheimer

had no idea of any definitive diagnosis, but

when he autopsied her nervous tissue upon

her death, he found an anomaly. Alzheimer

observed atrophied gray matter around the

entire brain, and bundles of neurofibers

and plaques. He died only a

few years later, never to fully

understand the magnitide

of his discovery. However,

the scientific community

realized Alzheimer had

unveiled one of medicine’s

most mysterious puzzles,

raising an entirely new set

of questions that researchers

are still attempting to answer.

Recently, a team of

researchers led by Dr.

Stephen Strittmatter at the

Yale School of Medicine

has come to the forefront

of answering some of

the mechanistic questions

underlying the disease. The

team has elucidated a key step in the

Alzheimer’s disease pathway — a discovery

with revolutionary implications for drug

development. Still, some of Alzheimer’s

initial questions have yet to be answered.

What is Alzheimer’s disease?

Alzheimer’s disease is typically associated

with forgetfulness. Beginning with minute

IMAGE COURTESY OF STEPHEN STRITTMATTER

Alzheimer’s disease manifests itself through myloid plaques leading to

damaged nerve terminals.

day-to-day details, patients eventually forget

even the family members that are nearest to

them. This forgetfulness is characteristic of

dementia, and Alzheimer’s disease is the most

common type of dementia, accounting for

about 70 percent of all cases. While dementia

manifests itself primarily with age, it also may

be genetic or acquired.

Physiologically, dementia results from the

formation of neurofibrillary tangles from

hyperphosphorylated tau

proteins in neurons. When

the hyperphosphorylated

tau forms, it aggregates

near microtubules. Kinesins,

molecular motors that

transport vesicles away

from the synapse, travel on

microtubules “like a railroad,”

Strittmatter described.

When neurofibrillary

tangles aggregate along the

microtubule, they impair the

transportation mechanism

of the axon. In other words,

neurofibrillary tangles create

roadblocks for travelling

kinesins. This results in the

impairment of neuronal


MEDICINE

IMAGE COURTESY OF JOSEPH WOLENSKI

Amyloid beta precursor protein, when cut by the incorrect secretase enzyme, can

form amyloid beta plaques, leading to Alzheimer’s disease.

synapses, and thus memory loss, in dementia

patients.

Alzheimer’s disease involves seven separate

stages, ranging from no impairment to very

severe decline. Initially, the disease was only

characterized in post mortem cases in which

the patients had blackened areas of dead

neurons. Today, scientists know that this

increased darkening is caused by the presence

of increased amyloid beta (AB) plaques and

hyperphosphorylated tau protein. But what

causes these neuropathologies?

AB plaques are made of AB protein,

which is actually found naturally in the

human body. Normally, the protein forms

when Amyloid beta precursor protein (APP)

is cut by the enzyme alpha-, followed by

gamma-, secretase. If there is a mutation in

the presenilin 1 gene, the AB protein is cut

incorrectly. These incorrectly cut AB can

aggregate and form amyloid beta plaques.

When APP cuts the original AB incorrectly,

an insoluble form of amyloid beta protein

results. This insoluble form aggregates into

oligomers, which can then form AB plaques.

These plaques distinguish Alzheimer’s

disease from other forms of dementia, and

their formation can also trigger increased

phosphorylation (hyperphosphorylation) of

the tau protein. Tau protein is normally found

in neuronal cells to stabilize microtubules;

however, when tau is hyperphosphorylated,

it forms the neurofibrillary tangles, which

further impair the memory of Alzheimer’s

patients.

These neurofibrillary tangles and AB

plaques cause the deterioration of and

reduction in the number of synapses in

the brain of an Alzheimer’s patient. Thus,

the insoluble AB plaques disrupt neuronal

function based on their concentration,

structure and length. The AB plaques interact

with membrane surface proteins, gangliosides,

and calcium permeable neurotransmitter

mediated receptor channels. When these

AB plaques interact with those proteins in

the cell membrane, neuronal activity and

synaptic function is impaired. Specifically, it

results not only in synaptic malfunction, but

also the loss of dendritic spines.

These membrane proteins are “docking

sites” for proteins that activate dangerous

signaling pathways. One such membrane

surface protein is the prion protein.

Mutations in the prion protein can result

in neuropathological disorders such as mad

cow disease, but this protein also serves as a

“docking site” for the amyloid beta protein

in the case of Alzheimer’s.

When AB levels increase, more AB

binds to the prion protein. This results in

overexpression of the Fyn kinase mediated

pathway and impairs synaptic activity, which

manifests as Alzheimer’s disease. Because

the extracellular A-beta plus prion protein

complex is involved in intracellular signaling,

researchers knew the prion protein complex

must have been linked to a signaling hub

that mediated the transfer of signal from the

extracellular protein complex to the nucleus.

This signaling hub is known as a G-protein

coupled receptor.

The Strittmatter Lab: Forerunners in Novel

Techniques

The G-protein coupled receptor is where

the work of the Strittmatter Lab comes

in. The team of researchers has recently

discovered the identity of the signaling hub:

mGluR5, a metabotropic glutamate receptor.

This receptor contains seven transmembrane

spanning alpha helices and is a G-coupled

protein receptor. In other words, when

the neurotransmitter glutamate binds to

the receptor, it activates many downstream

signaling cascades essential for proper

cellular function. Normally, the glutamate

is responsible for calcium release pathways

and src homology signaling cascades. It also

activates the Fyn kinase pathway responsible


Neurons that have amyloid beta molecules bound to them are marked in green.



MEDICINE


IMAGE COURTESY OF MEDICINE AT YALE

above left: The complete Alzheimer’s pathway, with the discovered mGluR5 G-protein coupled receptor. above right: Professor

Stephen Strittmatter, lead investigator in the discovery of the mGluR5 receptor.

for downstream phosphorylation, and other

similar pathways such as the MAPK pathway,

JNK pathway, and Cdk5 pathway.

However, when amyloid beta oligomers

bind to the prion protein, the mgluR5’s

function is altered. In fact, as Strittmatter

emphasized, “the A-beta causes the mGluR5

receptor to signal a lot more to downstream

pathways, leading to chaos and confusion in

the cell.” In this way, the balance of pathways

to which the mGluR5 receptor signals is

skewed tremendously over time. As the

concentration A-beta oligomer increases, it

is more likely to bind to the prion protein

and overstimulate downstream pathways.

Overtime, this desensitizes the mGluR5 such

that it does not even respond to glutamate

binding. This impairment of mGluR5

activity impairs the postsynaptic function

of the neuron, resulting in destruction of

synapses and neuronal deficiency: otherwise

known as Alzheimer’s disease.

Strittmatter’s research is a major contributor

to the recent push for new methods of drug

development for Alzheimer’s disease. Most

drugs currently target the gamma and beta

secretase, however this results in impairing

other functions of the cell. Similarly, drugs

targeting the AB plaques are only useful if

the Alzheimer’s is caught early on; otherwise,

the AB plaques have already developed and

cannot necessarily be degraded.

Though many drugs attempt to attack

a disease without analyzing the possible

implications of their treatment, Strittmatter’s

research gives drug companies a specific

target. Strittmatter mentioned, “drug

discovery should occur in parallel with

laboratory research; as soon as a new pathway

mechanism is discovered, drug companies

should see if it can be a potential target

for drugs.” As the cofounder of Axerion

Therapeautics, he is in the ideal position to

“make these parallel discoveries and translate

scientific advancements into clinical trials.”

