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Yale Scientific Magazine
VOL. 90 ISSUE NO. 5
CONTENTS
DECEMBER 2017
NEWS 6
FEATURES 25
ON THE COVER
12
15
GUIDE TO THE
GALAXY
The Milky Way Galaxy has long been
studied as a model for other galaxies
in the universe. However, Yale professor
Marla Geha is part of a collaboration
exploring just how different the
Milky Way might actually be
DEMYSTIFYING THE
GENES BEHIND
BREAST CANCER
Researchers at Yale University have
developed a new way to study
proteins, which led to discovering
the function of BRCA1 breast cancer
genes and its interaction with other
genes in the role of tumor expression
18 FIGHTING
PARKINSON’S
Yale scientists found two potential
enymes to target via cell therapy to
tret the common variety of Parkinson’s
disease with Gaucher disease.
These two enzymes regulate the pathology
of the specific lipids that accumulate
due to Gaucher disease
BIRD BRAINS
20
New disovery in skull and brain development
in skull and brain development
has implications for greater
understanding of evoloution of reptiles
and birds
22 MACROPHAGE
MESSENGERS
The communiction between nervous,
immune and metabloic systems
changes as people age. A team led
by Christina Carmell and Vishwa Deep
Dixit of the Yale School of Medicine
disovered a subset of microphages
that could open the door to new strategies
to keep people healthier longer
More articles available online at www.yalescientific.org
December 2017
Yale Scientific Magazine
3

q a
&
►BY SANDRA LI
Even isolated islands such as the
Galápagos are affected by anthropogenic
environmental change. Unfortunately,
one affected group is the Galápagos giant
tortoises, whose populations have decreased
by ninety percent in the past three
centuries, in large part due to hunting in
recent years. The C. elephantopus species
from Floreana Island is considered
extinct, and the C. abingdoni from Pinta
Island recently joined its ranks in 2012,
when the last individual, named Lonesome
George, died. However, a November
2015 international expedition to the
remote Galápagos Islands provides hope
that these extinct tortoises can be revived.
Researchers from Yale went on an expedition
to Isabela Island to locate descendants
of the original Floreana and
Pinta tortoises. These tortoises were likely
thrown off ships by mariners onto
Can we bring back extinct Galapagos turtles?
IMAGE COURTESY OF WIKIMEDIA COMMONS
►Lonesome George was the last Pinta Island
tortoise. His death in 2012 marked the extinction of
another species of the Galápagos giant tortoise.
non-native habitats where, over generations,
they mixed with the native species
to create genetic archives of the now-extinct
species. After analyzing the DNA of
150 tortoises, researchers identified 65
with strong ancestral connections to the
Floreana tortoise, 23 of which now reside
in a captive breeding center.
The Floreana tortoise breeding program
is expected to generate thousands
of offspring for the Floreana Island. For
the first time in 150 years, these mega-herbivores
can be returned to their
native land, returning balance to the ecosystem.
“It is a really exciting prospect to
restore a species that we once thought
was extinct,” said Dr. Joshua Miller, a
member of the 2015 expedition and a
current postdoctoral researcher at the
Yale Department of Ecology and Evolutionary
Biology.
►BY STEPHANIE SMELYANSKY
There are many forms of alternative
energy, ranging from solar to
wind. A problem with these forms of
energy, however, is that their availability
is inconsistent, so they must
often be stored for future use. But
what if there were an alternative energy
resource that is available consistently,
all day, every day? Scientists at
Columbia think that the evaporation
of water from lakes might just be that
energy resource.
The scientists at Columbia used B.
subtilis, a common soil bacterium,
to harness the energy released from
evaporating water. B. subtilis forms
spores—a hardy, dormant form of
the bacterium—that expand and
contract in response to relative humidity
in the environment. The researchers
plated these spores onto
small films that could contract with
them. By altering humidity levels in
Can evaporation drive energy production?
IMAGE COURTESY OF WIKIMEDIA COMMONS
►Researchers at Columbia have high hopes for
bacterial colonies that can produce mechanical
energy in response to evaporated water.
the environment, they were able to
induce expansion and contraction
in the spores and thus in the films.
As the films expanded and contracted,
similarly to human muscle,
the motion could be converted into
an energy strong enough to turn on
a small LED light bulb or to power
a small car.
While this technology is incredibly
promising, it’s still a long way
off from serving the public. Details
ranging from how to implement
large scale construction of these
devices to how to circumvent the
legal issues surrounding water access
rights prevent this invention
from becoming a part of your local
community lake tomorrow. However,
this technology poses a lucrative
alternative to fossil fuels, and
maybe even to other forms of environmentally
friendly energy.

F R O M T H E E D I T O R
NEW LETTER
We are natural storytellers, and science is one of the best stories to tell.
After all, science is full of noble quests to discover the secrets of our natural world. The
characters of science are fascinating: some quirky, most kind, all with a burning passion for
their labor of love. And the stakes of science can be high, ranging from the privacy of our
digital lives to cures for rare and debilitating diseases.
In every issue, we seek to uncover the most fascinating breakthroughs in science. From
seeing how lizard skulls evolved into bird skulls (p. 20) to understanding Parkinson’s disease
by studying a much rarer cousin of the disease (p. 18), the journey of science ranges over a
very wide span of topics. Our cover article this issue describes the galaxy that we live in, and
why researchers believe that it is rather unique compared to other galaxies (p. 12). We also
pursue the deadly killer of breast cancer and seek to understand how one gene, BRCA1, is
able to cause so much damage (p. 15). And we even fight death itself, learning how our bodies
break down with age to find ways to keep the old healthy (p. 22).
While the results of science can make our lives more fulfilling, the journey to reach there
can be equally exciting. The methods of modern scientific exploration - using lasers to probe
neurons (p. 26), creating breathalyzers to monitor exercise (p. 35), or programming bacteria
to grow proteins (p. 32) - challenges our imagination. The diligent scientists who work at
these goals are just as amazing, from undergraduate who work on cell structures (p. 36) to
doctors who fight disease and discrimination (p. 37). Every advancement in science is made
by groups of researchers struggling to solve mysteries of our world. Their tales inspire us to
do the impossible and persevere in the face of challenges.
And science is always relevant. New innovations create safer ways to replace dangerous oil
pipes (p. 7) and create better vaccines to fight off the flu (p. 9). And beyond the endless new
biomedical and engineering technologies, other discoveries - on the origin of diseases (p. 11)
or the rescue of monkeys (p. 6) - define our human spirit.
We write because the story of science fascinates us. New discoveries challenge past paradigms
and propose new world-views, as scientists aim to discover more fundamental truths
in our study of the universe. These stories have impact far greater than merely other scientists,
influencing the fundamental beliefs of humanity.
As this year draws to a close, we thank you for being with us as we have explored these stories
together. Our staff and masthead have tirelessly worked to write, produce, edit, design,
and publish this magazine, and we could not have told these stories without a willing listener.
We are excited for the many more science stories to be told in 2018, and to continue being
part of this fantastic community of scholars and friends.
A B O U T T H E A R T
Chunyang Ding
Editor-in-Chief
Since this is my final cover as Arts Editor, I
just want to thank everyone who ever picked
up a copy of the YSM in the last 12 months
for giving me a chance. Just kidding, it’s really
thanks to the incredible production and writing/editing
team that this magazine is what it
is today — so thank you all for giving me the
chance to draw galaxies, DNA, mushrooms
and more. I’ve grown as an artist and as a fan
of this magazine with each issue, and I hope
that this final cover design — a fanciful depiction
of a prism of light through our very
own Milky Way — articulates that feeling.
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NEWS
in brief
Cayo Santiago: No Monkeying Around
By Sarim Abbas
IMAGE COURTESY OF LAURIE SANTOS
►The monkeys of Cayo Santiago
comprise some of the best-studied
primates on the planet.
Off the coast of Puerto Rico lies Cayo Santiago,
a 38-acre island home to one of the oldest
primate field sites in the world. But in the
aftermath of Hurricane Maria, the well-being
of its locals and monkey population is at risk.
Scientists have studied Cayo Santiago’s
monkeys for decades, looking at group dynamics,
development and genetics. “It’s one
of the only sites in the world with such a
large population of habituated monkeys,”
said Laurie Santos, a psychology professor
at Yale University who studies animal cognition.
“It’s really the one site where I can
do my cognitive studies of primates on that
large a sample.”
The island is a mere 38 acres, and the monkey
residents can roam freely on the island
without fear from predators. Scientists from
at least nine universities work on the island,
including faculty from Yale Universiy and
the University of Puerto Rico.
But on September 20th, the island’s monkey
population and locals were in the direct
path of Hurricane Maria, a hurricane that
ravaged much of the Caribbean. Now, researchers
and affiliates are rushing to ship
food, clothes and other supplies to help aid
recovery.
Though all monkey groups on the island
have been accounted for, the devastation
to infrastructure, vegetation and fresh-water
sources will no doubt impede their livelihood.
And for many locals—most of them
in the researchers’ employ—the situation is
even more dire. “Some of our long-term staff
and their families have lost everything they
own,” Santos said, “and everyone in the town
has not had power, phone service, or water
for an entire month.”
Despite lackluster official support, researchers
hope their shipment of supplies
will help alleviate the hardship. But until the
locals get back on their feet, all operations on
the island remain on hold.
Hot and Cold: Temperature and Virus Transmission
By Daniel Fridman
IMAGE COURTESY OF WIKIMEDIA COMMONS
►Aedes aegypti mosquitos spread
many diseases, including DENV-2,
chikungunya, Zika, and yellow fever
viruses.
In recent years, news has covered the
emergence and spread of mosquito-transmitted
viruses including Zika, chikungunya, and
dengue. Scientists and public health officials
work to understand, predict, and ultimately
prevent outbreaks. A new Yale study, conducted
as a collaboration between the labs of Paul
Turner and Jeffrey Powell in the department of
Ecology and Evolutionary Biology, investigated
the effect of temperature and mosquito genotype
on the infection rates of Aedes aegypti mosquitos
by a type of dengue virus (DENV-2).
Knowing that temperature affects mosquito
susceptibility to infection, the researchers sought
to determine how various mosquito and viral
genotypes affect infection rates at different
temperatures. The researchers studied two
populations of the A. aegypti mosquito from two
locations in Vietnam—Hanoi and Ho Chi Minh
City, with average temperatures of 23°C and
28°C respectively—and infected them with two
isolates of DENV-2 originating from the same
locations.
“There is a lot of variation in temperature
in these regions,” said Andrea Gloria-Soria, a
member of Turner’s lab and first author of the
study. “We hypothesized that mosquitos adapt
to the temperature where they live, affecting
virus transmission.” After a 10-day incubation
at temperatures of 25°C, 27°C, or 32°C, the
researchers quantified the number of mosquitos
infected with dengue virus. Their findings showed
that different mosquito populations respond
differently to temperature, with mosquitos from
warmer climates being more susceptible to
DENV-2 infection at colder temperatures.
Local temperatures may influence the risk of
dengue virus outbreaks, and introduction of
mosquitos adapted to warmer climates to cooler
geographic areas may increase infection rates.
“Many people in cooler regions don’t think about
mosquito viruses as a problem, but if mosquitos
are introduced at the right moment, they can
survive and transmit the virus, presenting a
greater risk for outbreaks,” said Gloria-Soria.
6 Yale Scientific Magazine April 2017 www.yalescientific.org

