YSM Issue 91.1

Yale Scientific 

Established in 1894 

THE NATION’S OLDEST COLLEGE SCIENCE PUBLICATION 

MARCH 2018 VOL. 91 NO. 1 | $6.99 

SNEAKING 

ORGANS 

PAST THE 

IMMUNE SYSTEM 

15 

DELIVERING 

18 

A TALE OF ICE 

20 

BRAVING 

THE INHIBITOR AND SNOW 

THE COLD

Yale Scientific Magazine 

VOL. 90 ISSUE NO. 5 

CONTENTS 

MARCH 2018 

NEWS 6 

FEATURES 25 

ON THE COVER 

12 SNEAKING 

ORGANS PAST THE 

IMMUNE SYSTEM 

Current research done by Mark Saltzman 

and Jordan Pober combines 

techniques from multiple fields— 

nanoparticle delivery and transplant 

techniques—to improve long-term 

results after transplant surgery. 

15 

DELIVERING THE 

INHIBITOR 

Cancer, diabetes, and many other 

diseases involve dysregulation of 

the same signaling pathway critical 

for regulating protein function. 

Researchers have developed a 

drug delivery system facilitating the 

inhibition of proteins implicated in 

the disruption of this pathway. 

18 

A TALE OF ICE AND 

SNOW 

Why do clouds behave the way they 

do, sometimes producing snow and 

ice and rain? Yale professor Amir Haji-Akbari 

investigates these processes 

using computational techniques. 

20 

BRAVING THE 

COLD 

Yale researchers identify a genetic 

adaptation in certain species of 

rodents that reduces their sensitivity 

to the cold, allowing them to hibernate 

in temperatures just above 

freezing. 

22 DIVERGENCE 

What makes the human brain so 

unique? Although it is around three 

times larger than the brains of our 

closest living relatives, the complexity 

in the connections between cells and 

the differences between cells themselves 

hint at a deeper explanation. 

www.yalescientific.org 

More articles available online at www.yalescientific.org 

March 2018 


3

Q&A 

HOW COLD CAN WATER GET? 

By Alice Tao 

Way colder than you’d think! In fact, water 

doesn’t always freeze when the temperature 

reaches zero degrees Celsius, the 

value regularly cited as the freezing point 

of water. Under certain conditions, water 

can undergo “supercooling” and exist in 

a liquid state far below its usual freezing 

point—at temperatures as low as -42.6 degrees 

Celsius. 

Previously, researchers encountered difficulties 

determining the lowest possible 

temperature of liquid water due to the rapid 

rate of ice crystal formation. In Germany, 

Robert Grisenti at the GSI Helmholtz Centre 

for Heavy Ion Research is developing 

new techniques for accurate measurement 

of the temperature of supercooled water 

with greater precision than ever before. 

Grisenti’s team began by spraying microscopic 

droplets of water into a vacuum. The 

exceptionally low pressure in the vacuum 

DO PENGUINS SNACK? 

By Hannah Verma 

Male emperor penguins have long 

been thought to make the ultimate sacrifice: 

fasting for almost three months 

as they guard their eggs. As it turns out, 

however, the penguins are not quite as 

selfless as they’ve previously been portrayed. 

Researchers from the Scripps 

Institution of Oceanography discovered 

that male emperor penguins sometimes 

break their fast during the incubation 

period. 

Typically, females leave the egg with 

the males for approximately for three or 

four months; the male’s feet keep the egg 

warm by cradling it with a fleshy layer 

of skin. Scientists have long thought 

that the male penguins stay by the 

egg’s side at all times during this period. 

They often spend these bone-chilling 

Arctic months sleeping to preserve 

their energy, but they still lose up to 

IMAGE COURTESY OF PEXELS 

Grisenti’s team supercooled water to -42.6 degrees 

Celsius. 

IMAGE COURTESY OF FLICKR 

Two emperor penguins stand protectively over a young 

chick. 

causes fast evaporative cooling, where 

evaporation cools the tiny water droplets 

much faster than ice can form. With 

the understanding that droplet size is 

proportionally related to temperature, 

the researchers determined the droplets’ 

temperature by measuring their size 

with a laser that had 10-nanometer precision. 

They calculated a record low for 

liquid water, -42.6 degrees Celsius. 

Supercooled water and its transformation 

into atmospheric ice occur naturally 

in the Earth’s upper atmosphere. 

“Atmospheric climate models need an 

accurate representation of such processes 

for a realistic description of cloud formation 

and precipitation,” Grisenti said. 

The hope is that this research can ultimately 

provide leading climate scientists 

with better insight for developing more 

reliable climate-predicting models. 

half of their body weight. It is such a 

challenging task that some emperor 

penguins do not survive the winter. 

Other males, however, have other 

ideas. After tracking several emperor 

penguins, the researchers observed 

that these males snuck off 

in the middle of the night to hunt 

for fish in the open water. This phenomenon 

is thought to be more 

common among penguin colonies 

based near the southern coast, 

where the journey to the ocean is 

much shorter. These “early feedings” 

are significant because they 

increase the male’s chance of survival 

in the winter. By snacking, the 

male makes it far more likely that 

he will successfully incubate the egg 

and ensures the chick’s chance at 

life in the coming months.

Science belongs to everyone. 

From doctors and biomedical engineers to astronomers and ecologists, science forms the 

roots from which we grow. With science, we explore our planet and beyond, from modeling 

the mysteries of the clouds in our sky (pg. 18) to imaging the galaxies that exist beyond the 

scope of our sight (pg. 30). We attempt to describe the life that surrounds us, including bird 

feather patterns (pg. 9), dog behavior (pg. 11), and butterfly evolution (pg. 34). We push the 

limits of science to create new technologies and innovations such as quantum computers 

(pg. 6), infrared imaging satellites (pg. 7), and dandelion lab tools (pg. 35). 

But perhaps most importantly, science contributes to people. From exploring depression 

(pg. 8), to inspiring young researchers (pg. 36), to challenging diabetes (pg. 32) and 

attacking HIV (pg. 10), science drives our emotional, mental, and physical progress. Our 

lives are supported and shaped by the scope of our scientific understanding and thus we 

are defined by science and science is defined by us. This now brings us to you, the readers, 

and the people that we hope to inspire. 

Our cover article this issue gives hope towards a future of both improved organ transplant 

outcomes and of increased transplant organ viability and thus availability (pg. 12). 

This future is an encapsulation of the discoveries that mark years of progress in many 

fields of research, where each breakthrough is built on the previous. But what are we 

building towards? 

The interconnected nature of science creates a pattern of progress that cannot begin to 

be described as uniform. A step in one direction may lead to many in another, and thus the 

nonlinearity of scientific discovery becomes increasingly evident. It is our responsibility 

as scientific journalists to explore the direction of each scientific path and ultimately map 

these fields of discovery. We attempt to guide you through what seems to be a labyrinth of 

research and progress. We aim to understand science and share this understanding. 

With our new 2018 masthead comes a new era of writing, editing, and design. We maintain 

the same scientific excitement and curiosity that our predecessors celebrated and 

shared with us. We cherish your continuing support and your high expectations, both of 

which serve as inspirations for future improvement. I asked earlier what we are building 

towards; the reality may be that we approach nothing in particular. Rather, we build towards 

everything. Just as the universe expands, science reaches in all directions. It is driven 

by the passions of people and thus represents the ideas of all. Science is shared and we are 

lucky to be the ones to share it with you. 



THE NATION’S OLDEST COLLEGE SCIENCE PUBLICATION 

MARCH 2018 VOL. 91 NO. 1 | $6.99 

SNEAKING 

ORGANS 

PAST THE 

IMMUNE SYSTEM 

DELIVERING 

A TALE OF ICE BRAVING 

15THE INHIBITOR 18 20 

AND SNOW 

THE COLD 

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

Sharing Science 

A B O U T T H E A R T 

Eileen Norris 

Editor-in-Chief 

I’m so excited to serve as arts editor this upcoming 

year with YSM’s amazing board! For my 

first cover piece, I wanted to capture the magnitude 

of a new breakthrough in organ transplant 

technology. I illustrated a surgeon’s hands 

cradling a precious kidney, an organ that tens 

of thousands of Americans are in desperate 

need of, that has been treated by a nanoparticle 

drug delivery system represented in glowing 

green. By decreasing the frequency of organ 

rejections, more patients will receive their vital 

organs more quickly-making this a wonderful, 

revolutionary development in medicine. 

Editor-in-Chief 

Managing Editors 

News Editor 

Features Editor 

Articles Editor 

Online Editor 

Copy Editors 


M A G A Z I N E 


MARCH 2018 VOL. 91 NO. 1 

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NEWS 

in brief 

THE ROLE OF ERROR IN QUANTUM 

COMPUTING 

By Victoria Dombrowik 

COURTESY OF QUATRONICS LABORATORY 

An image of a mother board, the most 

important piece of a binary computer. 

The future of information technology may 

be in the qubit. The term, a combination of 

quantum and bit, is used to refer to an electronic 

circuit that functions as the basis of 

quantum computing. It relies on the principle 

of superposition, which holds that a physical 

system may exist simultaneously in two different 

states. While the computer bits of today 

can store information in either a 0 or 1 

state, qubits are capable of storing a 0 and 1 at 

the same time, expanding the ability to cache 

data exponentially. Such a device could function 

with unimaginable speed and precision, 

making considerable advancements in fields 

like medicine and cyber security. 

The next step is to build a quantum computer 

that is capable of using qubits. The 

foremost problem facing developers today is 

the extreme sensitivity of quantum systems. 

Even a slight interaction of the qubit with 

the surroundings could lead to decoherence, 

or a slow collapse of the quantum mechanical 

properties of the system, which would 

in turn lead to errors in calculations. Michel 

Devoret, the F. W. Beinecke Professor of Applied 

Physics at Yale University, and his team 

at the Quantronics Laboratory are investigating 

a method to improve coherence through 

the use of quantum error correction, which 

protects the integrity of the qubit. Quantum 

error correction does this correcting for both 

decoherence and quantum noise, which is the 

uncertainty in the original quantum system. 

They believe that mastering this technique 

will lead to the design of systems that remain 

coherent indefinitely. Devoret was also optimistic 

about the future of the quantum computer. 

“There is no roadblock, no physics that 

would prevent it. If it is possible, then humans 

will find a way to create it.” 

TRIGGERING THE RESPONSE 

By Alice Li 

PHOTOGRAPHY BY WIKIMEDIA COMMONS 

An image of a healthy human T-cell. 

You probably had a sore deltoid muscle 

after your flu vaccine this year. This is because 

this standard shot is delivered straight into 

muscle. But there’s another problem besides 

you getting a sore shoulder: by injecting the 

vaccine into the muscle, the vaccine bypasses 

most of the potent cells needed to initiate 

an immune response, meaning high vaccine 

doses must be given to stimulate immunity. 

In an epidemic, however, there might not be 

enough vaccine to immunize everyone with 

the high doses needed for muscle injection. 

To find a better injection site, a team 

of scientists led by professor Stephanie 

Eisenbarth from the Yale School of Medicine 

investigated immune cells responsible for 

generating an effective vaccine response. 

The team knew that antigens in the vaccine 

activate immune cells called T-follicular 

helper cells (Tfh), which in turn enable a 

second type of immune cell, the B-cells, to 

make antibodies. However, the scientists 

found that another type of immune cell, 

called Type 2 dendritic cell, recognizes the 

antigens from vaccines and presents them to 

Tfh cells, which then activate B-cells in an 

immune cell relay race. 

Vaccinating into muscle misses most of the 

dendritic cells needed to initiate the response 

chain. Instead, the findings, published in 

Science Immunology, suggest a new injection 

site for your next flu shot: the skin. “If we 

deliver the vaccine through the skin, then 

we are presenting the vaccine directly to the 

dendritic cells,” said Eisenbarth. This means 

that existing vaccine stores less likely to run 

out in the case of an epidemic, and that the 

vaccine can be more widely available. 

This new delivery method creates a more 

effective immune response and requires 

only one-tenth of the original dose. While 

injecting into the skin is more painful, the 

10-fold increase in efficiency outweighs the 

additional discomfort. 

6 Yale Scientific Magazine March 2018 www.yalescientific.org

in brief 

NEWS 

UNDER THE SEA: UNUSUAL MANTLE 

BEHAVIOR 

By Tiger Zhang 

Though hidden, Earth’s interior is full of 

activity. Heat from Earth’s interior drives 

plate tectonics, the movement of giant slabs 

of the Earth’s crust. At certain areas, such 

as along the coast of Chile, one plate slides 

under another, sinking into the mantle in 

a process called subduction. New research 

by Yale geoscientists Kanani Lee, associate 

professor of geology and geophysics, and 

graduate student Jie Deng helps explains why 

subducting plates do not sink directly down, 

but stagnate at around 1000 km in the lower 

mantle. 

The researchers studied ferropericlase, the 

second most abundant mineral in Earth’s 

mantle, under high temperature and pressure 

conditions simulating Earth’s interior. By 

looking at how ferropericlase’s melting 

behavior affects its viscosity, or its resistance to 

flow, the researchers hypothesized that around 

1000 km below Earth’s crust, ferropericlase 

helps create a region in the mantle a hundred 

times more viscous than the surrounding 

rock. 

This layer would hinder the sinking of 

tectonic slabs, causing the slabs to buckle 

and stagnate. In the other direction, the layer 

would affect mantle plumes, such as those 

beneath Hawaii and Iceland, that contribute 

to volcanic activity. The layer’s high viscosity 

would slow down and deflect plumes of hot 

rock rising from Earth’s core, causing the 

plumes to bend sideways. 

“There have been other ways to explain 

the stagnation of subducting slabs, however 

this mechanism also explains the deflection 

of rising plumes,” Lee said. This new theory 

is the first to account for both stagnation of 

subducting plates and deflection of mantle 

plumes. 

COURTESY OF WIKIMEDIA COMMONS 

Volcanic activity in hot spots such as the 

Hawaiian Islands is fed by rising plumes 

of hot rock. The upward movement 

of the plume is altered by the high 

viscosity rock present around 1000 km 

below the Earth’s surface. 

NIGHTTIME LIGHTS, DATA, ACTION 

By Erica Lin 

Close your eyes and imagine yourself on 

the moon. It is night, and before you, the 

glow of cities, sprawl, and human activity 

illuminate Earth. 

Yale Professor of Geography and 

Urbanization Karen Seto and Ph.D. 

Candidate Eleanor Stokes spend their time 

marveling at these lights—but not with their 

bare eyes. Instead, they see through the eyes 

of Visible Infrared Imaging Radiometer 

Suite (VIIRS), a real-time sensor on the 

NASA/NOAA Suomi-NPP satellite that 

collects high-resolution nighttime imagery 

of Earth. 

The Seto Lab processed raw VIIRS 

imagery and analyzed nighttime light 

intensity patterns for cities across the globe. 

They discovered that after accounting for 

confounding factors like light pollution or 

moon reflectance, VIIRS data acts as a proxy 

for electricity usage within individual cities. 

The connection between nighttime lights 

and electricity usage may seem intuitive, 

but previous metrics have typically relied on 

national rather than localized data, leading 

to misgeneralizations about individual cities’ 

energy usages. Thus, VIIRS provides more 

precise energy usage analyses. “I’m very 

excited about the scope, that it’s global, yet 

we also look at the within-urban scale to 

assess the world,” Stokes said. 

Cities can use the new data to tackle 

local sustainability issues. Potential VIIRS 

applications include facilitating disaster relief 

planning, foreign urbanization development, 

and transportation sustainability. For 

example, tracking road connectivity via 

lights could pinpoint traffic-congested 

zones in need of redesign, and tracing light 

usage after earthquakes may reveal areas 

with limited resource access. Indeed, VIIRS 

can drive sustainability efforts by using 

data relevant to each glowing city in our 

illuminated world. 

PHOTOGRAPHY BY NASA EARTH OBSERVATORY 

Nighttime lights map of the United 

States 


March 2018 


7

NEWS 

psychology 

KNOW TOO MUCH? 