Future Implications

Immunotherapy techniques that would

utilize antibodies to target the a-beta binding

site on the prion protein are currently

being researched. Strittmatter is particularly

interested in targeting the mGluR5 receptor

and prion protein with drugs, as these two

components are in the “middle” of the

pathway to Alzheimer’s disease. What is

particularly interesting about the Strittmatter

lab’s discovery is that for the first time, drugs

can be developed that do not target the

beginning of the Alzheimer’s cycle (the AB

plaques), or the last component of the cycle

(the neurofibrillary tangles). Rather, because

the missing middle link in the Alzheimer’s

pathway has been discovered, Strittmatter

and Axerion Therapeutics have a novel target

in mind with their small molecule approach.

“Never before has an emphasis been placed

on this new approach midway through the

Alzheimer’s pathway; we’re not going as

far downstream as tau,” said Strittmatter.

Instead, they are targeting the prion protein

and the mGluR5: the middle men.

About the Author

Naaman Mehta is a junior in Morse College. She is also the Outreach Chair for the

Yale Scientific Magazine. She works in the Horvath Lab of Comparative Medicine and

also conducts research at the School of Public Health.

Acknowledgements

The author would like to thank Professor Stephen Strittmatter for taking the time to

share his research.

Further Reading

• Lee, Hyoug-Gon, et al. “The role of metabotropic glutamate receptors in Alzheimer’s

disease.” Acta Neurobiologiae Experimentalis (Warsaw). 64, no.1 (2004): 89-98.


PSYCHOLOGY

FEATURE

The Science of Social Media:

New Research Links Virtual and Psychological Worlds

BY APARNA NATHAN

Every day, millions of new status updates are posted on Facebook.

Twitter is flooded with hundreds of millions of 140-character

tweets. What if we could use this sea of information to learn

more about the internet users behind it? Researchers at the University

of Pennsylvania and the University of Vermont are finding

ways to take advantage of the data that social media offers to gather

information about human nature. Using innovative approaches to

data analysis and psychology,

their results have shown surprising

correlations between

online personas and real

personality traits.

At the University of Pennsylvania’s

Positive Psychology

Center and Computer

& Information Science

Department, researchers are

venturing into new territory:

the intersection of psychology

and computer science.

Using computer models

to quickly work through

the data gathered from

75,000 subjects, researchers

analyzed Facebook status

updates for key words. These

Facebook vocabularies had

surprising correlations with

the subjects’ personalities,

which were determined

using personality surveys. Extroverts and introverts had radically

different lexicons: one of the most popular key words for extroverts

was “party,” while introverts commonly used “Internet.”

Members of the Computational Story Lab at the University of

Vermont have chosen to tackle data from another social media

giant, Twitter. Researchers analyzed the linguistic data from over

10 million tweets from 373 urban areas in the United States and

determined the level of happiness associated with words in the

tweets. Based on a list of 10,000 commonly-found words in the

English language, each word was given a “happiness score” by

crowdsourcing opinions from the users of Amazon’s human intelligence

marketplace, Mechanical Turk. The scale of 1 (low happiness)

to 9 (high happiness) ranges from words like “earthquake,”

with a score of 1.9, to “rainbow,” which scores an impressive 8.1.

The results of the University of Vermont researchers’ analysis

created a remarkably thorough picture of the American people’s

happiness. The features on a map generated by this data correlated

with national census data, with some of the saddest areas corresponding

to high poverty rates and low life expectancy, indicating

that Twitter information is a surprisingly accurate tool to measure

wellbeing. Looking for happiness? Go west. Four of the happiest

states included Colorado, Utah, Nevada, and Idaho, while California

was home to many of the happiest individual cities.

University of Vermont researchers are also maintaining a website

featuring a “Hedonometer.” Derived from the Greek words for

“pleasure” and “measure,” the Hedonometer measures the happiness

of the nation. The website plots the daily happiness average

for each day’s Twitter posts. Data from as early as September 2008

show a noticeable oscillation

between happier weekends and

less happy weekdays. Peaks

occur regularly, often on holidays.

Low points, on the other

hand, seem to correspond to

specific events. Deaths and

tragedies were leading causes

of dips in happiness: Michael

Jackson’s death in 2009 and

the Newtown shooting in 2012

featured some of the sharpest

decreases in happiness, at least

according to Twitter.

A notable quality of these

studies is the new approach

to psychology that they adopt.

IMAGE COURTESY OF MIT TECHNOLOGY REVIEW

Various words and phrases from Facebook statuses can be used to identify

differences between introverts and extroverts, males and females, age

differences, and even happiness levels of different populations.

The typical methods used by

researchers to probe into the

minds of subjects are not

always entirely effective. Subjects

may remain reserved and

may not reveal the true thoughts

running through their minds. However, by analyzing subjects in the

environment of social media, researchers are able to inconspicuously

observe as the subjects freely express themselves without

their usual restraint. This unfiltered stream of consciousness may

be one of the richest sources of psychological data that researchers

are able to access.

Professor June Gruber, director of the Positive Emotion &

Psychopathy Lab at Yale, has witnessed firsthand the revolutionary

effects of social media. “Social media opens up completely

uncharted territory for exploring social connections across the

globe, and in rapidly transmitted social exchanges,” she said. “We

have been using Facebook as one candidate example to explore the

nature of friendship formation and wellbeing at the global level for

the first time across billions of people. Social media is changing

the landscape of what questions we can ask as psychologists and

the breadth of data accessible to answer those questions.” The

recent studies at the University of Pennsylvania and the University

of Vermont have illuminated the elusive human psyche in unprecedented

ways. This research is using modern methods to answer

age-old questions about psychology and will certainly open new

doors into the human mind.



FEATURE

TECHNOLOGY & ART

Art Thou Shakespeare?

New Technology May Solve History’s Great Art Mysteries

BY THERESA STEINMEYER

Art historians would like to think that they know what

Shakespeare looked like. There are only two verified images of the

great poet: an engraving published in his First Folio and a bust from

his birthplace, Stratford-upon-Avon. But when historians examine

the “Cobbe portrait,” a painting of an unidentified man that some

claim to be the Bard of Avon, they wonder if his sharp chin, long

nose, and high cheekbones could truly belong to the renowned

playwright. The unconfirmed portraits

of Shakespeare are just one piece of a

historical puzzle from which science is

lifting the curtain.

In 2012, electrical engineer Amit

Roy-Chowdhury teamed up with art

historian Conrad Rudolph to develop

a software that can objectively pick

out similarities between portraits’

facial features. Roy-Chowdhury,

a professor at the University of

California, Riverside, brings to the

table a background in image and video

analysis. Having used these techniques

in biomedical imaging, multimedia,

homeland security, and a variety of

other projects, Roy-Chowdhury is now

applying this background to art. The

result is a method that can determine

whether two portraits portray the

same face. Using their data, Roy-Chowdhury and Rudolph hope to

unravel some of history’s greatest art mysteries.

To determine whether the subjects of two portraits match, Roy-

Chowdhury’s team completed an objective analysis of each portrait,

noting the size and relative locations of key facial features. First, a

digital mesh was applied to locate twenty-two “fiducial points” on

each portrait. These fiducial points are scattered across each face

and mark locations such as the corners of the eyes and mouth.