in brief
NEWS
Solarizing Through Social Networks
By Ashwin Chetty
If your friend installed solar panels, you
most likely would too. Recently, researchers
investigated community campaigns in
Connecticut that took advantage of these
effects, in a study led by Duke professor
Bryan Bollinger and Yale professor Kenneth
Gillingham. They found that increased
visibility of solar panels in neighborhoods,
word-of-mouth campaigns, and town events
can make solar installation “contagious.”
The Solar Energy Evolution and Diffusion
Studies 1 (SEEDS 1) project focused on
analyzing Solarize campaigns, which aim
to increase solar adoption. Specifically, the
researchers studied Solarize campaigns in
Connecticut that used two main strategies:
grassroots marketing and group pricing, a
pricing scheme that reduces cost of solar
installation as more people install solar
panels. Gillingham and Bollinger found that
group pricing did not lead to increased solar
installation. However, 20-week campaigns
were more effective than 10-week campaigns
by allowing for more word-of-mouth.
Gillingham and Bollinger are now working
on a SEEDS 2 project, asking another research
question: “How can these campaigns reach
low and moderate-income households?” Their
hypothesis is that changing the messaging of
the campaign to focus on either the community
aspect or the financial attractiveness of solar
installation will increase solar adoption in
these households. In South Carolina, they
are investigating whether access to shared
solar—owning a share of a solar farm instead
of installing panels on a rooftop—increases
solar adoptions by low and moderate-income
households.
“In the past, people have just run the
campaigns, and we were the first ever to test
how to run the campaigns,” Gillingham said.
Even though the research is still ongoing, solar
advocates can immediately apply these findings
in solar adoption campaigns around the country.
PHOTOGRAPHY BY SUNNIE LIU
►Gillingham and Bollinger found
that increasing solar planet visiblity
through local outreach efforts can
increase solar installation.
Yale Startup Hopes to Deploy Pipe-Inspecting Robots
By Linh He
Big changes are on the way in the petroleum
industry. Soon, a new player will help detect
pipeline corrosion: robots. Dianna Liu, a
former Exxon-Mobil worker and now Yale
School of Management student, founded the
company ARIX with recent Yale graduates
Petter Wehlin ’17 and Bryan Duerfeldt ’17 to
explore how robotics and predictive analytics
technology could be tapped for the oil
industry.
“Like any large company that deals with
operations…[the petroleum industry] is very
dangerous, and they prioritize safety,” Liu said.
However, limited technology exists to ensure
the safety of workers searching for corrosion
in the pipelines that carry petroleum. Liu, who
previously interned in a biomedical company,
was inspired by how technology has improved
the quality of medicine, and wanted to apply
technology to the petroleum industry as well.
Her idea was a promising solution that
holds potential in tackling a $5.4 billion
dollar corrosion issue within the U.S. oil and
gas industry. ARIX’s robots could prevent
human workers from undergoing dangerous
processes to inspect pipe corrosion in
petroleum plants. Rather than having human
workers hang by ropes and walk on unstable
scaffolding to inspect pipes, ARIX proposes
using robots that could travel on the outside
of the pipes while inspecting specific points
along the pipeline. Furthermore, ARIX’s robot
inspection technology can quickly provide
more comprehensive data than people could.
ARIX has received much attention since its
founding. The prototype technology received
the $25,000 Miller Prize from the Tsai Center
for Innovative Thinking at Yale, and has
gained recognition from companies and
investors. While still in its early developing
stages, ARIX has already caught the interest
of the petroleum industry. For now, ARIX
will continue focusing on fine-tuning
the technology, and in the long run, will
potentially look to apply the technology to
other industries beyond gas and oil.
PHOTOGRAPHY BY TANVI MEHTA
►Dianna Liu (center), Petter Wehlin
(right), and Bryan Duerfeldt (left) are the
three co-founders of ARIX.
www.yalescientific.org
April 2017
Yale Scientific Magazine
7

NEWS
medicine
ACTIVATING THE IMMUNE SYSTEM
Fighting fungi by capturing sugars
►BY ALLIE FORMAN
For many Yale students, the word “fungus” might call to
mind the dining hall’s hybrid mushroom and beef burgers.
But fungus also has another unsavory meaning—fungal infections
are a major public health concern and can be deadly,
particularly to patients with weak immune systems such as
those with organ transplants, HIV, or cancer.
Fungal infections are responsible for roughly half of
AIDS-related deaths globally Candidemia, a fungal infection
common in organ transplant patients, has a 30-40% mortality
rate. While antifungal treatments exist, they can have side
effects, similar to how chemotherapy can damage a cancer
patient’s body while destroying cancer cells. Furthermore,
fungi are capable of developing resistance to conventional
therapeutics.
Dr. Egor Chirkin and Dr. Viswanathan Muthusamy, researchers
in the Spiegel lab of the Yale Chemistry department,
collaborated with Merck to generate a novel antifungal
compound that would minimize such side effects and prevent
the development of resistance. Their recent paper describes
how Chirkin and Muthusamy designed and tested a
compound that can activate the body’s own immune system,
destroying fungal cells without harming the patient’s own
cells.
“What the field is moving toward is clean killing of pathogenic
cells without a lot of side effects,” said Muthusamy, who
headed the biology aspect of the study. “What better to do it
with than your own immune cells, which are meant to fight
these diseases?”
The scientists were able to harness the power of the immune
system by creating a small molecule with two different
ends, so that one end of the molecule binds to the fungus,
and the other to antibodies already present in human blood.
“On one side, we need something which can always interact
with antibodies, the antibody-recruiting terminus.
On the other side, we need something which can interact
with the pathological cells, some specific target which is expressed
only on the fungal cell wall,” said Chirkin, who used
his chemistry background to design and synthesize potential
molecules.
The researchers began by creating modified versions of a
molecule called calcofluor, which selectively binds to chitin,
a sugar found in fungal cell walls but not human cells. Because
there was not a good test to measure the efficacy of
the molecules Chirkin created, Muthusamy devised a novel
test. The common human pathogen C. albicans was treated
with different antibody-recruiting molecules targeting fungi
(ARM-Fs). When the ARM-F was able to recruit antibodies
to the fungal cell, the complex could be recognized and
“eaten up” by human immune cells. Looking for fluorescently
labeled fungal cells, the scientists were able to quantify how
efficiently the fungal cells were eaten up by the immune cells.
“It is very unique in biology to target fungal cells using
immune effectors; it is not usual in the literature, so we had
to develop our own assays to test the efficacy of these compounds,”
said Muthusamy. This new methodology can be
used by scientists in the future to continue study in the field.
In addition to avoiding side effects, an advantage to the
ARM-F approach is that fungi are unlikely to develop drug
resistance. Unlike common antibiotics, which quickly become
obsolete, an ARM-F drug could likely be used without
drug resistant strains developing. Chitin, the target molecule
on fungal cell walls, is a sugar polymer. While proteins evolve
quickly to evade our immune defense system due to errors
in DNA replication, sugars are not coded for by DNA and
therefore do not possess the same ability to quickly mutate.
“Chitin is a key element of the fungal cell wall, and it is
a polysaccharide. This is a chemical substance, so the fungus
really cannot change it. The fungus can make less of
it, but that also would reduce its chance of survival,” said
Muthusamy.
Moreover, small molecules tend to be more stable than
other drug compounds and can be ingested, unlike biological
molecules. This means that a drug from an ARM-F could
likely be taken orally as a pill—much easier than an injection
or other delivery method.
While this study holds promise, the molecule must undergo
further testing before it can be used on patients. So far, the
ARM-F has only been tested in cells. The molecule must next
undergo rigorous testing in mouse models before entering
clinical trials. If all goes well, many patients stand to benefit
from this work.
►Candida albicans is a common fungal pathogen.
IMAGE COURTESY OF ISTOCK
8 Yale Scientific Magazine December 2017 www.yalescientific.org