The downside of genetic testing for depression 

BY SUNNIE LIU 

Picture yourself as a participant in a study: you receive a kit 

containing mouthwash and a color-changing strip of paper. 

Sleek text on the professional label reads “Saliva Self-Testing Kit 

for 5-Hydroxylindoleacetic Acid.” Following the instructions, 

you rinse your mouth and hold the test strip to your tongue, 

immediately transforming the test strip from blue to brownish 

green. While this kit may appear to be a saliva-based genetic 

test, it is actually a placebo test. However, you were not the only 

person fooled; 786 participants in the study also believed that 

the kit was a real genetic test. 

In this study, Yale psychologist Woo-Kyong Ahn and Columbia 

University postdoctoral research fellow Matthew S. Lebowitz explored 

the negative effects of genetic testing for depression, which 

had been mostly overlooked during the growing popularization 

of personalized genetic testing for explaining and predicting 

health issues in the twenty-first century. Public opinion is shifting 

to believe that depression and other mental disorders, like physical 

diseases, stem from biological causes, leading to higher interest 

in genetic testing for mental disorders. 

“There was hope that genetic testing would further decrease 

the stigma around mental health issues,” Lebowitz explained. 

However, only recognizing the benefits of genetic testing leaves 

out details about potentially adverse consequences, resulting in a 

dangerously overoptimistic view of genetic testing. This recently 

published Yale Thinking Lab study helped show the emotional 

downside of genetic testing that so often gets ignored. 

The researchers divided the participants into three groups: a 

depression gene-absent group and two depression gene-present 

groups. The test strip turned brown for all three groups, so all 

the participants received the same placebo test results, but the researchers 

randomly assigned different meaning to the results. The 

gene-absent group was told they did not carry the gene that would 

make them more susceptible to depression, while both gene-present 

groups were told that they carried the gene. 

One of the two gene-present groups watched a short intervention 

video explaining that genes alone cannot make a person depressed 

because complicated factors—such as epigenetics, which 

turn genes on or off, the interactions between many different 

genes, and environmental and experiential factors—also play important 

roles in the development of depression. The other group 

did not. Finally, all three groups completed a Negative Mood Regulation 

(NMR) scale, which measures how well one expects to be 

able to control one’s negative emotions in the future. 

The gene-absent group reported higher NMR scores than the 

two gene-present groups, suggesting that the gene-present groups 

felt less confident in their ability to cope with depressive symptoms 

than the gene-absent group. In other words, the people who 

thought they were genetically predisposed to depression felt more 

helpless and hopeless in regulating their mood, and thus, viewed 

themselves as more susceptible to depression. “We basically created 

depression in three minutes,” said Ahn. 

Adding further complexity, the gene-present group shown 

the educational video scored significantly higher on the NMR 

scale than the gene-present group who did not watch the video. 

This difference in NMR scores demonstrates that the educational 

video effectively mitigated the negative effects of the genetic 

testing on the people who believed that they were genetically 

disposed to depression. 

Personalized genetic testing for susceptibility to depression and 

other mental disorders is already common among the general 

public and will most likely become even more prevalent in the 

future. Ahn thinks the popularity of genetic testing keeps growing 

because it promises easy answers, even if they may be misleading. 

“Genetic testing is a way for people to simplify this complicated 

world, but problems arise with oversimplifying,” said Ahn. 

Celebrating only the beneficial aspects of genetic testing overlooks 

its negative implications, potentially leading to tragic clinical 

effects. For example, this study showed that genetic testing for 

depression could actually increase one’s risk for depression, because 

test results showing genetic predisposition to depression exacerbate 

people’s pessimism in their ability to cope with and overcome 

depressive symptoms. This negative consequence of genetic 

testing is especially concerning because faith in one’s own possibility 

of overcoming depression can be a self-fulfilling prophecy, 

so abandoning self-confidence can prevent improvement. 

The researchers hope their results will spark thoughtful consideration 

of genetic testing. “I would like for people who are otherwise 

gung-ho about rolling out genetic testing in all fields to be 

more cautious,” said Lebowitz. 

COURTESY OF DR. AHN 

Photograph shows closed container of “Saliva Self-Testing Kit for 

5-Hydroxylindoleacetic Acid,” the fake genetic testing kit used in 

the study. 


ecology 

NEWS 

THE SINGLE BIRDS’ BAR 

The evolution of super-black feathers in birds-of-paradise 

BY MIRIAM ROSS 

IMAGE COURTESY OF WIKIPEDIA 

The feathers of the superblack bird of paradise trap all of the light. 

Just like a teenager before a first date, male birds-of-paradise 

spend hours checking their looks and practicing their dance 

moves. But unlike a teenager, who might change clothes five 

times before leaving the house, male birds-of-paradise wear the 

same outfit their whole life, so they make it as flashy as possible. 

Their plumage is astonishingly black, much more so than any tuxedo. 

A new study by Yale researchers Todd Harvey and Richard 

Prum examined what causes the velvety, super-black quality in 

the feathers of these birds. 

Understanding the processes behind bird coloration is important 

to understand evolution, sexual selection, and speciation. 

Birds-of-paradise have some of the most intricate courtship 

dances and feather coloration in the world, making them 

ideal to study. The researchers hypothesized that the birds’ super-black 

feathers evolved to intensify the perceived brightness 

of neighboring colorful feather patches, appealing more to females 

during the courtship dance. 

Two processes contribute to bird feather coloration. Molecular 

pigments absorb light only at specific wavelengths, reflecting 

the rest to produce color. The second process, known as structural 

absorption, generates color by scattering light at multiple 

angles. In both cases, we see the reflected light as color. A material 

that reflects all light will appear white, and a material that 

absorbs all light will look black. 

The researchers discovered that the birds’ super-black color 

comes from this second process of structural absorption. When 

light is scattered, the feather absorbs some of that scattered light. 

By causing more scattering, structurally absorbent objects like 

bird feathers can take in more light and appear much darker. 

Bird-of-paradise feathers look so black because they are essentially 

trapping all the light. 

The researchers studied the function of this structural absorption 

in feathers from seven different bird-of-paradise species. 

They discovered that super-black feathers structurally absorbed 

99.95% of incoming light, the most efficient rate of any natural 

material. The shape, position, and texture of feather barbs and 

barbules, hook-like structures holding the feather together, all 

affect the coloration. The experimenters found that the barbule 

arrays of super-black feathers tilted vertically, forming deep and 

curved structural cavities. 

The scientists hypothesized that the tilted feather microstructure, 

combined with the courtship dance, evolved to elevate vibrant 

feathers to their maximal brilliance. In both butterflies and 

birds-of-paradise, super-black areas are located next to structurally 

colorful feathers. The super-black feathers make other colors 

appear brighter by eliminating the environmental signals females 

typically use to judge color intensity. Specifically, they override 

specular highlights, the spots of light that show up on illuminated 

shiny objects, and define physical boundaries. The feathers absorb 

all the incident light, making the neighboring colors seem so radiant 

they lose their boundaries and hover in space. 

The researchers also found that super-black feathers have a 

strong directional reflectance bias, making them look darkest 

when facing a viewer head on. Male birds-of-paradise strut their 

stuff at a particular angle relative to watchful females, consistent 

with the optimal angle for a super-black appearance. 

However, only feathers used in the courtship dance were super-black. 

Other feathers, such as those on the birds’ backs, reflected 

more light. The difference in structure and color between 

feathers involved in the courtship dance and those that are not 

was striking, suggesting a highly specialized purpose. “Other organisms 

that evolved super-black, a West African viper, or a butterfly...in 

both cases they evolve this super-black material for a 

different purpose than our birds-of-paradise,” said Harvey. “Our 

birds-of-paradise are not developing it for camouflage...they’re developing 

it because it makes them shockingly beautiful to a mate.” 

But much research remains to understand in what ways structural 

absorption and multiple scattering of light affect the female 

birds’ color correction. Moving forward, Prum’s lab will likely focus 

on how female birds-of-paradise perceive a male’s plumage 

during a courtship dance. Furthermore, the researchers hope that 

super-black feathers will inspire new biomimetic materials. Structural 

absorption has major potential for a variety of mechanical, 

thermal, and solar technologies, like the lining inside space telescopes. 

Perhaps, like a male bird-of-paradise, the next batch of 

space photography will blind us with its beauty. 


March 2018 


9

NEWS 

medicine 

ERADICATING HIV 

Targeting latently-infected T-cells 

BY GRACE CHEN 

IMAGE COURTESY OF NIH 

Scanning electron micrograph of a T cell infected infected with HIV. 

One of the most pressing problems today in the effort to 

eradicate HIV is latency. Infected T cells may harbor the virus 

but lie dormant for years, making up a latent reservoir 

that evades the drugs, which effectively kill only active cells 

replicating the virus. Researchers have recently discovered 

a new way to uncover cells harboring latent forms of the virus, 

opening the door to a new approach to extinguishing 

reservoirs of infected T cells inside a patient’s body. 

Recently published in Nature Scientific Reports, the 

project was headed by Linda Fong, a graduate student in 

the laboratory of Kathryn Miller-Jensen, Associate Professor 

of Biomedical Engineering at Yale University. Her 

team studied five cell-signaling pathways in an attempt 

to distinguish infected cells from healthy ones. Signaling 

pathways are essential in multicellular organisms, since 

they facilitate how external and internal stimuli trigger 

changes in cells. These changes include events like releasing 

a hormone or expressing a gene. Before Fong’s team 

could study these pathways, however, they needed to reactivate 

the latently infected T cells. 

To do this, several classes of latency reversing agents 

(LRAs) were used to stimulate the cells. One type of LRA 

functions by opening up the cell’s chromatin, where the 

virus’s genetic information is found, to allow for the transcription 

and expression of the HIV genome; others are 

able to activate specific proteins leading to expression of 

the HIV genome. These agents are currently of great interest 

to HIV researchers looking to “activate-and-kill” the latent 

reservoir. 

Once the T cells were treated with LRAs, researchers 

compared levels of kinase phosphorylation in infected cells 

and healthy ones. Kinases are enzymes that play an essential 

role in cell signaling pathways by transferring a phosphate 

from ATP, a molecule in which energy is stored, to another 

molecular substrate—usually a key protein in a cell signaling 

pathway—effectively activating or deactivating the 

protein. This transfer releases energy so that the signaling 

pathway can continue. The researchers realized that infected 

cells exhibit a significantly higher level of kinase phosphorylation 

than do healthy cells. Mathematical analyses 

further confirmed that the extent of variation in phosphorylation 

between infected and healthy cells was sufficient to 

differentiate them. This increased level of phosphorylation 

in infected cells indicates that the virus has managed to deregulate 

crucial cell processes, shedding light into one of 

the many ways the virus impacts the cells harboring it. 

“You can imagine that if scores of scientists were working 

on this, you could find so many other pathways that are 

dysregulated,” Fong said. “That comes back to pathway engineering 

and the idea that you can get a cell to do what you 

want if you understand its circuitry.” 

Previous research has compared latently infected and 

healthy T cells in a state prior to reactivation by LRAs. 

These studies were unable to find an accurate, specific way 

to distinguish latently infected T cells from healthy cells. 

These findings could have meaningful clinical implications, 

and Fong is working towards eventually conducting 

trials in HIV patients. For now, she has transitioned from 

testing healthy cells that are manually infected with HIV to 

working with cells extracted from the blood of HIV-positive 

patients. Ultimately, Fong and her team hope that their 

work will enable more selective and specific eradication 

strategies that target only infected T cells while leaving the 

healthy ones intact in patients with HIV. 

IMAGE COURTESY OF LINDA FONG 

Linda Fong pipettes her samples in the Miller-Jensen Lab. 


evolutionary biology 

NEWS 

THINKING ON FOUR FEET 

Peering into the mystery of canine eye contact 

BY GRACE NIEWIJK 

PHOTO BY LINDA CHANG 

Eye contact may have facillitated the healthy relationship between 

humans and dogs. 

Humans use eye contact all the time, from bonding with 

our babies to sharing an awkward glance with someone 

during an embarrassing situation. Eye contact isn’t just 

for humans though—dogs use it too. Man’s best friend has 

learned to use eye contact to connect and communicate 

with humans extraordinarily well. Researchers at Yale’s Canine 

Cognition Center (CCC) set out to learn more about 

how this behavior developed over the course of the domestication 

process by comparing dogs, wolves, and dingoes. 

We can learn a lot about ourselves by observing the 

behavior of animals that spend a lot of time around us. 

“Across domestication, dogs have come to learn from humans 

in much the same way as human children learn from 

adults, so dogs and dingoes offer us the unique opportunity 

to examine how these human-like abilities may have 

evolved,” said Yale graduate student Angie Johnston. Johnston 

works in the CCC alongside Laurie Santos, Ph.D., 

who directs the center, observing canine behavior to answer 

these types of questions. 

Back in 2015, a Japanese group found that both dogs and 

humans experience a rush of oxytocin—a hormone associated 

with bonding and warm fuzzy feelings—when they 

make eye contact with each other. In contrast, wolves that 

underwent the same experiments rarely made eye contact 

with their handlers and didn’t show similar oxytocin 

spikes even when their eyes did meet. 

For dogs, eye contact has practical uses that extend beyond 

warm fuzzy feelings. When dogs were given a difficult 

puzzle to solve, they looked at their owners more 

frequently, seeking help or looking for solutions based on 

where the human’s gaze is directed. On the other hand, 

labs that compared dogs’ problem-solving behavior to 

wolves’ found that the wolves tackled the puzzle independently 

and mostly ignored the humans. 

The CCC added nuance to these previous studies by collecting 

observations from Australian dingoes that underwent 

the same experiments. Wolves are considered the standard 

undomesticated ancestor; in contrast, dingoes associate frequently 

with humans but have never been selectively bred 

like dogs. The last shared ancestor between dingoes and 

modern dogs existed roughly 5000 years ago. As a result, dingoes 

represent an intermediate step in canine domestication. 

By studying dingoes, researchers can notice subtle effects 

of complete domestication that may be overlooked 

when comparing dogs to wolves. “If we see differences in 

dogs and dingoes, it’s coming from a really tiny window 

of domestication,” said Santos. The dingoes in this recent 

study made eye contact with humans less often than dogs, 

but more often than wolves, indicating that some motivation 

to make eye contact developed even before the tiny 

window separating dingoes and dogs. 

“Our study in particular suggests that eye contact between 

humans and canids may have evolved relatively early 

in the domestication process, before humans began actively 

breeding dogs,” said Johnston. “This is significant 

because it suggests that one of the most foundational aspects 

of canine social cognition was already being shaped 

very early in domestication.” 

The results led researchers to hypothesize that the 

bond between humans and dogs may have developed in 

two stages. Early efforts at domestication might have favored 

dogs that showed some tendency to make eye contact, 

since that would have elicited some of the same warm 

fuzzy feelings as parent-child eye contact. Once some 

bond was established, humans probably started treating 

dogs as social partners, which would have prompted dogs 

to start learning eye contact as a form of communication. 

Looking ahead, Johnston expresses enthusiasm about 

how she expects this research to move forward. She’s especially 

interested in diving deeper into social cognition 

and the communicative aspects of eye contact. She 

points out that understanding domestication and canine 

cognition not only helps unravel history but can also 

have practical implications for our day-to-day interactions 

with the canines in our lives. “Understanding more 

about how the bond between our two species develops 

may help promote healthy relationships between people 

and their pet dogs, therapy dogs, service dogs, and emotional 

support dogs,” she said. 


March 2018 


11

FOCUS 

biotechnology 

Sneaking Organs 

Past the Immune 

System 

By SONIA WANG 

Art by SUNNIE LIU 

12 Yale Scientific Magazine April 2015 www.yalescientific.org

The diagnosis comes in: patient X has end-stage 

renal failure. His kidneys no longer work, and he has 

the choice of either staying hooked up to a machine 

for dialysis treatment a few times each week, or 

obtaining a transplant organ. Luckily, he is able to 

receive a donated kidney—hard to come by. 

biomedical engineering 

FOCUS 

But a new diagnosis comes in three 

months after the surgery: his new kidney 

is failing. His body has rejected the new organ, 

and his immune system is slowly eating 

away at it. Once again, he is forced to begin 

dialysis treatment, depending on a blinking 

machine to carry out the same function that 

his kidneys used to do. 