Together, they enable the computer to collect data on features like

the subject’s forehead, chin, and ears. By comparing two different

portraits, Roy-Chowdhury was able to generate a similarity score for

each pairing. The higher the similarity score, the more likely that the

two portraits shared a subject. With

this information, art historians and

curators can decide for themselves

whether the subjects in two portraits

are the same.

In the July 2013 “Ultimate Tut”

episode of the PBS series “Secrets of

the Dead,” Roy-Chowdhury showed

how this technology could be applied

to determine whether one of King

Tut’s death masks had actually been

created for the young pharaoh, or if

it had actually been designed for Tut’s

step-mother, Nefertiti. Comparing the

fiducial points on Tut’s mask with those on a bust of Nefertiti, he

concluded that the mask had likely been created for the latter. “The

purpose of doing this is to come up with an objective measure and

a number,” said Roy-Chowdhury to PBS. “This number cannot be

obtained just by staring at those faces.”

Tut’s death mask is just one of countless instances where

Roy-Chowdhury’s technology is applicable. According to a 2013

paper from his lab, other test subjects

include unverified images of Sforza,

Mary Queen of Scots, and Constanze

Mozart.

However, even Roy-Chowdhury’s

software cannot solve all of these

mysteries. For social reasons, artists

might have altered the appearances of

their subjects, making it more difficult

to determine whether a portrait match

is legitimate. Portraiture is an imprecise

art, dependent on medium, angle, and

artist style. Therefore, Roy-Chowdhury

expects variations in portraits of the

same figures. In his study of King Tut’s

death mask, he concluded that an 85

percent similarity score between Tut’s

mask and Nefertiti’s bust was close

enough to claim that the mask was

probably created for Nefertiti.

And for people like Shakespeare who may have sat for portraits

multiple times throughout their lives, the technology may fail to

adjust for facial changes caused by aging. As Roy-Chowdhury’s

team develops its software to account for some of these problems,

the lack of a large identified portrait database poses an additional

challenge. While researchers were able to work with a few

confirmed images of Shakespeare, they may not be as lucky with

other historical figures.

Nevertheless, Roy-Chowdhury’s software offers art historians

a chance to get to know some of history’s favorite characters.

With hard data to aid the naked eye, they will be able to recognize

Shakespeare with confidence.

IMAGE COURTESY OF UC RIVERSIDE

Electrical engineer Dr. Amit Roy-Chowdhury from the University of California, Riverside.


We all owe much to the humble chloroplast. These tiny, solarpowered

organelles, found only in plants, are responsible for

photosynthesis. Photosynthesis converts carbon dioxide into sugary

fuel for plants, and creates the oxygen we breathe as a byproduct.

Yet chloroplasts have potential to do even more. By using genetic

engineering to “hijack” photosynthesis, a team of scientists hopes

to transform them into biological factories for other organic

chemicals — ones we can use in

medicine and industry.

This year, Poul Erik Jensen

and colleagues published the

results of their first chloroplastmodifying

experiment. They

successfully stimulated these

organelles to produce dhurrin, a

chemical used by plants to defend

themselves against herbivores.

Although dhurrin is not

medicinally useful, its successful

synthesis in chloroplasts is

a good indication that other

plant-derived chemicals,

including ones with medicinal

qualities, may not be far behind.

Using photosynthesis, future

experimenters may “convince”

chloroplasts to produce many

products that are useful to

humans.

Photosynthesis takes place in

two parts, the “light reactions”

and the “dark reactions.” The

light reactions come first, and are fueled by the power of the sun.

When light rays hit the leaves of a plant, their energy is absorbed by

chloroplasts and used to rip electrons from water. These electrons

are high in energy, and can be used as fuel for other chemical

reactions. Transfer molecules carry these electrons deeper within

the chloroplasts, where they are used to power the dark reactions.

The purpose of the dark reactions is to

convert carbon dioxide into sugar, which

plants use as a source of food. But sugar

production is a multi-step process, and

creates many unintentional byproducts.

One of these byproducts is oxygen,

and another is the amino acid tyrosine.

Tyrosine has no use to the chloroplast,

and leaves the organelle after being

synthesized. But in other parts of the cell,

enzymes will convert some of this tyrosine

into dhurrin. In short, photosynthesis

naturally causes the production of

dhurrin, but only in very small amounts,

and not in the chloroplast itself.

BIOENGINEERING

FEATURE

Revamping Photosynthesis:

Genetically-Modified Chloroplasts May Produce Useful Medicines

Jensen’s team aimed to modify this system, driving the chloroplast

to make dhurrin on its own. To do so, they had to relocate the cell’s

dhurrin-producing enzymes, moving them into the chloroplast.

If these enzymes were located in the chloroplast rather than

the cytoplasm, they would encounter tyrosine as soon as it was

produced. The enzymes would then immediately convert that

tyrosine into dhurrin.

The enzymes could be moved,

it turns out, by modifying their

DNA blueprints. Enzymes, like

all proteins, are built according

to strict instructions. These

instructions are written in the

“language” of the genetic code

and are stored in a molecule

called DNA. If a molecule’s

DNA instructions are changed,

the cell will build it differently

— or in this case, transport it

to a different location. Jensen’s

team modified the code for

each dhurrin-producing

enzyme, changing the “targeting

sequence” that specifies the

enzyme’s destination.

If all went as planned, Jensen’s

genetically-engineered cells

would send their dhurrin-making

enzymes to the chloroplasts.

There, the enzymes would

encounter tyrosine, transforming

it into dhurrin on the spot. The

whole process would be powered by photosynthesis — as soon as

the genetically-engineered plants were exposed to light, they would

start making large amounts of dhurrin.

To test whether their modifications had succeeded, the scientists

exposed their genetically-engineered plants to light. After allowing

photosynthesis to proceed, they ground the plants up and tested their

chloroplasts for the presence of dhurrin.

The experiment worked. The chloroplasts

of Jensen’s plants were making dhurrin on

their own, and in much higher quantities

than usual.

Jensen’s team succeeded in moving

an entire biological synthesis pathway

from the cytoplasm into the chloroplast.

Only small modifications were required

for the genes involved, and the team

is hopeful that other processes could

be similarly relocated. Geneticallyengineered

plants may soon be churning

out pharmaceuticals, powered entirely by

sunlight.

IMAGE COURTESY OF MOLECULAR EXPRESSIONS

Cutaway view of a chloroplast. The light reactions take place

in the thylakoids; the dark reactions take place in the stoma.

BY ETHAN FRANCE



FEATURE

SOCIAL SCIENCE

Mythbuster: Vikings

Savages or Social Butterflies?

BY ELENA MALLOY

Between 800 and 1150 A.D., the very mention of the word

“Viking” would strike fear into the heart of any European. Originally

from Scandinavia, the Vikings invaded much of medieval Europe,

including Britain, France, and Germany. Their raids would come

quickly and without warning, and simply the sight of the dragonhead

prows on the Viking ships would make a seasoned warrior blanch.

History remembers the Vikings as ruthless raiders, “sea wolves,”

and heathen savages. But violent history aside, scientists have also

uncovered a complex society with a strong sense of community.