medicine
NEWS
HOW GENES AFFECT YOUR FLU VACCINES
A new direction in bioinformatics
►BY JESS PEVNER
IMAGE COURTESY OF BRIAN SNYDER, RETUERS
►A nurse prepares a flu shot, inserting the vaccine into a
needle syringe.
Each year, 132 million Americans flock to doctors’ offices,
pharmacies, and clinics for flu shots. With the onset
of “flu season” each year, 41% of the population opts to
get vaccinated. Currently, flu shots are the most effective
way to protect against infection. Despite this, they are only
about 60% effective in adults over the age of 65.
Why does the flu vaccine work for some, and not for others?
The answer, according to a recent study, may lie in our
genes. Dr. Albert Shaw led scientists at Yale University and
four other research centers to find that certain genes correlate
to stronger immune responses. This discovery paves
the road for further genetic research and provides insight
into the future of vaccination.
“We set out to study why people respond differently to
the vaccines. We used the flu vaccine because it is very
commonly used throughout the country and you can collect
a large number of patients,” said Ruth Montgomery,
co-author of the study and associate professor at the Yale
School of Medicine. As Montgomery implied, an important
aspect of the study is its size. The genetic data used
came from four independent institutions. In total, over 500
individuals participated in the study. The data spans five
years of flu vaccination seasons. In combination, these factors
make the conclusions of the study more reliable.
“A big part of our study was comparing responses to vaccination
with younger and older people. In general, older
people have a much less efficient and successful response
to vaccination,” Montgomery said. The ages of the participants
fell into two groups: either under 35 or above 60
years old. Interestingly, the results for the study differed
between the two age groups. The cluster of genes, or “signature,”
that correlated to a stronger immune response in
younger people did not help the older group. Similarly, the
beneficial signatures for the older group did not prove significant
to the younger group. “The older people who respond
use different genes and cellular pathways than the
younger people who respond,” said Montgomery. This
means that our immune responses to vaccination change
with age—a potential subject for further investigation.
The researchers identified the genes that influenced immune
response by examining the younger people that did
not respond well to vaccination. Nine individual genes and
three sets of co-expressed genes were found to impact response
to the flu vaccine. “The beauty of this study was
combining those young non-responders across a number
of different universities and research programs and using
computational tools to try to understand what might
lead to a poor vaccine response in a young healthy donor,”
Montgomery said.
Montgomery cites much of the study’s success to our increased
ability to use computational processes to analyze
biological data. Researchers gathered 47,000 RNA transcripts,
which are a form of genetic information in our
cells, from each patient. With over 500 participants in the
study, this amounts to more than 23 million transcripts in
total. Without the aid of computer algorithms, this massive
amount of data would be impossible to process. With
the bioinformatics analysis led by Dr. Steven Kleinstein,
researchers were able to synthesize the data and make significant
conclusions.
The results of this study point to possible innovations in
vaccination. With the knowledge that older people process
vaccines differently from younger people, scientists
may develop different methods to boost the effectiveness
of vaccines for older people. “It is possible for some sort of
therapeutic approach to boost those immune responses—
or perhaps with a better understanding of the pathways, we
can modify what goes into the vaccination for older people,”
Montgomery said.
Since the study only examined the flu vaccine, scientists
are not yet sure if these genes help in immune responses
to other vaccines. “It’s not always clear whether the results
from this study will apply to responses to other vaccines,
so that would require more study to understand,” she said.
All in all, the work of these collaborators provides exciting
insight into the genetics behind immune response and
opens new doors for future research on vaccines.
www.yalescientific.org
December 2017
Yale Scientific Magazine
9

NEWS
applied physics
THE SOUND OF QUBITS
Acoustics may contribute to the next computing revolution
►BY ANDREW RICE
IMAGE COURTESY OF WIRED
►The current state of building a quantum computer. Quantum
computers must be kept in extremely cold environments to
prevent heat from being absorbed by the system, which disrupts
quantum states.
Potentially the most powerful computing tool ever created,
quantum computing technology is likely to continue
to advance in the coming decades. What makes quantum
technology special is its computational power, allowing it
to have a wide range of applications. Among these are the
abilities to break RSA encryptions, which are used by many
governments to encode information on a classical computer,
and to analyze vast amounts of data very quickly.
However, building a quantum computer is difficult because
it poses the challenge of finding a system efficient for
both quantum information processing and effective control
of quantum states. Recently, a collaborative effort by
the Schoelkopf Lab and Rakich Lab at the Yale Quantum
Institute has shown promise in using sound waves to store
quantum information. Their method would increase efficiency
and reduce production costs, which could cause major
advances in the field of quantum computing.
For the last eighty years, the world has relied on classical
computers, which operate using values of zero and one to
store information and solve problems that cannot be worked
out by hand. Classical computers use two-state physical systems,
like transducers or magnets, to define the complete
physical state of a system, and then apply algorithms to manipulate
those states to solve different problems.
Quantum computing breaks from the realm of classical
computing by utilizing the fundamentals of quantum mechanics
to encode information. For a quantum particle with
two possible states, a particle is said to be in a superposition
of both states, meaning the particle can be in both at
the same time. Upon measurement, the particle randomly
chooses one of these states.
These particles are called qubits, or quantum bits, and are
quantum representations of a physical system. Just like a
classical bit, a qubit is a piece of information that can be
used in computation. However, instead of dealing with certainty,
quantum physics deals with probabilities, and thus
the state of the qubit is a probabilistic representation of the
two possible states it could occupy. Using these odd probabilities,
quantum computers can solve complex problems,
including breaking computer encryptions to access secret
data. The possibilities are endless.
Some of the most difficult challenges with quantum computing
are maintaining a particular quantum state and finding
a physical system that can be used to store quantum information.
This is because quantum states are very fragile
and are susceptible to change by any interaction with the
environment around them.
In September 2017, the Schoelkopf Lab and Rakich Lab
at the Yale Quantum Institute announced their success using
a simple-to-produce and very robust device that uses
sound waves to store quantum information. The apparatus
uses a piezoelectric transducer to couple the qubits to
sound waves. The qubit system shows a dramatic increase
in coherence time from previously demonstrated experiments,
giving scientists more control and predictive power
over the qubit.
Furthermore, the apparatus used to couple the qubits to
sound waves requires relatively simple fabrication methods.
“I think that our work demonstrates that it’s possible
to couple superconducting quantum circuits and mechanical
resonators in a simple and high-performance way,” said
Yiwen Chu, lead author of the recent breakthrough and
a post-doctoral researcher in the Schoelkopf Lab. “This
makes them accessible and robust enough to be used in
more complex quantum devices in the future.”
This finding comes at an important and exciting time
in the development of quantum mechanical applications.
“Quantum computing is one of the main examples of how
we can harness quantum mechanics to do something useful,”
said Chu. “Much like other applications of physics,
quantum mechanics is also undergoing that exciting transition
from us being able to understand the physics to being
able to build something useful.”
As quantum systems become more complex and demonstrate
more precise control of qubits, the ultimate goal of
building a quantum computer able to solve even more complex
problems than currently possible will become a reality.
Contributions like this will prove to be the key to their progression
into a more mature and feasible application, making
the once most difficult problems seem trivial.
10
Yale Scientific Magazine December 2017 www.yalescientific.org

evolutionary biology
NEWS
LYME AND PUNISHMENT
Human activity likely affects the spread of Lyme disease
►BY VICTORIA DOMBROWIK
IMAGE COURTESY OF THE CDC
►Black-legged deer tick on a blade of grass. Ticks are the
main vectors of Lyme disease
Local Connecticut lore names Plum Island, the home of a high
security government laboratory, as the source of Lyme disease.
The controversial theory claims that infected ticks were accidentally
released from the facility in the early 1970s. The truth, however,
may be more compelling. Recent research, led by Katherine
Walter of the Yale Department of Epidemiology and Microbial
Diseases, suggests that the pathogen has existed for around 60,000
years. Furthermore, it may be human impact, not scientific meddling,
that has caused the sudden surge in sickness.
Strange things appeared to be afoot in Lyme, Connecticut
during the summer of 1976. The town had experienced
a record number of juvenile arthritis cases that year, which
puzzled many physicians and researchers. To make matters
worse, complaints of severe joint pain, headaches, and fever
were spreading like wildfire. What had begun as an isolated
incident swiftly transitioned into a widespread phenomenon,
affecting adults at the same rate it has children.
The mysterious symptoms were later all classified under one
ailment: Lyme disease. Named for the town first believed to be
its epicenter, Lyme is now reported to be the most common vector-born
disease in the United States. According to the Center
for Disease Control and Prevention, there were over 28,000 confirmed
cases in 2015 alone. To examine the spread of Lyme however,
one must first examine its vector, the blacklegged tick.
When one thinks of ticks, the connotation tends to be quite
negative. These small parasites are the often invisible threat
associated with outdoor activity in the late summer and fall.
Their resemblance to spiders, with which they share the same
subclass, is equally unnerving. What makes the blacklegged
tick potentially dangerous however, is the pathogen it carries.
First clinically described in 1982, Borrelia burgdorferi is one
of the few bacteria that seems to directly interact with the cell
tissues it infects, rather than producing a microbial toxin. It
also has an extremely low rate of replication, which allows it
to remain undetected in a host for some time. This creates
difficulties in prescribing treatment, as many patients are unaware
of the infection until it becomes chronic.
Although researchers now have an understanding of the
effects of a B. burgdorferi infection, little is known about
its evolutionary origins. Additionally, it is still unclear why
the United States has seen such a rapid increase of Lyme in
the past 30 years. Walter and her team at Yale have attempted
to expand the current understanding the bacterium.
Walter became interested in the pathogen’s history while a
graduate student in the Yale Department of Epidemiology
and Microbial Diseases. “Looking at molecular evolution
is like looking at records,” Walter said. “Often, the records
for infectious diseases are incomplete.” Her research team
attempted to explain the sudden surge of illness by examining
the genome of B. burgdorferi, using data compiled from
nearly thirty years of fieldwork.
The results of the research proved to be astonishing. They
suggested that B. burgdorferi has been present in the northeastern
United States for around 60,000 years. This differs
from the original theories, which tend to focus on evolutionary
change or pathogen introduction as the cause of its emergence.
Furthermore, the findings point to human activity as
the leading factor in Lyme’s dispersal.
To put this into perspective, imagine the northeast 60,000
years ago. It did not contain the vast expanse of cities and roadways
characteristic of today. The landscape was likely composed
of forests and thick underbrush, making it an oasis for
ticks. Urban development and industrialization have greatly
infringed upon the habitat of the animal hosts, and therefore,
of the tick. In addition, climate change has contributed to consistently
warmer seasons, which in turn have afforded ticks a
longer lifespan. Ironically, while global warming may prove
detrimental to humans, it will promote the survival of parasites.
Increased vigor, as well as sustained migration, will continue
to broaden the scope of Lyme disease in the near future.
There is, however, a glimmer of hope. A research team
from the Cary Institute of Ecosystems found that ticks
seem to dislike dry weather. Nymphs, the intermediate
stage in a tick’s lifespan, experience more difficulty securing
hosts in arid conditions.
If the United States continues to see a decrease in annual
precipitation, it may also see a decline in the prevalence of
Lyme disease. For now, scientists like Walter and her team will
continue to track and study the disease, helping us better understand
our relationship with the environment around us.
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December 2017
Yale Scientific Magazine
11