This story is not uncommon: around fifteen 

to twenty percent of kidney transplants 

fail within five years of transplantation. Currently, 

the main way physicians attempt to 

decrease the rejection rate is by giving patients 

drugs that suppress the immune system, 

thereby reducing the body’s ability to 

attack and reject the transplant. 

But Yale researchers are seeking to develop 

a new way to reduce immune rejection. A 

long-standing study done by Yale professors 

Mark Saltzman and Jordan Pober in collaboration 

with researchers at Cambridge University 

seeks to use carefully designed, tiny 

nanoparticles to deliver drugs to transplant 

organs before they are placed in the body. 

They hope their process will improve longterm 

outcomes for transplant patients. 

America’s transplant problem 

The organ transplant waiting list is a national 

list compiled by the United Network 

for Organ Sharing (UNOS), a non-profit established 

to manage the federal organ transplant 

system and to objectify the complex 

matching process between donors and recipients. 

Factors such as a patient’s medical 

urgency, the compatibility between donor 

and recipient, and the time on the waiting 

list guide how organs are distributed. 

Despite this, there are around 116,000 

people waiting for a vital organ transplant, 

while in 2017 there were only about 35,000 

organ transplants. The average wait time for 

a liver transplant is around 11 months; for a 

kidney transplant that number increases to 

5 years. 

Even after a patient receives a transplant, 

there’s still no guarantee that their new organ 

will prove an effective treatment. In the case 

of a bad match between the recipient and 

donor, the recipient’s immune system will 

recognize the new organ as a foreign object 

and will attack it, sometimes damaging it irreversibly. 

Though transplant rejection can 

be minimized using drugs that suppress the 

immune system, these immunosuppressant 

drugs can make the patient more susceptible 

to other diseases. 

Patients need a more targeted approach to 

prevent the immune system from destroying 

the transplant, but also allow normal immune 

function to occur—perhaps through 

a delivery system of some sorts. Enter Professor 

of Biomedical Engineering Mark 

Saltzman, who has long worked on using 

nanoparticles to create better drug delivery 

systems. 

Small but mighty 

What is the smallest object visible to the 

human eye? Those with imperfect vision 

might squint to see the words on a page in 

front of them. Others might say a human 

hair, just 0.1 millimeters wide, or 10 percent 

of the width of your typical credit card. The 

typical human cell is far smaller than what 

the eye can see—around ten cells can fit in 

the thickness of a single average hair. But 

on the nano-scale, thousands to hundreds 

of thousands of tiny nanoparticles can fit 

across a hair. 

Science has turned its focus to nanoparticles 

as a potential drug delivery mechanism 

because of their size. Because they are so tiny, 

they not only have a comparatively large surface 

area available for reactions, but also are 

able to cross cell and tissue barriers that current 

delivery systems cannot, making them a 

more efficient system for drug delivery. 

The key is finding ways to engineer 

nanoparticles to target specific cells, such as 

delivering growth-suppressing drugs to tumors 

in cancer patients. Nanoparticles can 

IMAGE COURTESY OF FLICKR 

Nanoparticles can be used to target drug 

delivery to specific types of cells. 

be designed with specific properties to increase 

their effectiveness—for instance, by 

giving them a positive charge to interact better 

with the drug they are carrying. Antibodies 

that recognize and bind to characteristic 

targets on the cell types of interest can also 

be attached to the surface of the nanoparticles 

to make the delivery more specific. 

In a typical transplant organ, the circulating 

blood from the host primarily interacts with 

cells that line the blood vessels of the transplant 

organ called endothelial cells. White 

blood cells, the fighters of the immune system, 

are found in the blood and interact with 

major histocompatibility complex (MHC) 

proteins found on the surface of the endothelial 

cells. If an MHC protein not typically 

produced by the body is found, then the white 

blood cells hone in on those cells and initiate 

inflammatory responses, which can then kill 

the cells of the transplant organ. 

IMAGE COURTESY OF WIKIMEDIA COMMONS 

A kidney facing end stage renal disease. After 

kidney failure, patients can only be put on 

dialysis or undergo transplant surgery. 


March 2018 


13

FOCUS 

biomedical engineering 

perfused for one to two hours, we could treat 

them in other ways to make them less prone 

to rejection,” Saltzman said. 

The researchers decided to target CD31, 

a protein found on all endothelial cells. 

Nanoparticles coated with antibodies able to 

recognize CD31 were injected into the perfusion 

device while blood passed through 

a donor kidney, along with a non-targeted 

set of nanoparticles without the antibodies. 

The results, a colorful set of images showing 

where each set of nanoparticles accumulated, 

indicated that targeted particles could 

accumulate to levels two to five times higher 

than in the control group, whereas some 

areas showed profound targeting with levels 

up to ten times higher than the control. 

“That was one surprise. No one ever 

looked at where particles go in a human organ 

before at this level,” Saltzman said. “It 

allowed us to make some hypotheses about 

what would give you the best distribution 

through the kidney.” 

But by effectively showing that nanoparticles 

can be targeted to the endothelial cells of 

an organ through machine perfusion, the researchers 

are one step closer to engineering 

a drug delivery system that can use machine 

perfusion to improve transplant outcomes. 

Combining past and present 

Yale professor Mark Saltzman’s lab works on nanoparticle drug delivery systems. 

Some approaches now aim to mask the 

transplant organ from the immune system 

by decreasing the amount of MHC protein 

recognizable as foreign. Jordan Pober, Professor 

of Immunobiology at Yale, has long 

been interested in the role of endothelial 

cells in the immune response. Together with 

Saltzman, he worked on a project in which 

MHC protein was deleted in a mouse with 

a transplanted human artery by delivering 

molecules called small interfering RNAs 

(siRNAs) through a nanoparticle delivery 

system. This effectively prevented the immune 

system from attacking the transplant 

and allowed the new organ to heal. 

But another problem with current drug 

delivery systems is that injecting drugs into 

the bloodstream may not get to the target at 

sufficient levels to be effective. Thus, Pober 

and Saltzman began collaborating with researchers 

from the University of Cambridge 

to create a system able to treat organs to improve 

long-term outcomes, before they are 

even transplanted into the body. 


There is still far more to go, and the researchers 

have received another grant to 

work on the project. “It’s a new area. We’re 

treating human organs outside the body, and 

[there are] studies we need to do to show this 

is safe before we can use them in humans,” 

Saltzman said. “But I love the mystery.” 

Right now, the research on machine perfusion 

has shown that scientists can target 

endothelial cells, but getting to the right targets—the 

cells on the transplant organ—is 

another question. “Now the question is can 

we improve the delivery, but also can we 

choose the right targets,” Pober said. Saltzman 

and Pober hope to combine their research 

on knocking down MHC proteins in 

the transplant organ with their research on 

machine perfusion, in hopes of creating a 

new transplant treatment system to improve 

outcomes. 

“There just aren’t enough organs. Now 

there are two things you can do about that: 

one, to have people who have [transplants] 

to keep from losing them, and second, using 

tissue engineering to keep [transplants] 

from the invading immune system,” Pober 

said. They hope to decrease the frequency of 

the first. 

In the future, hopefully cases like Patient X 

will be far less common through the help of 

treatments being developed by Saltzman and 

Pober’s labs. And with an increase in viability 

of organs, perhaps the organ transplant 

waiting list will decrease and more people 

will receive life-saving treatments. 

Targeting from the start 

Ex vivo normothermic machine perfusion 

(NMP) is a mouthful to pronounce, but it may 

be the key to improving transplant outcomes 

and increasing the number of transplant organs 

available. The process involves pumping 

warm blood at body temperature through a 

transplant organ outside of the body, keeping 

the organ alive for longer and helping to 

repair damage to the organ. This allows even 

organs that previously did not seem viable to 

become suitable for transplantation. 

“We thought, if these organs were being 

ABOUT THE AUTHOR 

SONIA WANG 

SONIA WANG is a current senior in Jonathan Edwards College majoring in Biochemistry and 

Economics. She used to be managing editor and news editor for the Yale Scientific, and looks 

forward to writing more for them this semester. She currently works in the Joan Steitz lab on 

microRNA degradation. 

THE AUTHOR WOULD LIKE TO THANK Mark Saltzman and Jordan Pober for giving their time to 

this article. 

FURTHER READING 

Tietjen, Gregory T., et al. “Nanoparticle targeting to the endothelium during normothermic machine 

perfusion of human kidneys.” Science translational medicine 9.418 (2017): eaam6764. 


DELIVERING 

THE INHIBITOR 

Delivering therapeutic treatments 

to cancer, diabetes, and 

neurodegenerative targets 

by Mindy Le 

art by Elissa Martin 


December 2017 


15

FOCUS 

organic chemistry 

Within our bodies’ cells, 

a myriad of chemical 

reactions orchestrate life. 

These reactions ensure our health and are 

essential to all of our bodily functions, including 

metabolism and homeostasis within 

the bodily environment. But when these reactions 

are unable to function properly, disease 

can result. 

One of the important chemical reactions 

that occur in our bodies is protein tyrosine 

phosphorylation, which is a modification 

of newly synthesized proteins. When regulation 

of this reaction is disturbed, diseases 

such as diabetes, cancer, and neurodegeneration 

arise. Jonathan Ellman, Professor of 

Chemistry and Pharmacology at Yale, and 

his team of researchers have developed a 

method for delivering therapeutic drugs to 

target certain proteins involved in the dysregulation 

of the protein tyrosine phosphorylation 

pathway. 

Striking a balance 

During protein tyrosine phosphorylation, 

a phosphate molecule is added to an amino 

acid called tyrosine, which is a common 

building block of proteins. To help the reaction 

happen more efficiently, this addition 

is catalyzed by an enzyme called protein tyrosine 

kinase. Kinases are a class of proteins 

that add phosphates to other molecules. 

Proteins tyrosine kinases act concurrently 

with protein tyrosine phosphatases (PTPs), 

which remove phosphate groups from tyrosine. 

The body requires a proper balance of 

these kinases and phosphatases to ensure a 

proper balance of tyrosine phosphorylation 

levels on proteins within our cells. 

The wide and seemingly unrelated range of 

diseases related to dysregulation of protein 

tyrosine phosphorylation pathways suggest 

a universal importance for these molecules 

within our bodies. Specifically, it highlights 

the significance of the enzymes that catalyze 

such reactions. Of particular interest are the 

aforementioned PTPs, a family of enzymes 

with the general function of removing phosphate 

groups from tyrosine. For example, 

bacterial PTPs have interestingly been found 

to exacerbate infections such as tuberculosis. 

Medical interest in PTPs arose due to their 

implications in human disease. However, 

challenges involving PTP-based drugs have 

made such research and drug development 

difficult. “PTPs continue to be challenging 

targets for progressing inhibitors to the clinic 

because their active sites are highly conserved 

and charged,” Ellman said. Active 

sites are areas within enzymes such as PTP 

that specifically bind to protein targets. For 

PTPs, the target is the phosphate group on a 

tyrosine found within different kinds of proteins. 

Because PTP active sites are charged 

and conserved, meaning that they possess an 

electrical charge and are universal to many 

PTP types, designing drugs to specifically 

target and successfully react at the active site 

is tricky. “Thus, it is difficult to develop inhibitors 

that are potent and selective against 

a specific PTP while also having appropriate 

physicochemical properties to be effective 

drugs, such as level of polarity to efficiently 

cross cell membranes,” Ellman added. 

Motivated to study PTPs, Ellman tackled 

the problem of PTP drug development 

by designing a platform to inhibit PTPs for 

disease treatment. The platform consists of 

glutathione-responsive selenosulfide prodrugs 

that have a specific function of inhibiting 

PTPs. Prodrugs are inactive precursors 

to drugs that, once processed by the body, 

can exert their biological function in a controlled 

manner. This selectivity in the prodrug’s 

mechanism is crucial for designing and 

understanding how the prodrug acts within 

the human body. 

The mechanism 


As part of their drug delivery system, Ellman 

made use of the natural concentration 

differences of this molecule, glutathione, in 

order to deliver their PTP inhibitor. Glutathione 

is an antioxidant important for preventing 

damage to our cells. 

Glutathione (GSH) is an antioxidant important 

for preventing free radical damage 

to our cells, which is spontaneous damage 

that occurs all over our body due to things 

like ultraviolet (UV) radiation from sunlight 

and even from the body’s own metabolism. 

GSH is synthesized in our body from food 

sources obtained from our diet. Because 

there is a large difference between GSH levels 

inside and outside of our cells, the research 

group used this natural difference in 

concentration to activate a specific PTP inhibitor, 

which comes from a novel group of 

chemicals called selenosulfide phosphatase 

inhibitors. This class is named after the key 

part of the inhibitor structure responsible 

for labeling the enzyme: the inhibitor targets 

a sulfur-containing group found within 

the phosphatase enzyme, hence the “sulfide” 

in the name. The researchers chose the 

GSH-responsive motif as a method for prodrug 

delivery due to these cellular properties. 

The drug’s mechanism of action relies on 

its selenosulfide pharmacophore, the part of 

the drug that is responsible for its pharmacological 

interaction, which reacts with cysteine, 

an amino acid in the active site of PTP, 

to form a product that inhibits PTP. The inhibitor 

is useful because its structure contains 

sites available for certain molecules to 

be added in order to change the potency and 

selectivity of the inhibitor for a specific PTP. 

The researchers then took their platform 

further by developing specific PTP inhibitors 

that could act against two PTP targets: 

the virulence factor mPTPA secreted by Mycobacterium 

tuberculosis and the striatal-enriched 

protein tyrosine phosphatase (STEP), 

a tyrosine phosphatase that is specific to the 

central nervous system. They chose to do 

this as a proof-of-concept experiment to 

demonstrate the efficacy of their prodrug 

platform. Both molecules were found to inhibit 

their respective targets potently and selectively. 

Drug efficacy in the test tube 

Tuberculosis, the lung disease that infects 

one-third of the world’s population 

and causes over one million annual deaths, 

is caused by the Mycobacterium tuberculosis 

bacterium. On top of that, over 50 million 

people develop multidrug resistant tuberculosis, 

and current treatments for this disease 

are limited. As such, when two PTPs secreted 

by the bacterium, mPTPA and mPTPB, 

were identified as potential drug targets, this 

discovery spurned new interest in developing 

tuberculosis treatments. “Tuberculosis 

drug resistance is a serious, ongoing prob- 


organic chemistry 

FOCUS 

lem and often occurs through mechanisms 

that limit a drug’s accessibility to its biomolecular 

target. Tuberculosis PTPs are intriguing 

because the bacteria secrete these 

enzymes, rendering them much more accessible 

than the targets of most tuberculosis 

drugs, which reside within bacterial cells. 

However, additional research is needed to 

validate mPTPA and mPTPB as drug targets,” 

Ellman remarked. 

This work also addressed a key problem 

in PTP inhibitor development. Namely, 

there is a high amount of structural similarity 

among PTPs that makes it difficult 

to achieve high selectivity of their developed 

inhibitors. The researchers evaluated 

the selectivity of their mPTPA inhibitor 

against a collection of known human PTPs, 

and also a generic cysteine protease, which 

is an enzyme that breaks down proteins using 

a key cysteine amino acid found within 

the protein of interest. Here they found that 

their mPTPA inhibitor had great selectivity 

against each enzyme in this panel, indicating 

that their inhibitor could act in a controlled 

and predictable manner. 

Drug efficacy in a biological setting 

After testing their PTP inhibitors in a testtube 

setting, the next step was to evaluate their 

prodrug in a cellular context. However, in animal 

models, it was found that both mPTPA 

and mPTPB inhibitors were needed for significant 

antibacterial activity. Because they 

chose only to develop an inhibitor against 

mPTPA at this stage of their research, they instead 

decided to develop selenosulfide prodrug 

inhibitors to another PTP target in order 

to do a more simple and straightforward analysis 

of the prodrug activity in the cell. 

