YSM Issue 91.3

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TABLE OF CONTENTS

VOL. 91 ISSUE NO. 3

More articles available online at www.yalescientific.org.

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23

PASS THE LIPIDS

Yale Researchers investigated a certain class of proteins active in metabolic communication between certain cellular

organelles and how dysfunction of these proteins contribute to neurodegenerative disease.

SECRETS OF MOSQUITO SPIT

Yale Researchers have identified a salivary gland protein in mosquitos called mosGILT that partially inhibits the speed and

cell traversal of the parasite that causes malaria, a promising discovery for the development of new antimalarial treatments.

A LOOK INTO ALZHEIMER’S

A team of researchers at Yale has developed a new method for Alzheimer’s detection using PET imaging. This method

may be used in developing experimental treatments that effectively prevent the progression of this disease.

LUMENS & HERTZ

COVER ARTICLE: Physicists from the Rakich Group at Yale have created a groundbreaking silicon-based laser, using

interactions between light and sound.

POWERED BY THE SUN

Researchers at Yale demonstrate how different semiconductor surface facets affect the efficiency and sustainability

of solar fuel cells.

www.yalescientific.org

October 2018

Yale Scientific Magazine

3


Q&A

CAN A VIDEO GAME MAKE YOU A BETTER PERSON?

By Georgia Woscoboinik

It’s possible! Led by PhD candidate

Tammi Kral, researchers at the University

of Wisconsin sought to develop a

video game that would teach empathy

to adolescents. They conducted a study

to investigate whether a video game

could effectively improve children’s empathic

accuracy, or their ability to correctly

infer the thoughts and feelings of

others. To accomplish this goal, the researchers

created a game called Crystals

of Kaydor, which was intended to teach

the subjects how to recognize emotional

cues. They tested the empathic accuracy

of children who played the game

by assessing their behavior during tasks

requiring empathy and monitoring the

activity of brain circuits underlying empathy

by conducting fMRI scans before

and after the subjects played the game

for a two-week period.

By Andrew Zheng

It’s no surprise that city life impacts

the ecosystem it replaces. Especially

when it comes to birds, it’s easy to observe

the effects of urbanization. From

telephone wires for perching to bread

crumbs for eating, city life seems to

suit our avian friends. A team led by

researcher Adriana Dorado-Correa of

the Max Planck Institute for Ornithology,

however, asserts that birds are not

necessarily cut out for the urban jungle.

Their most recent research focuses specifically

on the effect of noise pollution

on telomere loss. Telomeres are compound

structures at the ends of chromosomes

that help prevent damage to

chromosomes. The loss of these structures

could be detrimental to the formation

of new cells and embryos.

In Dorado-Correa’s study, the team

IMAGE COURTESY OF FLICKR

Old fashioned video games, the predecessors of the

game used in the study.

DOES CITY LIFE IMPACT BIRDS?

IMAGE COURTESY OF FLICKR

Birds often are stereotyped as being accustomed to city

life. However, this might very well not be the case.

While the researchers found no

significant difference in behavioral

assessments of empathic accuracy

as a result of playing Crystals of

Kaydor, the brain scans revealed a

significant increase in activation of

empathy-related neural circuits as

well as strengthened connectivity

between brain networks involved in

empathy. These results suggest that

video games can be useful in improving

empathy-related brain function

and neural connectivity. As an

empathy training platform, video

games could be extremely impactful

because of their engaging nature and

burgeoning popularity among adolescents.

However, further research

is necessary to determine whether

these changes in our brains significantly

impact our behavior.

bred zebra finches and put them in

different noise environments: one

group was exposed to traffic noise

during breeding, one group was exposed

during growth, and a control

group did not deal with any traffic

noise. Though telomere length decreased

with age in all cases, which

was expected, the group exposed

to noise during growth had shorter

telomeres than did those with noise

during breeding and those not exposed

to noise. Therefore, Dr. Dorado-Correa

and her team were able to

conclude that traffic noise negatively

affects birds the most during growth.

These findings elucidate how traffic

noise affects birds’ growth and give

cause for better management of traffic

noise.

4 Yale Scientific Magazine October 2018 www.yalescientific.org


SCIENCE SURROUNDS US

While the Yale Scientific Magazine aims primarily to shed light on the scientific

research that happens both at Yale and beyond, it is important to remember

that the products of scientific progress can be observed as we walk through

everyday life. From technology to conservation, our society is built around the

effects of science—whether or not we are conscious of them.

If we look closer at the articles in this issue, we can see the “real-life” potential

hidden between the lines of research and data. From new discoveries in mosquito biology

and malaria transmission (pg. 16) to investigations into the mechanism of human

papilloma virus transport (pg. 8), science likely has its most obvious impacts on

modern medicine. Beyond the realm of medicine, however, teams of scientists drive

progress in technology, from solar fuel cells (pg. 23) to new materials for bulletproof

vests (pg. 30), and in conservation, such as the effects of hippopotamus excretion

THE

(pg. 11). The scope of science is limitless.

Our cover article this issue looks into a Yale

team’s use of real-world effects science phenomena

to engineer novel laser systems that

combine the power of both sound and light

waves (pg. 21). The resonance used to amplify

this team’s laser system is the same concept that

EDITORdrove

the massive oscillations of London’s Millennium

Bridge in 2000. Even the most complex

laser systems can be representative of the basic

science that drives both innovative research

and experiences in the natural world.

Thus, while scientific research can certainly

be seen as amazing work, it is undeniable that

IN-CHIEF

science is also very normal. We are excited to

share the work of students and professors to our

readers, and we are even more excited to spread

an awareness of science. We have worked with

Yale-NUS in Singapore to shed light on scientific

education and to facilitate a global spread

of ideas (pg. 25). We hope that both scientific

SPEAKS

education and scientific journalism can bring

science into the spotlight that it merits.

Eileen Norris, Editor-in-Chief

ABOUT THE ART

Current innovations in silicon photonics are

generating incredible excitement. By generating

laser light using a combination of light and

sound waves, we are now able to send and process

information at unprecedented speeds. I

chose to depict this incredible process with an

illustration of the chip’s nanoscale waveguide

used to confine light and sound waves, creating

maximum interaction, and the resulting

amplified light beaming forth.

Ivory Fu, Arts Editor

MASTHEAD

OCTOBER 2018 VOL. 91 NO. 3

EDITORIAL BOARD

Editor-in-Chief

Managing Editors

News Editor

Features Editor

Articles Editor

Online Editor

Copy Editors

PRODUCTION & DESIGN

Production Manager

Art Editor

Photography Editor

Outreach Designer

Webmaster

BUSINESS

Publisher

Operations Manager

Advertising Manager

Subscriptions Manager

OUTREACH

Synapse President

Synapse Vice President

Social Media Coordinator

Outreach Coordinators

STAFF

Carli Roush

Ellie Gabriel

Isabella Li

Amber Braker

James Han

Matt Tu

Lukas Corey

Tiffany Liao

Stephanie Smelyansky

Anna Sun

Lauren Kim

Marcus Sak

Diyu Pearce-Fisher

Georgia Woscoboinik

Andrew Zheng

Hannah Geller

Jack McArthur

Khue Tran

Hannah Ro

Philena Sun

ADVISORY BOARD

Priyamvada Natarajan

Sandy Chang

Kurt Zilm, Chair

Fred Volkmar

Stanley Eisenstat

James Duncan

Stephen Stearns

Jakub Szefer

Werner Wolf

John Wettlaufer

William Summers

Scott Strobel

Robert Bazell

Craig Crews

Ayaska Fernando

Robert Cordova

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Katie Schlick

Richard Li

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Miriam Ross

Britt Bistis

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Megan He

Goh Rui Zhe

Jennifer Miao

Chloe Hong

Joshua Yan

William Langhorne

Doyoung Jeong

Nicholas Archambault

Kenny Wang

Xiaoying Zheng

Ethan Garvin

Matthew Kegley

Ali Brocato

Eileen Norris

Diane Rafizadeh

Stephanie Smelyansky

Allie Forman

Charlie Musoff

Will Burns

Conor Johnson

Marcus Sak

Joshua Matthew

Sunnie Liu

Ivory Fu

Eric Wang

Laurie Wang

Alice Wu

Kevin Chang

Jiyoung Kang

Allie Olson

Tanvi Mehta

Jessica Trinh

Nasser Odetallah

Leslie Sim

Seth Anderson

Lisa Wu

Maria Lee

Brett Jennings

Katrina Starbird

Eric Chien

Annie Yang

Raquel Sequeira

Liliane Tran

Lauren Gatta

Anusha Bishop

Elissa Martin

Alice Tirard

Sunnie Liu

Tammy Liao

Michelle Barsukov

Chunyang Ding

Sol Bloomfield

Jon Michel

Kate Kelly

Astronomy

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We reserve the right to edit letters before publication. Please send

questions and comments to ysm@yale.edu. Special thanks to Yale STC.


HELP OR

HARM?

Rethinking common

surgeries

BY: CARLI ROUSH

What if

a straightforward

medical procedure you had

as a child could drastically increase your

risk of health complications far into the future?

Tonsillectomies, adenoidectomies, and adenotonsillectomies,

surgeries commonly performed on young patients, are

often meant to treat or eliminate breathing problems or middle

ear infections. However, they may ultimately do more harm than

good.

Stephen Stearns, a professor of Ecology and Evolutionary Biology

at Yale University, along with colleagues Sean Byars from

the University of Melbourne and Jacobus Boomsma from the

University of Copenhagen, evaluated the long-term health risks

of such surgeries for children nine years old or younger. Using

information from the Danish Health Registry, the researchers

found that young children who have these surgeries are more

likely to suffer from upper respiratory diseases, infectious diseases,

and allergy-related diseases later in life.

The most significant increase in risk is seen in that of upper

respiratory diseases; those who received a surgery of interest in

their first nine years are about two to three times more likely

to contract an upper respiratory disease than those who do not

undergo such surgery in this time.

Although this is a shocking number, it may not warrant a call

to ban these surgeries. “I think what this paper really does is

reinforce something that otolaryngologists had already been

doing to a certain extent, and that is watchful waiting,” said

Stearns. The scientists who conducted this research hope that

increasing awareness of the hidden risks associated with these

surgeries will encourage physicians to more carefully consider

the removal of these valuable organs.

Agroup of Yale researchers made an unexpected discovery

when experimenting with aminoglycoside antibiotics.

Studying their effects in mice models, the team

found that in addition to fighting bacterial infections, these

antibiotics may increase antiviral resistance.

Initially, the researchers were hoping to gain better insight

into what role bacteria in the vaginal mucosa might play in

the variable severity of herpes infections.

“A lot of people have herpes and most people get a primary

infection...But a small subset of people get chronic recurrences,”

postdoctoral associate Smita Gopinath stated. “We

don’t really know why some people get those. So we thought

that there may be something significant about the bacteria

in those people that might explain their recurrent flare-ups.”

They treated mice models with the antibiotic neomycin,

then infected them with genital herpes. The mice were found

to have increased antiviral resistance. But, upon treating mice

without subsequent exposure to bacteria, they found neomycin

to still help strengthen the mice’s antiviral response. This

suggested that it was not the bacteria causing antiviral resistance,

but the antibiotic itself.

Neomycin does this by tricking the mice’s cells into thinking

a viral infection has already occurred. This causes cells to

increase expression of interferon-stimulated genes which help

the mice fight off the infection.

While the researchers warn not to use antibiotics to treat viral

infections, they think these results have potentially paved

the way for a new kind of antiviral treatment. “It actually is

effective against different kinds of viruses...You can give this

antibiotic to mice intranasally and it protects them

against influenza,” Gopinath said. “So this has

the potential down the road to be

an interesting antiviral,

but not yet.”

ANTI-

BIOTICS

The unexpected upsides

BY: AMBER BRAKER

6 Yale Scientific Magazine October 2018


Imagine if we could turn all the world’s saltwater into drinking

water using a simple filter with tiny pores to catch salt particles.

Such purification technology, which could save millions of lives,

may be possible using materials called nanophase-separated block

copolymers (BCPs). Currently, however, production issues prevent

BCPs from commercial feasibility. Mingjiang Zhong, assistant professor

in Yale’s Department of Chemical & Environmental Engineering,

has discovered a way to address this problem.

The most common BCP structures are linear diblock copolymers,

string-shaped polymers whose two ends repel each

other. When multiple strings are put in close proximity, their

opposing ends seek to distance themselves from one another,

forming tiny gaps of around 10 to 200 nanometers. The challenge

comes when a separation under 10 nanometers—a size

necessary for applications ranging from desalination to increasingly

small computer chips—is desired.

“Once the polymer chain gets smaller and smaller, the immiscibility,

or repulsion of the two ends of the BCPs, is decreased,” said

Zhong of current BCP technology, which can only achieve such

small gaps using expensive materials and processing techniques.

To address this challenge, the scientists developed Janus graft

block copolymers (GBCPs), BCPs that link multiple linear diblock

copolymers together to form a structure that resembles

a bottlebrush. This structure maintains repulsion of the individual

BCPs at increasingly small sizes without sacrificing processing-

and cost-effectiveness.

Since publishing his research in Angewandte Chemie, Zhong

has focused on scaling the technique to ensure large-scale feasibility.

He is collaborating with other Yale researchers to apply

GBCPs in desalination membranes and microelectronics,

with the hope that this new technology

will bring exciting developments

across many

fields.

NANOSCALE

POLYMERS

New, inexpensive applications

BY: ISABELLA LI

ROBOT ROLE

MODELS

Promising therapeutic

potential

BY: ELLIE GABRIEL

We

often take for granted our ability

to detect social cues such as facial

expressions and body language. For many

children diagnosed with autism spectrum disorder

(ASD), this social-communicative ability is not innate and

instead must be learned. Unfortunately, most schools do not have

effective programs for teaching these skills to children with ASD.

But what if the solution lies in the homes of the children? A ten

million dollar collaborative project led by Brian Scassellati, Yale

Professor of Computer Science, recently explored a new therapeutic

approach that emphasizes personalization and on-demand

access.

In the study, an autonomous robot ran thirty-minute skills-learning

sessions every day for one month with twelve children and

his/her caregivers. The sessions, which were tailored by the robot

to the individual, consisted of games that fostered social and

emotional understanding, perspective taking, and ordering. At

the end of the in-home study, subjects showed improved eye contact,

more attempts to initiate conversation, and more frequent

responses to prompts. Significantly, they also exhibited progress

outside of the sessions with people other than their caretakers.

The effects of the study diminished one month after it concluded,

but Scassellati aims to make the gains more permanent by implementing

the technology for longer durations and is optimistic

about the potential of this socially-assistive robot.

“In the home, we had no control over the environment. These

robots had to be very flexible and intelligent to deal with variations,”

said Scassellati. Thus, if the robot can act within homes,

it can act anywhere. While robots alone cannot replace human

therapists, they can certainly reinforce their efforts.

www.yalescientific.org

October 2018

Yale Scientific Magazine

7


NEWS

cell biology

CELL-PENETRATING PEPTIDES

HPV’S way out

BY JAMES HAN

Human papillomavirus (HPV) is a sexually transmitted

virus that can cause a variety of unpleasant symptoms, including

genital warts and cervical cancer. While the Center

for Disease Control (CDC) estimates that around 79 million

Americans are infected, most people with HPV do not develop

any symptoms. Despite its prevalence, the intricacies of

HPV are not fully understood, particularly how HPV infects

and takes control of host cells.

HPV is a small, non-enveloped DNA virus. Enveloped viruses

can usually infect a cell by fusing to its outer membrane

like two bubbles combining to form one, but non-enveloped

viruses are unable to use this mechanism. Instead,

HPV utilizes a cellular process called endocytosis to enter

the cell. In endocytosis, the cell membrane wraps around an

object and pinches off, creating a small bubble called an endosome

containing the object. Scientists have known about

this mechanism for some time, but to actually infect a cell,

HPV must find a way to the nucleus. In past studies, scientists

have found that HPV uses the retrograde transport

pathway—which goes from the Golgi body to the endoplasmic

reticulum. This pathway is the reverse of how materials

are usually transported in the cell. However, scientists were

still unsure how HPV escaped the endosome to first enter

the retrograde pathway.