astronomy FOCUS
Imagine sitting at a movie theater watching the latest blockbuster movie about space. Because
of its vast size, a galaxy pulls in smaller and slower-moving galaxies, trapping them in its orbit.
Eventually this larger galaxy begins stripping away bits of mass from the smaller galaxies and,
eventually, its own stars. You find yourself sitting at the edge of your seat, awaiting what happens.
As exciting as this phenomenon seems, it’s not science fiction, but reality. What’s more, it’s
not just any galaxy—it’s our very own Milky Way.
Galaxies are born in dark matter, a mysterious
substance that comprises about
90% of our universe. The Milky Way is a
central galaxy, meaning it has smaller galaxies,
called satellites, caught in its gravitational
pull. Our galaxy has long been
studied to increase our understanding of
the universe. Specifically, researchers have
based their predictions about dark matter
and the formation of galaxies based
on their observations of the Milky Way’s
satellite population. However, researchers
have discovered that the Milky Way
might be an outlier. Marla Geha, professor
of astronomy at Yale University, is a
leader in this area of research—no other
research group has tried to do a project
as ambitious as hers, requiring extensive
time and resources. By studying 8 galaxies
similar to the Milky Way, Geha’s team
have provided researchers with incredible
new insight—the Milky Way Galaxy may
be more unique than we think.
A taste of the Milky Way galaxy
It is believed that galaxies form in the
center of dark matter structures. Galaxies
emit light from their stars—the more stars,
the brighter the galaxy. Within the Milky
Way, two satellite galaxies, called the Small
and Large Magellanic Clouds, are currently
forming stars from gas. All other satellites
have been stripped of their gas as the Milky
Way eats away at the materials composing
the satellites, a process that occurs when
smaller galaxies orbit the Milky Way.
Researchers have heavily based their predictions
about how galaxies form based off
their research on the Milky Way’s satellite
galaxies. However, Marla Geha, along with
Risa Wechsler, professor at Stanford University,
are interested in how the Milky Way
compares to other galaxies in our universe.
“We have a default assumption that whatever
is in our neighborhood is what we see
everywhere but maybe this isn’t the case,”
Weschler said. The behavior we see in our
own galaxy may not be typical of many other
galaxies in the universe.
The beginning of a SAGA
IMAGE COURTESY OF NASA
►The Magellanic Clouds are the only two
star-forming dwarf galaxies found orbiting.
Geha and Weschler, along with their research
team, were interested in exploring
other satellite galaxies beyond the Milky
Way. To investigate these other galaxies,
they started the “Satellites Around Galactic
Analogs” (SAGA) Survey. The purpose
of this survey is to investigate 100 galaxies
similar to the Milky Way galaxy and to
compare their satellite galaxies. Successfully
doing so has implications on how researchers
view galaxies. For example, satellite galaxies
are of interest because it may provide
clues about dark matter and its interaction
with galaxies. When satellite galaxies become
caught in the gravitational pull of
larger galaxies, it is likely dark matter is at
play, though it remains unknown how the
satellite becomes embedded in what is essentially
a halo of dark matter. Moreover,
the behavior of these satellites, such as their
ability to form stars, provides clues about
the relationship between dark matter and
satellites, and why some satellites have lost
the ability to actively form new stars.
To begin their research on both analog
galaxies and their satellites, the team used
already established catalogs to select galaxies
similar to the Milky Way. The researchers
based their criteria on how similar these galaxies
were in luminosity as well as whether
they had a similar large-scale environment.
Galaxies that passed these criteria were added
to the SAGA Survey for further analysis
of their satellite galaxies. Of all the galaxies
►The bright spots in the image are stars in
the Small Magellanic Cloud.
in the catalog, the team has so far added 79
galaxies to the SAGA and have fully investigated
satellites on eight of these analogs. The
next step is examining these galaxies more
closely and searching for embedded satellites
caught in the gravitational pull of these
galaxies which may provide clues of similarities
shared with the Milky Way.
A (red) shift in perspective
IMAGE COURTESY OF NASA
Researchers detect satellite galaxies
through their brightness, an indicator of
the number of stars within it. Images of
galaxies are readily available in published
research catalogs. The research team used a
method called photometry, a procedure to
detect light intensity from these galaxy images.
However, photometry poses a problem—there
is no way to tell whether this
galaxy is circling another galaxy. “It’s like
holding a series of galaxy images up of and
trying to decide which is a satellite—you
just can’t know,” Geha said. If researchers
could find a way to measure the distances
between these galaxies, they may be able to
uncover the behavior of these galaxies.
One method the research team used in
uncovering this data was to analyze the
spectra of the galaxies. By scattering the
light emitted by the galaxy, they were able
to observe the characteristic wavelengths of
the light energy emitted. Similar to scattering
white light with a prism to release its
rainbow colors, Geha and the team took
images of galaxies and separated the light
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December 2017
Yale Scientific Magazine
13

FOCUS
astronomy
into many different wavelengths, or colors.
Objects moving away from the Milky Way
emit less intense light and subsequently undergo
a shift in wavelength toward the red
end of the color spectra where wavelengths
are longer. Therefore, a galaxy with a larger
redshift is moving further away. By gathering
this information, the researchers were better
able to understand the position of potential
satellite galaxies, filling in the missing gap in
knowledge about whether these galaxies are
indeed satellites of a central galaxy.
However, using this process to obtain redshifts
comes with its own set of difficulties.
For example, spectroscopy is expensive and
time consuming. In addition, the slower
that a galaxy moves, the fainter and harder
it becomes to detect the redshifts. Though
the research team was able to target over
17,000 redshifts, the spectra obtained may
be not only from galaxies themselves, but
also from stars and other objects. Therefore,
they needed to further filter out the
redshifts corresponding to galaxies from
those caused by other natural phenomena.
To create a more efficient system for detecting
redshifts of galaxies, the researchers
observed the relative wavelengths of satellite
galaxies and their redshift range. They
found a range in which the redshifts were
similar among satellites, indicating that
redshifts in this range were the most likely
to correspond to satellite galaxies. By going
back over their collected sample of redshifts
and selecting redshifts that fell within
the “satellite galaxy” range, they were able
to leave out redshift data from unwanted
sources. Using this refined redshift information,
researchers were able to locate 25
satellites from analog galaxies, providing
us a new perspective on the nature of many
potential satellite galaxies in the universe.
The SAGA continues
IMAGE COURTESY OF NASA
►The Milky Way Galaxy has long been studied,
and houses numerous satellite galaxies.
While the study has surprised the research
team, there still remains much to
uncover, and they are just getting started.
The team is leading in this field—there
is no other research team doing such an
ambitious project. Once the SAGA is completed,
scientists will better understand
the Milky Way from a cosmological standpoint
and how it compares to other analogs.
“We’re really proud of the progress
we made and we are well underway in answering
the question of how atypical our
galaxy may be,” Geha said.
With a goal of analyzing 100 analog
IMAGE COURTESY OF WIKIMEDIA COMMONS
►Using optical telescopes, more than
10,000 distant galaxies can be seen.
galaxies similar to the Milky Way, the researchers
are already analyzing the data
of other analogs for their satellites. With
more efficient methods for detecting redshifts,
the team can more effectively locate
even the faintest satellites. While Geha is
not certain what the rest of their data will
indicate once they finish analyzing all satellite
galaxies, she believes it might take as
few as two to four years to finish the survey
and make more conclusions. “Once
the SAGA Survey is complete, I think
we will really understand our galaxy in a
much broader context,” Geha said. Until
then, the SAGA continues in uncovering
the mystery of our galaxy.
ABOUT THE AUTHOR
JESSICA TRINH
The Milky Way Galaxy—an outlier?
The process of obtaining redshift information
to determine satellite galaxies is
a slow process, but it comes with a great
payoff. The team’s analyses of these satellite
galaxies have revealed an interesting finding:
the analog galaxies contain mostly star
forming satellite galaxies. Unlike the Milky
Way, the results from the 8 analog galaxies
indicated 26 of the 27 satellite galaxies are
actively forming stars. “If more information
supports this finding, we need to start
reevaluating how we view our own satellite
galaxies in the Milky Way,” Wechsler said.
JESSICA TRINH is a sophomore Neuroscience major in Branford College.
She is the Vice President of Synapse and is excited to teach middle schoolers
about STEM. She also teaches health education in New Haven middle schools,
nutrition counseling at HAVEN Free Clinic, and is currently leading a research
project on nutrition.
THE AUTHOR WOULD LIKE TO THANK Dr. Marla Geha and Dr. Risa
Wechsler for their time and enthusiasm for sharing their research.
FURTHER READING
Geha, M., Wechsler, R.H., Mao, Y.Y., et al. 2017. “The SAGA Survey I: Satellite
Galaxy Populations Around Eight Milky Way Analogs. The Astrophys. J. 847, 1-21.
Geha, M., Wechsler, R.H., Bernstein, R., et al. 2017. The SAGA Survey.
Retrieved from http://sagasurvey.org
14 Yale Scientific Magazine December 2017 www.yalescientific.org

DEMYSTIFYING
the genes
behind
CANCER
by LESLIE SIM || art by LAUREN TELESZ
The BRCA1 gene has been studied
for over two decades due
to its relationship with cancer
growth, with researchers hoping
to elucidate the processes and mechanisms
of BRCA1 in order to effectively
create cancer treatments. On the surface,
we can only observe the physical symptoms
of cancers affecting millions every
year. Delve one step deeper within the
body, and it becomes clear how the growth
of malignant cancer tumors has severe
weakening effects on every bodily system,
from the immune system to other organ
systems. Zoom one final step deeper,
and the root cause is revealed: the genes
we are born with are intricate yet delicate
structures that can be impacted by the environment
or through its own replication
and functions. It is these genes and their
mutations that greatly affect one’s chances
of rampant cancerous growth. One of the
genes that has been identified as a culprit
in such tumor growth and excessive cell
replication is BRCA1.
Over the last twenty-five years alone,
since the BRCA1 gene was discovered,
about 70 million women have been diagnosed
with breast cancer and ovarian cancer.
The BRCA genes have been identified
as significant factors in the role of cancer
growth, but scientists have never been able
to explain exactly why and. It’s been over
two decades—the number of people who
are affected by cancer is increasing and our
time is dwindling.
Fortunately, researchers in the Sung Lab
at Yale, led by Patrick Sung and Weixing
Zhao, have tackled the problem by developing
their own system of protocol to discover
the function of BRCA1 and its interaction
with other genes in the role of
tumor expression. Despite failures in other
labs for years, the Sung lab was certain
that given the right amount of experience,
time, and careful work with the genes and
proteins of interest, they would be able to
build upon previous research to further
study the elusive gene in a novel way.
The Mysterious BRCA1 Gene
BRCA1 is a gene that produces proteins
that prevent cells from multiplying uncontrollably—a
process responsible for eventually
forming a tumor. Although the gene
has been studied extensively over the last
two decades, it has remained a mystery exactly
which proteins BRCA1 is responsible
for expressing and how it interacts with
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December 2017
Yale Scientific Magazine
15