New research conducted by Ralph Kenna and Padraig Mac Carron at

Coventry University suggests that the Vikings formed social networks

that resemble those of today. Kenna and Mac Carron achieved this

by using statistical modeling to analyze ancient Viking texts — proof

of the oft-overlooked fact that science and the humanities can, at

times, go hand-in-hand.

Kenna and Mac Carron analyzed eighteen stories from the Sagas

of Icelanders, an epic about the Vikings settling Iceland around

1,000 years ago. This text was specifically chosen because it occurs

in a relatively short period of time and contains a large number of

characters, many of which appear in multiple sagas. The individual

tales are diverse and rich in content. One, the Njáls saga, describes

tribal feuds between 960 and 1020 A.D. Another, the Vatnsdaela saga,

follows an individual named Ingimundur as he moves to Iceland with

his family after hearing the prophecies of a fortune-teller.

From these eighteen stories, including the Njáls and Vatnsdaela

sagas, Kenna and Mac Carron mapped out the travels of over

1,500 characters, keeping track of where the characters went and

their meetings with other individuals — both friendly and hostile.

Then they used this data to create web-like networks for each story,

representing each character with a dot and connecting the dots of

characters that had interacted with one another. With the help of

these networks, Kenna and Mac Carron could visualize the social life

of each character: they could see friends, enemies, friends of friends

— even how often and where interactions took place. It was, in a

nutshell, Facebook for Vikings.

While each saga had its own network, combining the five major saga

IMAGE COURTESY OF THE GUARDIAN

A page of the Sagas of Icelanders. It is one of the original

copies available in the Vikings’ native tongue.

The traditional Viking mode of transportation was by ship.

networks — Egil, Vatnsdaela, Laxdaela, Gisla, and Njáls — revealed

an astonishing degree of overlap. This indicated that characters were

closely connected not only to their immediate friends and family, but

also to those that appeared in other sagas, often through a network

of mutual friends.

While analyzing all eighteen stories, the researchers noticed that

one particular saga type did not have complex social networks: the

outlaw saga. These tales are heavily focused on one individual, often

someone who is forced to live in isolation. For instance, the Gisla

saga describes an outlaw who is on the run for many years until finally

being killed; not surprisingly, almost all the dots in the Gisla saga’s

network are restricted to one area. But aside from the occasional

exception, most stories — such as the Vatnsdaela and Laxdaela sagas

— feature extensive, tightly intertwined networks. Kenna and Mac

Carron call these family sagas.

Since its publication, the study has fallen under some scrutiny

because the Sagas of Icelanders may not have been historically

accurate. These are oral tales that could have been elaborated upon

when written down. Luckily, there are revealing clues that support

their validity. In 1995,

Scientific American published

an article about the title

character in the Egil saga,

a Viking with a skull that

resisted blows. The article

showed that it was medically

possible for Egil to exist,

suggesting that the sagas

could be at least somewhat

grounded in fact.

History, perhaps, has not

been kind to the Vikings.

People often remember

them as savage invaders, but

Kenna and Mac Carron’s

findings serve as a reminder

that Viking civilization was

in fact highly developed, or

at least developed enough

to form complex social

networks. Hopefully with

more research to verify this

study, history classes can

begin presenting a more

balanced depiction of the

Vikings.

IMAGE COURTESY OF KEY STAGE HISTORY UK

IMAGE COURTESY OF SCIENTIFIC AMERICAN

An image of a skull deformed

by Paget’s disease. In this

condition the bone is abnormally

thick because of huge growth.

This could have been the same

condition that the Viking Egil

had, allowing him to withstand

axe blows to the head.


FOOD SCIENCE

FEATURE

Debunking Science: Science a la Carte

The Chemistry and Physics Behind the Bread

BY WILLIAM CHANG

There’s more happening on your plate than you think. Molecular

gastronomy uses modern science to examine cooking — in terms of

the physical and chemical transformations of everyday ingredients

as well as the creative and visual aspects of food preparation. What

molecular gastronomists discover may open up new possibilities for

inventive chefs and provide a more innovative dining experience for

consumers. Molecular gastronomy also explains the science behind

some interesting food-related phenomena.

How Does Color Affect Taste Perception?

Say someone is presented with two identical scoops of vanilla ice

cream, one served in a white bowl and one served in a black bowl.

Does the ice cream taste the same either way? A recent study suggests

otherwise. In a joint study between the University of Oxford and

the Polytechnic Institute of Valencia, researchers prepared identical

strawberry mousses on black and white plates and asked participants to

rate each sample’s perceived sweetness, flavor intensity, quality, as well

as their overall liking of the sample. In all four attributes, the mousse

on the white plate scored higher on average than the mousse on the

black plate, suggesting a strong connection between the perception of

food and plate color. Such findings could prove useful to restaurants

and other related industries in the marketing of food products.

extract; then, the

caffeine is filtered out.

The resulting lowcaffeine

extract acts as

a chemical sponge that

soaks up caffeine from

new batches of beans

without compromising

their flavor. After

absorbing the caffeine

from each batch of

beans, the extract can

be cleaned and reused.

Running the extract

through a layer of

charcoal, usually coated

with sucrose, absorbs

the caffeine to which it was bound.

IMAGE COURTESY OF MOLECULAR GASTRONOMY NETWORK

Molecular gastronomy gives rise to

some eccentric cuisine. The arugula

spaghetti here was prepared using an

air-filled syringe and agar-agar, a heatresistant

gel extracted from algae.

In the direct solvent method, coffee beans are directly rinsed with a

solvent, typically methylene chloride or ethyl acetate, which dissolves

caffeine and removes it from the beans. The beans are then collectively

steamed to recover the solvent. As this method only removes a small

amount of caffeine per cycle, coffee beans are typically rinsed multiple

times until the level of caffeine has been satisfactorily reduced.

What Affects the Taste and Texture of Wine?

IMAGE COURTESY OF SCIENCE DIRECT

Two identical mousses on differently colored plates.

How is Coffee Decaffeinated?

Coffee is ubiquitous. What begins as a lowly bean becomes a

high-profile beverage whose image is plastered across billboards

and featured in TV ads, finding its way into the hands of millions.

And thanks to decaffeinated

coffee, people who are

sensitive to caffeine can still

enjoy the taste of coffee

without any of the negative

side effects stemming from

caffeine.

There are two main

methods of decaffeinating

coffee: water processing and

the direct solvent method.

In water processing, green

coffee beans are soaked in

water to create a concentrated


IMAGE COURTESY OF ANDERSON’S COFFEE

Decaffeinated coffee beans

that are ready for consumption.

“Good things come to those who wait.” This old English proverb

was not just endorsing the virtue of patience; it was commenting on

the pleasure of having a fine glass of Bordeaux. But what affects

each wine’s taste and texture, and why do some wines age differently

from others? The answer boils down to three things: tannins, acids,

and fruit.

Tannins are naturally occurring biomolecules that can be found in

fruit skins and seeds. They add a bitter and astringent taste to wine,

giving it what is called a “dry” texture. More importantly, tannins are

a key factor in aging wines. As time passes, tannins within the wine

will bond to one another and eventually pool as sediment, giving the

wine a smoother feel. Thus, the more tannins a wine has, the more of

a texture change it will undergo.