Daniel DiMaio, Yale Waldemar Von Zedtwitz Professor

of Molecular Biophysics and Biochemistry, Genetics,

and Therapeutic Radiology, has been working with papillomaviruses

since the 1980s and decided to investigate

the mechanism HPV uses to get out of the endosome and

into the cytoplasm inside the cell to enter the retrograde

transport pathway. DiMaio and his team hypothesized

that the virus might utilize cell-penetrating peptides

(CPPs) to poke through the membrane of the endosome

and expose a binding site, signaling the cell to induct the

virus into the retrograde transport pathway, giving it a

path towards the nucleus.

To test this hypothesis, DiMaio and his team used a

protein called green fluorescent protein (GFP), which

glows green. They investigated whether the protein stuck

through the endosome membrane into the cytoplasm using

a test called a split GFP assay. In this test, a portion

of the GFP protein is fused to the end of the CPP, while

the other part of GFP is circulated in the cell’s cytoplasm.

If the CCP with the attached GFP piece did indeed stick

through the endosome membrane into the cytoplasm,

the two GFP pieces would come together like a puzzle,

and green fluorescence could be seen. When DiMaio and

his team used the assay on HPV infected cells, the cells

glowed green, supporting their CCP hypothesis.

Pengwei Zhang, the lead author of the paper and a postdoctoral

fellow in DiMaio’s lab, noted that there are still several

questions to be answered. She envisions many applications

of this new discovery, including the delivery of drugs, peptides,

nanoparticles, and other therapeutic substances into

the cells. She also stressed that CPP’s high efficiency makes it

an excellent candidate for this sort of delivery.

Along with being a novel delivery method, DiMaio lists

three key results of this experiment: a deepened understanding

of cell biology—particularly CPPs; a more complete

knowledge of how papillomaviruses work; and potential

clues on how to prevent infection. “If we can block the cell

penetrating step or block the ability of the virus to bind to the

retromers, that would block infection,” said DiMaio.

Both DiMaio and Zhang are excited about the direction

of future HPV research. DiMaio notes that, although many

people are not vaccinated, the current HPV vaccine already

works well. He plans to explore additional possible antiviral

treatments to help those who are not vaccinated or cannot

afford vaccination. Zhang hopes to answer further questions

about the CPP, such as the impact of pH on its function. She

suggests that therapeutic strategies for HPV may shift focus

to target the CPP, rather than oncogenes—cancer causing

genes—in HPV.

Though this discovery has filled a gap in scientists’ understanding

of HPV function, DiMaio believes that the field is

focused on improving deficiencies in the current vaccine,

rather than creating new drugs with different targets. It may

be years before the CCP discovery is transformed into a new

drug or vaccine. “Going from proof of principle to a medicine

is a very long process,” said DiMaio.

PHOTOGRAPHY BY JAMES HAN

Zhang observes the results of the lab’s experimentation through

a microscope.

8 Yale Scientific Magazine October 2018 www.yalescientific.org


psychology

NEWS

WIRING OF PSYCHOPATHIC BRAINS

Neural networks hold clues to psychopathy

BY MATT TU

Psychopathy is a relatively uncommon mental disorder,

yet its socioeconomic burden on society can be extremely

damaging. Psychopaths lack full emotional awareness

and decision-making skills possessed by non-psychopathic

individuals, making them more likely to deceive others,

make rash decisions, and ultimately commit crimes. In

fact, while only one percent of the general population are

considered psychopaths, that figure rises to twenty-five

percent in prison populations.

Although psychopathy is well-diagnosed by comprehensive

tests, the underlying neural mechanisms that cause

psychopathy are still unclear. Only in last decade have researchers

begun to study the differences in brain activity

between normal and psychopathic brains. Specifically, these

studies focus on analyzing “neural connectivity,” or how

different areas of the brain communicate with each other.

Traditional methods of analyzing neural connectivity

can determine whether or not certain regions of the

brain send signals with each other, but cannot determine

how efficient these networks are. In other words, imagine

knowing that a package was delivered from New York

to Los Angeles, but not knowing what route the package

took. However, Scott Tillem, a PhD candidate in Yale’s Department

of Psychology, has been using a novel approach

in connectivity analysis to study psychopathy. His approach

not only determines which regions of the brain are

communicating with each other, but also how efficiently

they communicate and how these networks are wired.

For example, a less efficient network would send packages

through thousands of local post offices via a “line configuration,”

while a more efficient network would send the

packages to a centralized hub and to their final destination

via a “star configuration.”

To investigate how psychopathic brains differ from

normal ones, Tillem had 172 participants first undergo

a psychopathy evaluation to determine their degree of

factor one and factor two traits. Factor one traits include

superficial charm, difficulty forming relationships, and

lack of empathy, while factor two include impulsive behavior.

Then, each participant underwent an electroencephalogram

(EEG) brain scan, where electrodes placed

around a participant’s head recorded electrical activity

in different areas of the brain. Lastly, Tillem analyzed the

EEG data to determine the efficiency and connectivity of

the participants’ brains.

Tillem found that participants with high levels of factor

one psychopathic traits had less efficient neural communication,

and that their neural connectivity is more line-like.

This inefficiency could explain why individuals with factor

IMAGE COURTESY OF ADOBE STOCK

The underlying neural causes of psychopathy are still unclear.

To tackle this problem, Yale researcher Scott Tillem has been

using a novel approach in connectivity analysis to determine

how the brain is wired in individuals with psychopathic traits.

one traits might only process the personal benefits of an action

and not the social or moral consequences of it, such as

breaking the law or damaging a relationship.

However, what surprised Tillem was that participants

with high levels of factor two psychopathic traits had hyper-efficient

neural communication, meaning that their

neural connectivity was even more star-like than the

brains of non-psychopathic individuals. A possible reason

for this, Tillem guesses, is that super high efficiency

comes at a price of lower reliability. That could explain

why individuals with factor two traits typically act normal,

but during times of high stress, tend to make reckless

and impulsive decisions.

Tillem’s research shines light on the neural underpinnings

of psychopathy, but also has major implications on

how the criminal justice system treats psychopaths. “Because

psychopaths might fundamentally process information

more slowly, are they equally responsible for crimes

committed in a time-pressured situation if they’re physically

unable to process all the relevant information?” said

Tillem. He also believes that his findings can inform police

officers, lawyers, and corrections officers of how to

better interact with psychopaths. “Instead of demanding a

response right away, giving psychopaths more time to process

questions and advice might allow them to adequately

respond to questions and take advice better.”

Tillem already plans to conduct a follow-up study with

significantly more participants, focusing on individuals

high on both factors of psychopathy. Ultimately, he hopes

that knowledge on the neural causes of psychopathy will

reach a point where a brain scan could determine if a patient

has psychopathic traits and if so, how to best accommodate

those individuals.

www.yalescientific.org

October 2018

Yale Scientific Magazine

9


NEWS

technology

MEMBRANES VERSUS MICROBES

Zapping antibiotic-resistant bacteria in our water supply

BY LUKAS COREY

Fishing can be quite the challenge, even for the experienced

fisherman. The challenge of removing every live fish

from the ocean thus seems rather silly, even without scaling

the problem down in size by orders of magnitude to the

world of microorganisms. Nevertheless, this is essentially

the challenge researchers in the Elimelech Lab at Yale University

and the Wang Lab at Shandong University have been

tackling for years as they attempt to remove antibiotic-resistant

bacteria from wastewater. Their new answer? Zap them!

Overuse of antibiotics in agriculture and in medicine have

greatly increased the risk of superbugs, bacteria resistant to

a broad spectrum of antibiotics, and the continues to worsen.

These antibiotic resistant bacteria accumulate in soil,

drinking water sources, and wastewater, where they are particularly

concentrated. Most current wastewater treatment

methods, usually involving adding chemicals, are of limited

efficacy and have no specific measures for targeting antibiotic

resistant bacteria. The result is an accumulation of resistant

and potentially pathogenic bacteria in water supplies.

In a recent paper published in the American Chemical Society’s

Environmental Science and Technology, the group

removed antibiotic-resistant microbes from wastewater using

photocatalysis membrane technology, a process which

separates microbes with a membrane and kills them under

Ultraviolet (UV). While membranes have been used in the

past for wastewater treatment, there were problems with

this design, which the new, photocatalysis membrane seeks

to solve, explained Yunkun Wang, an assistant professor at

Shandong University.

“Even if you use a filter, they will accumulate on the membrane

surface and can still transfer antibiotic resistance

genes,” said Wang.

Another powerful benefit of the new filtration technology

is its ability to treat massive amounts of water quickly, which

typical UV and chemical sterilization techniques do rather

inefficiently. Even standard membrane technologies have

this issue of scalability because the buildup of debris eventually

decreases water flow through the membrane.

The new photocatalytic method uses a polyvinylidene fluoride

(PVDF) membrane, a type of membrane woven with

holes around 16 nanometers in diameter. Most bacteria are

around two micrometers long, or more than a thousand

time bigger than these holes and unable to pass through.

The PVDF membrane is covered with titanium oxide, which

gives it photocatalytic properties and decreases the average

pore size to approximately six nanometers.

When UV rays hit the titanium oxide, they generate reactive

oxygen species, unstable oxygen atoms prone to reacting

with nearby molecules. These reactive oxygen species

kill bacteria caught on the membrane by smashing apart

their membranes.

Even more significantly, Wang and his colleagues found

that they were also able to break apart the sequences of

DNA responsible for making bacteria resistant to antibiotics.

When they tested wastewater before and after being

run through the photocatalytic membrane, they found up

to 1,000 times fewer copies of the antibiotic resistance genes

in the filtered water (although this varied for different genes

and their locations within the cells). Genes called integrons,

that help bacteria pick up antibiotic resistant genes, were

also found to be degraded.

They further tested the ability of the membrane to remain

debris free, a property called antifouling. Although titanium-treated

membranes have much smaller holes than regular

PVDF membranes, the photocatalytic membranes can

clean themselves by breaking up trapped debris and bacteria

with UV light. Titanium oxide-treated membranes were

found to recover original flux much better than untreated

membranes.

Despite the promise of such technology, Wang remains realistic

about its implementation in wastewater treatment facilities

or in water treatment in the near future.

“This kind of surface coating is a little expensive. If we can

find some other method that is very cheap, routine, and easy,

it would be better for sure.” He further points out that some

wastewater is colored or opaque, blocking UV light from the

membrane. However, he sees a lot of potential for electrochemical

membranes, a closely related strategy not involving

UV light. While questions and barriers remain in regards

to the implementation and further study of membrane

electrochemical ultrafiltration, it’s also clear our microorganism

fisherman have made progress—bacteria beware.

PHOTOGRAPHY BY SOL BLOOMFIELD

Yale and Shandong University researchers develop a new method of

filtering antibiotic-resistant bacteria from wastewater using UV light

and a titanium oxide coated membrane.

10 Yale Scientific Magazine October 2018 www.yalescientific.org


ecology

NEWS

HIPPOPOTAMI AS ENGINEERS

Organic matter affects water characteristics

BY TIFFANY LIAO

IMAGE COURTESY OF CHRISTOPHER DUTTON

Hippos defecating in a pool that will eventually become a “hippo

pool” and drop DO levels in the river downstream.

Hippos may not be able to do math or solve complicated

physics equations, but it turns out that they play a major role

as engineers in the environment. A joint team of researchers

from Yale University and the Cary Institute for Ecosystem

Studies have focused on the downstream effects of organic

matter produced by hippopotami on the Mara River for the

past four years. They found that the hippopotami waste results

in drops in the dissolved oxygen concentration levels in

rivers, resulting in mass killings of the fish in the streams and

creating a significant impact on the ecosystem.

The researchers observed the Mara river over the span of

three years. During this time, there were 55 flushing flows,

events where hippo pools (pools full of hippo waste) are

washed downstream, decreasing dissolved oxygen (DO)

concentrations and potentially killing the fish in the stream.

Out of the 55 flushing flows, 49 had DO concentration

drops by 0.04-5.5 miligrams per milliliter (mg/L).

“Most organisms need a certain amount of oxygen and

when that oxygen concentration falls below 30% or generally

2mg/L, then those organisms can’t survive because metabolism

shuts down,” said David Post, Yale Professor of Ecology

and Evolutionary Biology and a researcher on the project.

The typical DO levels in a river is around six to eight

mg/L. The lowest drop of 5.5 mg/L left the DO concentration

at around 0.5-2.5 mg/L, which indicates a fish kill.

Next, the team of researchers investigated a possible correlation

between hippo waste and the DO drops. The project occurred

in three stages: small scale microcosm experiments, experimental

streams, and whole ecosystem simulation. In the

first stage, the scientists put hippo waste in bottles of water and

measured dissolved oxygen over time. They observed that DO

content decreased overtime. However, since the bottles of water

were only representative of still water, the team decided to make

experimental streams as they were more accurate to a moving

river, allowing for reiterations and cycling of the water. In the

experimental stream, there was a drop in DO levels and then a

recovery, which occurred 8-12 hours into the experiment.

In the last portion of the study, the team constructed a dam

and flushed a hippo pool downstream. Similar to the earlier

experiments, DO levels at the beginning dropped significantly,

but rose again in a matter of hours. To Post, most surprising

part was the fact that the results were so consistent.

“It was quite surprising and reassuring that the results all tell

the same story. It is not often that this happens in science.”

What shocked Dutton the most was the frequency of these

flushing flows and the speed of the recovery. “If you didn’t measure

the DO levels like we did throughout long periods of time,

you wouldn’t even know this happened because in the span of

12 hours, the river is back to normal and the fish killed would all

be eaten by scavengers so no trace would be left,” said Dutton.

The extent of the effects of flushing events have only been

researched recently, but the repercussions on the environment

are extensive. The Mara is an important area for tourism

and sustaining the wildlife of the river is important. If

these flushing flows significantly shift the food chain by killing

the fish population, both the wildlife and the economy

could suffer. At the same time, fish kills could actually benefit

the rest of the ecosystem by providing food for scavengers.

“The nutrients of the river could be put back into the

ecosystem on land as the scavengers eat and defecate.

This life and death process is happening everywhere and

it is a fascinating system,” said Post.

Just as humans deposit waste into streams and rivers, degrading

our ecosystem, animal waste can affect wildlife and habitats.

However, this does not mean the waste humans produce is good

for the environment. Post emphasizes that humans create longterm

oxygen depletion whereas animals like hippos only create

periodic oxygen depletion. Essentially, human waste and animal

waste have effects on different time scales. So humans, don’t use

this as an excuse the next time you drop trash into the ocean.

PHOTOGRAPHY BY MICHELLE BARSUKOV

Yale researcher David Post holds a syringe system made up of light

meters for sample collection.

www.yalescientific.org

October 2018

Yale Scientific Magazine

11


PASS

THE

LIPIDS

UNCOVERING THE LINK BETWEEN LIPID

TRANSPORT & NEURODEGENERATIVE DISEASE

BY STEPHANIE SMELYANSKY | ART BY SUNNIE LIU


FOCUS

cell biology

The fundamental building block of life

is the cell, but that doesn’t mean that cells

themselves are static members of a bigger

being. Rather, cells are like tiny little factories

that perform specific tasks and manufacture

different products: fat cells metabolize

lipids, red blood cells carry oxygen,

muscle cells expand and contract to move

your body. To achieve all these remarkable

functions, however, subcellular compartments

within the cell, called organelles,

must work synergistically. Just like workers

in a factory, organelles need to be able

to communicate and exchange goods with

one another, yet exactly how these organelles

communicate is still a matter of much

debate. Researchers at Yale University in the

De Camilli and Reinisch labs tackled part of

this question by identifying the role that a

certain family of proteins plays in lipid exchange

between different cellular organelles.