FOCUS
genetics
IMAGE COURTESY OF ANTJE WIESE
►Engagement of the BRCA1-BARD1 complex in homologous DNA pairing. In this analogy, the lasso is BRCA1(red)-BARD1(green), the cowboy
is the recombinase RAD51, the large horse is homologous DNA, and the small horse is single-stranded DNA resected from double strand breaks
(DSBs). Caption courtesy of the Sung Lab.
other genes like BARD1. We do know that
the protein made by BRCA1 is involved in
a process called DNA repair, in which it interacts
with other molecules to find damage
within a molecule of DNA and then repair
it. This process is critical to normal cell
function because, when mutations arise,
whether accidentally or through environmental
factors, our bodies require a mechanism
to fix the errors in DNA before the
DNA can be used to produce flawed or unwanted
proteins. In normal humans, there
will be two copies of the functional BRCA1
gene present—one from the mother and
another from the father. As accumulation
of natural mutations or environmental factors
such as radiation from external agents
constantly damage DNA, one or both of the
copies of the gene that coordinates repair
may have mutations or be destroyed. If this
occurs, it is very likely that the DNA repair
mechanism to suppress tumor growth will
be unable to function normally, and there is
a high likelihood of cancer arising.
Among people who inherit just one functioning
copy of the BRCA gene, chances are
that over the years, the functioning gene
will be lost due to environmental damage,
and being devoid of the remaining functional
BRCA gene can eventually lead to
cancer. Mutations in both of the BRCA
genes, called BRCA1and BRCA2, are associated
with all forms of cancer but are
most strongly linked to breast and ovarian
cancer. While it is still a debate why mutations
in these genes primarily affect these
two types of cancers, some believe that
gene expression-related stress is higher in
cells where breast cancer originates. Estrogen-responsive
genes, such as the ones in
breast and ovary tissue, are therefore more
susceptible.
16 Yale Scientific Magazine December 2017 www.yalescientific.org

genetics
FOCUS
Solving the Mystery
BRCA1 has been a mystery for so long
in part because the protein encoded by the
BRCA1 gene is large and complex—with
many components that make it difficult to
work with when trying to avoid denaturing.
The first main challenge in their research was
purifying the protein itself. Proteins, in comparison
with other macromolecules such as
carbohydrates, are much more unstable due
to their various components and ability to
denature, or become inactive, in suboptimal
conditions. Sung says it took several years
of experience to finally design a method to
not only express a very large protein but also
work with the proteins without rendering it
inactive. The researchers working with the
protein had to work quickly and gently with
the delicate proteins in a room with a controlled
temperature in order to preserve the
proteins in their functioning state. Leaving
the protein in a high or low temperature environment
or leaving it out for longer than
about half an hour could denature it to the
point where it could no longer be studied.
Their novel approach allowed them to express
thousand-fold the amount of protein
that was previously possible.
After overcoming this obstacle, the team
was set on further studying the proteins. But
there was still one missing piece to the puzzle
– the BRCA-BARD1 complex required a
helping hand in performing their DNA repair
task.
The team hypothesized that the BRCA1-
BARD1 complex works with an enzyme
called Rad51 because they observed certain
properties in protein factors that suggested
a cooperation with Rad51. To test their
hypothesis, they purposely induced DNA
damage in BRCA1 and then placed purified
elements in a test tube to determine whether
the DNA repair system worked. If the DNA
repair mechanism was successful, then that
proved their hypothesis that Rad51 indeed
was the enzyme that cooperated with the
complex to carry out DNA repair.
They were able to conclude that Rad51
recognized the damaged DNA and paired
it up with an undamaged molecule of DNA
to initiate the DNA repair reaction. Furthermore,
the BRCA1-BARD1 complex is essential
to the DNA repair reaction—when the
complex was unable to form, the repair did
not take place, and mutations affecting either
BRCA1 or BARD1 decreased the effectiveness
of repair.
IMAGE COURTESY OF SUNG LAB
►Dr. Patrick Sung (right), and associate
researcher Dr. Youngho Kwon (left).
Cancer Treatment’s Bright Future
Patrick Sung said that his passion for research
originated in his intellectual curiosity
and realization as a college student that
cancer was a huge problem that needed to
be cured. His ultimate goal is to develop
drugs that target specific known pathways
to treat cancer, and despite the large strides
this recent paper represents in the field, his
work is far from done. After the discovery
of the cooperation between BRCA1,
BARD1, and the Rad51 enzyme, it still remains
a question how BRCA1 and BRCA2
function together. BRCA2 is also a part of
the complex and plays a definite role in the
DNA repair mechanism as well, but it is not
as clearly understood as BRCA1. With their
novel approach to successful protein purification,
these researchers hope to reconstitute
the larger complex including BRCA2
and determine its relation to cancer formation.
Moreover, they are interested in understanding
how mutations work so that
they can find a basis for using compounds
in cancer treatment.
While many questions remain targets of
Sung’s continued research, it is likely that
both the biological discovery and technical
contribution to the protein purification
process will lead to progress in treating
cancers. Now that researchers know how
the protein factors of BRCA1 function,
they can test it in combination with other
genes to see if they can sensitize cancer
cells to available cancer drugs and determine
the efficacy of those drugs—a process
that would help physicians optimize their
prescriptions for their treatments. On the
other hand, they can also use their knowledge
of how the genes bind and function
to develop new compounds that can regulate
DNA repair processes and eventually
be used in preventative cancer drugs. In
the future, the scientists would like to fully
understand the pathways of BRCA genes to
the point where, by studying an individual’s
genes, they can advise the patient about
how likely it is that they will have cancer
and when they might be most susceptible
to cancer so that they may plan their futures
accordingly.
The fight against cancer is well and alive,
as researchers around the world make
strides towards treatments and preventions.
As the Sung Lab passionately scrapes
away the mysteries of BRCA1, we can be
hopeful that we are well on our way towards
answers for curing cancer.
ABOUT THE AUTHOR
LESLIE SIM
LESLIE SIM is a first year in Jonathan Edwards College at Yale University
interested in cancer research and biophysics. She enjoys fencing, food
photography, and exploring New Haven streets aside from being a writer for
the Yale Scientific.
THE AUTHOR WOULD LIKE TO THANK the Sung Lab at Yale and would
like to thank, in particular, Professor Patrick Sung, Dr. Weixing Zhao, and
Dr. Youngho Kwon for sharing their knowledge with me in interviews and
expressing enthusiasm about cancer research.
FURTHER READING
Zhao, Weixing et al. “BRCA1-BARD1 promotes RAD51-mediated homologous
DNA pairing.” Nature, vol. 550, no. 360, 4 October 2017, pp. 360-365.
www.yalescientific.org
December 2017
Yale Scientific Magazine
17