Acidity is another important quality that must be considered when

a wine ages. Like tannins, acids also contribute to the taste of wine by

providing tartness. For winemakers, it is important to find the perfect

balance between acid and tannin levels to produce a well-rounded

wine. The acidity of a wine mainly depends on the type of grape used,

as some types of grapes are more acidic than others.

Unsurprisingly, a wine’s fruit content also affects its taste over time

by contributing fructose and glucose. The ratio of fructose to glucose

in a grape generally depends on the age of the grape: Grapes begin

with high glucose levels, but as a grape matures, levels of fructose

will gradually overtake levels of glucose. High levels of fructose in

overripe fruit can preserve a wine’s sweetness over time, but along the

same vein, they can also make a wine taste like rotten candy.


FEATURE

MATERIALS SCIENCE

DNA: The Bridge Between Computers and Graphene

BY MADELINE POPELKA

What if the building blocks of life could be used to create better

computers? For scientists at Stanford, that goal is one step closer to

becoming reality.

Professor Zhenan Bao and her team are finding ways to assemble

computer chips out of graphene, a two-dimensional molecule of

linked carbon atoms with the potential to transform the electronics

industry. She and her colleagues may have found the magic ingredient

necessary for quickly and automatically assembling graphene into the

transistors found in computer chips.

DNA, the instructions our bodies use to build cells, is a long and

skinny molecule with the perfect structure for building transistors.

Bao’s team developed a way to use DNA as a template, assembling

graphene ribbons that follow the shape of the DNA chains.

The resulting graphene transistors, which can be integrated into

computer chips, last longer and are more compact than their silicon

counterparts.

Transistors conduct electricity and have the unique ability to turn

their electrical currents on and off. The computer understands this

as binary code, a series of ones and zeros that store data. Bao’s team

worked to build field-effect transistors, which are the most common

type used in industry today. These are built from long, thin strips of

semiconducting material that can easily disrupt the flow of current.

Transistors run in parallel to their neighbors, so the more transistors

a computer has, the faster it can operate. The computing industry is

perpetually trying to improve its operating speed, but the limitations

on transistor size have hindered this race.

So far, silicon has been the favorite semiconductor for building

transistors. It is an extremely powerful element that is responsible for

the impressive computing power of modern machines. However, it

does have its limits. Silicon transistors cannot be built below a critical

size or else they will break down. In addition, the insulating bands

of semiconductors wear away over time, leading to current leakage.

Graphene, a single sheet of carbon only one atom thick, has the

potential to transform the transistor industry. It has been a popular

subject of study ever since its discovery in 2004 by Andre Geim

and Konstantin Novoselov. The two scientists won the 2010 Nobel

Prize in Physics for their ingenious method of producing graphene

from graphite, a common related compound. Graphite is made

up of layers of carbon sheets that slide against each other. Using

Scotch tape, Geim and Novoselov removed the layers one by one

until they had produced a single isolated sheet — graphene. Scientists

have found that when a sheet of linked carbon is separated from its

IMAGE COURTESY OF ANATOLIY SOKOLOV

DNA provides the template for assembling graphene ribbons,

and heat kick starts the chemical reaction that creates the

strips.

neighbor sheets, it gains some remarkable properties: Graphene is an

excellent conductor, very light, and extremely strong. It is also in a

very stable configuration.

Carbon sits directly above silicon on the periodic table. Both

elements have semiconducting properties, but carbon is able to

better withstand heat and degrading environments. Up until now

though, silicon in its pure compound form has been vastly easier

to manufacture than carbon semiconductors. And while the Nobel

Prize-winning method of producing graphene is reliable for creating

sheets, it does not have great control over the shape or dimensions

of the sheets. Producing transistors requires long, thin ribbons of

graphene.

Bao’s lab at Stanford is attempting to create a system for mass

producing these ribbons by using DNA from bacteria. By using the

DNA as scaffolding for assembling the graphene, the researchers

found that they could grow the graphene into the desired shape.

The first step in this process was chemically straightening the

DNA through a process known as “combing.” Combing pins the

IMAGE COURTESY OF ZHENAN BAO

DNA is infused with copper sulfates (Cu 2+ ), flooded with methane gas, and then subjected to intense heat to induce chemical

deposition of carbon nanoribbons


MATERIALS SCIENCE

FEATURE

IMAGE COURTESY OF ZHENAN BAO

Strips of graphene connect to electrodes, creating a working

field effect transistor.

ionized, or “frayed,” edges of a strand of DNA to a surface of liquid.

The DNA stretches taut as the liquid evaporates, just as skin feels

tight in the winter after all the moisture has been sucked out of it.

Next the DNA is bathed in copper salts, which are quickly absorbed

into the chains. The salts break up some of the bonds within the

DNA strand, leaving strings of carbon ions eager to bond with any

compound they can latch onto.

After the salts have been fully absorbed into the DNA, methane,

a carbon-rich gas, floods the surface above the DNA. The system is

heated up to 1000 degrees Celsius, providing enough energy for the

exposed carbon strands in the DNA to readily bond to the carbon in

the methane. The other elements of the DNA evaporate in the heat,

and the carbon compound deposits onto the surface below the DNA,

effectively creating a

shadow projection

of the chains. These

projections are the

long, thin ribbons

of graphene that

the researchers

were hoping to

manufacture.

To confirm

their experiments,

Bao’s team built a

working field effect

transistor from their

graphene strips,

successfully moving

current across the

device. They also

discovered that

strips that had been

created without the help of copper ions were nonconducting, thus

reaffirming the need for copper salts in the deposition process.

To demonstrate the potential of the DNA templating process,

Bao’s team also modified the initial “combing” procedure, creating

a crossed network of DNA instead of a linear one; as expected,

carbon was deposited on top in the exact same shape. In her paper,

Bao suggested that the designs of the graphene would be only

limited by the creativity of the DNA comber. Future projects could

even involve “DNA origami,” the twisting and shaping of DNA into

interesting geometric scaffolds.

In Stanford Engineering’s press release, Ali Jarvey, an industry

expert, praised the method. “This technique is very unique and takes

advantage of the use of DNA as an effective template for controlled

growth of electronic materials,” he said. “In this regard the project

addresses an important research need for the field.”

The DNA method is mechanizable, so these ribbons have the

potential to be produced in a factory in the near future. The DNA

strips could be combed by the millions, and the graphene strips

would be farmed en masse.

However, Bao admits in her paper that the method needs to be

perfected before it becomes ready for large-scale manufacturing.

Many of the strips deposited in multiple layers are more than an

atom thick. These strips are graphitic, not graphene, and lack the

necessary conducting abilities. Before mass production can start, the

team needs to find a way to only allow for one sheet of deposition

per strip.

Nevertheless, Bao’s discovery has made graphene a powerful new

player in the transistor industry. While household graphene transistors

are still several years out, there is no doubt that this exciting new

technology has vaulted some major hurdles of classical computing.

Graphene is useful for

both its strength and

its conductivity. It is

formed in sheets just

one atom thick, is in a

stable configuration,

and is also almost

completely transparent.