The two labs focused on the VPS13 family

of proteins, which coordinate lipid transfer

between the endoplasmic reticulum (ER),

the organelle where proteins and lipids are

made, and other organelles that have lipid

membranes such as the mitochondria. The

researchers found that VPS13 proteins coordinate

lipid transport in two ways: first, by

bringing the organelles closer together like a

cellular tether, and second, by transporting

lipids themselves in a special lipid storage

cavity. What makes this group of proteins so

noteworthy is the devastating consequence

that occurs when they break—deletion or

mutation to any of the VPS13 proteins is implicated

in several neurodegenerative diseases

including Parkinson’s disease.

Lipids: building walls inside the cell

Lipids are an essential building blocks of

the cell. While functionally diverse, all lipids

share a similar structure composed of

a fatty acid chain capped with a polar or

charged head group. Like oil in water, lipids

don’t dissolve in aqueous solutions

because the fatty acid group is hydrophobic,

or “water fearing.”

However, the polar

head group can

interact with

water because

water is also a polar molecule. This

causes lipids to spontaneously assemble

into bilayers in the water-based environment

of cells, with the hydrophobic fatty

acid chains pointing towards the center of

the bilayer and the polar head groups on

the outside. As a result, the hydrophobic

parts of the lipids are protected from the

aqueous solvent by the polar head groups.

Lipid bilayers are the basic component of

cell membranes and organelle membranes,

and hence play a crucial role in cell biology.

For example, the cell membrane helps

prevent the insides of cells from leaking out

or unwanted substances from the extracellular

environment from penetrating in.

Within cells, membranes are used to isolate

different metabolic processes, particularly

processes that generate or use molecules

that are toxic to cells.

Cells constantly build new membrane and

recycle old membrane to maintain metabolic

demands. This creates a need for cells to

be able to transport lipids to different compartments.

One way of doing this consists of

lipids moving from one location to another

on their own by assembling into structures

called vesicles. Vesicles are enclosed bits or

“bubbles” of cell membrane. When the vesicle

“bubble” reaches the target organelle, it

fuses with the target membrane, creating an

internal cavity through which the lipids can

be transported to the target location without

ever being exposed to the cytosol, or the liquid

inside cells. This is achieved by special

transport proteins that bring lipids from one

specific organelle to another.

From letters to emails: Evolution

of communication

Cells constantly

need new

lipid membranes to grow and divide; therefore,

it is incredibly important to understand

the mechanisms by which specific organelles

exchange lipids. Unfortunately, much is

still unknown about the proteins that mediate

lipid transport in different types of cells

from different organisms. Marianna Leonzino,

a postdoctoral fellow in the De Camilli

lab and the first author of the study, was curious

about lipid transfer in human neurons.

“One thing that we didn’t know in humans

is how two specific organelles were talking

to each other, and these organelles were the

endoplasmic reticulum and the mitochondria,”

Leonzino said.

In lower order organisms, like yeast, this

pathway is well characterized: a protein

complex called ERMES mediates lipid transfer

between the endoplasmic reticulum and

the mitochondria. However, ERMES doesn’t

exist in higher level organisms like mammals—somewhere

along the path of evolution,

ERMES was lost. “For me, that was a super

intriguing question: why would we lose

something along evolution that seems to be

so fundamental?” Leonzino said. This led her

to hypothesize that maybe there was another

group of proteins fulfilling the role that

ERMES plays in yeast. “There must be

something else that works better,

that we maintained,”

Leonzino added.

13 Yale Scientific Magazine October 2018 www.yalescientific.org


Eventually,

Leonzino

arrived at the VPS13

family of proteins. Two

and a half years ago, when she

began working on the project, little

was known about VPS13 proteins, especially

their role in lipid metabolism. Previous

studies on yeast, which have both ER-

MES and VPS13 proteins, demonstrated

the functional similarity of VPS13 and ER-

MES—while deletion of ERMES had no effect

on the yeast, deletion of both ERMES

and the VPS13 proteins killed the yeast,

suggesting that VPS13 proteins play a similar

role to ERMES. On the biomedical side,

several mutations in the VPS13 family were

known to occur in neurological diseases like

chorea acanthocytosis, a Huntington’s-like

disease, and Cohen syndrome. Combined,

studying the role of VPS13 proteins seemed

like a promising start to figuring out how organelles

transfer lipids, and what can happen

when that process goes awry.

VPS13: the missing link between mitochondria

and the ER

In their study, Leonzino and her colleagues

focused specifically on VPS13A, the protein

implicated in chorea acanthocytosis, and VP-

S13C, the protein associated with Parkinson’s.

They began by studying the role of these proteins

in fibroblasts, a type of cell found in connective

tissue in animals. “[Fibroblasts] can

be a good proxy to understand what the basic

role of these proteins are,” Leonzino said.

They found that the two proteins are located

in

a r e a s

w h e r e

organelles

are close together,

known as contact sites.

The VPS13 proteins act as tethers

between the organelles to keep

them close together while mediating lipid

transport. One side of each VPS13 protein

contains a conserved binding region

that tethers it to the endoplasmic reticulum,

while the other side contains a specific

binding region for another target organelle,

which is the endosome for VPS13C

and the mitochondria for VPS13A.

Structural biology studies of the VPS13

proteins in the Reinisch lab also showed that

the VPS13 proteins contain a large hydrophobic

cavity meant for transporting lipids.

Unlike other lipid transport proteins which

can fit only one lipid molecule at a time, the

VPS13 proteins can transport lipids in bulk

due to the sheer size of their hydrophobic

cavities. Interestingly, all of the VPS13 proteins

are incredibly similar structurally, with

minor differences in the binding regions that

target them to specific organelles, yet they

don’t seem to perform redundant functions.

A key implication of this study is that defects

in lipid transfer in cells can cause serious neurodegenerative

diseases, which was previously

unknown. According to William Hancock-Cerutti,

a graduate student in the De Camilli lab,

ABOUT THE AUTHOR

s o

little is

known about

the cellular basis

behind neurodegenerative

disease that it’s hard to

pinpoint individual proteins within

individual metabolic processes as the

source of disease. “It’s striking that there is this

family of four proteins that are all structurally

similar, so presumably have some overlap in

function, and they all cause neurological diseases,

but they all cause different neurological

diseases,” Hancock-Cerutti said.

However, despite the strong correlation

between VPS13 mutations and neurodegenerative

disease, there is still a long way to

go before any of this can be developed into

a useful therapeutic strategy. “I think we’re

still a long way away from thinking about

therapeutic implications given that the field

has so little understanding of where to intervene

therapeutically to slow or halt these

diseases.” Hancock-Cerutti said. Leonzino

agrees, saying that there is still a lot to figure

out behind the basic cell biology.

According to Leonzino, the next step is

to replicate these results in neurons. This is

more complicated, since mutations or deletions

of the VPS13 proteins in neurons

should lead to cell death as observed in neurodegenerative

disease. But there are a lot of

interesting questions to be answered on the

horizon. “We will try to better identify the

steps of the pathogenesis, how you go from

not having that lipid transfer to later having

neurons die,” Leonzino said. “Even though

these diseases are all pretty early onset, early

onset for neurodegenerative disease is

anywhere from your twenties to forties, so

it takes time for neurons to die. We will try

to figure out what happens in that time,”

Leonzine concluded.

STEPHANIE SMELYANSKY

STEPHANIE SMELYANSKY is a senior in Timothy Dwight College majoring in Molecular Biophysics

and Biochemistry and Chemistry. She is the current managing editor of the Yale Scientific

Magazine. Outside of her magazine responsibilities, Stephanie performs chemical biology

research in the Slavoff Lab and sings with the Yale Glee Club.

THE AUTHOR WOULD LIKE TO THANK Dr. Pietro De Camilli, Dr. Marianna Leonzino, and William

Hancock-Cerutti for their time and energy.

FURTHER READING

[1] Ah, M.; Kormann, B. The ERMES complex and ER-mitochondria connections. Biochem Soc. Trans.

40(2), 445-450, 2012. [2] Kumar, N. et al. VPS13A and VPS13C are lipid transport proteins differentially

localized at ER contact sites. J. Cell Biol. Aug, 2018.

www.yalescientific.org

October 2018

Yale Scientific Magazine

14


medicine

FOCUS

If you have ever been bitten by a mosquito, you

might already know that the red bump on your skin is

your body’s immune response to the injected mosquito

saliva. It turns out that when mosquitoes land on

you, they salivate while searching for a blood vessel

and then penetrate the skin with their needles. Unfortunately,

when a mosquito has been infected with

Plasmodium parasites, these parasites are transported

along with mosquito saliva into the animal host, ultimately

leading to malarial infection.

Mosquitoes have become an increasingly dangerous

global threat—particularly in tropical or humid climates,

where they not only thrive best but also transmit

numerous viral, bacterial, and parasitic diseases

including malaria and Zika. According to the World

Health Organization, malaria remains a major global

epidemic, with more than 200 million cases across 91

countries in 2016, but most occurring within sub-Saharan

Africa. Although malaria had been eliminated

in the United States in the 1950s, the CDC estimates

that there are roughly 1,700 annual diagnoses of malaria

across the country, a high incidence rate considering

the severity of the disease. Since Plasmodium

parasites enter an animal host during mosquito blood

feeding, targeting the mosquito’s saliva appears to be

one of the most plausible methods of preventing malaria

and developing new antimalarial therapies.

However, the relationship between mosquito saliva

and Plasmodium infection is disputed. While mosquito

saliva has previously been believed to enhance pathogen

transmission, recent studies suggest that saliva could

provide the host protection from Plasmodium infection.

Tyler Schleicher and Jing Yang recently co-authored a

paper in Nature Communications with Erol Fikrig’s

lab at the Yale School of Medicine that analyzed

the ability of a specific mosquito salivary

gland protein to decrease Plasmodium

speed and movement. Because Plasmodium

parasites are some of the

fastest microbes known, proteins

that can impede their

speed have tremendous

potential for

antima-

novel

larial therapies.

BY ANNA SUN

ART BY LAUREN GATTA

SECRETS OF

MOSQUITO SPIT

salivary gland protein mosGILT has

anti-malarial therapuetic potential

www.yalescientific.org

October 2018

Yale Scientific Magazine

15


FOCUS

medicine

PHOTOGRAPHY BY KATE KELLY

The basics of malaria transmission

The biological carrier responsible for transmitting

malaria is the infected female Anopheles

mosquito, which delivers Plasmodium parasites

into the skin of a host while also injecting its saliva.

Sporozoites, a term for the infectious stage

of the Plasmodium parasite life cycle, must then

locate a nearby blood vessel in order to travel to

the host liver and invade hepatocytes, or liver

cells, thus establishing malaria infection. While

navigating through the body, these sporozoites

possess the ability to enter and maneuver within

host cells as well as bypass the host immune

system. This dynamic process of cell traversal

therefore makes it difficult to catch the sporozoites

once they have entered the dermis. “We

are interested in the [Plasmodium] transmission

stage…because blocking establishment of

malaria at this earliest point represents a target

that might present a better opportunity than

treating the disease at the point when it progresses

to millions of parasites in the bloodstage,”

Schleicher said.

The secreted saliva serves to prevent blood

clotting and inflammation and thus better facilitate

the blood meal for the mosquito. However,

the array of proteins present in the saliva may

also affect pathogen transmission by promoting

pathogen survival or inhibiting their motility in

the body. “Analyzing individual components of

mosquito saliva allows for better characterization

of novel protein-pathogen interactions,”

Yang said. The researchers purified

Plasmodium sporozoites from

Anopheles

mosquito

saliva and identified

a

specific salivary gland protein that is directly

involved with sporozoite transmission: a mosquito-equivalent

of human gamma interferon

inducible thiol reductase (GILT) protein, called

mosGILT, that binds to the sporozoites and

partially inhibits their movement. In humans,

GILT is involved in protein unfolding as well

as antigen processing. Because the interaction

between the mosGILT protein and sporozoites

is similar for different species of Plasmodium,

the researchers used both human pathogen

Plasmodium falciparum and the rodent parasite

Plasmodium berghei to study the inhibitory

properties of the mosGILT protein on parasite

transmission. “It is important to know from our

work that we provide evidence that the interaction

between mosGILT and sporozoites occurs

in both species of the parasite, suggesting this

is a conserved interaction,” Schleicher emphasized.

The inhibitory nature of mosGILT protein

MosGILT is roughly twenty percent identical

to both the human and mouse GILT, which is a

useful measure for comparing protein function

between the species. Conservation of key amino

acid sequences suggests some similarity in

the catalytic regions among the GILT proteins.

However, the overall percent identity is low, and

identical protein residues do not necessarily indicate

the same protein activity. “In fact, the

C-terminus is extended in mosGILT compared

to the human and mouse equivalents, and when

this portion is deleted, the mosGILT does not

inhibit the motility of Plasmodium parasite as

before, indicating that the C-terminus sequence

is very important for the inhibitory ability of

the protein,” Schleicher added.

Although the exact interaction between

mosGILT and sporozoites remains unclear,

the researchers also discovered

that mosGILT levels

are high in the

mosquito

sal-

“We

hope

to develop

more effective

treatments against

mosquito-borne diseases.”


medicine

FOCUS

ivary gland, but it was not discernible in

the saliva itself. “We don’t know how the

mosGILT protein binds to the Plasmodium

sporozoite, but our experiments with

immunofluorescence staining and microscopy

studies have shown us that mos-

GILT binds to the surface of the parasite,”

Yang said. With these pieces of data, the researchers

concluded that the mosGILT and

sporozoite interaction begins in the salivary

gland of the mosquito at the sporozoite

surface, and then mosGILT is carried

from the gland and released with the saliva

and sporozoites into the host.

The sporozoites are still alive

After sporozoite invasion of the hepatocytes,

exoerythrocytic forms (EEF) develop

and each release merozoites, the next

stage of the Plasmodium life cycle. “Merozoites

can invade red blood cells, leading

to the blood-stage of the malaria infection

and the clinical symptoms associated with

malaria, such as chills and fever,” Yang explained.

Since cell traversal and consequent evasion

from the host immune system allow

the parasites to survive in the body, the researchers

also wanted to demonstrate that

mosGILT did, in fact, negatively impact

the sporozoite cell traversal activity. They

incubated rGILT, or purified recombinant

mosGILT, together with sporozoites and

observed significantly reduced cell traversal

activity. Additionally, pre-incubating

hepatic cells and skin fibroblasts with

rGILT did not lead to any indirect inhibition

of cell traversal, further confirming

that rGILT directly interacts with the sporozoites

to reduce cell traversal and motility

in the host.

However, sporozoite viability was not directly

affected when treated with rGILT in

vitro. Instead, the percentage of EEF-positive

liver cells increased, suggesting that the

sporozoites had continued to infect the hepatocytes.

“The viability assay in our paper

was direct evidence that rGILT does not

directly kill sporozoites or is immediately

toxic to them…because [otherwise]

we would expect the EEFs to

decrease, as the sporozoites

would

be dying

and not healthy enough to infect hepatic

cells in culture,” Schleicher stated.

Future directions

The study’s findings that salivary gland

protein mosGILT partially inhibits Plasmodium

sporozoite motility and cell traversal

has great consequences for the understanding

of malaria transmission and development

of new treatments. Next steps for

the researchers include a similar attempt

to identify the molecule on the surface of

the sporozoites to which mosGILT binds.

“If we are able to find the binding partner

of mosGILT, we can better understand the

mechanism of how mosGILT inhibits sporozoite

motility through cell traversal and

the overall reduction of speed,” Schleicher

said.

The researchers have already begun work

to create mosGILT knockout mosquitoes

using the CRISPR/Cas9 technique in order

to study the mosGILT-sporozoite pathway.

Furthermore, this research on mosGILT

will aid the development of novel antimalarial

therapies—perhaps through experimental

manipulation of mosGILT activity

or structure, or by synthesizing a new protein

with a similar but more efficient inhibitory

function. The researchers also understand

the significance of their research to

global health. “Our research not only applies

to the Anopheles mosquito and malaria,

but also to other mosquitoes that transmit

notable viruses including Zika, and we

hope to develop more effective treatments

against mosquito-borne diseases,” Schleicher

said. With these results, Schleicher

and Yang are making progress toward uncovering

the secrets of mosquito spit.