The second target, STEP, is a central nervous 

system (CNS)-specific tyrosine phosphatase 

that may be a therapeutic target for 

neurological disorders like Alzheimer’s disease. 

After testing a variety of potential prodrugs, 

they identified one that could inhibit 

STEP in rat cortical neurons. 

After demonstrating the activity and specificity 

of their PTP inhibitors, they reported 

their success in developing a prodrug strategy 

to facilitate the delivery of a novel class of 

PTP inhibitors into cells in an efficient manner. 

Their development of inhibitors for two 

PTPs that can selectively inhibit mPTPA and 

STEP very potently also acted as a robust 



Protein tyrosine phosphatase (PTP), shown here, is a target for treatment for several diseases 

including diabetes, cancer, and neurodegenerative disorders. Researchers at Yale have designed a 

method for delivering PTP inhibitors in order to restore balance of tyrosine phosphorylation levels 

within our cells. 

proof-of-concept demonstration, showing 

that their strategy for targeting PTPs is feasible 

and has great potential. 

Future promises of PTP-inhibitor drugs 

In the future, Ellman hopes to expand 

upon this research. “We intend to investigate 

a number of questions to advance the 

approach. For example, we will evaluate proteome-wide 

specificity of identified inhibitors,” 

he said. Of the inhibitors developed 

in his lab so far, their group will need to see 

how these inhibitors act across the entire 

proteome, which is the collection of all proteins 

present in our cells. In doing so, they 

can determine if the inhibitor acts on a different 

protein or group of proteins that was 

not anticipated, which could have severe 

consequences if the inhibitor targeted a protein 

essential for our survival. 

Furthermore, Ellman hopes to expand 

upon the collection of PTP inhibitors already 

developed in his lab. “We additionally 

intend to test the generality of the approach 

by developing potent and selective inhibitors 

of other PTPs as well as other enzymes,” 

Ellman said. If successful, this could result 

in a greater number of potential drugs for 

disease treatment involving PTP inhibition. 

For example, some PTPs have been implicated 

in cancer, and inhibitors of these enzymes 

have been suggested as potential 

drug candidates to be used in combination 

with immunotherapy treatments. Although 

such treatments would require more study 

and clinical tests, the future of cancer treatment 

using PTP inhibitors remains promising. 

The use of PTP inhibitors extends 

beyond cancer treatment, having vast implications 

in both neurodegenerative disorders 

and diabetes, two diseases with wide prevalence 

in society that warrant crucial further 

research and drug development. 

MINDY LE 

MINDY LE is a junior in Ezra Stiles College studying Molecular, Cellular, and Developmental 

Biology. She is an avid squirrel enthusiast who works in Professor Patrick Sung’s lab, researching 

DNA repair in the context of breast and ovarian cancer. 

THE AUTHOR WOULD LIKE TO THANK both Professor Jonathan Ellman and Caroline Chandra Tjin 

for their time and dedication to their research. 


Tonks, N. K. 2013. “Protein tyrosine phosphatases--from housekeeping enzymes to master regulators of 

signal transduction.” FEBS J. 280: 346-378. 


March 2018 


17

Surprises 

in the 

CLOUDS 

Understanding cloud 

behavior through 

computational modeling 

by CHRISTINE XU | art by LAUREN GATTA 

On some days during the coldest months 

of winter, we are greeted by fluffy snow 

falling from the sky when we venture outside. 

On other days, it’s rain or an unpleasant 

combination of freezing sleet and snow. 

What comes from the clouds on a given day 

might seem random, but scientists are coming 

up with new ways to predict these seemingly 

mysterious weather patterns. 

Amir Haji-Akbari, assistant professor of 

Chemical and Environmental Engineering 

at Yale, uses computational simulations to 

study how ice and snow form from microdroplets 

of water in clouds. Clouds are large, 

visible masses of condensed water vapor 

floating high up in the atmosphere; studying 

the behavior of the water molecules 

that make up these clouds can therefore 

help scientists understand different weather 

patterns. Haji-Akbari employs computer 

models to predict how the water droplets in 

clouds form into frozen particles in a process 

called nucleation, providing some insight 

into weather patterns. 

“Ice formation is a very important component 

of what happens in clouds. It’s a very 

important part of cloud microphysics, and 

the amount of ice you have in a cloud determines 

how likely it is to produce rain and 

snow,” Haji-Akbari said. 

Clouds contain water droplets that are light 

enough to float in the air without falling. 

These water droplets come from evaporating 

water from the Earth’s surface that condenses 

or freezes as it gets higher up in the atmosphere, 

often times around a nucleus such as 

a dust particle or an aerosol. Eventually, that 

water comes back to the Earth’s surface in the 

form of rain or snow. However, it is unclear 


environmental science 

FOCUS 

IMAGE COURTESY OF PIXABAY 

Computational techniques can be used to examine the processes that occur within clouds containing microdroplets of water that can condense to 

form ice and snow. 

how and when water droplets and ice crystals 

form, and scientists like Haji-Akbari are trying 

to develop new ways of understanding the 

physics behind these processes. 

In a recent study published in PNAS, Haji-Akbari 

investigated how the vapor-liquid 

interface affects the freezing of water molecules. 

He simulated the formation of two 

different types of ice crystal structures called 

the hexagonal cage structure and the double 

diamond cage structure. The hexagonal 

cage structures tend to be found in the kind 

of ice we see in everyday life, because their 

chemical structures make them more stable. 

Double-diamond cage structures, on the other 

hand, are typically found in cubic ice and 

only form at extremely low temperatures. By 

studying the behavior of these ice structures, 

Haji-Akbari analyzed how likely they were to 

form under various conditions. Specifically, 

he observed that the vapor-liquid interface 

in thin films of water promotes the formation 

of double-diamond cages. Haji-Akbari’s findings 

answer longstanding questions about ice 

formation near surfaces. 

In order to carry out his study, Haji-Akbari 

used computational techniques to simulate 

molecular behavior, which involves 

generating models to predict events on a microscopic 

scale in a way that wouldn’t be possible 

through traditional physical experimentation. 

One technique used was forward flux 

sampling, which maps out the pathway that a 

system takes during the occurrence of a rare 

event, such as ice and snow formation. 

“These are phenomena that occur very 

quickly, but you have to wait a very long time 

for them to occur,” Haji-Akbari said. “You can 

think of, for example, a power outage. You have 

to wait a long time for it to happen, but when 

it happens it happens in a matter of seconds.” 

Haji-Akbari studies how a system transitions 

from the pre-rare event to the post-rare event 

state, such as when ice forms in clouds. 

Haji-Akbari is now pursuing several other 

research questions that build on his past findings. 

He is interested in a phenomenon called 

contact freezing, in which a collision between 

a liquid droplet and a dry nucleating particle 

causes freezing. The question is whether 

the mechanical impact of the collision causes 

freezing, or whether this is due to an interaction 

between the solid-liquid and liquid-vapor 

interface. Additionally, Haji-Akbari is studying 

how new computational methods could better 

predict the waiting time required for rare 

events such as ice formation to occur. 

This research has many applications not 

only in understanding and predicting climate 

patterns but also in potentially developing 

strategies to address climate-related 

issues. For instance, cloud seeding is a 

technique already used in many parts of the 


world to induce rain. In cloud seeding, crystals 

such as salts are dispersed into clouds in 

order to provide additional nuclei for droplet 

condensation. Haji-Akbari’s research focuses 

on a related process, liquid droplets 

nucleating to form ice crystals. He hopes 

that research such as his will improve on the 

efficiency and safety of techniques to modify 

the weather, for instance to induce or prevent 

snow and ice formation. 

Haji-Akbari pointed out climate patterns 

around the world that have recently been 

disrupted by climate change, noting examples 

of drought in several countries. To him, 

asking and trying to address scientific questions 

about atmospheric dynamics can lead 

to a better understanding of our environment 

and even the ability to change the climate. 

“These are problems that are not only 

theoretically interesting, but also useful for 

the challenges that our society and our species 

face in the world,” Haji-Akbari said. 

CHRISTINE XU 

CHRISTINE XU is a senior in Saybrook College. She has been writing for Yale Scientific Magazine 

since her freshman year and was the previous News Editor. She enjoys both nonfiction and 

creative writing, and also does neurobiology research at the Yale School of Medicine. In the future, 

she hopes to pursue a career in medicine, research, and writing, and importantly would like to 

own a cat. 

THE AUTHOR WOULD LIKE TO THANK Dr. Haji Akbari for both his time and his enthusiasm in 

sharing his work. 


Haji-Akbari, Amir, and Pablo G. Debenedetti. “Direct calculation of ice homogeneous nucleation rate 

for a molecular model of water.” Proceedings of the National Academy of Sciences 112, no. 34 (2015): 

10582-0588. doi:10.1073/pnas.1509267112. 

Haji-Akbari, Amir, and Pablo G. Debenedetti. “Computational investigation of surface freezing in a 

molecular model of water.” Proceedings of the National Academy of Sciences 114, no. 13 (2017): 3316- 

321. doi:10.1073/pnas.1620999114. 


March 2018 


19

FOCUS 

neuroscience 

BRAVING 

THE COLD 

A genetic adaptation makes certain 

squirrels and hamsters immune to the cold 

by Elizabeth Ruddy 

art by Emma Wilson 

You step outside of your building, 

bundled up in four different layers and 

a marshmallow coat. Buried beneath 

scarves, hats, and gloves, it’s still not 

enough to keep the cold out. Your face 

stings from the biting wind, and you 

can feel icicles forming on your nose. 

There’s snow melting in your boots and 

you’ve long since lost the ability to feel 

your hands. You feel like you’ll never be 

warm again. While we may cower in the 

face of cold weather, for some animals, 

the cold is no big deal. In fact, they don’t 

even feel it. 

A team of researchers at Yale led by Elena 

Gracheva and Sviatoslav Bagriantsev 

are currently investigating a molecular adaptation 

in the Syrian hamster and a species 

of squirrel native to North America, 

called the thirteen-lined ground squirrel, 

that enables them to endure harsh winters. 

The body temperatures of these rodents 

adjust to match the air around them, 

enabling them to hibernate for months in 

temperatures just above freezing without 

noticing the gruelling winter. 

Bring on the cold 

The root cause of this ability comes down 

to genetics. “Being sensitive to the cold 

would prevent the rodents from hibernating, 

much like how being cold would 

prevent us from sleeping,” Gracheva said. 

Therefore, there must be some quirk in 

their DNA that allows them to withstand 

the extreme cold for such extended periods 

of time. 

In behavioral studies performed on the 

rodents, the researchers found that when 

While we may cower in 

the face of cold weather, 

for some animals, the 

cold is no big deal. In 

fact, they don’t even feel 

it. 

given the choice between two plates of 

different temperatures, the squirrels and 

the hamsters did not avoid the cold as 

strongly as mice did. This suggests that 

there are genetic differences among rodents 

that allow some species to endure 

the cold but not others. This diminished 

sensitivity to the cold could be 

caused by a number of different factors 

such as a reduced ability to perceive cold 

in the nerves responsible for registering 

temperature, known as somatosensory 

nerves, or a suppression of the instinct to 

avoid cold in the central nervous system 

of certain rodents. 

A cold-sensing protein 

In a study published in Cell Reports, 

Gracheva and her colleagues found that by 

imaging the somatosensory neurons of the 

rodents, they were able to isolate the adaptation 

to a specific protein called TRPM8. 

TRPM8 is an ion channel, which is a type 

of protein found in a cell’s membrane that 

allows specific charged atoms or molecules 

to pass through. Many ion channels open 

and close in response to certain stimuli in 

order change the electric potential of the 

cellular membrane, and thus are particularly 

important in allowing nerve cells to 

relay electrical signals to the brain. Specifically, 

TRPM8 is a cold-activated ion channel—when 

the temperature decreases, this 

channel opens and excites neurons, leading 

to generation of electrical signals that 

are transmitted throughout the rodents’ 

nervous system. “The neuron then sends 

electric impulses to signal to the brain that 


neuroscience 

FOCUS 

cold temperature has been encountered,” 

Bagriantsev said. 

Something different in the TRPM8 of 

the thirteen-lined ground squirrels and 

Syrian hamsters makes the protein insensitive 

to the cold. Upon isolating the protein, 

the researchers were able to identify 

the adaptation in a specific group of six 

amino acids, the building blocks of proteins, 

that are the difference between cold 

sensitive and cold insensitive organisms. 

Although the scientists do not know exactly 

when the hibernators developed this 

adaptation evolutionarily, they do know 

that the squirrels and the hamsters developed 

it independently. “They use different 

structural elements at the molecular 

level but arrive at the same end product, 

which is cold-insensitive ion channels,” 

Gracheva said. 

Because the adaptations were developed 

independently, there are slight differences 

in temperature reactions between the 

two species. Specifically, hamsters are 

slightly more sensitive to the cold than 

the squirrels. However, when compared 

to species without the adaptation, such as 

the mice, these differences are negligible. 

In a previous report published by the lab, 

researchers found that the thirteen-lined 

ground squirrel is also extremely resistant 

to heat, enabling it to survive in harsh climates 

such as deserts, though this ability 

stems from an adaptation in a protein 

other than TRPM8. 

Next steps 


The Syrian hamster has also demonstrated a 

marked tolerance for the cold. 

Now that the exact adaptation has been 

located, the researchers are working 

to reintroduce cold sensitivity into the 

TRPM8 of the squirrels and hamsters by 

substituting their key amino acids for the 

ones found in the mice. The researchers 

are also attempting the opposite—inserting 

genetic substitutions into the mice to 

see if they can become cold-insensitive. 

Through this research, the team has taken 

significant steps towards a better understanding 

of the hibernation puzzle. Scientists 

still do not fully understand what 

induces hibernation among certain species 

and how it is possible biologically. For 

example, little is understood about what 

causes heart rates to slow down, how these 

species go months without consuming nutrients 

or water, or how the animals do not 

lose bone mass during this time of inactivity. 

TRPM8 is one piece to the puzzle. The 

genetic adaptation explains how certain 

hibernating species can sleep through 

extremely cold temperatures. However, 

it is not that TRPM8 becomes cold-insensitive 

specifically for the hibernation 

period. Rather, the adaptation is encoded 

in their DNA such that they have this 

cold-insensitivity from birth. “We still 

don’t know everything about what causes 

hibernation,” Gracheva said. “It’s possible 

that certain genes do turn on when 

the rodents enter this state but TRPM8 is 

not specifically related to hibernation. It 

is cold-insensitive all the time.” 

In addition to studying hibernation, 

the group also plans to investigate whether 

cold-insensitive rodents can adapt to 

temperatures below ten degrees Celsius. 

The group’s goal is to the test the limit of 

the animals’ tolerance, as well as to try to 

understand how these animals ward off 

hypothermia. 

Potential human applications 

Don’t put away your jackets yet though, 

because even though the researchers are 


IMAGE COURTESY OF ELENA GRACHEVA 

Graphical abstract of the difference between 

the cold-insensitive rodents and the control 

group of mice. 

working on replicating the cold-insensitivity 

in mice, there’s a long way to go before 

we could even think about substituting 

the adaptation into humans. 

But there are other ways this research 

applies to humans—specifically in the 

field of medicine. For example, one major 

detriment to chemotherapy is that patients 

often develop an extreme aversion 

to even mild cold. It is possible that this 

research could be used to minimize these 

effects and help patients be able to better 

tolerate the cold. 

“This study furthers our understanding 

of how vertebrates, including humans, 

feel cold. It will help develop 

approaches toward better organ preservation 

and contribute to the development 

of novel techniques for lowering 

human body temperature, which is required 

during some medical procedures 

and may be useful for long-term space 

travel,” Bagriantsev said. 

So good luck tomorrow on your walk 

through the bitter February cold. Just 

remember to channel your inner thirteen-lined 

ground squirrel. 