IMAGE COURTESY OF UCSB COLLEGE OF ENGINEERING

IMAGE COURTESY OF US RESEARCH NANOMATERIALS

IMAGE COURTESY OF ARGONNE NATIONAL LAB



FEATURE UNDERGRADUATE PROFILE

Making a Cosmological Splash: Ben Horowitz ES ’14

BY GRACE PAN

For Ben Horowitz, a senior physics major in Ezra Stiles, happiness

is the combination of a blackboard, a classroom of eager learners,

and a sky of unexplored galaxies. As the co-founder of Splash at

Yale, Horowitz has worked with thousands of Yale undergraduates

and secondary school students in Connecticut — though many may

be unaware of the man behind the curtain.

For the past three years, Horowitz has been the president of

Splash at Yale, a program that invites high school students to attend

a diverse array of courses taught by Yale students. On top of this, he

balances his other endeavors as part of the Yale Undergraduate Math

Society and the Yale Drop Team.

Ironically, for most of his adolescent life Horowitz never

considered himself a particularly good student. “I’m pretty sure I

even got a C in geometry my freshman year,” he said, recalling his high

school self with a smile. But in his sophomore year of high school,

he started attending courses taught by MIT students as part of the

MIT Splash program. After enrolling in multiple math and physics

courses because “they sounded the most advanced,” Horowitz began

developing his then-nascent interest toward these highly theoretical

fields. In fact, he attributes much of his intellectual growth from

sophomore year of high school onward to Splash. “Splash made me

realize that in order to understand these really cool advanced topics,

you have to understand the basics,” said Horowitz.

Since Splash at MIT was so instrumental in broadening his mind,

Horowitz co-founded Splash at Yale with Sebastian Caliri, PC ’12,

in his freshman year. With some basic assistance from Learning

Unlimited, the blanket organization that supports college Splash

programs across the nation, Splash at Yale received around 170

students for its first program.

Since then, Splash at Yale has grown to attract more than 500

middle and high school students for 150 courses each semester.

These seminar-style courses range from introductory physics to the

history of American garbage. For the more artistically inclined, there

are courses on improvisational comedy, ribbon dance, and a cappella

music. Students can tap into their latent interests, as Horowitz himself

did years ago, and undergraduate teachers have the opportunity to

share what they are passionate about. Horowitz himself has taught

Themes of Modern Physics and Introduction to Cosmology, among

IMAGE COURTESY OF BEN HOROWITZ

Ben Horowitz poses with his friends from the Yale Drop Team,

which performs experiments in reduced gravity.

Ben Horowitz teaches

physics courses for the

Spring 2013 Splash and Fall

2013 Sprout initiatives, an

extension of the organization

Splash at Yale, which he cofounded

in his freshman year.

IMAGES COURTESY OF BEN HOROWITZ

other physics-related courses. He sees teaching not only as an

interactive and dynamic experience which should not be confined to

problem sets and papers, but also as a way for the teacher to build a

solid understanding of the material. “It’s a really nice way to study for

exams, teaching a class for that subject,” Horowitz said with a laugh.

Much of Horowitz’s inspiration for his cosmology classes stems

from his research in the lab of Professor Charles Baltay. Baltay’s lab

studies supernovae to analyze dark energy and the history of the

universe’s expansion. Horowitz got started late fall of his freshman

year, when he was invited by Baltay to join the lab, and has worked

there every semester since. Horowitz specifically studies RR Lyrae

variable stars (stars whose brightness pulsates in a predictable

pattern). He surveys different sections of the sky to collect data

on star brightness, and develops code to search his data for signs

indicative of RR Lyrae stars. “These stars can possibly trace the

density of our galaxy,” explained Horowitz. His results so far suggest

that our galaxy was formed by the coalescence of multiple balls of

gas and debris, as opposed to just one.

Horowitz plans to attend graduate school, perhaps to study early

universe cosmology. Although he has not picked out a school yet,

his dedication to teaching is certain to follow him. “Where I go, if

there’s a Splash program, I’ll be involved in it. If there isn’t, hopefully

there will soon be a Splash program,” Horowitz said. “I hope that

in another twenty years, it will be expected that any university has it!

Like a debate team or a marching band.”

And in the spirit of his Yale brainchild, Horowitz leaves students

with some optimistic words. “Get excited about something!” he said.

“You don’t have to stick with it, but if you figure out one thing you’re

really excited about and pursue it, you’ll have some goal to always

strive for.”


Art Meets Science: Emiko Paul ’91

BY PAYAL MARATHE

As a freshman at Yale, Emiko-Rose Paul was

a typical pre-medical student. Pre-med in the

1980s didn’t look so different from pre-med

now; like many others, Paul was a biology major,

trudging through the introductory prerequisite

courses. But every semester, there was one class

on her schedule that she always looked forward

to — art.

Whether it was design, figure drawing, or

lithography, Paul knew by the time she graduated

in 1991 that she loved art too much to leave

it behind. But she was also excited by science,

especially animal behavior and ecology. Rather

than choosing either path, she created her own at

the intersection of science and art. Since jumping

into the field of medical illustrations, Paul has

never looked back. She and her husband now

run Echo Medical Media, a medical illustrations

company named after their dog, Echo.

Paul’s career decision was influenced by people

she met at Yale. The first was her faculty adviser for biology, Charles

Remington, who specialized in entomology and evolution. “Senior

year, with his help, I did my thesis on the nymphal stages of the

American cockroach and accompanied it with watercolor plates that

showed changing patterns of the different stages,” Paul said. “It was

the first real idea I had that I could do something with art.”

Paul realized it was important to find something that catered to

her specific interests. As an undergraduate, she found her options

were often limited: Yale’s science curriculum was focused more on

molecular biology than her primary interest, organismal biology, and

Yale’s art program emphasized abstract painting over what she truly

enjoyed, life drawing. But in spite of these department restrictions,

Paul wanted to find a way to explore her true passions. She met

a man at the Yale Peabody Museum who was working on facial

reconstructions of early hominid skulls, and discovered he had gone

to a graduate program for medical illustrations. Paul was immediately

intrigued. “It was the first time I had heard of something like that,”

she said.

Hoping to pursue a similar path, Paul

spent her first two years after graduation in

Paris working on her art portfolio, and then

applied to graduate programs in medical

illustrations. In 1994, she enrolled in a

program at Johns Hopkins. Her curriculum

overlapped considerably with that of medical

school students; she spent her first year in

human anatomy and physiology classes

doing dissections, and most of her second

year observing surgeries. “Most people

don’t realize that every medical illustrator

had to go through some medical training,

and there’s a certain community of people

who have gone through all the hoops who

produce the best work,” Paul said.

After finishing her graduate program, Paul


IMAGE COURTESY OF EMIKO PAUL

Emiko Paul started a medical

illustrations company, Echo

Medical Media, in 2000.

ALUMNI PROFILE

FEATURE

worked as a medical illustrator for publishing

companies until she started Echo Medical Media

in 2000. The field has grown substantially in the

past two decades, which she views as one of the

most exciting aspects of her work. “Fortunately,

I picked a field that really evolves with you,”

she said. The field has expanded to include 3D

modeling, and medical illustrations are now

recognized for their broad range of applications.

Paul’s goal for medical illustrations has always

been to be a great communicator. “We want to

explain the beauty of science, to explain things

that can’t be seen by the human eye or things

that can’t be photographed,” she said, adding

that she thinks her background in biology and

medicine has been essential to her success.

She also sees real value in medical illustrations

because she likes using art to teach people

unfamiliar concepts. “My main focus was always

education,” she said. “For me, it’s not just

a pretty piece of art that keeps text interesting; it’s about the big

picture and how all media can be used together to communicate

something.”