ABOUT THE AUTHOR

ANNA SUN

ANNA SUN is a Molecular, Cellular and Developmental Biology major in Jonathan Edwards

College ‘21. She hopes to study the interaction between technology and medicine in order to

improve healthcare. Besides writing for the Yale Scientific Magazine, she is also involved in the

MCDB Student Advisory Committee at Yale and dances with Danceworks. In her free time, she

loves to spend time with her friends discovering the food scene in New Haven.

THE AUTHOR WOULD LIKE TO THANK Jing Yang and Tyler Schleicher for sharing their time and

enthusiasm about their research.

FURTHER READING

Schleicher, T. R, et. al.. “A Mosquito Salivary Gland Protein Partially Inhibits Plasmodium Sporozoite Cell

Traversal and Tramission.” Nature Communications 9, no. 1 (July 25, 2018).

www.yalescientific.org

October 2018

Yale Scientific Magazine

17


UNDERSTANDING A NEW IMAGING

TECHNIQUE ESSENTIAL FOR THE

FUTURE OF ALZHEIMER’S TREATMENT

A LOOK INTO

ALZHEIMER’S

B Y L A U R E N K I M

ART BY LILIANE TRAN

www.yalescientific.org

Octoberl 2018

Yale Scientific Magazine

15


FOCUS

neuroscience

Alzheimer’s is everywhere. 5.5 million

people are affected by this disease, and

this number is predicted to double by

2050. The fear associated with Alzheimer’s

has grown steadily with its rising media

popularity, elevating Alzheimer’s research

and education to an urgent level of importance.

Due to gaps in our understanding

of Alzheimer’s and an even greater lack

of effective methods for evading its onset,

studies on Alzheimer’s can be unscientific

and speculative—exercise more, improve

your diet, read more books. Maybe you

forgot where you put your keys, or took

two more minutes to find your parked car.

Is this merely a forgetful moment or a sign

of early symptoms?

One thing is for certain—the chances of

an Alzheimer’s diagnosis increases with

age. Fear of the unknown is understandable

when there is so much uncertainty

surrounding the nature of this disease.

Research by a group at Yale might alleviate

some of this anxiety. The group has developed

a new imaging technique for measuring

synaptic density in the brain and may

be able to catch Alzheimer’s early. Besides

being a technique for tracking Alzheimer’s

as it progresses, this method could be used

to evaluate reliable drug treatments–giving

hope and confidence to a disease shrouded

in fear and uncertainty. “We think this is

a useful biomarker for evaluating therapy,

and this will hopefully trigger more drug

development,” claims Ming-Kai Chen, a

member of the Yale research team.

Detecting Alzheimer’s: What a sick brain

looks like

Alzheimer’s causes many changes in

brain tissue that contribute to cognitive

decline. Yet, early detection is difficult

due to lack of reliable methods for differentiating

between the biological changes

associated with normal aging and early

pathologic symptoms. One known method

for early detection of Alzheimer’s is

measuring an amyloid protein that accumulates

and forms plaque in the brain.

By forming deposits of plaque, amyloid

may cause inflammatory responses that

AlZHEIMER’S IS

EVERYWHERE. 5.5

MILLION PEOPLE ARE

AFFECTED BY THIS

DISEASE, AND THIS

NUMBER IS PREDICTED

TO DOUBLE BY 2050.

PHOTOGRAPHY BY XINYUAN CHEN

The new imaging technique uses PET machines

to detect the amount of protein SV2A, a

method for directly measuring synaptic density

in the brain.

lead to cognitive decline.

Yet the accumulation of amyloid plaque is

also characteristic in the process of normal

aging, leading to the possibility of false positives

and unnecessary stress in normal aging

adults. “The challenge is the idea that amyloid

may accumulate decades before symptoms,”

said Adam Mecca, another member

of the Yale research team. Another biomarker

for Alzheimer’s is a protein called tau. Accumulation

of this protein forms neurofibrillary

tangles, which are toxic for the brain. In

addition to amyloid plaques and neurofibrillary

tangles, Alzheimer’s is characterized by

synaptic loss leading to cognitive decline.

“Amyloid deposits do not correlate well with

cognitive impairment, whereas synaptic

density may,” Chen added.

Synaptic connections and Alzheimer’s

Synapses are connections made between

nerve cells, so finding a direct way to measure

synaptic density would provide a way

to track the number of connections in the

brain. Such a technique would be an important

resource for detecting Alzheimer’s early,

tracking its progression, and developing

treatments. The mechanism for this disease

remains unknown, but detection of these

synapses in Alzheimer’s patients proves that

there are many related parts that contribute

to the cognitive decline of this disease.

Until now, the effects of Alzheimer’s

on synaptic density were measured only

after death. Yet the Yale research group

found a new method for detecting these

changes in patients with Alzheimer’s disease:

imaging the protein SV2A in the

brain. SV2A is a synaptic vesicle membrane

protein that regulates neurotransmitter

release. Neurotransmitter release

is how communication between neurons

19 Yale Scientific Magazine October 2018 www.yalescientific.org


PHOTOGRAPHY BY XINYUAN CHEN

Researchers and doctors can now read PET images

to directly measure cognitive decline using the

tracer 11 C-UCB-J to measure protein SV2A and

identify the synaptic density in the brain.

occurs. With the development of SV2A-

PET imaging, researchers are now able

to measure synaptic connections in the

brains of living humans using tracers that

bind to this protein.

Because the measurement of SV2A can

indicate synaptic density and synaptic loss,

it can be used to measure cognitive decline.

Researchers used a radioactive tracer,

called 11C-UCB-J, that binds to the SV2A

protein, and set out to compare whether

tracer binding of SV2A could be used as

a quantitative measure of synaptic density.

These measurements were taken using Positron

Emission Tomography (PET) scans,

an imaging test that uses radioactive tracers

to detect targeted areas in the body. PET

scans of patients injected with radioactive

tracer 11C-UCB-J can detect SV2A and

show how much is present.

Researchers found that patients affected

by Alzheimer’s had a reduced amount of

the tracer binding to SV2A in the hippocampus,

a region of the brain involved with

memory. This may be confirmation that the

cognitive decline of Alzheimer’s is directly

related to a reduction of synaptic density.

Furthermore, the measurement of protein

SV2A will help to evaluate changes in

synaptic density overtime. This may lead to

early detection of disease and faster drug

development. “There is so much variability

in this disease–in the way it progresses

and in the exact types of symptoms people

have,” Mecca said.

Prevention

Current medications for Alzheimer’s do

not stop the progression of disease and have

only a modest effect. “We do not recommend

early treatment right now with current medications

since there is no evidence that they

help during early disease stages,” said Mecca.

In addition, the potential benefit must be balanced

with the possible negative side effects

associated with medication use. For some patients,

current medications are more of a burden

than an aid. “Once the patient has lost

a lot of synaptic density, it may be too late,”

Chen said. As a result, future treatments may

need to begin as early as possible. The earlier

that experimental treatments may begin, the

better chance there is for it to work.

Though amyloid PET is a great tool for detecting

early signs of disease, and identifying

a high-risk population, these scans are not

helpful without effective preventive treatment.

“People are very knowledgeable, [and] if they

feel like they have something, they will find a

specialist to check if it is really cognitive decline

or just their anxiety,” Chen said. In this way, education

for detecting Alzheimer’s symptoms

is necessary, and self-awareness–differentiating

between accidentally forgetting your keys

on the way to work and getting lost on the way

home after taking the same route every day for

three years–is very important.

In addition to drugs, Alzheimer’s patients

may be treated for neuropsychological

symptoms, such as depression, anxiety,

or irritability. Educating family members,

finding resources for support, and enrolling

in behavioral therapy are all methods for reducing

the progression of this disease. For

some, the neurodegenerative decline of Alzheimer’s

seems to occur much faster than

others. Those with a strong family history

for this disease are at a higher risk for developing

Alzheimer’s, but inherited genetic

ABOUT THE AUTHOR

neuroscience

PHOTOGRAPHY BY XINYUAN CHEN

Dr. Mecca, a member of the Yale research team, is

pictured in front of PET images of the brain, which

exhibit the differences in synaptic density between

a normal adult and an Alzheimer’s patient.

Alzheimer’s from a single gene mutation is

extremely rare. “[Alzheimer’s] is an unavoidable

disease unless you can really find what

the cause for this disease is,” Chen said.

The research team hopes to increase the

number of participants in this study and

collaborate with other Alzheimer’s research

teams to better study the measurement of

synaptic density and cognitive decline–especially

how synaptic density changes over time.

In addition to studying synaptic density, these

researchers are pursuing other projects to further

explore the impact of other proteins and

signals in the brain that contribute to Alzheimer’s.

One project aims to use tracers to

identify a relationship between neurofibrillary

tangles and patterns of synaptic density.

“There is a lot we can do to characterize this

disease, and also some goals for developing

tools that can help us to do good clinical trials

to find disease cures,” Mecca said. The future

of Alzheimer’s research is a positive one. With

a better understanding for the mechanisms

of this disease, there is a greater chance at detecting

Alzheimer’s disease early and slowing

its progression–and maybe even preventing it

from ever occurring.

LAUREN KIM

LAUREN KIM is a sophomore prospective Neuroscience major in Timothy Dwight College. She has

been writing for the Yale Scientific since her freshman year. She also volunteers at Yale New Haven

Hospital in the Elder Horizons program and is a member of Yale’s varsity fencing team.

THE AUTHOR WOULD LIKE TO THANK Ming-Kai Chen and Adam Mecca for their time and

enthusiasm for sharing their research.

FURTHER READING

Chen, Ming-Kai, Adam P. Mecca, et al. “Assessing Synaptic Density in Alzheimer Disease With Synaptic

Vesicle Glycoprotein 2A Positron Emission Tomographic Imaging.” JAMA Neurology 75, no. 10 (2018):

1215. doi:10.1001/jamaneurol.2018.1836.

FOCUS

www.yalescientific.org

October 2018

Yale Scientific Magazine

20


FOCUS

applied physics

L U M

On June 10, 2000, hundreds of thousands of

eager pedestrians traversed the newly opened

London Millennium Footbridge. However,

as more and more pedestrians filtered across,

the bridge started to sway. Panicked, they

shifted their weight in the opposite direction

to counteract the oscillations. Yet, the pedestrians’

synchronous efforts only compounded

the swaying, and the amplitude of the bridge’s

oscillations increased. The problem became so

severe that the Millennium Bridge had to be

closed later in the day, only to be reopened two

years later, fitted with a $6-million damping

system designed to counteract this effect.

Extensive analysis led engineers to conclude

that resonance, the phenomenon in which

an external force with a particular frequency

amplifies existing oscillations, was behind

the dramatic movements of the Millennium

Bridge. But resonance can be useful, especially

when it comes to laser energetics. At Yale,

a team of physicists from Professor Peter Rakich’s

lab developed a new silicon-based laser

that uses resonant sound waves to amplify

light, representing a milestone in the field of

silicon photonics.

What is silicon photonics?

The field of photonics emerged with the

invention of the laser in 1960. In traditional

lasers, light of a specific frequency is emitted

by pumping atoms into an excited state,

leading to “laser gain.” When the increase

in energy reaches a certain threshold, lasing

occurs. The next big development in information

technology was optical fibers, which

transmit light signals through a glass core.

Light can encode more information in its

wave properties than electrons, with little

loss over thousands of miles.

However, optical devices used to process

optical signals are often bulky, spanning entire

table tops. Today, silicon-based photonics

offers the promise of miniaturizing these

systems onto single chips. Rakich believes

that silicon photonic systems can revolutionize

optics similar to how transistors revolutionized

the digital age by eliminating the

need for rooms full of vacuum tubes. More

importantly, silicon is a naturally abundant

element with a massive preexisting processing

infrastructure, serving the $400 billion

semiconductor industry. “If you’re building

things out of silicon, as a friend of mine

used to say, ‘You’re riding the silicon freight

train,’” Rakich said. However, it has proved

difficult to produce a laser based purely on

silicon—due to certain intrinsic material

properties, silicon is not predisposed to provide

laser gain. Silicon optical waveguides,

which are structures which guide light

waves in the medium, suffer from significant

dissipation of energy that could otherwise

have contributed to laser gain.

Stimulated Brillouin scattering in silicon

The new silicon system uses resonantly-driven

sound waves to provide the requisite laser

gain. It parallels the Millennium Bridge phenomenon,

with silicon as the bridge and light

waves as the pedestrians. Just as pedestrians

walking at a particular frequency caused the

bridge to oscillate, input light, also known as

“pump light,” generates elastic waves, commonly

known as sound, when oscillating at the natural

frequency of silicon. Here, the researchers

saw an opportunity to exploit a phenomenon

called Brillouin scattering, in which the resulting

sound waves in turn interact with the light,

moving some light energy into a lower-frequency

output channel. The process is self-amplifying—the

stronger the sound waves, the more

sound-light interaction, and the more energy

pouring into the output channel—to the point

where the sufficient gain for lasing is achieved.

But Brillouin scattering had never been

observed in silicon. It requires a “hybrid”

waveguide that can confine both light and

sound waves to the same region in silicon,

enabling their Brillouin interaction. This is

a difficult problem due to the structure of

silicon chips, which have a semiconducting

silicon layer atop a layer of silica—the oxidized

form of silicon. Light waves naturally

confine themselves to silicon, but sound

waves spontaneously dissipate their energy

down into the silica layer.

To address this problem, the Rakich group

devised a “suspended” waveguide that encompasses

a ridge along the center of the

silicon layer to conduct light waves, as well

as slots on a micrometer scale punched uniformly

along the sides of the ridge. These

form “hard boundaries” off which sound

waves can bounce, forcing them to stay within

the top silicon layer. The researchers then

wrapped the linear waveguide back on itself,

A N E L E C T R I C U N I O N

creating a “racetrack” for the waves to circulate

and amplify, leading to enough laser gain

to offset the energy loss and produce Brillouin

lasing in silicon for the first time.

Unique Brillouin behavior

The first of its kind, the new system does not

behave like a conventional Brillouin laser. Traditional

Brillouin lasers absorb light noise from

the input pump wave, so that the emitted light

becomes spectrally purified. In this system, however,

the emitted light was spectrally identical to

the pump light. Instead, output sound became

spectrally purified. For this new regime of Brillouin

lasing, the researchers had to construct a

new theoretical framework to understand it. “It

was all very different, very new physics,” said Nils

Otterstrom, lead author of the paper.

This system embodies original design concepts

that are important for Brillouin lasing in

& H E

21 Yale Scientific Magazine October 2018 www.yalescientific.org


applied physics

FOCUS

E N S

general. For one, it exhibits forward Brillouin

scattering, in which the output wave is emitted

in the same direction as the pump wave, due to

the hybrid nature of the waveguide. Conventionally,

if one were to pump light into a Brillouin-active

system, the output wave would

“rebound” back out of the system, interfering

with the input. Decoding such light output

from the input requires devices called circulators,

which have yet to be developed in silicon

photonic circuits. Forward scattering sidesteps

this problem—the new design concept makes

integration of Brillouin lasers into chip-scale

systems practical for the first time.

Secondly, properties of conventional Brillouin

lasers are dictated by the material from

which the waveguide is made. That is, for every

new laser frequency required, researchers

would have to make lasing occur in a new

material. As evidenced from this study, this

is hardly a trivial problem. In this system, a

range of frequencies can be produced by simply

varying the width separating the air slots

on the waveguide. “You could say, ‘I want this

oscillation to happen at these specific frequencies,’

and we can crank out a device that

does that. So it’s a very versatile design,” Rakich

said. The wide range of laser frequencies

potentially accessible would enable even more

fine tuning of silicon-based laser systems.