ELIZABETH RUDDY 

ELIZABETH RUDDY is a Sophomore Physics major in Berkeley. She enjoys dancing, writing for the 

Yale Scientific, and hibernating. 

THE AUTHOR WOULD LIKE TO THANK Professor Gracheva and Professor Bagriantsev for sharing 

their time for this article. 


Kimzey, S. L. “Temperature Adaptation of Active Sodium-Potassium Transport and of Passive Permeability 

in Erythrocytes of Ground Squirrels.” The Journal of General Physiology, vol. 58, no. 6, 1971, pp. 634– 

649., doi:10.1085/jgp.58.6.634. 


March 2018 


21

FOCUS 


DIVERGENCE 

The Molecular and Cellular Basis of the Human Brain Evolution 

by Anna Sun || art by Emma Healy 

Millions of years have passed since humans parted ways with our closest nonhuman 

primates on the evolutionary pathway. During this time, humans have developed 

languages and writing skills, harnessed fire and begun cooking, created 

innovative technologies that now govern our daily lives, and even studied how life itself 

works. So why have no other nonhuman primates ever rivaled our level of cognitive ability? 

In hopes of answering that very question, 

much debate among scientists today 

centers around the differences between 

the brain structures of humans and nonhuman 

primates. While some argue that 

the larger size of the human brain alone 

is responsible for higher-order thinking, 

others insist that there is more to the story. 

Perhaps in addition to increased size, 

the connections between cells and the 

different cells themselves provide a better 

explanation. André Sousa and Ying 

Zhu, researchers at the Yale School of 

Medicine, analyzed tissue samples from 

sixteen regions of the brain to further investigate 

the cellular and molecular differences 

between human and nonhuman 

primate brains. Examining individual 

gene expression differences in the brains 

of chimpanzees, macaques, and humans, 

these researchers discovered human-specific 

differences in the expression of the 

TH gene responsible for dopamine production 

and the MET gene that is related 

to Autism Spectrum Disorder, gaining 

insight into the basis of certain neurological 

and psychiatric disorders. 

Our closest relatives 

In order to determine human-specific 

differences in the brain structures, the 

researchers chose to study chimpanzees, 

our closest living relative, as well 

as the rhesus macaque, one of the most 

commonly studied nonhuman primates. 

“Ideally, the easiest way to study human 

brain evolution would be to analyze 

the brains of all extinct human species,” 

Sousa remarked. However, since 

the brain does not fossilize, he and his 

colleagues instead had to compare the 

human brain with the brains of our closest 

living relatives to determine which 

features are most likely human-specific. 

For ethical reasons, they could only use 

postmortem tissue for direct molecular 

experimentation. 

The researchers particularly analyzed 

the upregulation or downregulation of 



FOCUS 

genes, to correspondingly compare increased 

or decreased gene expressions 

in different parts of the brain in the 

different species studied. “What drives 

these differences in gene expression are 

often changes in regulatory non-coding 

regions,” explains Sousa. “Additionally, 

mutations in non-coding regions of 

DNA don’t change the protein product, 

but rather change when, where, and how 

much is produced.” 

Because humans and chimpanzees diverged 

from a common ancestor more 

recently than they did from macaques, 

the researchers were able to use these 

three branches of a much more extensive 

evolutionary tree in order to narrow 

down the origins of a modified 

gene. For example, if a specific gene 

appeared to be upregulated in humans 

but downregulated in both chimpanzees 

and macaques, then this would indicate 

a human-specific change. Similarly, if 

a gene was upregulated in humans and 

macaques, but downregulated in chimpanzees, 

then this would demonstrate a 

chimpanzee-specific change. This gene 

regulation would then correspond to an 

increase or decrease in the production of 

proteins in cells and thus a change in the 

trait, or phenotype, displayed by each 

species. 

A glance at brain structure 

The human brain is about three times 

larger than the chimpanzee brain. The 

primary assumption is that a bigger 

brain should be able to hold more information 

and form more complex circuits 

between nerve cells. “We believe 

that instead of one big change in brain 

structure that accounts for a lot of differences, 

there are actually many small but 

distinct differences in human brains that 

“ 

This image shows the molecular characterization of TH+ cells. 

Instead of one big change in brain 

structure that accounts for a lot 

of differences, there are actually 

many small but distinct differences 

in human brains that add 

together to make big differences. 


” 

- André Sousa 

add together to make big differences, for 

example, in cognition,” Sousa said. 

Uncertain of where they would find 

the most differences in the brains of the 

three species, the researchers approached 

this study without a main brain region of 

interest. Because the neocortex is known 

predominantly for its role in higher cognitive 

function, they hypothesized that 

the greatest number of differences across 

the species would be located in this region. 

Their data demonstrated that, as 

expected, most genes were similar and 

therefore conserved among humans, 

chimpanzees, and macaques. However, 

the most interspecies differences in 

changes in gene expression were actually 

discovered not in the neocortex but in 

the striatum, a region of the brain primarily 

involved in voluntary movement, 

planning, and reward. “This is likely because 

it is a transition station between 

the neocortex and other regions of the 

brain, so changes in this region may also 

lead to changes in the neocortex,” Zhu 

reasoned. 

The key is in dopamine 

IMAGE COURTESY OF ANDRE MIGUEL SOUSA 

All primates have dopamine, a crucial 

neurotransmitter responsible for motor 

control and emotional responses. The 

researchers discovered that the TH gene, 

responsible for the production of dopamine, 

was more expressed in the human 

striatum than in the striata of chimpanzees 

and macaques, which indicates that 

humans most likely have more dopamine 

in the striatum than in the other 

species studied. “There are two possible 

explanations for this observation,” Sousa 

said. “First—there are exactly the same 

number of TH cells among the three species, 

but each human cell is producing 

considerably more dopamine; or second—humans 

have more TH cells than 

chimpanzees and macaques.” Because 

these comparisons were made at the 

tissue level, the researchers performed 

cellular-level analysis and were able to 

conclude that the latter case was true: 

humans have more TH cells in the striatum 

than the other two species. In fact, 

chimpanzees and the other non-human 

African great apes (bonobos and gorilas) 

March 2018 


23

FOCUS 


have no TH cells at all in the neocortex. 

All primate species have dopamine production 

centralized in specialized structures 

of the midbrain. However, it is a 

novel discovery that humans likely have 

another localized production of dopamine 

in the neocortex. “This is important 

because it is the first time we showed 

that cells in the neocortex are also able to 

produce dopamine,” Sousa said. 

Additionally, since TH was expressed 

less in the neocortex of both chimpanzees 

and gorillas, this suggests that the 

expression of the gene was absent in the 

most recent common ancestor of the African 

great apes and reappeared in humans 

somewhere recent along the evolutionary 

timeline. 

Dopamine’s involvement in motor 

control, learning and memory, and the 

reward system therefore holds great relevance 

to human evolution and even 

modern neurological diseases. For example, 

Parkinson’s disease, a neurodegenerative 

disorder that particularly affects 

movement, is caused by a lack of dopamine 

from the death of dopamine producing 

cells. “This loss of cells may also 

be related to some form of intellectual 

impairment, but this is purely hypothesized 

right now,” Zhu commented. 

Still unraveling the mystery 

In addition to the TH gene, this study 

found small but distinct differences in 

other genes, including MET and ZP2. 

Specifically, the MET gene, which is associated 

with autism spectrum disorder, 

was enriched only in the human prefrontal 

cortex, an area of the brain related to 

very high cognitive functions. A potential 

area of research would involve studying 

whether this increase in MET levels 

in the prefrontal cortex makes humans 

more susceptible to autism. 

As for the ZP2, this gene was found only 

in the human brain and not in chimpanzees 

or macaques. “What’s most surprising 

about this gene is its location,” Sousa said. 

This gene, which has been studied extensively 

in the context of the reproductive 

system, is crucial for the recognition and 

mediation of the sperm in the egg. Future 

research could also be directed at studying 

this particular gene in order to figure out 

what it is also doing in the brain and how 

Human TH+ interneurons synthesize and transport dopamine. 

it got there. With the discoveries of this 

study in mind, researchers could examine 

these specific genes to gain clearer insight 

into the genetic and molecular changes in 

evolution of the human brain. 

Future direction 

“We believe that there is a cumulative 

effect of all of these small changes we 

found that helps explain the evolution 

of the human brain and differentiate it 

between the brains of nonhuman primates,” 

Sousa said. Human-specific differences 

have huge implications for the 

onset of neurological diseases, such as 

Parkinson’s disease, in which a depletion 

of TH + cells in the neocortex could be 

detrimental to cognitive function. Additionally, 

this study focused solely on 

adult brains among the three species, but 


IMAGE COURTESY OF ANDRE MIGUEL SOUSA 

the researchers are interested in expanding 

their research to cover other human 

developmental stages in hopes of learning 

about the differences in how brains 

change over time. 

A possible addition to future research 

would be to include a more extensive 

comparison including many more species. 

The interspecies comparisons between 

humans, chimpanzees, and macaques 

in this study already demonstrate 

substantial differences between humans 

and our closest nonhuman primates, 

which could then possibly affect the way 

we employ animal models to study human 

disorders or develop pharmaceutical 

drugs. “Although we have made a 

big step towards understanding cellular 

and molecular distinctions in the human 

brain, there is still much work to do,” 

both researchers conclude. 

ANNA SUN 

ANNA SUN is a prospective Molecular, Cellular and Developmental Biology major in Pierson 

College ‘21. She is very interested in bioinformatics and plans to spend this summer in a 

laboratory conducting genetics research. In addition to writing for the Yale Scientific Magazine, 

she is involved in the MCDB Student Advisory Committee at Yale and loves to spend time with her 

friends discovering the food scene in New Haven. 

THE AUTHOR WOULD LIKE TO THANK Dr. Sousa and Dr. Zhu for sharing their time and enthusiasm 

about their research. 


Enard, Wolfgang. “The Molecular Basis of Human Brain Evolution.” Current Biology, 24 Oct. 2016, 

doi:10.1016/j.cub.2016.09.030. 


FEATURE biomedical engineering 

BY ANTONIO MEDINA 

PRINTING OUT THE MIND 

Bioprinting 3-D organs with soft, tissue-like materials 

IMAGE COURTESY OF ZHENGCHU TAN 

The second harmonic microscope onstructed by the researchers 

used here to image a glass capillary. 

Cars, toys, knick-knacks and prototypes—the array of objects 

that can be brought to life with a 3D printer is vast and 

growing. 3D printers are getting more impressive, capable of 

making anything from usable engine parts to full-scale houses. 

Now, an even greater goal is within reach: printing the brain. 

3D printing technology has recently made significant breakthroughs 

in diverse fields, including medicine, engineering, 

and design. We live in a world where a technician can print a 

prototype of an invention in just a few hours. The ability to create 

a 3-D object, one that models the intricacies of a physical 

system that was once only imaginable on a computer screen, 

has opened the doors to hundreds of applications, particularly 

in the field of biomedical engineering. These ambitions are 

coming to fruition thanks to the work done by researchers at 

Imperial College London, whose novel 3D printing process 

creates material that can closely model the human brain. 

Models of the human body made by 3D printing have been 

around for the past 20 years. For example, Yale researchers at 

the Center for Engineering Innovation and Design successfully 

printed a large-scale model of a neuron in 2015. Academically, 

this provides a new “dimension” to the way students and neuroscientists 

can observe and study the human neural system. Bioprinting 

takes this technology one step further. 3D bioprinting 

uses the same techniques as a standard printer, which ejects material 

to construct precisely mapped layers, but uses a combination 

of cells and hydrogels as its material instead. 

Bioprinting technology has already made waves in drug 

testing, regenerative medicine, and even surgical tissue transplants. 

The challenge of using these printers with real people, 

however, is that whatever is produced often cannot accurately 

represent an actual human organ; the product might be too 

stiff or too dense, or it might misbehave when placed in the 

same conditions as the organ it is modeled after. 

Fortunately, cryogenic freezing is a promising solution: a 

team of researchers at Imperial College London has developed 

an innovative modification to standard bioprinting in which 

a solution of a composite hydrogel (CH) is frozen rapidly to 

produce material that is as soft as the tissue in the brain or 

lung. The procedure uses precision technology to accomplish 

a process known as rapid cooling. When a liquid material is 

cooled below its freezing point, it transitions into a solid. The 

final product is much harder than the liquid, in the way water 

is much “softer” than ice. Controlled cooling slows down 

the moving molecules of a liquid until they can’t move around. 

These molecules try to arrange themselves in the most tightly 

packed way possible so that when the material freezes, it is 

stiff. This rearrangement of molecules takes some time, so if 

one can rapidly freeze a material, the final product will be a 

much softer, more flexible solid because the molecules didn’t 

have time to pack optimally. 

Using this principle, the new cryogenic bioprinting procedure 

uses dry ice to rapidly freeze the CH ink solution as it 

extrudes layer by layer. The result, according to Zhengchu Tan, 

the postgraduate researcher spearheading the procedure, is 

something that now enables the creation of arrangements that 

match complicated biological structures, such as the tissue in 

the brain. The innovative procedure provides an alternative to 

cast molding organ replicas, where the hydrogel is poured into 

a mold. “That’s how they’re normally made, but you can’t get 

complex geometries like that—hollow geometries,” Tan said. 

By using a 3D printer, one can now create the complex interiors 

of distinct shapes and textures, not just the exteriors. 

Another significant consequence of the cryogenic freezing 

method is that the printed tissue behaves similarly to the brain 

in the appropriate environment. “The resulting material structure 

is as soft as the brain, so while it does hold its shape, the 

brain is also deformed under gravity, and that’s a massive issue 

during neurosurgeries,” Tan said. Their bioprinted tissue successfully 

models this behavior. When hydrated and kept in the 

same conditions as the brain, the material is also able to keep 

its shape or deform as necessary. 

Tan’s research paves the way for enormous opportunities in 

medical research. It may soon be possible that 3D printed organs 

can replace live subjects for drug testing or risky surgical 

practices. Day by day, layer by layer, bioprinting technology 

overcomes challenges in innovative ways. With each advancement, 

more medical dreams become reality as we print our 

way to a better future. 


FEATURE environmental science 

IT’S GETTING HOT IN HERE 

Global warming takes its toll on sea turtles 

BY ISAAC WENDLER 

Sea turtles are the latest species affected by the rising 

temperatures characteristic of global warming. Researchers 

at the National Oceanic and Atmospheric 

Administration (NOAA) fisheries have shown that the 

rising ocean temperatures caused by global warming are 

resulting in a greater number of newborn female sea turtles 

than males. 

Sea turtles, like many reptiles and fish, undergo temperature-dependent 

sex determination (TSD). In organisms 

affected by TSD, the sex of a member of the species 

is determined by the temperature of the embryo 

during development. Sea turtles nest on the beach, so 

in this case, the increasing heat of the sand is directly 

responsible for an individual’s sex. In general, a higher 

temperature is correlated with a higher percentage of female 

individuals in a sea turtle population. This finding 

is well-established in the field of ecology, but this study 

marks the first time that the trend has been found in major 

populations of wild sea turtles. 

As both ocean temperatures and terrestrial sand temperatures 

continue to rise on beaches across the Great 

Barrier Reef, a greater number of sea turtle populations 

are giving birth to generations of mostly-female offspring. 

In fact, the percentage of female adult offspring 

in some populations has been observed to be as high as 

86.8 percent. 

This imbalance can be bad news for the species, as 

such high frequencies of females can lead to an overall 

decrease in male fertility. In general, a population must 

have a stable ratio of sexes in order to achieve an ecological 

balance and, if this ratio is not achieved, the species 

may eventually be driven toward extinction. 

Although this news is troubling, especially for the ecosystems 

in and around the Great Barrier Reef, this study 

also marks the development of a novel method for studying 

sea turtles, one that can be generalized to the study 

of other species. 

The conventional method of reviewing the sex frequency 

of sea turtle populations was by anatomical examination 

of a nest, which is far more impractical and 

less revealing than the genetics-based method used in 

this study. 