Studying the Few to Serve the Many
By Sunnie Liu || Art by Lisa Wu
18
Yale Scientific Magazine December 2017
The ultimate goal is to provide the greatest
amount of happiness for the greatest number
of people, according to philosopher Jeremy
Bentham.1 Take the U.S. government for example:
it awards grants to scientific research
that provides the most benefits for the maximum
number of people.
As a result, scientific research on disease in
America usually centers around the most common
health issues. The National Institute of
Health reports that the three diseases that received
the most federal funding in 2016 were:
cancer, cardiovascular disease, and HIV/AIDS,
which affect patient populations in the hundreds
of thousands. However, researchers like
Yale professor Dr. Pramod Mistry are studying
uncommon diseases to help underserved patients
with rare health problems.
He combined his work on the rare Gaucher
disease with the Chandra neurology laboratory’s
work on the much more common Parkinson’s
disease, a neurodegenerative disorder that
affects movement. In a recent paper in The Journal
of Neuroscience, this joint project, led by Yale
graduate student Yumiko Taguchi, showed that
the mutations that predispose patients to Parkinson’s
disease are the same mutations responsible
for Gaucher disease. For the first time,
the scientists pinpointed the common mechanism
linking Parkinson’s and Gaucher disease,
setting the foundation for potential new treatments
for Parkinson’s disease that target proteins
directly associated with the pathway.
Underserved patients
While learning about health problems that
affect a large part of the population is certainly
important, Mistry always had an interest in rare
diseases. “At a very human level, I was touched
by how underserved these patients were by the
medical profession,” explained Dr. Mistry.
His passion for helping the underserved patients
with rare diseases led him to study Gaucher
disease—a genetic disorder caused by mutations
in a gene called GBA. These mutations
reduce or eliminate the ability of the enzyme
to break down certain fatty molecules, also
known as lipids, leading to the accumulation
of lipids at toxic levels within cells, damaging
tissues and organs.
Over the years, Mistry encountered a number
of case of patients with Gaucher disease who
also developed Parkinson’s disease. Mistry partnered
with the Chandra lab to study the biology
underlying this correlation. “It was known that
mutations in GBA are the most common risk
factor in developing Parkinson’s disease, but we
now wanted to determine the molecular mechanisms,”
stated Taguchi. The researchers hoped
that to learn more about the relationship between
Gaucher and Parkinson’s disease at a molecular
level, and, by extension, discover potential
targets for treating Parkinson’s disease.
Behind the scenes of Parkinson’s disease
In order to understand the correlation between
Parkinson’s and Gaucher disease, one
must first understand how Parkinson’s develops.
Parkinson’s disease is characterized
by the formation of Lewy bodies, abnormal
clumps of protein that develop inside nerve
cells. Aggregation of the protein α-synuclein
comprises the majority of Lewy bodies, so
mutations in the gene that encodes α-synuclein
lead to Parkinson’s disease.
Although mutations in the gene that encodes
α-synuclein are the direct cause of Parkinson’s,
there are particular risk factors that make these
mutations more likely to happen. Normally,
people have two copies of the gene that creates
this protein. If someone has a mutation in only
one copy, they won’t show symptoms because
the other copy of the gene can make enough
GCase1 protein for normal human function.
However, if someone has Gaucher disease, they
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medicine
FOCUS
IMAGE COURTESY OF MASHANGEL WEBSITE
►Yumiko Taguchi, the Yale graduate student
who led the effort on this research project.
have a mutation in both copies of the gene, so
they cannot generate sufficient GCase1 protein.
Interestingly, both patients with a mutation
in only one copy of the gene and patients with
mutations in both copies—Gacuher disease patients—are
more susceptible to Parkinson’s disease.
Those with just one mutated copy of the
gene have a 5-fold increased risk, and those with
two mutated copies have an even higher risk at
20-fold. The scientists wondered how GCase1
mutations might give rise to Parkinson’s disease.
GCase1 protein plays a key role not only
in Parkinson’s, but also in Gaucher disease.
In patients with Gaucher disease, the protein
does not break down a particular complex
lipid GlcCer into the normal simple lipid
products, so both the original and produced
lipids build up. The accumulation of these lipids
characterizes Gaucher disease. Thus, the
researchers proposed that the original complex
lipid GlcCer may contribute to the development
of Parkinson’s disease.
Since mutations that encode α-synuclein
and Gaucher disease both correlate with
Parkinson’s disease, the scientists wanted to
study the relationship, if any, between α-synuclein
and Gaucher disease. A test tube study
showed that the lipids accumulating in Gaucher
disease accelerate the build-up of α-synuclein.
The findings also pinpointed the two
lipids, GlcSph and Sph, that promote more
α-synuclein aggregation than any other lipids
in human cells and neurons.
Justin Abbasi, an undergraduate Yale student
who worked on this research project, summarized
the results: “The proposed mechanism
was really exciting to think about because it
made sense: the lipids build-up caused by Gaucher
disease leads to a protein build-up that
characterize Parkinson’s disease.
After the scientists determined the link between
Parkinson’s disease and the lipids associated
with Gaucher disease, they decided to test
how Gaucher disease mutations affected the
manifestation of Parkinson’s disease. This time,
however, they wanted to conduct the experiments
on mouse models instead of in test tubes.
Relationship status: It’s complicated
The researchers were curious about how
the abnormal breakdown of lipids seen in
Gaucher disease impacted Parkinson’s disease,
so they looked at the lipid levels in the
brains of young mice with Parkinson’s disease.
The scientists discovered that the accumulation
of the lipid GlcSph at concentrations
seen in Gaucher disease produces an
increased amount of the protein α-synuclein.
In addition, the researchers noticed that
as the concentration of GlcSph increased, its
effect on α-synuclein aggregation increased.
These two findings suggest that the accumulation
of GlcSph may exacerbate the aggregation
of α-synuclein in the brain.
Another relationship studied was that of
the accumulation of lipids in the brain and
the mortality of mice with Parkinson’s disease.
The data showed that the mice with Parkinson’s
disease died prematurely, implying that
the mutations in the GBA gene accelerated the
development of Parkinson’s disease. The scientists
also found that the mice who died prematurely
had five times as much of the protein GlcCer
as normal, suggesting a strong correlation
between Parkinson’s disease-related morbidity
and increased lipid levels in the brain.
Connecting these two ideas, the scientists
concluded that for mice with Parkinson’s disease,
α-synuclein aggregated in regions where
GlcCer had built up.
There is no I in team
“Unfortunately, there is no cure to Parkinson’s
disease. You can relieve the symptoms, but that’s
it,” lamented Yumi. However, this new study
provides hope for patients suffering with Parkinson’s
disease: the scientists were able to pinpoint
specific enzymes in the metabolic pathway
that lead to the form of Parkinson’s disease
that stems from mutated GBA genes. Out of all
the various lipids that accumulate due to Gaucher
disease, the researchers found that the
build-up of GlcSph caused the biggest increase
in the risk of developing Parkinson’s disease because
GlcSph accelerated α-synuclein aggregation
the most. Thus, targeting the enzymes involved
with GlcSph offers a potential treatment
for Parkinson’s disease. The data pointed to two
particular enzymes, ASAH1 and glucocerebrosidase
2 (GBA2), as the most promising targets
for treating Parkinson’s disease.
None of these findings would have been
possible without the teamwork between Mistry,
with his Gaucher disease expertise, and the
Chandra Lab, with its neurology expertise. This
case is one of the many important interdisciplinary
science research projects changing the
way we understand disease. Mistry supports
interdisciplinary research as a way for different
branches of knowledge to converge in discovery.
“Any meaningful science now is team science.
The more collaborations you do, the better and
more meaningful your results are going to be,”
asserted Mistry.
Not-so-random mutations
ABOUT THE AUTHOR
SUNNIE LIU
SUNNIE LIU is a first-year prospective art and history of science, medicine, and public
health double major on the pre-med track in Morse College. She writes, photographs,
designs, and illustrates for the Yale Scientific Magazine and volunteers to teach
science and mental health to students in New Haven.
THE AUTHOR WOULD LIKE TO THANK Yumiko Taguchi, Justin Abbasi, Dr.
Sreeganga Chandra, and Dr. Pramond Mistry for their time and for their enthusiasm
about their research.
FURTHER READING
Neudorfer, O., N. Giladi, D. Elstein, A. Abrahamov, T. Turezkite, E. Aghai, A. Reches,
B. Bembi, and A. Zimran. “Occurrence of Parkinson’s Syndrome in Type 1 Gaucher
Disease.” QJM 89, no. 9 (September 01, 1996): 691-94. Accessed October 20, 2017.
doi:https://doi.org/10.1093/qjmed/89.9.691.
www.yalescientific.org
December 2017
Yale Scientific Magazine
19

FOCUS
evolutionary biology
B I R D
BRAINS
by SARAH ADAMS
art by ISA DEL TORO
The head is arguably one of the most distinct features of vertebrates. Sensory organs accumulated into a mass at the
front of the body over the course of evolution have now become a seminal feature of evolution. Protecting this vital
organ is the skull, a bony structure that must closely encase the brain throughout its entire development—from embryo
to adult. It seems only natural for the skull and brain to be closely connected to each other throughout development.
How can two structures evolve as one entity?
Recently, researchers at Yale formally
mapped out this relationship between reptile
and bird brain and skull roof development
for the first time. “Mammals tend to
be more popular to study in developmental
biology because of their complexity compared
to lower vertebrates like reptiles,” said
Bhart-Anjan Bhullar ‘05, assistant professor
of geology and geophysics at Yale. “But,
because of the large size of mammalian
brains, some fundamental structural relationships
can become obscured.” In human
embryos, for instance, the forebrain rapidly
grows over smaller parts of the brain in
the back of the head, making it difficult to
track the relationship between the skull and
brain during development. Reptiles and
birds, on the other hand, have a clearer regions
of the brain that correspond to certain
regions of the skull, making it easier to
track how the skull forms over parts of the
brain. Through combined approaches in
fossils research and developmental biology,
researchers have been able to show for the
first time that the growth and evolution of
the brain has also triggered corresponding
changes in structure and shape of the skull
for millions of years.
Separate but together
In order to understand how the brain
and skull work together, the fossil record
can help distinguish how skull is separated
into different parts that correspond
to different parts of the brain. “The brain
has three partitions in all vertebrates: the
forebrain, midbrain, and hindbrain,” said
Matteo Fabbri, graduate student and lead
author of the published paper. “These partitions
enable embryonic cells to differentiate
into certain bones.” Fabbri and others
at the Bhullar Lab used 3D morphometric
analyses, which visualized patterns of
variation in the brain and skull into different
groupings based on shared qualities, to
examine the skull-morphology and deep
history of the brains of Reptilia and Aves.
“The forebrain will signal to the frontal,
the midbrain signal to the parietal, and the
posterior brain regions will signal to the
back of the skull,” said Fabbri. The presence
of this partition, present in mammals
and reptiles alike, means that it has major
implications for the morphology of the
skull and how it evolves with these parts of
the brain over time.
The research team also examined different
stages of the embryo of various reptiles
by taking eggs at different stages of incubation,
then looking inside of the shell to examine
what the embryo looked like that that
moment. This close examination enabled the
Bhullar Lab to closely study the link between
brain and roofing bones of the skull in early
development. “Logic in developmental biology
is very different from how we think with
the fossil record, but both have the same aim:
to understand why a reptile is like this and a
bird is like this; they are simply complementary
ways of approaching the question.” said
Fabbri. While the fossil record has long been
used to frame the evolutionary relationship
based on morphological differences at
a macro-level, comparative embryology allows
for the developmental level of relation
to be addressed in evolution. The Bhullar
Lab also used CT scanning—which combines
many X-ray measurements to create
an cross-sectional image of an object without
cutting into it—to examine the bone-tobrain
relationship in embryos for the first
time. Despite the physical differences of an
alligator, lizard, and modern-day chicken,
this technology simultaneously visualized
20 Yale Scientific Magazine December 2017 www.yalescientific.org

evolutionary biology
FOCUS
and compared their developing brains and
skull roofs, revealing that they all share the
same developmental pattern.
All three taxa showed direct, one-to-one
correspondence between the developing
forebrain and midbrain with the earliest
stage of development of the frontal and parietal
(roof and sides) bone areas of the skull.
For every degree of development by the
brain, the skull develops to the same extent.
This one-to-one correspondence in embryos
between major parts of the brain and early
skull-roof elements’ developments shows
that the nature of the relationship between
the brain and skull shifts during avian lineage
evolution. Previous studies assumed
that the avian frontal had a fused origin that
caused the resulting shift in avian skull-roof
element identity. These findings collectively
support the notion that the brain is important
in patterning the skull roof.
Not only did Fabbri and the Bhullar Lab
find that there was there a shift in morphology
and relative size to skull from reptiles to birds,
but also in allometry of the brain and skull.
Allometry is the proportional change relative
to body size—specifically the brain and skull
in this case. In this case, there was negative allometry
between the brain and skull during
development of reptiles, meaning that the
brain is relatively large in early developmental
stages, then becomes smaller with respect to
the skull during growth. Birds, on the other
hand, exhibit positive allometry with a large
brain at the hatching stage relative to the skull;
the brain continues to expand during development
into adulthood. “This also shows that
brains in Aves are peramorphic,” Fabbri said,
meaning that although birds retain juvenile
cranial characters observed in dinosaurs and
other reptiles, at the same time, they also exhibit
positive allometry in brain development.
Such differences in development also cause
the evolutionary differences between birds
and reptiles to become more pronounced in
the tree of life.
A collaborative effort
Combining the developmental research
approach with the fossil research approach
could be difficult at times. “We needed to
create comprehensive and inclusive data, but
also needed to be careful.” said Fabbri. “It can
be easy to misinterpret data in the direction
that you were going for.” Nevertheless, after
many correlation tests, the statistical support
was strong behind the embryo’s one-to-one
correspondence between skull and brain development,
showing their co-developmental
relationship. While the fossil record is useful
for examining morphological similarities
and differences across species, it leaves out
gaps in comparative morphology and can
sometimes lead to mistakes in research. This
research’s use of both comparative embryology
and the fossil record more broadly serves
as a reminder to interpret developmental
data within a phylogenetic framework by
fossil records or comparative morphology to
determine homology as a whole.
Moving forward
Officially recognizing the link between the
skull and brain patterning in reptiles and
birds is a significant step in understanding
IMAGE COURTESY OF MATTEO FABBRI
►Coloring of skull patterning in a chicken skull. Pink represents the frontal skull area, green
represents the parietal skull area, and white represents neurocranial skull area.
how certain morphologies have developed
in reptiles and birds. However, the fact that
bird brains continue to grow further over the
course of their lifetimes compared to other
reptile brains may be due to bird-specific
adaptations such as flight. The research also
represents a larger statement about evolution
itself. “Ultimately, this shows that evolution
is simple and more elegant than it seems.”
Bhullar said. “Now that we have this mapped
out, we better know where to look for gene
expression responsible for these changes.”
The next stage in research may seem more
complicated with a new lens at the genetic
level, but the combination of fossil records
and developmental biology methods and
spirit of collaboration in asking these big
questions are sure to lead to even bigger answers
in the future.
ABOUT THE AUTHOR
SARAH ADAMS
SARAH ADAMS is a prospective Ecology & Evolutionary Biology major in
Morse College ‘20.
THE AUTHOR WOULD LIKE TO THANK Matteo Fabbri and Professor
Anjan Bhullar for sharing their time for this article.
FURTHER READING
Fabbri, Matteo, et al. “The skull roof tracks the brain during the evolution
and development of reptiles including birds.” Nature Ecology & Evolution,
vol. 1, no. 10, Nov. 2017, pp. 1543–1550., doi:10.1038/s41559-017-0288-2.
www.yalescientific.org
December 2017
Yale Scientific Magazine
21