Thirdly, the system does not suffer from cascading,

a phenomenon observed in conventional

Brillouin lasers. Otterstrom compares

cascading to transferring water from one bucket

to another. A laser system involves transferring

water, or energy in this analogy, from a

pump bucket into the output bucket. Cascading

occurs when the output bucket has a hole

leaking into another bucket, generating a secondary

Brillouin laser. “We have been able to

plug the hole in the first bucket so we can get an

optimal amount of power into it,” Otterstrom

said. More power means a purer output laser.

Looking forward

The silicon Brillouin laser has important

applications due to its pure sound output and

unique lasing properties. Rakich and Otterstrom

call sound waves the “unsung heroes of modern

technology.” This is because the highly precise

clocks that are integral in global positioning systems

(GPS) and computers use sound waves to

keep time. Spectrally clean sound output from a

silicon chip would go one step further in miniaturizing

these timekeeping systems. Moreover,

lasers are currently used in high-precision gyroscopes

on aircraft, where rotation results in detectable

phase changes in the light wave. “Maybe

someday we will get to a state of refinement

where devices on a chip like this could be cheaper,

smaller, more efficient than a fiber-based device.

But there is more work to be done,” Rakich

said. One of the more immediately accessible

improvements is to increase the energy transfer

efficiency mediated by Brillouin scattering.

For Rakich, the most rewarding part of this

result is not what the new silicon system promises,

but the needs-driven scientific approach it

demonstrates. The development of the silicon

laser was motivated by thinking hard about the

problem and determining the properties it demanded,

before choosing the best material for

the problem. “To me, what's more exciting about

this result is that we took something that by all

conventional wisdom shouldn’t have the [Brillouin]

effect, we've made a laser out of it, and we can

[use this approach] for any material,” Rakich said.

O F L I G H T A N D S O U N D

In any case, by uniting photonics with semiconductor

electronics, this new Brillouin laser

provides a powerful route to customize onchip

light in silicon-based optical circuits. It

provides a glimpse into a yet remote but possible

future in which computers run on light.

PHOTOGRAPHY BY CHUNYANG DING

Silicon-based laser apparatus in the Rakich Lab.

ABOUT THE AUTHOR

MARCUS SAK

MARCUS SAK is a sophomore majoring in Chemistry in Trumbull College. He is Copy Editor for

the Yale Scientific Magazine. He also works in Prof. Scott Miller’s lab, currently studying peptidecatalyzed

atroposelective naphthol-quinone couplings.

THE AUTHOR WOULD LIKE TO THANK Nils Otterstrom for an enthusiastic and thorough discussion

of the work featured in this piece, and Prof. Peter Rakich for taking time to share his research and

vision.

FURTHER READING

Otterstrom et al., “A silicon Brillouin laser”, Science (360), 1113–1116 (2018)

A R T B Y E L I S S A M A R T I N

www.yalescientific.org

October 2018

R T Z

Yale Scientific Magazine

22


FOCUS

materials science

On June 10, 2000, hundreds of thousands of eager

pedestrians traversed the newly opened London

Millennium Footbridge. However, as more

and more pedestrians filtered across, the bridge

started to sway. Panicked, they shifted their weight

in the opposite direction to counteract the oscillations.

Yet, the pedestrians’ synchronous efforts

only compounded the swaying, and the amplitude

of the bridge’s oscillations increased. The problem

became so severe that the Millennium Bridge had

to be closed later in the day, only to be reopened

two years later, fitted with a $6-million damping

system designed to counteract this effect.

Extensive analysis led engineers to conclude

that resonance, the phenomenon in which an

external force with a particular frequency amplifies

existing oscillations, was behind the dramatic

movements of the Millennium Bridge. But resonance

can be useful, especially when it comes to

laser energetics. At Yale, a team of physicists from

Professor Peter Rakich’s lab developed a new silicon-based

laser that uses resonant sound waves to

amplify light, representing a milestone in the field

of silicon photonics.

What is silicon photonics?

The field of photonics emerged with the invention

of the laser in 1960. In traditional lasers, light

POWERED

BY THE

SUN

23 Yale Scientific Magazine October 2018 www.yalescientific.org

H O W S U R F A C E

PROPERTIES OF IRON

ORE AFFECT SOLAR

FUEL EFFICIENCY

of a specific frequency is emitted by pumping

atoms into an excited state, leading to “laser

gain.” When the increase in energy reaches a

certain threshold, lasing occurs. The next big

development in information technology was

optical fibers, which transmit light signals

through a glass core. Light can encode more

information in its wave properties than electrons,

with little loss over thousands of miles.

However, optical devices used to process

optical signals are often bulky, spanning entire

table tops. Today, silicon-based photonics

offers the promise of miniaturizing these systems

onto single chips. Rakich believes that

silicon photonic systems can revolutionize

optics similar to how transistors revolutionized

the digital age by eliminating the need

for rooms full of vacuum tubes. More importantly,

silicon is a naturally abundant element

with a massive preexisting processing

infrastructure, serving the $400 billion semiconductor

industry. “If you’re building things

out of silicon, as a friend of mine used to say,

‘You’re riding the silicon freight train,’” Rakich

said. However, it has proved difficult to

produce a laser based purely on silicon—due

to certain intrinsic material properties, silicon

is not predisposed to provide laser gain.

Silicon optical waveguides, which are structures

which guide light waves in the medium,

suffer from significant dissipation of energy

that could otherwise have contributed to laser

gain.

Stimulated Brillouin scattering in silicon

The new silicon system uses resonantly-driven

sound waves to provide the requisite

laser gain. It parallels the Millennium Bridge

phenomenon, with silicon as the bridge and

light waves as the pedestrians. Just as pedestrians

walking at a particular frequency caused

the bridge to oscillate, input light, also known

as “pump light,” generates elastic waves, commonly

known as sound, when oscillating at

the natural frequency of silicon. Here, the

researchers saw an opportunity to exploit a

phenomenon called Brillouin scattering, in

which the resulting sound waves in turn interact

with the light, moving some light energy

into a lower-frequency output channel.

The process is self-amplifying—the stronger

the sound waves, the more sound-light interaction,

and the more energy pouring into the

output channel—to the point where the sufficient

gain for lasing is achieved.

But Brillouin scattering had never been ob-


materials science

FOCUS

IMAGE COURTESY OF WIKIMEDIA COMMONS

Raw hermatite is an important mined iron ore.

served in silicon. It requires a “hybrid” waveguide

that can confine both light and sound

waves to the same region in silicon, enabling

their Brillouin interaction. This is a difficult

problem due to the structure of silicon chips,

which have a semiconducting silicon layer atop

a layer of silica—the oxidized form of silicon.

Light waves naturally confine themselves to silicon,

but sound waves spontaneously dissipate

their energy down into the silica layer.

To address this problem, the Rakich group

devised a “suspended” waveguide that encompasses

a ridge along the center of the silicon

layer to conduct light waves, as well as slots on

a micrometer scale punched uniformly along

the sides of the ridge. These form “hard boundaries”

off which sound waves can bounce, forcing

them to stay within the top silicon layer.

The researchers then wrapped the linear waveguide

back on itself, creating a “racetrack” for

the waves to circulate and amplify, leading to

enough laser gain to offset the energy loss and

produce Brillouin lasing in silicon for the first

time.

Unique Brillouin behavior

The first of its kind, the new system does

not behave like a conventional Brillouin laser.

Traditional Brillouin lasers absorb light noise

from the input pump wave, so that the emitted

light becomes spectrally purified. In this

system, however, the emitted light was spectrally

identical to the pump light. Instead, output

sound became spectrally purified. For this

new regime of Brillouin lasing, the researchers

had to construct a new theoretical framework

to understand it. “It was all very different, very

new physics,” said Nils Otterstrom, lead author

of the paper.

This system embodies original design concepts

that are important for Brillouin lasing in

general. For one, it exhibits forward Brillouin

scattering, in which the output wave is emitted

in the same direction as the pump wave, due

to the hybrid nature of the waveguide. Conventionally,

if one were to pump light into a

Brillouin-active system, the output wave would

“rebound” back out of the system, interfering

with the input. Decoding such light output

from the input requires devices called circulators,

which have yet to be developed in silicon

photonic circuits. Forward scattering sidesteps

this problem—the new design concept makes

integration of Brillouin lasers into chip-scale

systems practical for the first time.

Secondly, properties of conventional Brillouin

lasers are dictated by the material from

which the waveguide is made. That is, for every

new laser frequency required, researchers

would have to make lasing occur in a new

material. As evidenced from this study, this is

hardly a trivial problem. In this system, a range

of frequencies can be produced by simply varying

the width separating the air slots on the

waveguide. “You could say, ‘I want this oscillation

to happen at these specific frequencies,’

and we can crank out a device that does that.

So it’s a very versatile design,” Rakich said. The

wide range of laser frequencies potentially accessible

would enable even more fine tuning of

silicon-based laser systems.

Thirdly, the system does not suffer from cascading,

a phenomenon observed in conventional

Brillouin lasers. Otterstrom compares

cascading to transferring water from one bucket

to another. A laser system involves transferring

water, or energy in this analogy, from a

pump bucket into the output bucket. Cascading

occurs when the output bucket has a hole

leaking into another bucket, generating a secondary

Brillouin laser. “We have been able to

plug the hole in the first bucket so we can get an

optimal amount of power into it,” Otterstrom

said. More power means a purer output laser.

A R T B Y R I C H A R D L I

ABOUT THE AUTHOR

Looking forward

The silicon Brillouin laser has important

applications due to its pure sound output and

unique lasing properties. Rakich and Otterstrom

call sound waves the “unsung heroes

of modern technology.” This is because the

highly precise clocks that are integral in global

positioning systems (GPS) and computers

use sound waves to keep time. Spectrally clean

sound output from a silicon chip would go one

step further in miniaturizing these timekeeping

systems. Moreover, lasers are currently used in

high-precision gyroscopes on aircraft, where

rotation results in detectable phase changes in

the light wave. “Maybe someday we will get to a

state of refinement where devices on a chip like

this could be cheaper, smaller, more efficient

than a fiber-based device. But there is more

work to be done,” Rakich said. One of the more

immediately accessible improvements is to increase

the energy transfer efficiency mediated

by Brillouin scattering.

For Rakich, the most rewarding part of this

result is not what the new silicon system promises,

but the needs-driven scientific approach it

demonstrates. The development of the silicon

laser was motivated by thinking hard about

the problem and determining the properties it

demanded, before choosing the best material

for the problem. “To me, what's more exciting

about this result is that we took something that

by all conventional wisdom shouldn’t have the

[Brillouin] effect, we've made a laser out of it,

and we can [use this approach] for any material,”

Rakich said.

In any case, by uniting photonics with semiconductor

electronics, this new Brillouin laser

provides a powerful route to customize onchip

light in silicon-based optical circuits. It

provides a glimpse into a yet remote but possible

future in which computers run on light.

DIYU PEARCE-FISHER

DIYU PEARCE-FISHER is a senior Biomedical Engineering major and premedical student in

Berkeley College. She is working in Kathryn Miller-Jensen’s lab studying the role of IL-10 on

macrophage polarization.

THE AUTHOR WOULD LIKE TO THANK Dr. Ke Yang for the time and efforts and Professor Gary

Brudvig for providing further insight and perspective into the future work.

FURTHER READING

"End-On Bound Iridium Dinuclear Heterogeneous Catalysts on WO3 for Solar Water Oxidation,” Y. Zhao,

ACS Central Science, 2018.

www.yalescientific.org

October 2018

Yale Scientific Magazine

24


SCIENCE IN THE LIBERAL ARTS:

a reflection from Yale-NUS College

by Goh Rui Zhe

Yale-NUS College ‘20

A central tenet of the liberal arts is that good education

should evoke introspective examination of long-held assumptions

and beliefs in learners. This is usually thought to

be the role of philosophy, which never takes any knowledge

for granted, and the creative arts, which imagine new worlds

to make us question our own. Science, on the other hand, is

thought to be the cornerstone of many fundamental beliefs.

The beliefs that the earth revolves around the sun, and that

things fall because of gravity, are grounded in the authority

of science. The vast majority of us accept these facts unquestioningly,

without bothering to ask why they are regarded to

be true. At Yale-NUS, this is regarded to be a problem—and

justly so because the authority of science sometimes perpetuates

problematic dogmas. For this reason, scientific studies are

occasionally thought to be in need of the critical introspection

that the liberal arts celebrate.

Science, like any other discipline, has its fair share of dogmatism;

however, I think that the spirit of science is very much

in line with the critical reflection that the liberal arts hope to

promote. Essentially, science is about understanding the world

from a third person perspective. A significant component of science

involves reducing qualitative observation into quantitative

data which can be accessed, verified and analyzed by a third party.

This has led to the creation of a language of numerical units,

statistical methods and naming conventions that try, as much as

possible, to strip our observations of their subjective biases. In

arguments, science encourages us to take the view that is best

supported by empirical evidence. The spirit of empirical inquiry

makes us more willing to subject our fundamental assumptions

about the world to empirical scrutiny by exploring relevant evidence

and allowing our views to change in light of this evidence.

In my opinion, this spirit of empirical inquiry is what science

has to offer to the liberal arts. At Yale-NUS, we have a

core module named Scientific Inquiry (SI). The aim of SI is

not to impart the technical knowledge of science, but to cultivate

the spirit of empirical inquiry. SI prepares students to

make calculated decisions, implement effective policies, and

create new theories about the world based on careful empirical

research. However, SI has not been well received by Yale-

NUS students. Many students who studied science in high

school feel that the lessons in SI is too simple to be stimulating.

In contrast, students who have not had much exposure

to science prior to college do not find these scientific questions

exciting enough to warrant the effort needed to grasp

the challenging technicalities of the course.

For science education to work well in the liberal arts, I

think that we need to broaden our notions of what scientific

questions are. The questions that SI addresses—is evolution

fact or fiction? Is climate change natural or man-made?—are

scientific questions, but they are also textbook debates that

have already been resolved in the minds of the average college

student. Few students at Yale-NUS think that natural selection

is false, or that human activity is not responsible for

global warming. As such, SI reinforces common beliefs, instead

of making students question them. This works against

the spirit of empirical inquiry.

Instead of revisiting past debates, science education should

tackle current controversies. One very heavily debated topic

at Yale-NUS is the relationship between biological sex and socially

constructed gender. I see a wealth of fascinating empirical

questions in this debate which can be addressed by methods

in evolutionary biology, neuroscience, psychology and

sociology. These are difficult questions, but what better place

to discuss these problems than in a liberal arts setting?

There are many ways to frame and answer questions about

the world. The empirical method is an important one because

it aspires to adopt a bias-free perspective to understanding

the world. The pursuit of this perspective has value

in itself as it causes students to recognize the biases in

their fundamental assumptions, and critically evaluate their

worldviews. As such, the spirit of empirical inquiry should

be actively cultivated through science education in the liberal

arts by allowing students to formulate their own questions

instead of endorsing past knowledge.

www.yalescientific.org

October 2018

Yale Scientific Magazine

25


FEATURE cell biology

NOVEL NEURONS

What makes up your mind?

BY SAMI ELRAZKY

Nothing is closer to us than our brains, but their complicated

workings make understanding them no easy task. Billions

of specialized cells called neurons work together, each

using a combination of electrical and chemical signals to

communicate with each other. Tiny gears in one of the universe’s

most complex clocks, these cells weave together into the

beautiful organ that sits between your ears. If you’re confused

about how things like basket cells and medium spiny neurons

can be the building blocks of your very consciousness, you’re

not alone. Neuroscience is a field dedicated to answering this

question, and another recently discovered, colorfully named

neuron may change neuroscientists’ approach.

The use of mouse models has been common in the study

of neurological diseases for decades, and for good reason.