The research team, led by Dr. Michael Jenson, makes 

use of a combination of both endocrinology and genetic 

markers on sea turtles they find in the water. These 

markers can then be traced back to the specific nesting 

location of the turtle, which can then show the conditions 

of the nest, including temperature. With this approach, 

the researchers are not forced to travel across 

many different nest locations in order to examine the 

turtles inside. 

Although the status of the sea turtle population of the 

Great Barrier Reef is likely not on most people’s minds, it 

serves as an omen as to what may come if global warming 

is not curbed. After all, these turtles are only one of 

many species affected by the consistent warming of the 

planet. This relentless force influences other groups as 

well: polar bears, whose habitat is melting by the day; 

coral, whose shells are weakening from the acidification 

of the oceans; maybe even humans, whose sources of 

food are dwindling as ecosystems around the world begin 

to decay. 

Dr. Mary Beth Decker, professor in the Yale Department 

of Ecology and Evolutionary Biology, has some 

sage advice for those who want to help the fight against 

global warming. “Communicate with your state, federal, 

and local representatives and encourage them to make 

good policy decisions with respect to energy and climate. 

You can also always talk with your friends and family 

and encourage them to do the same,” Decker said. 

IMAGE COURTESY OF WIKIMEDIA 

The heat of the sand that sea turtles nest on is directly responsible 

for their sex. 


genetics 

FEATURE 

IMMUNE TO OUR FOOD 

Fast food, slow recovery 

BY LESLIE SIM 

IMAGE COURTESY OF THE LATZ LAB 

Dr. Latz and Dr. Christ of the Latz Lab at University of Bonn. 

Our world is plastered with weight-loss advertisements. 

For every McDonald’s commercial, there is another one 

for Lean Cuisine or Weight Watchers. In America, obesity 

and health have become national concerns, as over a 

third of the adult population is obese—a record high. It 

seems that unhealthy eating habits don’t just contribute 

to obesity; they also have long-term consequences that 

originate from our immune systems and DNA. 

Our immune systems have a memory similar to that of 

our muscles and brains. For example, our immune systems 

are able to recognize pathogens such as the influenza 

virus so that in the case of a second infection, we 

know how to fight the infection. This evolutionary advantage 

in humans allows us to ward off infections and 

illnesses on the daily. Without our innate immune system’s 

memory, we would die from the common cold. 

The Latz lab at University of Bonn, in which postdoctoral 

fellow Anette Christ has researched the immune 

system, has delved into these health concerns with a scientific 

mindset. By pairing a problem we see in society 

with curiosities about the innate immune system and its 

response to certain types of diets, the researchers discovered 

that the immune system responds similarly to the 

typical Western fast food diet—high in fat, high in sugar, 

and low in fiber—as it does to pathogens and infections. 

The experiment was performed on three groups of 

mice: one was fed a standard healthy chow diet, a second 

was fed a Western diet, and a third group was given 

a Western fast food diet and then switched over to the 

chow diet after a period of time. After performing genetic 

analyses on the different groups’ bone marrow cells, the 

Latz lab discovered the presence of signatures linked to 

inflammation and immune cell differentiation called inflammasomes 

that release inflammatory messengers in 

the group of mice on a Western diet. Inflammasomes are 

usually only triggered by bacterial infections in order to 

keep the immune system ready for a subsequent infection. 

These signatures were originally observed in the group 

that had switched diets, but they later disappeared after 

the mice were put onto chow diet. Although still curious 

about how exactly these signatures recognize characteristics 

of the Western fast food diet, the lab was surprised 

to discover that the immune system may treat high-sugar, 

high-fat foods the way it treats bacterial infections. 

Furthermore, they found that the Western fast food 

diet affects histone-packaging in the DNA, which means 

certain portions of the DNA unwind to cause a change in 

the expression of genetic material of the cell. These epigenetic 

changes coupled with inflammation have been 

shown to play a major role in the development of atherosclerosis, 

diabetes, and heart disease in the mice. This 

finding suggests that nutrition and diet choices can have 

major consequences on our health. 

The next step in this research is determining whether 

it applies to humans. In the near future, Christ hopes to 

conduct a clinical study in which healthy volunteers will 

be exposed to different diets for several different time 

periods. While this study will have more variables, she 

believes that it will produce results similar to those of the 

study she has already performed with the Latz lab. 

As health gurus and health movements are on the rise, 

we often find ourselves wondering which diets are the 

best for us: vegan? vegetarian? A raw diet? The answer 

is probably none of the above. “There is no ‘correct’ diet 

out there for us,” Christ said. Everyone is different—due 

to different food resources and traditional cuisines, people 

from different races or geographical locations may 

have varied intestinal environments and genetic makeups 

that complicate the answer. It’s nonetheless important 

for people to be informed about what types of foods 

they should choose for themselves in an attempt to live 

a healthy life. We are what we eat, and our immune systems 

agree. 


March 2018 


27

DISEASE DOUBLE WHAMMY 

Crohn’s disease and Parkinson’s disease are now linked by the LRRK2 gene 

BY MARCUS SAK 

ART BY ELISSA MARTIN 

At the 2016 Summer 

Olympics in Rio, seven years after 

being diagnosed with Crohn’s disease (CD), Kathleen 

Baker set a swimming world record and bagged two medals. It 

was after she had just set two national swimming records for her 

age group back in 2010. Diagnosed, but with no effective treatment, 

she would suffer from stomach cramps, nausea, and whooping cough, 

dividing her time between doctors’ offices and pool practice. Baker’s 

story is even more remarkable considering that she will never be cured 

of CD. She gives herself biweekly injections. Like Baker, the other 

million or so CD patients worldwide, usually diagnosed in their 

teenage years, fight similar battles—they try to keep alive their 

dreams of going to college, getting married, and pursuing careers. 

Judy Cho, MD, Professor of Medicine and Gastroenterology 

at Mount Sinai, heads a research group that works to identify 

the genetic bases of CD and related inflammatory diseases. The 

researchers hope that understanding the complex network of 

interdependent molecular processes in cells will lead to a cure. 

CD is extremely challenging to treat and manage, but Cho finds 

treating CD to be personally rewarding. “CD is my favorite disease 

to treat, because I wound up treating a lot of young adults 

with whom I could make a big difference,” Cho said. 

One big step towards a better understanding of CD was 

recently taken in a study led by Cho and Inga Peter, Professor 

of Genetics and Genomic Sciences at Mount Sinai. 

This four-year-long study, involving 51 collaborators from 

26 institutions, identified mutations in the LRRK2 gene 

(pronounced “lurk-two”) strongly associated with CD. Since 

LRRK2 has long been known to be the major genetic cause for

the neurodegenerative disorder Parkinson’s disease (PD), this study 

provides a direct link between seemingly unrelated CD and PD and 

hints at a common molecular basis for both diseases. 

From its inception, this genetic study was unusual—the researchers 

did not start with a hypothesis. Like any other disease, they knew 

that certain variants in the genetic code were responsible for CD. 

As such, they began by screening hundreds of thousands of possible 

gene variants in order to compare the genes of CD patients with those 

of healthy subjects. This initial comparison was done on 5,699 Ashkenazi 

Jewish patients, since CD is more common in this population. 

The researchers succeeded in identifying two categories of mutations: 

risk mutations, which were more likely to be found in CD 

patients, and protective mutations, which were more common in 

healthy subjects. The mutations were determined to lie within the 

LRRK2 gene, which was implicated in cellular processes central to 

CD. The strong association between LRRK2 and PD raised many 

questions, and it gave the project a direction. 

To establish a proper link between CD and PD, the researchers 

focused on individual mutations and expanded their screening to 

include 24,570 CD and PD cases plus healthy controls. Ultimately, the 

individual variants associated with CD were also strongly linked to 

PD; furthermore, they correlated in the same direction—risk variants 

for CD were also risk variants for PD, and vice versa. This suggested a 

similar genetic architecture underlying the two diseases. 

At this point, a problem arose. Mutations in LRRK2 are inherited 

together with those in its gene neighbors, so association signals were 

also being detected from its neighboring regions. To prove that it was 

LRRK2 responsible for CD and not a neighboring gene, the researchers 

turned to computational biology. They constructed a model of all 

gene-gene interactions in the intestine, and then stripped it down to 

the essential CD genes, intentionally excluding the genes known to 

be involved in PD, including LRRK2. They then ran a simulation of 

CD, knowing that only the genes required for CD would be pulled 

back into their system. LRRK2 was the only gene in its neighborhood 

that came up. 

Up to this point, the researchers had been working based on statistical 

evidence alone. Now came the most challenging part: to determine 

whether the identified LRRK2 variants indeed led to biological 

effects. Peter and her coworkers recalled CD carriers registered with 

Mount Sinai Medical Center, from whom they obtained blood for 

biological testing. “For a genetic epidemiologist, functional studies 

are the most frustrating because you have no control over the data,” 

Peter said. The risk variant worked—in functional studies, cells that 

carried this variant exhibited traits characteristic of experimental 

models of CD and PD. Unexpectedly, there was no indication that 

the most strongly correlated protective variant had any functional 

significance. The researchers had seemingly wasted a whole year of 

collecting and testing blood samples. 

Peter and her coworkers quickly moved on to the second most 

promising neighboring protective variant; testing revealed that it 

was the variant actually responsible for CD. Interestingly, all people 

who were recalled for additional blood draws had both protective 

variants, which explained why the statistical evidence alone was misleading. 

This costly detour lays out an important lesson in genetic 

studies. “In this type of analysis, statistical significance is not everything,” 

Peter said. Often, statistics cannot account for the complexity 

of biological processes. 

Having confirmed the effects of the mutations on human cells, 

medicine 

FEATURE 

the researchers moved on to the clinical scale, where they examined 

the effects of LRRK2 mutations on the disease course. They 

found that the risk mutation led to CD onset at a younger age, so 

Peter wants to include LRRK2 mutations as markers during genetic 

screening, which would allow clinicians to determine whether a 

patient is susceptible to CD early on. 

For Peter, incorporating LRRK2 in genetic screening is just a first 

step. The discovery that the risk mutation leads to an overactive 

LRRK2 protein implies that drugs could be developed to inhibit 

LRRK2 and, thus, treat CD. Many PD studies have shown encouraging 

results. In one study, LRRK2 inhibitors were found to rescue brain 

cell degeneration in mice. In trying to reverse PD, however, the inhibitors 

also had unforeseen effects on other cells that use LRRK2. More 

research is needed on this cell type-specific targeting. The protective 

variant is a promising candidate, as it reflects the natural biochemical 

pathways that cells evolved to protect themselves against CD. 


Crohn’s disease intestinal cells, which are responsible for the inflammation, 

observed under microscope. 

Regardless of whether a drug can be developed, this study has 

far-reaching implications for PD treatment. PD is notoriously hard 

to treat because it does not show symptoms until years after its onset, 

at which point treatment is no longer effective. As CD has an earlier 

age of onset, clinicians can use the identified LRRK2 mutations to 

determine which CD patients are at high risk of PD and administer 

preventative measures. 

Ultimately, the discoveries made use of a multipronged treatment 

of mountains of data, including computational biology, statistical 

analysis, as well as clinical and functional studies. “No one sophisticated 

bioinformatics approach will allow you to get to the bottom of 

the problem,” Peter said. She believes that this study demonstrates an 

important research strategy: attack the problem from as many angles 

as possible, and then confirm, confirm, and reconfirm the findings. 

CD is still far from curable. Based on the findings in this study, 

Peter and her coworkers are examining the effect of LRRK2 inhibitors 

on reversing colon inflammation in mice. This push is driven by 

the promise of genetics in answering many biological problems. “I 

think we’re going to enter a golden age of medicine, where instead 

of being a descriptive science, medicine is going to be a molecular 

science,” Cho said. 


March 2018 


29

BIG BANG GIVE 

ME A TWIRL 

by Urmila Chadayammuri 

art by Jason Yang 

Radio telescopes reveal surprisingly neat rotation 

in extremely young galaxies 

“We are made of star stuff.” These timeless words from astrophysicist 

and space evangelist Carl Sagan are more than poetic rhetoric. The carbon, 

nitrogen, oxygen and silicon—so central to life on earth—and the 

iron in our blood are all produced when hydrogen fuses into heavier 

elements in the cores of massive stars. The nuclear fusion process is 

what powers these stars to light up our sky. As the stars age and die, they 

release these elements into the gas around them, which will eventually 

form planets, sometimes populated by sentient organisms that build 

telescopes to peer back out into where they came from. 

A team led by Renske Smit, a postdoctoral fellow at Cambridge University, 

recently measured the star-forming gas in two galaxies that sent 

us light when the Universe was just one seventh of its current size. This 

means that any photon—a packet of light—that left a source at that time 

would, therefore, have its wavelength stretched out, or made redder on 

the electromagnetic spectrum, by this same factor. Astronomers say the 

galaxies are at “redshifts” of 6.8. In effect, we are seeing these galaxies as 

they were when the Universe was just 800 million years old. 

Using the Atacama Large Millimeter Array (ALMA), a collection of 

radio telescopes in the high, dry Chilean desert, Smit looked for the light 

emitted by carbon atoms. When a carbon atom collides with another 

particle, the energy of that collision can kick one of the outer electrons of 

the carbon to a higher energy level, which is called collisional excitation. 

But electrons like to stay in the lowest energy states available, so it will 

soon jump back down. In the process, it releases a photon of wavelength 

157.7 micrometers, which matches the energy difference between those 

two electron levels. 

Quantum mechanics dictates that an atom will always emit a photon 

of exactly the same wavelength for a given electron transition. However, 


astronomy 

FEATURE 


The James Webb Space Telescope is a space telescope developed in 

coordination with NASA. 

if the atom is moving away from us, this wavelength will get longer and 

redder; if it is moving towards us, the light gets shorter and bluer. This 

is known as the Doppler effect; most of us experience the aural version 

of it every time an ambulance drives past, its siren getting shriller as it 

approaches and then dropping as it drives away. 

Since the Universe is expanding away from us, light coming from 

its most distant sources is red-shifted. Smit explains that the brightest 

emission in the most distant galaxies, which has optical wavelengths in 

a lab, becomes redshifted into the mid-infrared. In her PhD thesis at 

the Leiden observatory in the Netherlands, Smit used the infrared space 

telescope, Spitzer, to measure redshifts precisely for a very large sample 

of galaxies. The CII line, with a wavelength of 157.7 micrometers, is 

already in the infrared, but it gets further redshifted into longer radio 

waves. This is exactly what ALMA can detect. 

“Getting time on ALMA is hard,” said Pascal Oesch, former postdoctoral 

fellow at Yale and now assistant professor at the University of 

Geneva, a co-author on the paper. The entire array of telescopes must be 

reconfigured every time a researcher wants to look at a different range 

of wavelengths. “You really have to know the redshifts and locations of 

the targets, and Renske constrained those tightly with her Spitzer observations,” 

Oesch said. 

Now picture a disk of swirling gas, moving clockwise. Rotate the disk 

so you’re viewing it from the side. Gas to the right half of the disk will 

appear to be moving towards you, and on the left it’ll be moving away 

from you. If there were carbon atoms emitting photons at exactly 158 

micrometers everywhere in the disk, you’d think the light from the right 

side of the disk actually had a wavelength shorter and bluer than that, 

and that from the left larger and redder. Now think of two coins sitting 

on this disk, at different distances from the center. As the disk rotates, the 

coin farther from the center moves a longer total distance than the one 

closer in. In other words, the velocity of the disk is greater at larger radii. 

So the 157.7 micrometer line is redshifted increasingly more the further 

left you look from the center, and blueshifted more the further you look 

right. The line gets broadened into a bell shaped curve, the width of 

which tells you how fast the gas in the disk is rotating. 

Current simulations of galaxy formation in the early Universe show 

these galaxies colliding with their neighbors often in what are called mergers. 

These mergers disrupt the formation of any disks, and tend to leave 


The Atacama Large Millimeter Array (ALMA) is a collection of radio 

telescopes in the Chile, five kilometers (sixteen thousand feet) above sea 

level. Since light from a single source in the sky lands at slightly different 

points on each telescope, the images can be combined using a technique 

called interferometry to get extremely high resolution. Together, the 

telescopes can see fainter objects than any one of them could on its own. 