Paul has no regrets about her decision to pursue medical

illustrations instead of sticking to the pre-med path and becoming a

surgeon. “I’m sure a part of me would have been fine [as a doctor],

but my general temperament is more on the artistic side than the

hard science side,” she said. Luckily, she found something she

genuinely loves to do. Paul works from a home studio, using the

Internet to correspond with clients all over the world. “One of the

real pleasures is continually learning new techniques, meeting great

scientists and working with great authors,” she said.

But a true sign of her success is how immersed she is in her day-today

work. Paul enjoys every project she does, whether it’s illustrating

for a textbook or designing a magazine cover. She proudly called

herself a workaholic. “I’ve been doing this for 20 years,” she said,

“and I still love it as much today as I did when I started.”

Paul’s medical illustration

of breast cancer cells being

destroyed by bioengineered

antibodies won the 2011 Science

& Engineering Visualization

Challenge.

IMAGES COURTESY OF EMIKO PAUL


FEATURE

BIOENGINEERING

Engineers Program Chemical Reactions Using DNA

BY CHRISTINA DE FONTNOUVELLE

Thanks to the power of computer programming, we can control

many actions with extreme precision, from the scenery of a video

game to the movements of a surgical apparatus. These actions are all

defined by a code with a set of precise rules — a code quite similar in

function to biology’s own DNA. Now, biochemists at the University

of Washington have begun harnessing the coding power of DNA to

precisely control chemical reactions, just as computer code controls

the virtual world of a video game.

Like computer programs that direct machines to undertake specific

and repeatable tasks, DNA instructs cellular machinery to undertake

a specific set of chemical processes. However, a fundamental

difference between computer programs and biochemical systems

is that the latter is much more difficult for scientists to control.

While modifying a computer program often involves only minor

adjustments, modifying a biochemical system currently requires

IMAGE COURTESY OF YANG LIANG

An artist’s rendition of a chemical reaction “program” on the

screen, being carried out by a “chemical computer.”

rebuilding that system from scratch.

For decades, scientists have realized the potential of “programming”

chemical reactions, but the difficulty of precisely controlling

molecules has hindered any major breakthroughs until now. This

year, a team of engineers from the University of Washington, led by

Assistant Professor of Engineering Georg Seelig, set out to create a

system for studying and fine-tuning chemical reactions with DNA —

a programmable biological computer of sorts.

“I think this [approach] is appealing because it allows you to solve

more than one problem,” said Seelig in a September University of

Washington Today article. “If you want a computer to do something

else, you just reprogram it. This project is very similar in that we

can tell chemistry what to do.”The basis of this DNA programming

was simple, but its execution proved complicated. The “instructions”

the researchers provided to the system were custom-designed

strands of DNA. These DNA strands were allowed to react with one

another and form new combinations, just as a computer processes

the programmer’s instructions to generate output. Since the four

subunits of DNA follow a basic base-pairing rule — adenine binds

to thymine, and cytosine binds to guanine — the team could precisely

control the outcome of the reaction by simply tweaking their original

IMAGE COURTESY OF TRUNEWS

An engineering team at the University of Washington and their

colleagues aim to “program” chemical reactions using DNA.

input. This can involve changing the sequences of certain DNA

strands, or adjusting how much of each strand that gets mixed into

the “computational soup.”

The reactions that Seelig’s team programmed used the basic

language of chemistry. For example, A + B g C + D meant that

signals A and B should be transformed to signals C and D. The

researchers proved that this “program” produced C and D not only

reliably but also in the right amounts and at the predicted rate. Thus,

these programmed chemical reactions behaved exactly as they would

in a native environment.

In addition to controlling simple, one-step processes, the team

also programmed entire reaction cascades, in which the output of

one reaction becomes the input for the next. Again, these reactions

produced the expected output at the predicted rate and quantity.

Seelig’s team then used their DNA reactions to mimic the function

of a real computer: by applying an algorithm, the DNA program was

able to solve a complex computing problem. Specifically, it could

compare the concentrations of two inputs, X and Y, and decide

which one was in the majority. While this computing problem seems

simple for a human brain to decipher, engineered DNA strands that

are capable of making decisions represent a step forward in the field

of molecular programming.

“We start from an abstract, mathematical description of a chemical

system and then use DNA to build the molecules that realize the

desired dynamics,” said Seelig. “The vision is that eventually, you can

use this technology to build general-purpose tools.”

As the field of DNA programming is still in its early stages, this

new approach is not yet ready for application to the medical field.

However, researchers hope that learning to program more complex

chemical reaction systems will have important applications. For

example, this molecular programming technique could be used to

make molecules that self-assemble within living cells. These could

act as “smart” sensors that detect specific abnormalities and respond

accordingly, perhaps by direct drug delivery to the abnormal cells.

Seelig’s team recently received $2 million from the National Science

Foundation as part of an initiative to spur research in molecular

programming. Seelig and his team will use this funding to continue

their research and work toward applications that may change the face

of biotechnology.


TRIVIA

FEATURE

IMAGE COURTESY OF SCIENCE DAILY

The new DNA extractor

takes only two minutes

to separate and purify

samples.

1

Technology Can Extract

Your DNA in the Same

Amount of Time It Takes

to Microwave Popcorn

A new device created by NanoFracture

and engineers from the University

of Washington can extract DNA from

bodily fluid samples in two minutes, a

tenth of the time it took previous technologies.

A simple mouth swab from

the supposed criminal is inserted into

the device, where microscopic probes

touch the saliva and apply an electric field.

The electric field attracts particles in the

saliva to the probe tip, and the size of the

probe determines which size of particles

sticks to the surface. These micro- and

nanoscale tips are designed for DNA

size molecules, so larger particles swerve away. After two minutes, the

DNA is separated and purified from the sample and ready for analysis.

2

Kiss and Tell: You Kiss It, They Can Tell

Watch where you put those lips, because forensic scientists

can now identify lipstick brands from the scene of the crime.

This information is surprisingly useful because people are not aware of

how much comes in contact with their mouths: cups, cigarettes, and

sometimes the victim’s lips. Matching lipstick can place suspects at the

crime scene or prove physical contact between suspect and the victim.

Previous methods of lipstick analysis were destructive and therefore

not used very often. Researchers from the University of Kent have

now developed Raman spectroscopy, a technique that can analyze

lipstick through the transparent layers of an evidence bag without

compromising the piece of evidence. Raman spectroscopy detects the

laser light scattered by a material to identify it. The vibrational energy

of the lipstick molecules scatters some of the incoming light at altered

wavelengths. The microscope captures these altered wavelengths to

create a Raman spectrum, which is a characteristic vibrational fingerprint

that can be matched to the Raman spectra of known lipsticks.

3


Five Things You Didn’t Know

About Forensics Technology

By Claudia Shin

Behind the drama, the world of CSI relies on an arsenal of ever-evolving technologies.

Read on to learn about two-minute DNA extractors, lipstick analysis, and how to be

the perfect criminal.

IMAGE COURTESY OF TECHNOL-

OGY REVIEW

4

Forensic Scientists Can

Identify You From Any

Photo

Facial recognition is wonderful for

matching two faces that are looking

directly at the camera. Unfortunately these

comparisons tend to be difficult because

facial recognition software compares mug

shots with security camera footage, which

often shows faces at different angles.