Mice and humans share many genes and have similar neurological

circuits. Additionally, and most importantly, mouse

brains can be readily altered on the genomic, biochemical,

and physical level for the sake of experimentation. However,

there are limitations. From disease symptoms to cortex

structure, there are differences between mouse and human

brains that make it difficult to translate the results of

mouse brain studies to human neurology. A recent collaborative

study between the Allen Institute and the University

of Szeged shows that an even more basic difference may lie

in the cellular makeup of the two brains. The study, led by

Ed Lein of the Allen Institute for Brain Science and Gabor

Tamas of the University of Szeged, provides transcriptomic

and morphophysiological evidence—that is, relating to a

cell’s genes, shape, and firing properties—for the existence of

a type of neuron not found in mouse brains.

In a fortunate coincidence, the two teams converged on the

same discovery. The Allen Institute had been profiling the

genetics of the neurons in the outermost layer of the human

neocortex, the part of the brain dedicated to higher reasoning

functions like cognition, spatial reasoning, and language, using

a technique called single nucleus RNA sequencing. They

separated the cells of the neocortex, isolated the nuclei in different

tubes, and profiled the genes present, giving them a

readout of what genes are turned on in each of the cells.

At the same time, the University of Szeged had been profiling

the same region based on cell morphology and electrical

behavior. The morphology or shape of a neuron can give insight

into other neurons with which it is interacting, while its

electrical properties, like how fast the neuron sends signals,

can tell us how the cell processes signals in the overall neurological

circuit of the brain.

It was only after the two groups came into contact with

each other that they realized that they had characterized

the same novel cell, dubbed the “rose hip cell” after its

compact, bushy shape.

Further investigation found that this cell had not been found

in mice brains, and while the specific function of the cell has

yet to be determined, its existence has implications for how

neuroscientists study neurological processes in the future.

“Human brains aren’t just larger mouse brains,” said Trygve

Bakken, a lead author on the study. Even though mouse models

have helped neuroscientists study the human brain, the fact

that there are differences between the two brains at the very

cellular level could act as a catalyst to promote a shift from

the traditional mouse models to more analogous neurological

models. These could be brain samples from nonhuman primates

or artificially cultured cerebral organoids, both of which

could potentially serve to model the neurological processes

that mice may be unable to.

Cognitive science, the study of how we think and process

information, is an interdisciplinary field. Neuroscientists, biologists,

psychologists, and many other scientists come together

to try and solve the puzzle of our mind; when a major discovery

in one field is made, the effects of that discovery can

ripple through other fields, changing their approach to the

brain. While the rose hip cell’s effect on our cognition is not

yet known, its discovery could mark the beginning of an era of

increased understanding of what makes up the human brain,

and what makes it special. “We’re on a new threshold of understanding

not just for the rose hip cells, but for all the different

types of neurons in the brain—what are their characteristics,

how similar are they to those of the mouse, and that is going to

allow us to untangle how they are all interconnected, and ultimately

how the circuit works,” Bakken said.

IMAGE COURTESY OF TAMAS LAB, UNIVERSITY OF SZEGED

A rose hip neuron, or a “rose hip cell” that has a compact bushy shape.

26 Yale Scientific Magazine October 2018 www.yalescientific.org


applied physics

FEATURE

SEAS OF ELECTRONS, WAVES OF PEOPLE

What do subatomic particles tell us about behavior in crowds?

BY RICHARD LI

IMAGE COURTESY OF WIKIPEDIA

A police and protester is an example of a more complicated crowd with

two different types of actors. For example, policemen might amicably

interact with themselves, but engage with the protesters in a hostile way.

Imagine you are at your favorite band’s concert. Searching

for the best place to stand, you avoid the spaces that prevent

you from getting a good view of the band, perhaps by moving

closer to the stage, but you also want to make sure that

your surrounding space isn’t overcrowded. You drift here

and there, and eventually, you come to a spot where a sufficient

compromise is reached. Everyone else at the concert

shuffles around in the same way.

The exact evolution of crowds over time can be complex, but

if its members all share similar preferences, then perhaps we can

infer something about its broader, more general behavior. Based

on this principle, Physics Professor Tomás Arias of Cornell University

and his team recently created and successfully tested a

novel method for modeling the overall behavior of such crowds,

based on techniques used in physics.

Using the rationale employed in the above concert example,

Arias and his team concluded that two main, independent factors

affect how we individually pick our spots within a crowd:

both how unfavorable a given location is and the crowdedness

of that location. Hence, by minimizing both of these factors, everyone

in the crowd should be content. Arias’ model assumes

that the details of specific interactions between individuals are

relatively inconsequential to the crowd’s overall behavior.

Unexpectedly, Arias realized that this framework highly resembled

a seemingly unrelated concept in physics, density functional

theory (DFT), which is one of his areas of expertise. As

the name suggests, a core component of DFT is the notion that

information about electron density alone predicts much of the

overall behavior of molecular or atomic systems no matter the

specific interaction between individual electrons or other factors.

Likewise, the team theorized that by merely observing how

the crowd’s population density fluctuates over time, information

about the individual’s spatial preferability and crowdedness

may be inferred. Moreover, if one can determine these two factors,

then one might determine how the overall crowd behaves.

Next, the team renamed the factors of spatial preferability and

crowdedness, calling them vexation and frustration functions,

respectively, as a reference to their analogous variables in DFT,

potential (V) and functional (F). “We got the thesaurus out to

try and find English words that start with the letters F and V,

that also marked the mood of crowd behavior,” Arias said. This

conceptual parallel between Arias’ model and DFT is significant

because, in both cases, the variables are minimized.

To test the model, the senior experimenter of the team, Itai

Cohen, set up experiments observing groups of flies confined

to certain spaces and tracked their population densities. These

spaces were heterogeneous: some parts of the same environment

varied in temperature, and other spaces varied in terms

of their geometry. Shockingly, the team not only successfully

extracted the frustration and vexation functions from the fluctuating

density of the flies, but conversely, using this newfound

information, they were able to model the behavior of flies in different

environments to a high degree of accuracy.

This is one of the first experiments to model a socially dynamic

system without relying on other pre-existing frameworks.

“The beauty of this paper is that we didn’t try to artificially force

the model to fit ideas from physics, because we didn’t model the

crowd as if they were a gas or a fluid of some sort. We constructed

our model based simply on a set of reasonable, socially plausible

assumptions instead,” Arias said.

Such promising results demonstrate that the team’s model

could be widely applicable to real crowds. For example, it may be

possible that by observing how the density of the crowd fluctuates,

concert organizers could compute the maximum amount

of people to let in at a given time to avoid dangerous trampling

incidents. They could also analyze the crowd in real time, and

quickly determine which doors may need to open or close to

relieve pressure, making public venues safer.

Indeed, the team hopes to move forward by extracting the

vexation and frustration functions in real-time and by examining

time-dependent crowds where the number of individuals

going in and leaving a venue varies. They are also working

on examining more complicated crowds with more than

one type of actor. For instance, the interaction between police

officers and protesters is not only an interesting scenario

to consider, but a pertinent one. It’s uncanny how well DFT

can be used to model human behavior—maybe we’re really

just electrons after all.

www.yalescientific.org

October 2018

Yale Scientific Magazine

27


FEATURE physical chemistry

Everybody knows that ice floats in water.

Some may also know that this is due to differences

in the structure of water molecules

in ice versus in water. In ice, the molecules

are frozen in place in rigid lattices with

spaces between them, but in water, they flow

around amorphously, making ice less dense

than water. In a recent development, however,

researchers have found a different way

to align these water molecules in an ice-like

structure without even reducing the temperature.

Earlier this year, a team of three engineers

from Rice University in Houston, Texas, led

by Rouzbeh Shahsavari, completed an indepth

study about how water forms ice-like

structures when placed in nanotubes. These

nanotubes are extremely small hollow tubes

that have a diameter less than a thousandth

that of human hair—not dissimilar from a

regular drinking straw, except shrunken by

a factor greater than a million. In their research,

the engineers were able to calculate

the theoretical optimal size of the nanotube

NANOTUBES

CHANGE

THE SHAPE

OF WATER

n anotubes can freeze water

regardless of temperature

BY JAU TUNG CHEN

for these ice-like structures, and to experimentally

verify these predictions.

Since 2006, it has been known that water

takes on unique structural properties when

placed in confined spaces. For example,

studies have shown that water confined between

two hydrophobic surfaces can form

low-density water. Its unique structural

properties are primarily due to strong hydrogen

bonds that water molecules are able

to form with each other, and possibly with

the material used to enclose them. As such,

the structure of water in bulk is complex because

water molecules, with structure H2O,

each contain two hydrogens and one oxygen

atom. They can be thought of as special

magnets that each have two north poles and

one south pole—we can try to arrange all

of them together in a stable configuration,

ignoring the fact that such magnets do not

exist in reality. Forming any such structure

already seems complicated. Now, we can

imagine the case in which the water molecules

are confined externally, analogous

to having a boundary of specific magnetic

poles placed around this group of special

magnets. We quickly see how this becomes

a complex computational problem of trying

to arrange the water molecules to best

fit their constrained space and how this can

give rise to the unique structural properties

of water.

Even before this recent study by Shahsavari’s

team, the use of nanotubes to confine

water had already been briefly studied.

Past research has shown that water molecules

can form pentagonal, hexagonal, and

even heptagonal structures when placed

in these nanotubes. However, the lack of a

complete and systematic study of this phenomenon

intrigued Shahsavari,

who then decided to study it

in more depth. In particular,

Shahsavari’s team aimed to

develop a more comprehensive

theoretical model of the

structure of water molecules in

nanotubes and the conditions

necessary for the ice-like structure

to form.

To develop their theory, the

engineers first used molecular

models to compute the

strength of the force between

water molecules and the

molecules on the inner surface

of the nanotube. They found that

the primary force between them is the weak

28 Yale Scientific Magazine October 2018 www.yalescientific.org


physical chemistry

FEATURE

van der Waals force, a distance-dependent

force that

occurs because of

random but correlated

fluctuations in the

polarizations of both

molecules. To understand

this, we can imagine

each molecule as a

regular bar magnet that

is spinning rapidly and

randomly. If we place

two such bar magnets

close together, they

will sometimes attract

each other when oppo- s i t e

poles happen to face each other,

but sometimes repel each other when the

same poles happen to face each other. On

average, we will expect a net force of zero

if the spinning is truly random. However,

in the case of molecules, due to a consequence

of quantum dynamics, these random

fluctuations—or spinnings—are not

truly random, and are instead correlated

with each other, giving rise to an overall

average attractive force between the molecules.

By computing the magnitude of this

force between water molecules and the molecules

on the inner surface of the nanotube,

Shahsavari’s team showed that it was strong

enough to freeze water molecules in rigid

lattices in the nanotube, forming the desired

ice-like structures.

Having understood the mechanism behind

the formation of these ice-like structures,

the engineers proceeded to investigate

the physical conditions required for these

structures to form. In theoretical simulations,

as well as in lab experiments, Shahsavari’s

team altered various parameters of

the nanotube, including its diameter and its

material—carbon and boron nitride. “The

dependence [of structure formation] on

the tube diameter was surprising for boron

nitride nanotubes,” Shahsavari said. On

second thought, however, this dependence

makes perfect sense. Imagine the cross section

of the nanotube—a circle—as a ring of

parents trying to manage some young kids,

who are running around haphazardly inside

this ring—like the water molecules flowing

amorphously in the nanotube. “If the nanotube

is too small and you can only fit one

water molecule, you can’t judge much, but

if the nanotube is too large, then the water

keeps its amorphous shape,” Shahsavari said.

Analogously, if the ring is too small and only

has

one kid in it, no structure

can form. If the ring is too large, only kids

along the edge of the ring will be held in

place by parents, leaving most of the kids

still running around haphazardly within the

ring. It is only when the ring is of the optimal

size, when there is approximately the

same number of parents as there are kids,

that each parent can hold on to one kid, and

form a stable structure within the ring. “At

a diameter of about 8 Angstroms [8 hundred-millionths

of a centimeter], the nanotubes’

van der Waals forces start to push water

molecules into organized square shapes,”

Shahsavari said.

According to Shahsavari, the most challenging

part of their research was conducting

of experiments at such small scales. Indeed,

when operating with individual molecules

of water and nanotubes that are a millionth

the size of a regular drinking straw, simple

actions like adding water into the tube requires

extreme precision and care. In addition,

examining the arrangement of water

molecules in the nanotube is certainly not

as simple as looking at them; the engineers

utilized Raman spectroscopy—a method to

observe the vibrational and rotational frequency

modes of molecules in a system—to

deduce

t h e

a r -

rangement

of water molecules

in the nanotube.

Looking to the future, researchers

can now capitalize on this ability to control

water at the molecular level. A broad variety

of applications are possible: for example,

nanotubes could be used as energy-storing

nanocapacitors. Alternatively, these nanotubes

could be used as nanochannels to

transport water—or potentially other material—at

extremely small scales, particularly

because water flows through nanochannels

much faster than typical channels, due to reduced

friction with the surface. Shahsavari

is hopeful that nanotubes will eventually be

made into precise nanoscale syringes, which

can be used to deliver specific drugs to targeted

body cells. All in all, this comprehensive

study by Shahsavari’s team might just

revolutionize the way we manipulate liquids

at a molecular level.

IMAGE COURTESY OF ROUZBEH SHAHSAVARI

Water molecules are organized into square

shapes when placed in a carbon nanotube

(both left and right are nanotubes of

different diameters).

www.yalescientific.org

October 2018

Yale Scientific Magazine

29


FEATURE materials science

GETTING

A GRIP

Designing Stress-Resistant

and Energy-Storing Materials

BY MIRIAM ROSS | ART BY ALICE TIRARD

IMAGE COURTESY OF WIKIMEDIA

Carotid arteries in cows are auxetic, which gives

them resistance to breakage and injury.

The lead hero of Marvel Studios’s

“Black Panther,” T’Challa, is known

for his iconic black full-body suit. One

of its signature properties is the ability

to store and later release energy from

an enemy’s physical blows. A new microstructure

designed by a team led by

Eesha Khare at the University of Cambridge

in London holds the potential for

developing similar energy release mechanisms

fit for Wakanda. The new design,

named the s-hinge, makes materials

better able to overcome the stress from

applied forces. By modifying the s-hinge

slightly, the researchers also developed a

IMAGE COURTESY OF FLICKR

The muscular grip of eagles inspired the

researchers to develop their own s-hinge.

IMAGE COURTESY OF WIKIMEDIA

Researchers compared the new s-hinge’s design

to a honeycomb auxetic structure.

latching mechanism that can store and

release energy more efficiently.

The s-hinge design is an improvement

to auxetics, a class of super-strong materials

that are defined by how they respond

to an applied force. Unlike most

materials, auxetics become thicker when

stretched and thinner when compressed

as opposed to a rubber band, for example.

Nature has many instances of, and

uses for, this class of materials. For example,

the carotid arteries in cows are

auxetic, which seems to make them

more resistant to breakage and injury.

Materials science researchers are currently

developing auxetic materials for

uses ranging from bulletproof armor

and shock-absorbent sports shoes to

stronger prosthetics and hip implants.

Khare’s team was initially pushed to create

a new design because of several flaws

in auxetic material design, primarily a

vulnerability to damage from the stress

of withstanding force. The new s-hinge

design improves upon the standard honeycomb

structure: the honeycomb’s sharp

corners gather stress into small areas,

making the structure more vulnerable to

weakening over repeated cycles of stress

from applied force, a process called fa-

30 Yale Scientific Magazine October 2018 www.yalescientific.org


materials science

FEATURE

tigue. Auxetic and stress-resistant structures

found in nature, like the muscular

grip of eagles and the locking joints in

fleas’ feet, showed a specific hinge structure

similar to a tessellation of heart patterns,

which inspired the researchers to

develop their own s-hinge.

The s-hinge’s main new properties are

increased elastic deformation, or a structure’s

ability to return to its original shape

after being put under stress, and tunable

Poisson ratios, a measure of how much a

material expands perpendicular to an applied

force. Auxetic materials are defined

by having negative Poisson ratios, which

is why they become thicker when they are

stretched and thinner when compressed.

The s-hinge’s tunable Poisson ratios

allows it to switch between a negative

and a positive Poisson value. Essentially,

the s-hinge structure can go from being

a regular material to being an auxetic

material, which makes it especially flexible

and resistant to damage from stress.