FOCUS
cell biology
MACROPHAGE
MESSENGERS
Specialized immune
cells as targets for
metabolism in aging
before
after
now possible with specialized immune cells
by Charlie Musoff || art by Sunnie Liu
22 Yale Scientific Magazine December 2017 www.yalescientific.org

cell biology
FOCUS
Areceding hairline, a wrinkly forehead, and a saggy butt are considered undesirable
hallmarks of aging, according to representations in popular media. When people
think about anti-aging, they usually think about reversing this type of surface-level effect.
Everyone has seen beauty campaigns promising to tighten one’s skin or prevent balding,
but the larger causes and effects of aging go far beyond the symptoms in one’s appearance.
While it cannot be argued that the dramatic
increase in the human lifespan over the past
five hundred years reflects positive advancements
in medicine, hygiene, and other health
systems, a longer life comes with an increased
risk of chronic disease. Age is the biggest risk
factor for every chronic disease we know of,
including cancer, cardiovascular disease, and
neurodegeneration, but three different specialists
treat each one. People are not getting
older in a healthy way in large part because
modern medicine does not treat aging in a
disease in and of itself.
Professor Vishwa Deep Dixit and post-doctorate
fellow Christina Camell of the Yale
School of Medicine took up this challenge
and worked to understand aging and its effects
together as one connected disease. They
focused on inflammation, the body’s response
to wound or injury, as a process known to
be a primary trigger of age-related disease.
While in young people, an immune response
will respond to infection and then subside,
in the elderly these patterns of inflammation
never abate, which causes stress and dysfunction.
Dixit and Camell drew a link between
this inflammation and the fat accumulation
also characteristic of aging. The nexus of this
connection lies in macrophages, which are
specialized immune cells. The researchers
found that a class of hormones called catecholamines
directly communicates with a
previously undiscovered subset of macrophages
called nerve-associated macrophages,
which use the nerves to promote lipolysis, or
fat breakdown. Sustained inflammation in
aging increases concentrations of proteins
that degrade these catecholamines, which,
in turn, prevent lipolysis. In other words, as
the mice they used aged, an inability to clear
inflammation decreased catecholamine levels,
which resulted in fat accumulation. This
research implicates crosstalk between the
immune, nervous, and metabolic systems in
the disease of aging, which may provide new
avenues for research to promote wellness in
the elderly.
The deficit
To understand the immune system’s role in
aging and lipolysis, Camell and Dixit initially
needed to flesh out the intersection between
these two processes and the role catecholamines
played in them. Two-year-old mice,
the equivalent of 65-year-old humans, were
shown to release less fat from their adipose
tissue, or fat reserves, than did young ones.
Surprisingly, when the aged mice were given
catecholamines, their rate of lipolysis and
consequent fat release returned to normal,
that is to say that aged fat acted like young fat
when given catecholamines. When cells that
store fat called adipocytes were taken from
these aged mice and grown alongside macrophages,
however, the bounce-back in lipolysis
was no longer observed. Conversely, the addition
of young macrophages to old fat restored
lipolysis. These results were a first clue: catecholamines
promote lipolysis, but something
about aged macrophages specifically reduces
this breakdown of fat. The first major finding,
therefore, was that macrophages in the adipose
tissue control the decrease in lipolysis
observed in aging.
The next step was to figure out the specific
mechanism by which this deficit in fat breakdown
occurs. The researchers analyzed gene
expression in aged macrophages and found
that they express more genes implicated in
catecholamine metabolism than do young
ones, which solidified the link between the
age of the macrophages and their ability to
facilitate lipolysis with catecholamines. One
protein associated with both aging and inflammation
is NLRP3, which forms part of
a larger complex called the inflammasome.
Dixit and Camell found that the activation of
the NLRP3 inflammasome prevented the release
of fats from adipose tissue. On the other
hand, when the researchers engineered mice
without the gene responsible for the production
of NLRP3, they were able to break down
fat normally even as they aged.
Chit-chat
The researchers wanted to see if they could
uncover an underlying biological mechanism
that would explain these observations. To
accomplish this goal, they performed RNA
sequencing analysis, which gives a complete
picture of gene expression, and saw that the set
of genes responsible for catecholamine degradation
in aging macrophages was dependent
on NLRP3. Sustained NLRP3 inflammasome
activation—sustained inflammation—thus,
seemed likely to shift the gene expression
profile of macrophages towards the aged one.
A gene called GDF3 that controls fat accumulation
and showed the strongest positive
correlation with aging was reduced down to
the level of young mice when NLRP3 was
knocked out, which corroborates this evidence.
The NLRP3 knockout also showed
restored-to-normal levels of genes implicated
in fat breakdown and catecholamines’ proper
functioning. On the flip side, this result
indicated that an increase in NLRP3 and its
resultant inflammation in aged macrophages
promoted the degradation of catecholamines
that results in reduced lipolysis.
To visualize the location of macrophages
relative to catecholamines, the research team
used reporter mice, which are mice specially
engineered to have fluorescent proteins
in specific cell types. Using these markers,
Camell was surprised to find macrophages
in a pattern never previously observed. “The
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December 2017
Yale Scientific Magazine
23

FOCUS
cell biology
macrophages are actually lining the nerve,”
she said. “They almost look like they’re hugging
it.” This configuration led Camell to conclude
that she had discovered an entirely new
subset of macrophages, termed nerve-associated
macrophages, that represents the intersection
of the nervous, immune, and metabolic
systems. These immune cells directly
access the catecholamines from the nerves,
which allows them to regulate levels of these
hormones in the adipose tissue. Where before,
the exact relationship of the nerve, the
released catecholamine, and the adipocyte
was unclear, now macrophages have been
established as a direct and crucial link. This
immediate connection allows the nerve-associated
macrophages to influence both lipid
metabolism and inflammation, two primary
factors that contribute to aging, via their control
over the concentration of catecholamines
present in the adipose tissue.
Learning how to manipulate this system
was a final step to cement the validity of these
findings. Aged macrohpages were found to
overexpress an enzyme called MAOA that
is implicated in catecholamine degradation,
so the researchers treated aged mice
with a MAOA inhibitor and saw increased
fat breakdown. This result confirms the link
between catecholamine degradation and resistance
to lipolysis in aging. To sum up the
model, when catecholamines are released by
still functional nerves in aged individuals, inflamed
macrophages have excess biological
“machinery” like MAOA that degrades the
catecholamines, so the hormones are broken
down before they can act on the adipocyte to
promote lipolysis. This more complete picture
gives researchers a better comprehension
of the complicated crosstalk between the nervous,
immune, and metabolic systems and
how it influences fat breakdown in aging.
The life in your years
Down the road, an understanding of these
intersecting communication patterns has
far-reaching applications in treatment for aging
in line with its classification as a chronic
disease. The aforementioned class of MAOA
inhibitors is currently used as treatment for
depression, but if research worked to localize
these drugs such that they do not affect
the brain, this therapeutic avenue would
be promising. With lower levels of MAOA
comes higher levels of catecholamines, which
can restore lipolysis in aging individuals. An
IMAGE COURTESY OF CHRISTINA CAMELL
►Nerve-associated macrophages, shown in green, seem to hug sympathetic nerves, shown
in white.
alternative target is GDF3, the NLRP3-dependent
protein that inhibits fat breakdown.
While GDF3 is a single upregulated protein
under the overarching control of the NLRP3
inflammasome, NLRP3 itself is required for
fighting off infection, so drugs to block this
protein can increase the risk of certain infections.
Instead, neutralization of GDF3 is an
indirect way to achieve the same goal. If aberrant
inflammation via GDF3 can be prevented,
cells of the adipose tissue will show better
lipolysis. Regardless of the mechanism, these
strategies work to influence the crosstalk
between macrophages and their associated
nerves, which, in turn, influences fat metabolism.
The communication between the nervous,
immune, and metabolic systems that
this research establishes integrates almost
every organ system and so has clear potential
to address the disease of aging as a condition
that impacts all aspects of human health.
When viewed through an even broader
lens, this research is about improving people’s
healthspan, the time during which an individual
is in good health. To clarify the relationship
between catecholamine degradation
and inflammation is to draw the links between
the immune, nervous, and metabolic
systems that, for example, can be implemented
to mitigate neurodegenerative and other
age-related diseases. Ultimately this research
may represent a key to healthier aging. “Our
goal is not to simply increase lifespan,” Dixit
said, “but to add life to the years that exist.”
An understanding of the mechanisms controlling
lipolysis, however narrow of a focus,
can help to achieve this universal ideal: to add
life to your years.
ABOUT THE AUTHOR
CHARLIE MUSOFF
CHARLIE MUSOFF is a sophomore molecular, cellular, and developmental
biology major in Davenport College. Besides being Yale Scientific’s Outreach
Designer, Charlie enjoys running, singing with the Baker’s Dozen, and
teaching with Community Health Educators.
THE AUTHOR WOULD LIKE TO THANK Christina Camell and Professor
Vishwa Deep Dixit for their time and insights.
FURTHER READING
Pirzgalska, Roksana M, et al. “Sympathetic Neuron-Associated Macrophages
Contribute to Obesity by Importing and Metabolizing Norepinephrine.” Nature
Medicine, 9 Oct. 2017, doi:10.1038/nm.4422.
24 Yale Scientific Magazine December 2017 www.yalescientific.org