That is why biometrics researchers

from Florida Atlantic University developed

a new computer algorithm to construct

a three-dimensional face from a twodimensional

image. This computer algorithm

uses lighting and viewing angle in

the 2D image to create a 3D image. When

both the mug shot and security camera

Fast Food Felonies: Unhealthy Criminals Are

More Likely to Get Caught

As if you really need another reason to eat healthy, apparently

you are more likely to get caught if you eat processed food.

Sweaty fingerprints with a high salt content leave a corrosive impression

on metal, and salty sweat comes from unhealthy eating.

Even after metal objects are wiped clean of fingerprints, new forensic

fingerprinting technologies developed

at the University of Leicester can identify

corrosive impressions from the salty sweat

that remains on metal surfaces. Before now,

fingerprints were detected using deposits

left by the finger, which are easily wiped

away. But since corrosion is permanent, fingerprints

on metal evidence — doorknobs,

gun handles, even bullets retrieved from

corpses — cannot be erased.

An example of a bullet with a corroded fingerprint that was

easily detected with black conducting powder.

IMAGE COURTESY OF TRUNEWS

A two-dimensional

driver’s license photo

can be analyzed by

computer software

to construct a three

dimensional image.

footage are converted from 2D to 3D, facial recognition is able to

match faces that previously were incompatible.

5

Hips Don’t Lie: Pubis Determines Age and

Sex of Corpses with 95 Percent Reliability

When corpses are mutilated or aged, the age and sex of

the corpse is no longer obvious, and it turns out the pubis, a pelvic

bone located in the lower frontal region of the hips, is the best way

to track down that information.

Researchers from the University of Granada created a new computing

system that analyzes the pubis region of corpses. The system

divides the pubis into four regions and then compares those regions

to a database of known structures organized by age and sex. The

new system can determine the age and sex of the corpses correctly

95 percent of the time.


FEATURE

BOOK REVIEWS

Einstein and the Quantum:

BY ANDREW QI

In his new book, Yale Physics Professor A. Douglas Stone recounts

Albert Einstein’s oft-overlooked role as a pioneer of quantum physics.

At once a storyteller, historian, and scientist, Stone crafts a narrative

of the daring physicist’s tumultuous academic career. Moreover, he

describes the significance of Einstein’s achievements in quantum

theory in clear and compelling terms, accessible to anyone with a

penchant for a good story.

Stone sets his story in a pivotal era in theoretical physics at the

beginning of the 20 th century. Newly acquired experimental data were

at odds with established theories of classical physics, hinting at cracks

in the long-accepted Newtonian model. It was then that a young

Einstein found himself living in a cramped Swiss boarding house,

investigating a curious quirk in a paper by his renowned contemporary

Max Planck. These inquiries led Einstein to a paradoxical conclusion:

that light existed simultaneously as particle and wave, in discrete

packets or “quanta.” Einstein’s attempts to reconcile this apparent

contradiction with the contemporary understanding of physics

would come to represent the birth of quantum theory.

This would not be the end of his involvement, however. Stone

takes care to trace Einstein’s influence throughout the evolution of

the field, from his definitive 1917 paper on the quantum theory of

radiation, to his influence on the seminal theories of others, such as

Nernst, Schrödinger, and Heisenberg.

Perhaps Stone’s most noteworthy achievement is explaining

the intellectual issues of the day that Einstein grappled with, all

without getting lost in abstruse mathematics. Instead, Stone weaves

This Is Your Brain On Music

BY AMEYA MAHAJAN

According to musician-turned-scientist Daniel J. Levitin, most

people would not consider studying music through the lens of

science. In his book This Is Your Brain on Music, Levitin attempts to

overcome this barrier and analyze how the human brain responds

to music. As a former musician and sound engineer himself, Levitin

puts his own experience with the music industry to use in explaining

how our brains interpret, process, and respond to music.

The title of the book suggests an eventual epiphany or bold

conclusion about music and human psychology. However, Levitin’s

approach is surprisingly conservative: He simply guides the reader

through an elementary analysis of music and how it triggers

responses in the brain. For example, Levitin describes how the brain’s

cerebellum interprets rhythm, a process that allows us to tap our feet

in time with a song. Similarly, he correlates emotional responses

to music with the amygdala, pitch distinction with the A1 auditory

cortex, and so on.

The content is not revolutionary, but enriching nevertheless

for musicians and non-musicians alike. With the help of Levitin’s

occasional analogies (correlating musical intervals with “jumps”) and

popular music references to the likes of Jimi Hendrix and the Beatles,

even a novice reader can examine music with a new perspective.

Admittedly, the book’s presentation and style are sorely lacking. The

first two chapters are a rundown of musical theory that are presented

in a block-text format, only sporadically interspersed with analogies.

Once past the first two chapters, ideas often felt incomplete. The

the Quest of the Valiant Swabian

Rating: &&&&&

together technical explanations and rich

historical interludes — stories rife with

noble breakthroughs, petty politicking,

and colorful personalities. For instance,

Stone details Einstein’s churlish rejection

of authority figures, from his setting off

an explosion in a laboratory course to

his dismissing professors as a “group of

whores” — even after becoming a professor

himself.

However, as youthful defiance faded into contemplative reflection,

Einstein grew increasingly skeptical of newer extensions of quantum

theory founded in probability, going as far to denounce it in a famous

paper now known as the “EPR paradox.” Stone sources both personal

letters and publications to depict a man who devoted a lifetime

pursuing a new theory, only to renounce it when it challenged his

own philosophical convictions.

At its heart, Einstein and the Quantum is the story of the birth of an

academic discipline, humanized by the intensely personal stories of its

founders. Stone’s efforts to relay physics in the language of popular

history are valiant and often entertaining, although the lay reader may

still find his explanations on the finer points of theoretical physics

daunting. Nevertheless, Stone manages to bring a typically esoteric

science to life; more than a simple retelling, the narrative evokes an

empathetic understanding of a man at the crossroads of a revolution

that he could not believe in.

Rating:

&&&&&

feeling of coming full circle was rare at

best, and Levitin’s abrupt transitions from

simple to complex topics are jarring —

the reader barely has time to understand

the different types of sound, for instance,

before Levitin launches into the physics of

music. Furthermore, tangential distractions

are peppered throughout the book. A

discussion on the difference between the

mind and brain seems off-topic, and Levitin

provides no connection to the book’s main message before reverting

to an explanation of music theory.

Finally, many of Levitin’s anecdotes seem to serve no purpose in

illuminating the reader, and instead appear self-serving. An entire

chapter devoted to meeting biologist Francis Crick only addresses

neuropsychology and music concretely in the last five pages, while

the majority of the chapter is filled with personal accounts that have

little relevance to the book.

This Is Your Brain on Music takes a promising idea and attempts

to explain it to a broad audience. To find this book an entertaining

read, the dedicated reader must get through the first two chapters

and sift through tangled discussions in search of a few enlightening

ideas. For most, however, this endeavor is not worth the effort. The

disjointed style and organization detract too much from the subject

at hand, leaving a powerful topic only somewhat explored.


CARTOON

FEATURE

Scrutinizing the Specimen

BY CELINA CHIODO



YSM Issue 87.1

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