This property is particularly important

for future practical applications, where

a material’s performance depends on its

resistance to repeated stress.

To make their new design, the researchers

created a computerized simulation on

ABAQUS software and modeled different

aspects of auxetic materials’ behavior under

applied stresses. Designing accurate

simulations is important to materials science;

if successful, they allow future researchers

to build off the original design

idea. This study’s simulation compared

the properties of the common honeycomb

design to those of the new s-hinge

design. After running simulations, the

researchers 3D printed both an s-hinge

and a honeycomb auxetic structure and

experimentally tested them according to

the simulation. During 3D printing, another

advantage of the s-hinge design was

made apparent: structures like the honeycomb

are vulnerable to defects in the 3D

printing process that the s-hinge design

avoids, such as rounded corners or badly

connected edges.

Following examples of smooth hinge

geometry in nature, such as the Venus

flytrap, the researchers improved that

s-hinge’s stress distribution by designing

the hinge to bear stress throughout its entire

length, not disproportionately in the

corners. The s-hinge structure distributes

stress by replacing the straight edges of

the honeycomb with carefully designed

arcs that are both flexible and capable of

being made on a 3D printer.

Next, the researchers compared their

predictions from the simulation to their

experimental results from the physical 3D

printed models. They found that the simulation-predicted

results matched their

experimental data. This suggested not

only that the s-hinge design was durable

and successful, but also that the modeling

simulation was reliable and could be used

to design new auxetic material structures.

In the experimental conditions, the researchers

proved that the s-hinge was far

better at distributing stress and recovering

from damage compared to the honeycomb

THE NEW DESIGN, NAMED

THE S-HINGE, MAKES

MATERIALS BETTER ABLE

TO OVERCOME THE STRESS

FROM APPLIED FORCES.

model. The s-hinge’s increased flexibility

will allow materials that were formerly

too weak or fragile to be used for auxetic

structures, such as glass and ceramic,

which will ultimately expand auxetics’

range. In particular, the s-hinge design

outperformed the honeycomb in a repeated

cyclability test in which forces were

applied periodically. This cyclical stress

imitates what the structures would have to

withstand in practical applications.

The honeycomb and s-hinge’s different

responses to stress stem from the two

categories of how a material can react

to applied force: plastic deformation or

elastic deformation. Elastic deformation,

as previously described, is the amount of

force a material can withstand before irreparable

damage is created. Plastic deformation,

on the other hand, happens

when the force applied surpasses the

threshold for irreparable damage. When

the force is removed, the structure will

have permanent damage and be unable

to recover completely. Compared to the

honeycomb, the s-hinge was more durable

because it has a higher range of elastic

deformation.

To exhibit further the s-hinge’s ability

to recover from strain, the researchers

altered a 3D printed Batman logo.

They adjusted the angles of the arcs to

turn the previously positive Poisson ratio

into a negative one, which changed

the amount of stress the material could

withstand from that of a normal material

to that of a stronger, auxetic material.

The researchers envision this property

extending new possibilities to materials

science, such as designing structures to

change shape when they are compressed.

Inspired by the s-hinge’s resistance to

stress, the researchers also designed a

latching mechanism based off the general

s-hinge design. The latch works to

gather and save the structure’s elastic

energy, or the potential energy created

when the material is under stress. Similar

ways of latching or storing elastic

energy are very common in nature, and

they are used in a variety of ways. The

Venus flytrap is a common example, as

are muscle structures of birds of prey.

Their tendons can pull their talons shut

with extreme force, and because of their

latching properties, the birds do not

have to repeatedly contract their muscles

in order to hold their grip.

The talons of birds of prey catch our

interest because they can exert force

without having to continually reapply

it. But most natural structures function

by reapplying force cyclically, and the

researchers designed the materials with

this in mind. Like an eagle’s talons, the

s-hinge was modeled to distribute stress

more efficiently, and its tunable Poisson

ratio allowed the hinge’s structure

to change, becoming stronger as force

is applied. Additionally, the accuracy

of the researchers’ computer modeling

simulation will make designing future

auxetic materials far easier. Ultimately,

the researchers envision designing a new

class of smart materials, capable of reacting

with a Venus flytrap’s adaptability,

that could lead to a new field of material

robotics. Robots built with ‘smart materials’

could store energy without a continual

application of force, and release

that energy in reaction to many different

kinds of stimuli. Perhaps a material like

that used in T’Challa’s suit isn’t as far out

of reach as we think.

www.yalescientific.org

October 2018

Yale Scientific Magazine

31


Scientists are stopping

seizures at their

source with a new,

dry drug delivery

method that is efficient,

effective, and

electrophoretic, or

STOPPING

keeping an eye on the ion

by BRITT BISTIS

art by ELLIE GABRIEL

THESE FINDINGS

DEMONSTRATED THE

EFFECTIVE USE OF AN

IMPLANTABLE DRUG-

DELIVERY SYSTEM IN

VIVO TO CONTROL SEI-

charge-based. This

new strategy could

swiftly and efficiently

stop epileptic seizures.

According to

the CDC, epilepsy

affects approximately

1.2 percent of the

United States’ population,

with 3 million

adults and 470,000

children affected by

this disorder. With

such a high prevalence,

finding an

effective drug treatment

that allows for

precise control and

manipulation of electrical neurochemistry

with minimal side effects is paramount.

Epileptic seizures are characterized by

abnormal neural electrical activity. While

they can stem from many different causes,

they are all inhibited by the neurotransmitter

γ-aminobutyric acid (GABA), and

many seizure treatments are geared toward

facilitating GABA delivery, production, or

reuptake inhibition. The two broadest categories

of seizures are general and partial

seizures, and the latter responds especially

poorly to traditional systemic drug treatment,

which affects the entire body.

Systemic drug treatments are not well-designed

for treating many neural diseases and

disorders in general due to the brain’s protective

barriers, such as the blood brain barrier,

and the drug’s inability to target specific neural

sites. The blood-brain barrier prevents

harmful chemicals in the surrounding fluid

from entering the brain. In order to penetrate

this barrier, the drug would need to be

present at such a high concentration in the

blood stream that it would have detrimental

effects to other tissues in the body.

Many systemic psychotropic, or neurochemistry-altering,

drugs that in lab experiments

have indicated strong anti-seizure

and remediating effects have also ultimately

proven to cause acute

severe side effects,

which leads these otherwise

effective drugs

to fail during clinical

trials. Further, systemic

treatments do

not allow for a high

level of precision and

spatiotemporal accuracy.

This precision is

critical if a drug is to

address neural disorders,

including focal

seizures, which have

a defined focal point

or source. While

other drug delivery

methods such as fluid

delivery systems

are directly implanted

into the brain and,

therefore, don’t have

to contend with the

blood-brain barrier,

these mechanisms release the molecules of

the drug with solvent, or fluid. This fluid

causes swelling, which can lead to modifications

in nearby neural networks.

To address and circumvent these challenges

to treating neural disorders, a team of

researchers affiliated with the Aix Marseille

Université and the University of Cambridge

designed a microfluidic ion pump implant to

deliver precise drug dosages more efficiently.

This method of drug delivery features dry

drug delivery capabilities, as it transports

the drug molecules without any solvent. The

researchers successfully used this ion pump

implant to identify seizures and deliver pre-

32 Yale Scientific Magazine October 2018 www.yalescientific.org


SEIZURES

biomedical engineering

FEATURE

at their source

cise amounts of positively charged ions of

neurotransmitter that effectively ended the

seizure-like event in mouse models. “These

findings demonstrated the effective use of an

implantable drug-delivery system in vivo [in

a living animal] to control seizures,” said Dr.

Adam Williamson of the Aix Marseille Université,

part of the team who developed this

new technology. This technology integrates

the principles of physics and biochemistry to

create, in essence, an electrochemical circuit

that can be implanted in the brain.

The microfluidic pump is strongly based on

previous designs of ion pumps and functions

as an electrochemical circuit. The implant is

placed locally by the focal point of the seizure

and the mechanism consists of a microfluidic

channel, a gold source electrode, and

two peripheral, plastic-coated electrodes.

The two outer electrodes function to record

neural activity. When seizure-like abnormal

electrical neural activity is detected, a voltage

is applied between an external electrode

and the source electrode, which triggers

the delivery of positively charged particles

through a negatively charged membrane,

the anion exchange membrane, to the target

outlet that releases the drug. Opposites attract

as the positive drug treatment particles

stored in the pump move across a negative

membrane to the outlet site.

The microfluidic ion pump has the added

advantage of being more sensitive to voltage

and being incredibly efficient, delivering

nearly all molecules to their intended target.

In their study, the research team used a

GABA solution known to inhibit seizure-like

activity as the drug treatment. GABA causes

negative chloride ion uptake, which lowers

the charge in the cell, preventing the neuron’s

firing capability.

Upon inducing seizure-like

events in mice, the probe

successfully recorded

the abnormal activity

and released

enough GABA

to readjust

and regulate

neural

activity, thereby

quickly stopping the seizure at its source.

After the probe had been implanted, seizures

could no longer be induced, illustrating this

method is highly effective. Further, the GABA

that was delivered to the seizure source site

was quickly broken down, indicating that

since the drug was so quickly degraded, it had

little to no adverse side effects.

While this technology is very promising—it

eliminates many formerly daunting

challenges in treating neural disorders—

this new technology is still limited in its applications.

Most importantly, the treatment

is reactionary. Since the mechanism senses

and responds to abnormal neural activity,

the treatment is only administered after a

potentially dangerous seizure has begun.

Even so, researchers have postulated that

seizures can be predicted with algorithms,

which would enable the mechanism to

halt a seizure before it happens. According

to Dr. Williamson, there are other key

limitations in the study. “The animals in

this study were anesthetized during experiments,

and more importantly, devices were

implanted at the source of epileptic activity,

at the exact source. This was only possible

because we defined the source experimentally,”

Dr. Williamson said.

The clinical implications of this new technology

for an electrophoretic dry drug delivery

method are broad. “A very optimistic

person would say that we are close to developing

an implantable device for the treatment

of epilepsy, equivalent to Deep Brain

Stimulation used in the treatment of Parkinson’s

disease. I would

encourage cautious optimism. Challenges

will need to be individually investigated and

integrated step-wise logically to move the

technology forward,” Dr. Williamson said.

While the new technology must be systematically

refined, it has the potential to treat not

just seizure disorders, but other deleterious

chronic neural disorders like Parkinson’s. By

minimizing adverse effects and extra solvent

molecules and maximizing precision and efficiency

of treatment in their electrophoretic

dry drug delivery method, Dr. Williamson

and his colleagues have developed a technology

that has a wide range of future potential

applications for treating neural disorders.

IMAGE COURTESY OF DR. ADAM WILLIAMSON

Setup of the probes in the brain: the microfluidic

ion pump probe was inserted in the exact

location in which the seizure-inducing drug was

injected, indicating this treatment method’s

high level of precision and accuracy. The Si

depth probe was used to record local activity

in the region.


COUNTERPOINT

B Y P H I L E N A S U N

Try breaking spaghetti into two pieces. It’s not as easy as it

sounds. If you take two ends of a strand

of spaghetti and bring them together,

the noodle will almost always

break into three or more

pieces. This counterintuitive

phenomenon has perplexed

scientists for decades,

stumping even American

theoretical physicist and

Nobel laureate Richard

Feynman, who sought to

explain why.

It wasn’t until 2005 that

French scientists Basile Audoly

and Sebastien Neukirch cracked

the code and discovered the underlying

forces that occur when spaghetti—or any long, thin rod—

IMAGE COURTESY OF JORN DUNKEL

is bent. Typically, the noodle will break at the point of highest

curvature, after which it wants to straighten itself out. This subsequently

creates a so-called snap-back effect, which sends a vibrating

wave down the noodle and causes multiple fractures—a

fracture cascade. In 2006, Audoly and Neukirch were awarded

the Ig Nobel Prize—a parody of the original Nobel that celebrates

unusual achievements in science—for their ingenuity in

solving this age-old puzzle. But their findings still begged the

question: can spaghetti ever break into two pieces?

Fast forward to 2018. Following months of breaking spaghetti

with a specially designed noodle-breaking apparatus,

a team of MIT researchers said, yes—but with a twist. In a

paper published in Proceedings of the National Academy of

Sciences, MIT researchers found that spaghetti can be broken

into halves by either twisting the noodle or compressing

it very slowly. Via the first method, the spaghetti strand must

be twisted by nearly 300 degrees in order to break into two.

“In order to get anything to break, you must apply supercritical

stress. This can be achieved through bending or

twisting,” said Jörn Dunkel, co-author of the project and Associate

Professor of Physical Applied Mathematics at MIT.

When a noodle is bent or twisted past its neutral straight

position, it wants to correct itself accordingly. The correction

creates waves that result in additional fractures. Dunkel’s

students Ronald Heisser and Vishal Patil discovered

that simultaneously applying bending and twisting stresses

to a noodle coerces it to break into two pieces.

When the noodle snaps, “The bending and twisting waves are

propagated at different speeds, so you never get supercritical

stress at some other location in the rod,” Dunkel said. The two

processes essentially distribute and dissipate the energy needed

to fracture spaghetti a third time. Hence, supercritical stress is

never attained, and a fracture never occurs.

The researchers also found a second way to break the spaghetti

into two through a process called quenching, or compressing

the noodle. If done at a very slow velocity, the noodle

breaks into two. On the other hand, if compressed

quickly, the noodle shatters into multiple fragments.

Dunkel likens the process of quenching to that of a vibrating

string on an instrument. When a low pitch is

played, the wavelength of the sound wave is high and

the frequency is low. This situation parallels the large

waves that result from slow compression of a noodle.

The low frequency and high wavelength of compression

divides the noodle at fewer points, which results in fewer

points of supercritical stress. Higher speeds of compression

induce waves with higher frequencies, which creates more areas

of supercritical stress, and, thus, more fracture points.

While the practical applications of this research are currently

unclear, Dunkel and his team’s research provides us with a better

understanding of how elongated rods behave under stresses of

bending, twisting, and quenching and paints a clearer picture of

how fractures work. After all, examples of fractures are everywhere

around us, like in broken bones and fracturing plate tectonics. The

results of this research may even provide a glimpse into how the

microtubules in our cells behave under duress, as Dunkel’s mathematical

models can fit rods made of

different materials, elasticities,

lengths, and radii.

For now, Dunkel reminds

us to appreciate

the scientific

SOLVING

THE AGE-OLD

SPAGHETTI

MYSTERY–

WITH A

TWIST

and mathematical

theories underlying

even the

most mundane

of phenomena.

“We like to

connect with

the broader

public, but one

should also remain

aware of the

broader theoretical

implications that

reach beyond breaking

spaghetti!” The next

time you snap spaghetti,

just remember that there’s

more than meets the eye.

34 Yale Scientific Magazine October 2018 www.yalescientific.org


epurposed By:

Katie Schlick

Rags to Riches

Excavating a 21st Century Waste Management Solution

Similar to the ghost-like greenhouse gases that

bloom from car exhausts, factories, and power

plants and then float into the atmosphere, the

manufacturing of a cell phone also employs the

concept of invisible waste. Yahya Jani, a postdoctoral

fellow at Linnaeus University in Sweden, says that

around 86 kilograms of invisible waste are involved

in the production of a single phone weighing

approximately 0.15 kilograms. After receiving his

PhD in Chemical Engineering in 2006, Jani has

received a second PhD, this time in Environmental

Science, by taking a closer look at waste. His

dissertation, published in March 2018, is the first to

reimagine landfills as useful stocks of resources.

For two years, Jani collaborated with different

universities in the Baltic Sea Region to gather data

from two landfills—Högbytorp in Stockholm

Sweden, which sees 700,000 tons of waste each

year, and Torma in Tartu, Estonia. Jani found that

over two-thirds of waste and two-fifths of waste

at Högbytorp and Torma could be recovered,

respectively. These fairly promising results at just two

of the thousands of landfills across the planet indicate

that countries can improve their hazardous, polluting

waste management systems in unprecedented ways,

potentially reversing the course of landfills currently

maxed out on storage capacity.