Source: The European Space Organization. 

behind gas clumps with lots of star formation in the center. “We expected 

the carbon emission to be pretty concentrated,” Smit said. Therefore, she 

only expected to see lines from the center of the rotating disk. Instead, the 

line-emission was extended enough that she could measure the velocity 

variations across the galaxy. “The fact that we could actually see the rotation 

meant that CII emission was more spread out,” Smit said. 

That was not the only surprise. The CII line emission is only generated 

if the carbon undergoes a lot of collisions, usually with electrons coming 

from dust. “We see the carbon line but we don’t see any dust, and that is 

a puzzle we haven’t solved yet,” Smit said. 

Oesch doesn’t think it’s that surprising to find so little dust in these galaxies: 

dust is released during a relatively late stage in a galaxies’ evolution, 

and since they are still so young, the stars simply may not have reached 

this phase of their lives. Further, he says, they may not have found 

dust because they were looking for a very specific kind. “You have to 

make assumptions of the temperature of the dust to predict how much 

emission you would see,” said Oesch. It is just another example of how 

carefully astronomers have to design their experiments to encompass all 

of the components of a galaxy that they’re interested in. 

Astronomers are also very careful about making inferences from 

small samples. Smit is excited about the upcoming James Webb Space 

Telescope, which will detect hundreds or even thousands of galaxies 

at these high redshifts. James Webb will have an IFU, or Integral Field 

Unit, a device that takes a spectrum on every pixel of the camera. 

“We’ll at least be able to get low resolution but large samples,” she said. 

Smit already has time on ALMA to look at six more galaxies, which 

will help us build a picture of how common galaxy disks really are in the 

early Universe. She is also preparing to observe one of these galaxies at 

a much higher resolution. “We’ll be able to see how organized the disk 

is, or if its messier than we thought. It’ll tell us about the physics of at 

least one disk in much more detail,” Oesch said. She emphasizes that 

this really a new frontier of observation. “Maybe it’s not a single disk— 

maybe it’s multiple clumps merging! We really haven’t been able to do 

any of this before.” 


March 2018 


31

FEATURE biomedical engineering 

Defeating 

Diabetes 

Advances in Cell Encapsulation 

Technology 

By EMMA HEALY 

Art by ANUSHA BISHOP 

A young boy is rushed into the Emergency Department after 

being discovered unconscious. He’s with his mother, who reports 

that earlier that evening, her son had been thirsty, nauseous, and 

urinating frequently. He’s now gasping for air, and his breath smells 

fruity and sweet, like a sugary pear candy. It’s the smell of ketone 

bodies, molecules produced by the liver that cells use as fuel, and 

their presence is indicative of ketoacidosis—a dangerous complication 

of diabetes. Ketone bodies are acidic, so as they accumulate, 

the blood’s pH drops, leading to hyperventilation, nausea, and, in 

extreme cases, severe neurological and cardiac complications. 

Given his symptoms, the boy likely suffers from type 1 diabetes, 

an autoimmune disease in which the patient’s immune system 

destroys islet cells in his pancreas. These cells are responsible for 

producing insulin, a hormone that helps your body absorb glucose 

from the bloodstream. Without sufficient insulin, blood sugar levels 

increase and contribute to disease. Diabetic ketoacidosis is a 

rapid-onset complication of type 1 diabetes that occurs because 

glucose is trapped in the bloodstream, so cells need an alternative 

source of energy—the ketone bodies—to keep functioning. 

Diabetes treatments focus on maintaining normal insulin levels 

with daily injections, which sound easier than they are. These insulin 

injections can be uncomfortable, and remembering to keep 

to a schedule can be stressful and tiring. Furthermore, figuring out 

correct doses can be challenging, as these injections serve multiple 

purposes: patients must inject to maintain background levels of insulin, 

prepare for meals, and correct high blood sugar. Complicating 

the issue, different insulin products act on different time scales, 

and each person’s insulin sensitivity is unique. There is always the 

risk of overdose, especially after a missed meal, which could lower 

blood sugar beyond safe levels. For these reasons, researchers at 

Cornell University are improving designs on an alternative treatment 

for type 1 diabetes: cell transplantation. “Instead of delivering 

insulin through injection, we are trying to develop a technology to 

deliver cells, which can sense the glucose concentration and secrete 

insulin autonomously,” said Duo An, the PhD candidate at Cornell 

who led the research. 

As with any transplant procedure, islet cell transplantation has 

risks. Since the cells are foreign to the host, the body recognizes 

them as invaders and launches an immune response. To prevent 

transplant rejection, patients must take immunosuppressive medications 

for the remainder of their lives, decreasing their ability to 

fight infectious diseases. Despite its dangers, immunosuppression 

is often a necessity unless the transplanted cells can be protected 

against the host’s immune system, as Cornell’s team is trying to do 

with cell encapsulation, a technique where they deliver cells within 

special membranes. 

Cell encapsulation is not a new procedure. Attempts to coat 

transplanted materials with protective membranes occurred in as 

early as the 1960s; however, the technology is far from perfect. Even 

a current and promising cell encapsulation system, called hydrogel 

microcapsules, has a critical flaw: the microcapsules are difficult 

to retrieve completely after implantation. “To cure type 1 diabetes 

patients, we estimate that 500,000 pancreatic cell aggregates are 

required, which means you need to put tens of thousands of these 

microcapsules into the patients,” said An. “Because they are individual 

microcapsules, it’s almost impossible to retrieve all of the 

materials.” Without a better way to remove the microcapsules from 

a patient, clinical application of these devices has been restricted. If 

the membrane failed or the cells died and the microcapsules could 

not be safely removed, the situation could be dangerous to the recipient. 

Recognizing this obstacle to cell encapsulation technology, 

the Cornell research team sought to design an encapsulation 


iomedical engineering 

FEATURE 

IMAGE COURTESY OF HEALTH.MIL 

For patients with diabetes, blood tests to monitor glucose levels are 

important for the management of the disease. 


Brown algae is an important component of alginate hydrogels, the 

material that made the cell encapsulation device biocompatible. 

device that is therapeutically successful, scalable, and retrievable. 

Their original concept was simple. “At the beginning, we were 

thinking, ‘What if we used a thread to connect all of these microcapsules, 

like a necklace? Then they can be easily implanted and 

retrieved through a simple procedure,’” An said. Interestingly, 

this preliminary design was inspired by a spider’s web—the necklace-like 

structure would look like a strand of spider silk collecting 

droplets of dew, and the thread itself would mimic the properties of 

adhesive spider silk. In the final design, however, the hydrogel was 

layered uniformly around the string and islet cells, more closely 

resembling a tube than a strand with beads. 

While the concept was simple, the design proved to be more difficult. 

The hydrogel, the islet cells, and the modified sutures used to 

make the underlying thread all had to be compatible. Coordinating 

these components required a diverse array of knowledge, which 

challenged the researchers. “I needed to learn from basic chemistry, 

materials science, cellular biology, and biomedical engineering. 

I even needed to have some medical knowledge for the surgical 

procedure,” An said. In the end, the team’s efforts paid off, and they 

built a successful device. 

The base layer for the device is a nylon suture, a biocompatible, 

medical-grade material that is often used for stiches. The suture 

was a good starting point, since it is commercially available and 

has been proven safe, yet it lacked certain properties that the researchers 

desired. Using a chemical treatment, they modified the 

sutures to contain small pores and to release calcium chloride. 

Both of these modifications improved the thread’s ability to bind 

uniformly to the hydrogel: the porous surface allowed the hydrogel 

to penetrate the thread and strengthen the adhesion, and calcium 

promoted chemical bonds between the materials. 

Once the modified thread had been made, the researchers crosslinked 

it with a hydrogel made from alginate, a biomaterial obtained 

from brown seaweed. The uniform layer of alginate hydrogel 

made the device biocompatible and prevented fibrosis, the thickening 

and scarring of tissue that sometimes occurs when foreign 

materials are implanted into animals. Blocking fibrosis around the 

device was critically important, since fibrosis would have blocked 

substances from diffusing to and from the device. While the cell 

encapsulation system is designed to protect transplanted cells from 

the immune system, it must still be semi-permeable so oxygen and 

nutrients can reach the cells. 

After fabricating the device, the researchers tested the system’s biocompatibility 

and its ability to correct diabetes in mice. They also 

performed experiments in dogs to test whether they could increase 

the scale of transplantation in a larger mammal. The thread-reinforced 

hydrogel microcapsule system was successful in each trial, 

causing little to no fibrosis around sites of implantation, demonstrating 

therapeutic potential in diabetic mice, and remaining intact for 

complete retrieval from dogs. These results are a major step forward 

for cell encapsulation technology, as the new device will likely minimize 

the risks associated with this type of transplantation, making it 

a more viable option for treating type 1 diabetes. 

At the moment, the Cornell team hopes to improve their cell encapsulation 

system, modifying it to become even more biocompatible 

and mechanically stable. They also want to scale up further, so 

they can deliver enough cells to cure a human patient. Research is 

ongoing in all of these areas, and the team eventually hopes to get 

the device into clinical trials. 

Type 1 diabetes currently affects over one million Americans and 

is most often diagnosed in children and young adults. For these 

children, the leading cause of diabetes-related death is diabetic ketoacidosis, 

and it occurs most frequently when someone fails to 

administer a proper dose of insulin. “The final goal of this research 

is to find a cure to type 1 diabetes, so that patients no longer need 

to get painful and tedious insulin injections every day,” An said. 

While we are still far from curing type 1 diabetes, a cell encapsulation 

device could simplify management of this disease, reducing its 

burden on millions of lives. 


March 2018 


33

FEATURE environmental science 

COUNTERPOINT 

WHICH CAME FIRST, THE BUTTERFLY OR THE FLOWER? 

by Annie Yang 

A butterfly lands on top of a flower and imbibes nectar with 

its coiled mouthpiece; the butterfly and the flower seem to 

be an inseparable pair. For a long time, our understanding 

of the symbiotic relationship between the two organisms led 

scientists to believe that Lepidoptera, the order of insects 

that includes butterflies and moths, evolved alongside the 

first angiosperms or flowering plants. However, a group of 

researchers recently discovered new evidence that suggests 

that the evolutionary history of Lepidoptera and angiosperms 

may not be as simple as scientists had previously delineated. 

Paul K. Strother, a researcher and professor at Boston 

College, visited microfossil paleontologist Bas van de 

Schootbrugge in Germany in 2012 because they were 

interested in looking for prehistoric remnants of freshwater 

algae. When the research team drilled into the Schandelah-1 

well, however, they inadvertently uncovered enigmatic scales 

in sediments from the late Triassic and early Jurassic periods. 

While they deduced that these were insect scales, they were 

unable to immediately conclude what insects they belonged 

to because many different insects have wings lined with 

thousands of these kinds of scales. Thus, they had to develop 

a method to extract the infinitesimal and delicate scales from 

the sample in order to determine their origin. 

Timo van Eldijk, an undergraduate at Utrecht University 

at the time, took charge of the laboratorial work. To isolate 

the scales, he exposed the sediments to harsh acids and then 

used a needle tipped with a piece of human nostril hair to 

transfer each one individually to a separate slide. He then 

IMAGE COURTESY OF TIMO VAN ELDIJK 

This image depicts a living descendant of a moth that did not 

possess a proboscis. Solid scales extracted from this group of 

primitive Lepidoptera support that the earliest butterflies and 

moths had jawlike mouthparts. 

examined the slides under a microscope and discovered that 

there were two types of scales in the sample: solid, round 

ones and hollow, jagged ones. By comparing the scales to 

previously classified specimens, van Eldijk determined that 

the solid scales belonged to the earliest Lepidoptera, who 

relied on mandibles or jawlike mouthparts to chew their 

food, corroborating the results of earlier insect evolutionary 

studies. 

The discovery of the newfound hollow scales, however, 

revealed something truly remarkable. Because hollow scales 

are characteristic of extant, or currently living, Lepidoptera, 

specifically the Glossata, a suborder containing moths 

and butterflies that have an elongated feeding and sucking 

mouthpart called a proboscis, the discovery of these hollow 

wings in the sample suggests that moths and butterflies had 

already evolved proboscises during the late Triassic period, 

nearly 70 million years before plants evolved flowers. 

If this is true and there were no flowers during the late Triassic 

period, what did moths and butterflies use their proboscises 

for? The researchers have considered the possibility that 

flowering plants existed earlier than fossil records show, but 

Strother finds this explanation unconvincing. “There are 

individual plant specimens [from the Triassic Period] that 

might have been what was to become of a flower,” Strother 

said. “But the thing is that there is always a glitch. There is no 

robust record to support early flowers claims.” He explains 

that the more plausible explanation is that they evolved 

the proboscis in response to the dry and arid climate. The 

appendage would allow them to feed on pollination droplets 

and saps from gymnosperms, or seed-bearing plants like pine 

trees, in order to replenish their lost moisture. 

The results of this research alter our understanding of 

Lepidoptera and angiosperm coevolution. The research 

suggests that the Lepidoptera fed primarily on gymnosperms 

but changed their feeding preferences when angiosperms 

evolved, consequently coevolving with them and forming the 

symbiotic relationship as we know it today. 

Since the scales that van Eldijk studied are only a small 

part of what was uncovered from the well, there are still 

vestiges of other organisms that have yet to be explored. 

Strother explains that the next step is to analyze the rest of 

the sample. Furthermore, because prehistoric fossil records 

are still largely elusive, the research team is also beginning 

to look at sediments from other time periods. “Now that we 

can recognize these things, what we want to do is to have 

a stepwise, continuous record of understanding. There is a 

punctuated record, so we are working to fill in for earlier 

times,” Strother said. 


FOCUS 

technology 

repurposed 

by 

Jau Tung 

Chan 

From Garden Destroyer to Lab Assistant 

Taraxacum officinale, or more commonly 

known as dandelions, are a well-known nuisance 

in gardens throughout the world because they 

infest crops. In a recent development, however, 

dandelions may have turned over a new leaf, 

having found a purpose in an unlikely setting: the 

scientific laboratory. 

Last year, a team of high school students, under 

the guidance of professors from Xi’an Jiaotong 

University in Xi’an, China, completed an in-depth 

study about how dandelion seeds can be used as 

pipettes to create and manipulate microlitersized 

droplets, a fifth the size of droplets from 

eyedroppers. In their research, they were not only 

able to capture and release consistent droplet sizes 

repeatedly, but were also able to model the droplet 

sizes quantitatively based on characteristics of the 

seeds, such as the length of their hairs. 

To use the dandelion seed as a pipette, the 

researchers first pushed the seed downward against 

a liquid surface to form a dip, much like the dip 

when someone stands in the middle of a trampoline. 

When they pulled the seed upwards out of the 

liquid, the seed remarkably did not completely 

separate from it. Instead, the hairs on the seed— 

which traditionally allowed wind to disperse 

the seed—formed the shape of a paintbrush tip, 

enclosing a droplet of the liquid within them. 

The key to the consistent droplet sizes—according 

to Feng Xu, one of the professors involved in 

the research—lies in a fine balance between two 

opposing factors: the surface tension of the liquid, 

and the stiffness of hairs on the seed. Surface 

tension is an elastic force on the surface of liquids, 

arising from the attraction of liquid molecules to 

each other, akin to how the elastic membrane of 

an inflated balloon keeps the balloon in a spherical 

shape instead of popping. Surface tension tends to 

reduce the droplet size. On the other hand, the stiff 

hairs on the seed tend to increase the droplet size 

by tending to straighten themselves out, similar to 

how a plastic ruler snaps back straight after being 

bent. The combination of these two effects creates 

a unique balancing point for droplet size, like the 

stalemate arising when both sides of a tug-of-war 

are equally strong. 