Pukeberg, a glasswork dumping site in Nybro,

Sweden, served as another test excavation site.

Cadmium, lead, and arsenic were extracted from

this site by the classic reduction-melting method,

which involves melting the glass into a solution,

and the transformed metals fall to the bottom of

the glass solution. This process ultimately had

a 99 percent success rate, demonstrating much

promise for future trials with extraction.

Cadmium, lead, arsenic, and zinc were also isolated

by various chelating agents, which bind to the

elements and mobilize them into releasing from the

surfaces of soil and glass of particle sizes less than two

millimeters. Testing a selection of extraction methods

was a critical supplement for the research because the

ability to characterize the waste in landfills around

the world is one of the first practical steps toward

remediation. Though pleased with the results of

these two extraction methods, Jani believes that there

are many more extraction methods that need to be

developed. He hopes to expand the body of science

on cost-effective resource extraction techniques in

order to propel these landfill reformations forward.

Jani’s work builds on the popular concept of a

circular economy—in which the outputs of the

system are recycled and then fed back into the

system, as opposed to the wasteful, single-use nature

of a linear economy, which would generally lead to

the dumping of waste products—as a mechanism

for embedding sustainability into development

and government. It adds one more composite layer

into the circle: the recycling, extraction, and reuse

of waste. Once implemented, the latest component

of waste management—the recovery of materials

and energy—would combat scarcity of resources,

as well as pollution that leaches from hazardous

waste materials. The technologies could even

extend to cleaning up hazardous wastewater and

harvesting nutrients. Particularly with such an

abundance of electronic e-waste—collectively, the

industry yields 750 million tons of it each year—

but such a lack of the rare earth elements needed

to create the number of electronics demanded, Jani

envisions the replenishment of needed resources

with what has already been used, or with what has

been carelessly left behind in landfills.

When asked about the best approach to tackle waste

management issues, Jani spoke of what he perceives to

be the triple helix of change: society, decision makers,

and academia. Uniting these three populations on a

global scale and directing their focuses toward open

dumping sites, which serve as troves of resources and

opportunity rather than as piles of waste to be buried,

can have profound impacts on the future of the

Earth. The transition requires a vast accompanying

shift in the global mindset toward considering waste

as a secondary resource. Tackling climate change

and other global environmental issues, however, will

require unprecedented levels of collaboration and

innovation; perhaps the next transformative climate

solution will actually emerge from the world’s rubble.

35 Yale Scientific Magazine October 2018


UNDERGRADUATE PROFILE

RACHAEL PUTMAN (TC ’19)

WHAT COMES BEFORE BABY STEPS?

BY HANNAH RO

PHOTOGRAPHY BY CARLI ROUSH

Rachael Putman tests the safety and efficacy of triplex gene editing

technology, which uses peptide nucleic acids.

Designer babies, genetic remodeling, risks in clinical trials: in

today’s rapidly evolving field of biomedical engineering, ethical

dilemmas rage. But for Rachael Putman (TC ’19), it’s simple:

“The whole point of medicine is to help people heal. If we can

take gene editing and make it do that in a safe and effective way,

then it’s something that we should pursue,” she said.

Putman, a Missouri native, matriculated to Yale College

without any prior research experience, but was quickly hooked

by Professor Mark Saltzman’s master class on in-utero brain

research. She reached out to Saltzman for a position in his lab,

and took her first steps in research. After honing her technical

laboratory and research skills under Saltzman’s tutelage, Putman

began investigating in vivo gene editing in mouse fetuses

alongside Adele Ricciardi, an MD-PhD student at the Yale

School of Medicine.

As a collaborative effort between the Saltzman laboratory

and the laboratory of Professor Peter Glazer, Putman and Ricciardi

are testing the safety and efficacy of triplex gene editing

technology, which uses peptide nucleic acids (PNA). Unlike

other gene editing techniques, such as CRISPR and TALEN,

PNAs allow for a safer gene repair by avoiding double-strand

breaks in the host DNA. Once the PNA is safely inserted into

the cell, it binds to the targeted mutation in the DNA and creates

a triple strand. The cell then recognizes and removes the

PNA-bound segment from the genome, creating a gap. A short

piece of DNA delivered with the corrected base pairs is then

used as a template to fix the gap created by PNA.

“We tried to focus on safety and see if we were getting any

off-target effects,” Putman said. “Through our analysis, we

couldn’t find any, which may give it an advantage over other

technologies like CRISPR.”

Putman and Ricciardi apply this gene editing pathway to cure

human models of disease, such as cystic fibrosis, β-thalassemia,

and sickle cell disease, in mouse fetuses. Nanoparticles that contain

PNA strands are delivered to mouse fetuses and the mice

are tested for the absence of disease after birth. “We were able to

show that we got disease improvement after birth; the mice were

healthy when they were born,” Ricciardi said.

A successful direction in this project led Putman to an even

more fundamental question: can we do this even earlier? In

other words, if site-specific genome editing works in fetuses,

could it work in single-cell embryos? In many genetic diseases,

organ damage can take place early on during the fetal stage of

development. However, these diseases can often be identified

at the embryonic stage if a mother undergoing in vitro fertilization

chooses to screen for genetic diseases before implantation.

If gene editing can be performed within the first days of

life, there is a possibility that the fetus will undergo completely

healthy organ development. With hopes of clinically translating

her work with mice embryos, Putman embarked on her

own project: Synthetic Nanoparticle Delivery to Mouse Embryos

for Site-specific Genome Editing.

For her work with these two projects, Putman received the

Arnold and Mabel Beckman Foundation award in 2017 and

presented her work at the Beckman Scholars Annual Research

Symposium for the following two summers in Irvine, CA. Putman

was one of two Yale College students in the class of 2019

to receive this distinction.

Outside her research, Putman is the president of Demos, a

service group that makes science education more accessible

to students in New Haven public elementary schools. She

also teaches a class about genetics to neighboring middle and

high school students through Splash at Yale. As Putman serves

younger scientists through her volunteer work, she attributes

her own successes to mentorship. “I had two really wonderful

teachers throughout middle school and high school,” Putman

said. “What they taught me was that we all have things we’re

good at and are passionate about. What is more important is to

follow your passions and see where they lead you.”

36 Yale Scientific Magazine October 2018 www.yalescientific.org


ALUMNI PROFILE

ERIC FOSSUM (PhD ’84)

THE MAN BEHIND THE CAMERA

BY KHUE TRAN

IMAGE COURTESY OF ERIC FOSSUM

Eric Fossum sits next to a computer screen displaying a CMOS image sensor.

Professor Eric Fossum (PhD ’84), 2018 recipient of the Yale Science

& Engineering Association Award for Advancement of Basic

and Applied Science, compares his work as an image sensor device

physicist and engineer to solving a puzzle. “It’s like taking knots

out of a ball of string,” Fossum said. “It’s helpful to have that background

in physics and engineering and if you have experience, you

know what things work and don’t work. Sometimes a new idea

flashes in your head and suddenly you get the idea.”

Fossum was born in Simsbury, Connecticut and attended

Trinity College from 1975 to 1979, earning a Bachelor of Science

in Physics and Engineering. He worked for a computer

company as a computer programmer throughout high school

and college to pay for his education. He then attended Yale University

for graduate school and earned a PhD in Engineering

and Applied Science. Fossum immensely enjoyed working with

the engineering school professors at Yale. He and other graduate

students called themselves the “Ma-Barker gang” in reference to

Fossum’s professors and mentors, Tso-Ping Ma and Richard C.

Barker. “I’ve worked on image sensors my entire life,” Fossum

said. “But Yale was the start of all that.”

In 1982, when Fossum was in his second year at Yale, he applied

for the Howard Hughes Fellowship, through which he was able

to spend the summer working for an aerospace company. He was

exposed to infrared imaging devices for defense applications and

became interested in exploring imaging devices for the rest of his

graduate education. Fossum was interested not only in camera devices,

but also in other imaging devices like the naked human eye.

“Image capture devices are interesting,” Fossum said. “They combine

physics and engineering—photons, light, optics, semiconductor

devices and microelectronic circuits—and a whole camera

system. You really get to work in many disciplines simultaneously.

Instead of seeing waveforms on an oscilloscope, you get to see a

picture from your work, which is rewarding.”

Currently, Fossum is a professor at Dartmouth and doing research

on the Quanta Image Sensor (QIS), an innovative image

sensor that has the potential to revamp the previous CMOS sensor

and the entire camera system. This new type of camera chip is

sensitive to single photons of light and, thus, could allow the user

to capture light at the smallest possible level. This produces images

of higher quality, even in situations of low light. The camera

chip can detect electromagnetic energy and can now measure a

million pixels, each one sensitive to a single photon of light. Fossum

says the chip has far-reaching applications, from the visualization

of distant objects in space to the capture of quality images

in dim light for consumer use. He and his former PhD students

are also currently working on Gigajot, a startup company based

in Southern California, to commercialize QIS.

Beyond his research, Fossum has always had a natural passion

for teaching, whether in science or other subjects. He

taught while at Yale and immediately took a faculty position

at Columbia University teaching electrical engineering after

graduate school. He finds his current job as a professor at

Dartmouth very rewarding and hopes that through his teaching,

his students recognize that engineering and the liberal

arts are more than learning equations and facts.

In his free time, Fossum likes to go out to his farm in New

Hampshire where he is able to face other challenges and work

directly on the task at hand. “You start with nothing and you

get to create something out of it—you can see what you have

done,” Fossum said. “When you work in science, you’re not always

sure what you accomplished at the end of the day.”

With that being said, Fossum definitely has plenty to show for

his work. In fact, the success of the CMOS sensor was due, in his

opinion, to the multitude of uses that have emerged for it in contemporary

society. Smartphone cameras that use CMOS sensors

are used daily for recreational photography or to be shared through

social media in capturing protests, social movements or, as Fossum

points out, acts of injustice such as the video recording of David

Dao, the man being dragged off the United flight. “Now that there

is a video recording of the circumstances, it changes your view of

the incident,” Fossum said. “A person can get justice when that

might not have happened without ubiquitous camera use.”

www.yalescientific.org

October 2018

Yale Scientific Magazine

37


21 LESSONS FOR THE 21ST CENTURY

B Y J A C K M C A R T H U R

Every day, millions of communications are sent around the globe that wouldn’t be possible without modern

technology. Though modern connectivity has many benefits, the sudden onset of the Technological Age has

turned the 21st century into a uniquely unpredictable era. Historian Yuval Noah Harari discusses a wide range

of possibilities for the future in his bestseller 21 Lessons for the 21st Century, a collection of 21 essays on looming

problems in the modern world and predictions for their consequences. Harari investigates closely how science

will change society, and how we can avoid a dystopia by making science accessible.

The Technological Age is changing the world in unprecedented ways. Nations can surveil their citizens and

censor their information intake, giving them a sovereignty over their citizens that fallen dictatorships would

envy. Technology may also be phasing out low-skilled jobs. In prior waves of automation, people who lost their

jobs moved into the service industry. Soon, however, Harari believes artificial intelligence will outperform humans

in cognitive abilities like communication skills and interpreting emotions. Will they overtake the service

industry, too? If AI integrates into the service industry, will it lead to a societal restructuring—like how the

Industrial Revolution transformed feudal Europe into a society with empowered workers?

In addition to changing the world we experience, Harari suggests technology could control our minds as well. We are

transitioning from one era, in which nations were united by loyalty to our tribes, to the next, where Big Data and AI know

IMAGE COURTESY OF NASACOMMONS FLICKR

scie

in

spot

exactly what information to feed constituents for their allegiance. Though Harari’s view of the future of technology is often

insightful, other times it borders on paranoid. He takes an extreme view on the future of this computer-manufactured

allegiance, saying that the biotech and infotech industries will soon allow us to kill thoughts at will. He also makes a bleak

analogy that Kim Jong-Un could one day have biometric sensors that determine if his propaganda elicits anger.

In this way, Harari warns of science’s becoming a tool of oppression, separating scientists and the powerful from

the ignorant. Harari believes that we can avoid this dystopian scenario if we can better communicate scientific ideas

to the public. This means having scientists appear in public debates, publishing documentaries, or even writing

sci-fi novels; art plays a key role in shaping people’s views of the world, and sci-fi can dictate how people feel about

scientific debates. From a political perspective, these are far more valuable than publishing papers in journals; they

create a more scientifically-aware population that will protect research endeavors for generations to come.

In a New York Times Op-Ed, Bill Gates agrees that Harari’s views are sometimes radically pessimistic. Gates

doesn’t foresee technology integrating as deeply into our lives. Notably, Gates disagrees with his claim that

data is the world’s most valuable resource, instead nominating real estate for the title. Though bleak at times,

Harari’s work is thought-provoking and raises some critical conversations about our global future.

38 Yale Scientific Magazine October 2018 www.yalescientific.org


As the string ensemble emerges, we’re treated to familiar footage: the shadow of the lunar module gliding

across the pockmarked surface of the moon, men in white button-downs with eyes glued to the consoles

in front of them, and finally, the landing and first steps. This time, a woman’s voice crackles over the radio,

and you’re forced ask—why weren’t the first people in space women? Mercury 13 is a 2018 Netflix documentary

that demands an answer to that question.

The story kicks off at the beginning of NASA’s manned spaceflight program in 1958. NASA appointed a

physician, Dr. Lovelace, to create and administer physical and mental tests on aspiring astronauts. Lovelace

felt that woman had a definite role in space, so with encouragement from Jackie Cochran, a close friend

and pioneer for women in aviation, he decided to recruit 25 outstanding female pilots to undergo the same

astronaut tests administered to men for his own Women in Space program. This testing involved injections

of 10-degree water in recruits’ ears, tube-swallowing, x-rays, and hours in sensory deprivation tanks.

Thirteen women passed the first phase of testing with flying colors. Officially called First Lady Astronaut

Trainees, they came to be known as the Mercury 13.

Before testing could continue, however, they were stopped by NASA. The program was over. But of course,

the future of women in space was not. Decades later, at the launch of Discovery’s STS-63 mission in 1995,

nce

the

light

IMAGE COURTESY OF NASACOMMONS FLICKR

the first female space shuttle pilot, Eileen Collins, took the microphone and told the entire launchpad at

Cape Canaveral, “If it were not for the Mercury 13, I would not be here today.” Before a montage showing

women on board the International Space Station, we get the best shot of the documentary: footage of the

surviving members of the Mercury 13 clapping, crying, and grinning, elated, as Discovery roars into the sky.

The ending of Mercury 13 leaves you misty-eyed and hopeful, like most stories about progress. However,

the documentary chose to tell a very specific narrative. Sally Ride and Mae Jemison, both historic “firsts” in

the story of women in space, are never mentioned by name, possibly because neither was a pilot; Mercury

13 is the story of thirteen female aviators, but given the focus on how the thirteen impacted the future of

women in space, these omissions seem odd. Perhaps the documentary could have done away with some of

the footage of planes and spent more time on the history of female astronauts between the Mercury 13 and

Eileen Collins. They could have expanded their history of women in aviation by exploring the roles women

of color, such as Bessie Coleman, played in the development of the field during the mid-19th century. Aside

from these missteps, Mercury 13’s bittersweet story still resonates today as STEM fields struggle to welcome

individuals they have excluded for ages.

B Y H A N N A H G E L L E R

ONE SMALL STEP FOR A WOMAN

www.yalescientific.org

October 2018

Yale Scientific Magazine

39


Welcome to Yale!

The Yale Science and Engineering

Association is here for you.

Founded in 1914, the YSEA is one of the oldest university student/alumni

organizations in the world with a focus on STEM.

Whether near or far from New Haven, we help our members realize their

goals and to connect in ways that strengthen the Yale science and

engineering community.

We are excited to be a part of your Yale journey, and we look forward to

supporting you at Yale and beyond!

Join us at: ysea.org

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Contact us at

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