By quantitatively modelling these forces and 

experimentally verifying their predictions, the 

researchers were able to optimize the system 

to hold the largest droplet size. They varied the 

number, distribution, and length of hairs on 

the dandelion seed. Xu recounts an unexpected 

result. “Nature optimized the dandelion seed 

to give it the capability to capture the maximum 

amount of liquid,” he said. In hindsight, this makes 

evolutionary sense, since dandelion seeds need 

maximal water for optimal growth. 

There currently aren’t many tools for creating 

and manipulating microliter-sized droplets. A 

significant advantage dandelion seeds have over 

regular micropipettes is that they are omniphilic, 

which means that they can be used for both water 

and oil. Most common materials can only do one 

or the other, but not both. 

That being said, there are certainly restrictions 

to this new laboratory tool. In order to release a 

droplet from the dandelion seed, the researchers 

must place the seed into a liquid with lower surface 

tension than that of the droplet liquid so that the 

droplet will be released. This condition limits the 

contexts in which the method may be used. Still, 

Xu is optimistic about using the dandelion seed to 

inspire new synthetic fiber structures—similarly to 

how Velcro was inspired by the clinging of burrs 

of the Burdock plant to clothes. For example, 

some synthetic materials can change their stiffness 

in response to environmental factors, such as 

temperature or light. If the fiber structure is 

manufactured from the dandelion seeds, then just 

by adjusting those environmental factors—without 

a need to even contact the structure—we can allow 

stiffness to win that tug-of-war with surface tension, 

thereby releasing the droplet anywhere we want. An 

added advantage of the consistent manufacturing 

of such fiber structures is that droplet sizes will be 

more precise than regular micropipettes. 

Looking ahead, future directions for this research 

include the manufacturing of such micro-scale 

synthetic fiber structures, and the adaptation of 

this method for other scientific tools. Currently, 

Xu is pursuing the latter, developing similar fiber 

structures to manipulate cells instead of liquids, 

which could potentially change the way human 

tissues are created. Ultimately, the researchers have 

uniquely repurposed a common garden weed into 

a scientific tool. 

35 Yale Scientific Magazine March 2018

COLIN HEMEZ (ES ‘18) 

THINKING DEEPLY ABOUT ENGINEERING 

BY JASON YANG 

UNDERGRADUATE PROFILE 

IMAGE COURTESY OF COLIN HEMEZ 

Hemez, a Goldwater Scholar, has been working in Professor Isaacs’ Lab at 

the Systems Biology Institute since sophomore year. 

Yale College senior Colin Hemez (ES ’18) cherishes long runs, 

rock-climbing, and sleep. These routines ground Hemez, allowing 

him to reflect on himself and the world around him. For Hemez, life 

is not about success or achievement; instead, it’s about thoughtfully 

exploring problems that are interesting and important. “I really think 

deeply about what kinds of problems I want to work on, maybe more 

deeply than I should,” said Hemez. His deep reflection has led him to 

genome-editing research, a double major in Biomedical Engineering 

and Art History, and the combined Bachelor’s and Master’s program 

through the Yale School of Public Health. 

Born in France but raised in New Mexico near Los Alamos National 

Labs, Hemez was exposed to the world of scientists from an early age. 

Naturally, during his first year at Yale, he joined the iGEM (International 

Genetically Engineered Machine) competition team at Yale. As 

a team, they conducted synthetic biology research and presented their 

findings at the annual iGEM International Jamboree. More importantly, 

Hemez got to know one of the team’s sponsors: his future research 

mentor, Dr. Farren Isaacs, Associate Professor of Molecular, Cellular, 

and Development Biology. 

Since sophomore year, Hemez has been working in Professor Isaacs’ 

lab at the Systems Biology Institute on Yale’s West Campus. Conventional 

biology is very bottom-up: it asks how specific molecules, genes, 

or pieces fit into the bigger picture. However, systems biology is more 

top-down, using many of the hottest recent developments in biology, 

including deep sequencing, DNA synthesis, and novel imaging tools 

to a get a broader view of biology. Very interdisciplinary, systems biology 

brings together molecular biologists, biomedical engineers, ecologists, 

and evolutionary biologists. 

“What really gets me excited about the work I do in the Isaacs lab 

is that it’s really at the intersection of basic science and engineering,” 

Hemez said. Hemez loves the study of science, but at the end of the 

day, he is an engineer by training. One of his most recent projects is 

understanding how bacteria whose genetic information isn’t stored 

in DNA can still interact with normal bacteria that use DNA. He explains 

that potential applications include engineering gut bacteria that 

have specific genetic capabilities and do not interact unintentionally 

with normal bacteria, as bacteria with alternative genetic codes cannot 

exchange genetic information with other bacterial community members. 

Not only is Hemez studying biological principles, but he also 

hopes to use them to better the world. 

So how does art history fit into all of this? Hemez’s interest in art 

history budded when he took an online course in high school. Though 

Hemez is not necessarily looking to find the intersection of biomedical 

engineering and art history, the technical analysis he performs in art 

history has, in turn, informed his scientific pursuits. “The visual stimuli 

we see around us are hugely influential on the way we make sense 

of the world. Science is communicated visually,” Hemez said. He hopes 

that future scientists will strengthen the way science is presented. In 

art history, he gets a chance to think deeply about specific works, and 

he believes that, in science, there is something to be gained in slowing 

down, closely analyzing, and “digesting,” as engineers must understand 

the motivations and ethics behind the problems they’re facing. 

Hemez feels very honored to be a Goldwater Scholar, one of only 

three Yale students in his class to be given this distinction. He additionally 

attributes his incredible experience in research to the Beckman 

Scholars program, which provides research support for 18 months, an 

exceptionally long time for a scholarship. “The Beckman Foundation 

really encourages the scientists they’re funding to dig deep into the 

problems they’re studying, to take their time with it, to see what comes 

out of it,” Hemez said. He values the process of deeply exploring science 

and letting his work evolve organically along various tangents, 

but he worries that many scientists fear the pressure to publish. 

Hemez hopes to apply his engineering to solving public health problems, 

particularly engineering microbial communities that work together 

to produce medicines, biofuels, and other important natural 

products. He knows that graduate school is essential to his goals, and 

could ultimately lead to a faculty position, which he believes would 

provide unparalleled freedom to work on useful projects that interest 

him. Hemez feels very grateful to Isaacs and his graduate student 

mentors, and is often humbled by their brilliance. Whatever Hemez’s 

future holds for him, he hopes to continue exploring his interests, all 

while thinking deeply about engineering problems. 


BY LISA WU 

ALUMNI PROFILE 

DR. HUGH TAYLOR (SM ‘83) 

LEADING RESEARCH IN REPRODUCTIVE HEALTH 

IMAGE COURTESY OF DR. HUGH TAYLOR 

Dr. Taylor’s laboratory has identified transdermal estrogen treatments 

(commonly referred to as the “patch”) as more effective at enhancing 

sexual function when compared to placebo and oral estrogen treatments 

Dr. Hugh Taylor (SM ’83) sort of wound up becoming Chief of Obstetrics 

at a prominent hospital. Taylor remarks that he was always 

interested in science, but he still didn’t necessarily expect to end up 

going to medical school, spend an additional four years in a laboratory, 

and rise through the ranks to become the Chief of Obstetrics and 

Gynecology at Yale-New Haven Hospital, as well as the Anita O’Keeffe 

Young Professor of Obstetrics, Gynecology, and Reproductive Sciences. 

Even once he entered medical school, he certainly didn’t expect 

to choose gynecology as his specialty. Taylor’s path was by no means 

completely pre-determined, but he ended up exactly where he needed 

to be—a reassuring reminder to millions of concerned pre-medical 

candidates that arbitrary chance and fate, as volatile and uncertain as 

they seem, can be a good thing. 

Taylor, like many other doctors and surgeons, grew up interested in 

science and in people. His path towards becoming a physician-scientist 

began at Yale, where a campus culture strongly centered on community 

involvement empowered him to commit to a life of public 

service. “I think the responsibility that comes with a Yale education 

is important,” Taylor said. For him, that responsibility compelled him 

to join a laboratory during his residency to learn more about using 

laboratory research to help patients. In addition to seeing patients, 

performing some of his field’s most difficult surgeries, and leading 

his department, Taylor now runs a laboratory that examines the underlying 

mechanisms of endometriosis, a disease in which the mucous 

membrane lining the uterus that thickens during the menstrual 

cycle becomes displaced. The experience has been a long haul and a 

long-term investment—overwhelming workload with little financial 

incentive—but he maintains that it is well worth the outcome. “As a 

doctor, I get immediate, personal feedback that my work is helping an 

individual. And as a scientist, I get to impact a much wider audience,” 

Taylor said. 

Taylor’s desire to benefit his community through his work also influenced 

his decision to specialize in gynecology. During medical 

school, Taylor was interested in several different medical specialties, 

but gynecology stood out as an area in which clear progress could be 

made. “I considered internal medicine, but OB-GYN was extremely 

exciting,” he said. “There were so many unsolved issues, and I saw 

some clear opportunities for research.” 

When it comes to reproductive health, the truth is that the United 

States is lagging behind the rest of the world. “It’s amazing that despite 

the United States’ status as one of the most developed nations, 

our country still has one of the highest rates of complications associated 

with pre-term delivery of babies in the world,” Taylor said. Taylor’s 

laboratory has been prolific in its efforts to close the gap; his laboratory 

has identified a group of stem cells in the uterus that have been 

linked to endometrial growth. They can be extracted with a simple office 

biopsy—a procedure that removes a small amount of tissue—and 

induced to develop into insulin-producing cells, cartilage, and neuronal 

cells. Taylor recently completed a four-year long study that found 

that when compared to a placebo and oral estrogen treatments, the 

transdermal estrogen replacement patch resulted in increased sexual 

function. However, transdermal hormone replacement therapy can 

still cause adverse side-effects. Consequently, Taylor emphasizes that 

the treatment of sexual dysfunction, like the treatment of any condition, 

should be modified specifically to each patient’s needs. “It’s all 

a part of a general effort in medicine, whether it be cancer or gynecology, 

to personalize therapy to deliver optimal results,” Taylor said. 

Taylor may have not have entered Phelps Gate with a definitive 

plan, but he was still able to embark on a medical career spanning the 

lab bench, patient care centers, and hospital conference rooms. “You 

should think big and dream,” he said. “It’s a big world, and there are 

a lot of opportunities in medicine to make the world a better place.” 


March 2018 


37

Science in the Spotlight 

The Evolution of Beauty 

By Megha Chawla 

PHOTOGRAPHY BY KELLY ZHOU 

4.5/5 

The Evolution of Beauty is a compelling 

and insightful look at beauty in nature 

through the eyes of Richard O. Prum, the 

William Robertson Coe Professor of Ornithology 

at Yale. The book is Prum’s response 

to decades of research in the evolutionary sciences that have 

embraced Darwinian thought and theory of natural selection, while 

woefully ignoring Darwin’s theory of sexual selection. Through a 

lifetime of observing birds in nature and researching the evolution 

of ornamental beauty, Prum contends to revive the arbitrary sexual 

selection hypothesis, or as he calls it, “Beauty Happens.” 

According to Prum, animals have subjective tastes and preferences 

and the agency to act upon them via mate choice. Prum 

compares adaptationists, who believe that all traits have evolved 

to provide a better chance of survival and communicate information 

about mate quality, to economic theorists, who expect actors 

in a free market to behave completely rationally and purposefully. 

“Of course,” Prum says, “Evolution, like markets, is spurred by 

the irrational and subjective choices of its actors.” He provides a 

motley of colorful examples from the bird world to support this 

hypothesis, like the evolution of the male peacock’s seemingly 

useless tail which may even be harmful to survival, but has persisted 

because the ladies like it. 

In the animal kingdom, it is often the female who chooses a mate 

among available males. Because of this, Prum’s argument also has 

a feminist flair. He describes how male and female ducks’ genitalia 

and the male bowerbird’s elaborate bower-building ritual might 

have evolved for the same purpose—to protect females from forced 

copulation. Prum even extends his hypothesis to the evolution of 

the female orgasm in great apes and the size and shape of the human 

penis, claiming that female sexual autonomy has led to their 

evolution—or, in his words, “Pleasure Happens.” 

The Evolution of Beauty is interdisciplinary at its core, and Prum 

passionately comments on evolution from multiple perspectives. 

While the book has been well-received—the New York Times named 

it as one of the ten best books of 2017—Prum says the response 

from the scientific community has been mostly mute. “I’m perfectly 

happy to lose the battle and win the war,” he said, hoping his work 

will inspire further research recognizing aesthetic preference as a 

strong force in evolution. 

On the whole, The Evolution of Beauty endures as a brilliant 

anthology of beauty and desire in the natural world, written in 

engaging prose that is vivid, graphic, and at times unexpectedly 

funny. Prum humorously and appropriately quotes Sean Hannity’s 

remarks on his research: “Don’t we really need to know about duck 

sex?” If you thought you, like Sean Hannity, didn’t care about the 

mating habits of ducks, or never gave them any thought at all, this 

book will make you strongly reevaluate your indifference. 


Science in the Spotlight 

The Great Quake 

By Vikram Shaw 

IMAGE COURTESY OF USGS 

5/5 

At 5:36 p.m. on Good Friday, March 27, 1964, 

a violent shaking disrupted a peaceful Friday 

night in the village of Chenega, Alaska. The 

villagers, primarily Alutiiq natives, noticed 

the water level of their cove rapidly recede, curiously 

exposing the bottom of the ocean floor. The villagers 

knew what it meant, but many of them did not have enough 

time to get out. Moments later, a thirty-five-foot-high wall of 

water came barreling towards them. 

In a compelling tale of disaster, resilience, and scientific discovery, 

New York Times journalist and Yale graduate Henry 

Fountain tells the story of the biggest recorded earthquake 

in the history of North America in his new book, The Great 

Quake. After Fountain wrote an article in the New York Times 

about the quake’s 50th anniversary, an editor at a New York 

book publisher told him that the story sounded like a good 

book. Fountain quickly mobilized, and by the end of 2015, he 

had visited Alaska for a couple of months and completed most 

of his research. “I wanted to tell the narrative of the people affected 

and tell the tale of science through the eyes of George,” 

Fountain said. 

George Plafker, a geologist who started with little knowledge 

of earthquakes but a lot of knowledge of the Alaskan 

backcountry, was one of the main players behind the scientific 

breakthroughs that the quake catalyzed. At the turn of the 

century, earthquake science was young and misguided. Eduard 

Suess, for example, put forth the leading earthquake theory of 

the time by comparing the earth to a drying apple that would 

wrinkle as it shrank. A small minority of scientists instead favored 

the emerging ideas—rejected by most—that would later 

become known as plate tectonics. It was not until after the 

Alaskan quake, however, that Plafker helped settle the debate. 

The book tells the stories of the two communities that were 

hit the hardest by the quake: Valdez, a small costal town that 

arose from the Gold Rush, and Chenega, a village of around 

eighty native Alaskans and an American schoolteacher. Following 

these two villages through the disaster, the book is both 

exciting to read and informative. Fountain makes sure that no 

details are spared when it comes to the moments leading up 

to and just after the quake. He also details the months on end 

spent by many geologists, including Plafker, who dedicated 

their lives to understanding what happened. 

Fountain closes his book with a sobering reminder: by several 

estimates, including Plafker’s, the Pacific Northwest is due 

for a megathrust earthquake—the same kind that occurred in 

Alaska. “The Northwest will probably have a quake like it in 

the next 50 years,” Fountain said. “They’re all expecting it to 

happen.” 


March 2018 


39

C A R T O O N S 

TEARS 

FELLOWSHIPS WISHING WELL: OUT OF ORDER 

MIDTERM SEASONAL SPECIALS 

THE ALL-NIGHTER 

ZOMBIE 

DROWN 

SORROWS 

IN SUGAR 

ENERGY 

DRINK 

EMOTIONAL 

SUPPORT 

THE LAST-MINUTE 

PANICKER 

DESPERATION 

QUADRUPLE 

SHOT 

ESPRESSO 

TEA BECAUSE 

YOU ARE ON 

TOP OF IT 

THE OBNOXIOUS 

OVERACHEIVER

YSM Issue 91.1

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