materials science
FEATURE
IMAGING OF DYNAMIC SURFACES
A new microscope images surfaces 5000 times faster
►BY JAU TUNG CHAN
IMAGE COURTESY OF ALAIN HERZOG
►The second harmonic microscope constructed by the
researchers, used to image a glass capillary.
Many industrial processes rely on chemical reactions occurring
along surfaces, such as the Haber-Bosch process that produces
ammonia on the surface of iron for fertilizer and other industrial
products. It may seem surprising, then, that there are presently
no good ways to observe these reactions on the molecular level in
real-time because of their speed and scale (they occur on a scale
smaller than the width of a human hair).
Earlier this year, however, researchers at the École Polytechnique
Fédérale de Lausanne, a research institution in Lausanne,
Switzerland, constructed and tested of a new type of microscope
that can do just that—look at surface chemistry on the micro-scale
in real-time. Using their microscope, the researchers measured, in
a matter of milliseconds, the variation in chemical properties of
a glass surface over micrometers. Their results were published in
August 2017 in Science.
The first of its kind, this microscope is known as a “wide-field,
structured illumination, second harmonic microscope,” which, as
its name suggests, utilizes a phenomenon called second harmonic
generation (SHG). SHG is a process that allows two photons—
particles of light—to combine under certain conditions, resulting
in a new photon with exactly twice the frequency. This is similar
to how two water droplets, when colliding with suitable orientations
and speeds, can combine to form a droplet with precisely
twice the volume.
For SHG, the new photon forms only when two original photons
interact with a non-centrosymmetric material—a material
without a central point about which the molecules can be reflected.
For example, a pizza in five slices is non-centrosymmetric,
while a pizza in six slices is centrosymmetric. The net number of
photons generated by SHG depends on the orientation of this
non-centrosymmetric material.
This property is what allows the researchers to use SHG in their
microscope. First, to reveal underlying chemical structures of a
glass-water interface, the researchers wetted the surface, causing
water molecules to selectively cluster on areas to which they
were more attracted, akin to how shaking a tray of sand with a
strip of glue collects sand along that strip. Next, the researchers
shined light onto the whole surface, showering it with photons.
Because water molecules are non-centrosymmetric, the amount
of SHG depends on the orientation of the water molecules, which
in turn depends on the surface’s underlying chemical structure.
By measuring the output of SHG photons coming from different
positions on the curved glass surface, the researchers were able to
reconstruct the chemical properties of the different parts of the
surface in 3D.
Since this microscope captures the entire surface all at once, it
captures images more than 5000 times faster than current second
harmonic microscopes. Most importantly, this increase in speed
does not sacrifice image quality. Sylvie Roke, the principle investigator
of the project, was herself pleasantly surprised about the
sensitivity of the microscope. “What I find amazing is that there
are so few oriented water molecules—just one nanometer of oriented
water molecules—and I can see them so brightly,” Roke
said.
The advantages of this new microscope hardly end there. Sapun
H. Parekh of the Max Planck Institute for Polymer Research
in Mainz, Germany, added that this microscope offers the additional
benefit of being operational even without precise control
of the environment—unlike most other methods to study surface
chemistry that require ultrahigh vacuums to operate. One
straightforward application of this microscope could be to improve
the industrial manufacturing of surfaces, such as solar cells.
By examining the surface chemistry of manufactured surfaces in
real-time, we can get immediate feedback on the manufacturing
processes, making its optimization easier and more efficient.
Roke foresees even more exciting applications for the new microscope,
such as imaging biological processes like neurons firing.
“Neurons communicate by electrostatic signals that travel across
the membrane,” Roke said. “What if I could use this method to
[image the] membrane of the neuron while it is signaling to other
neurons, without modifying the neuron?” This would be an impressive
step forward to understanding how neurons function,
since current technologies only allow us to observe neurons by
modifying them.
While there are still some nuances in second harmonic microscopy
that remain to be explicitly addressed, the researchers have
certainly accomplished a proof of concept with the new instrument.
As Parekh puts it, “What they showed is not the end application—it’s
just the beginning.”
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December 2017
Yale Scientific Magazine
25

FEATURE
neuroscience
NEURONS THAT CONTROL THIRST
The neural mechanisms that regulate water consumption
►BY MARCUS SAK
Water is essential for life. Its consumption is so intuitive, you probably
don’t recall the last time you drank up. The body must work
constantly to combat water loss caused by urine production, sweating,
and respiration, most often by inducing water intake. Though
water regulation is an essential process, the brain mechanisms that
govern thirst were unknown until now. “Thirst is an ancient and
extremely powerful motivational signal,” said Will Allen, a graduate
student in the Department of Biology at Stanford, where he and his
colleagues study neural pathways that motivate thirst. Their results
were reported in Science this September.
Animal behaviors, including thirst, are known to be motivated
by two distinct mechanisms. The first is “drive reduction,” whereby
thirsty animals learn to drink to avoid the “aversive state” of thirst.
The second mechanism works the opposite way: thirsty animals
have greater incentive than their satiated counterparts to drink for
the “reward” of satiety. Previous studies suggested that the latter reward
mechanism is more likely in the case of thirst, but could not
provide neural mechanisms to support this hypothesis.
The study at Stanford provided evidence that thirst is an “aversive
internal state” and is actually driven by the first mechanism. “This
study provides a neural implementation of a long-discarded theory
from psychology about how motivational drives produce behavior,”
Allen said. The conclusion was enabled by recently-developed techniques
that allowed researchers to selectively access, activate and
manipulate neurons in the brain.
To identify the specific group of neurons that encode thirst, the
researchers altered the genetic sequences of mice so that cells would
fluoresce in red during thirst. The fluorescence gene is aptly named
tdTomato. By comparing tdTomato fluorescence between water-deprived
and water-satiated mice, they were able to pick out the
cells that had increased activity due to thirst.
The researchers then isolated the tdTomato-positive cells before
using single-cell RNA sequencing to determine individual genetic
expression profiles. Based on these profiles, the researchers identified
two cell types. One of the cell types was concentrated in the median
preoptic nucleus (MnPO) in the hypothalamus region of the
brain. Since the hypothalamus is known to regulate many metabolic
processes, the MnPO neurons were expected to be the primary
motivators of thirst.
The researchers hypothesized that if the MnPO neurons indeed
motivate thirst, then artificially activating them should induce water
consumption. They inserted genetic “switches” into mice MnPO
neurons to turn thirst on and off with a laser beam and a fiber optic
implant. Photoactivation of the neurons in water-satiated animals
induced water consumption, and the rate of water consumption
scaled with frequency of stimulation. Water-deprived mice were
trained to press a lever to obtain water, such that photoactivation of
the neurons induced lever-pressing.
To determine that activity of these neurons causes an aversive
state, two experiments were performed. First, mice were put into
a chamber, one half of which photoactivated the neurons. Mice invariably
learned to avoid that half. In the second experiment, water-deprived
mice were provided a lever that turned off photoactivation.
They learned to vigorously lever-press, even though no
water was provided upon pressing. Moreover, the higher the frequency
of photoactivation, the higher rate of lever-pressing. Their
response indicated that higher levels of MnPO neuron activity are
more aversive, and result in stronger thirst.
Finally, the researchers investigated how MnPO neuron activity
decreases upon water intake. They proposed three mechanisms:
first, that neuron activity decreases due to anticipation of water; second,
that neuron activity decreases as water is consumed; and third,
that neuron activity continues until a certain satiety threshold, after
which it abruptly turns off. Once again, they inserted the tdTomato
fluorescence gene into MnPO neurons, allowing the neurons
to fluoresce with an intensity proportional to their activity. When
mice were allowed to press a lever to obtain water, their MnPO activity
decreased gradually over several minutes, much more slowly
than during free drinking. Once neuron activity reached a minimum,
the mice stopped lever-pressing. This indicated that MnPO
neurons receive quantitative real-time feedback from the body, and
adjust their activity accordingly.
The study shows how MnPO neurons regulate animals’ water-seeking
behavior, improving our understanding of how thirst
is motivated. It remains to be seen whether the alternative reward
mechanism has any role in thirst, how MnPO neurons know when
satiety is achieved, and what makes up the myriad secondary pathways
that enable such a small cluster of cells to elicit a coordinated
response, supporting the survival of animals for hundreds of thousands
of years.
IMAGE COURTESY OF WIKIMEDIA COMMONS
► Thirst is a primordial drive in response to the constant need to
combat water loss.
26 Yale Scientific Magazine December 2017 www.yalescientific.org

engineering
FEATURE
MAKING THE MOST OF TWISTS AND TURNS
►BY URMILA CHADAYAMMURI
Harvesting energy with carbon nanotube yarns
IMAGE COURTESY OF WIKIMEDIA COMMONS
►Carbon nanotubes are a carbon allotrope that exhibit remarkable
electromagnetic and mechanical properties.
Picture a bike ride along the seaside. Your T-shirt has a
built-in heart rate monitor to track your activity. Floating up
from the picturesque water are dozens, maybe hundreds of
balloons that feed into a charging station on the beach, where
you can recharge your phone to take a photo of the incredible
scene. This is the future that Carter Haines, associate research
professor at the University of Texas in Dallas, envisions.
Haines and his collaborators have figured out a way
to turn mechanical energy into electricity with the help of
carbon nanotube yarns.
At the heart of the method is a capacitor. The archetypal
capacitor is called a parallel-plate electrostatic capacitor, and
it consists of a positive and a negative electrode with some dielectric
medium in between. This dielectric is a material that
stores charge well; the electrodes, by contrast, are conductors
through which charge is quickly removed as a current. You
can charge a capacitor to a high voltage and then harvest the
energy inside it at a later time.
“You take a piece of rubber, coat carbon grease on both
sides to get electrodes, and as you stretch and release this
rubber you can change the capacitance and get energy out,”
Haines said. However, the trouble with electrostatic capacitors
is two-fold. First, of course, you have to charge them
up with an electronic circuit to start with. Second, a human
body, with its high conductivity, probably shouldn’t be near,
let alone touching, high voltages.
This is the beauty of electrochemical capacitors. Virtually
all electrochemical capacitors today have electrodes made of
carbon allotropes—different forms of carbon with its atoms
interacting in different ways—with high surface areas. Carbon
nanotubes are one class of such allotropes. First discovered by
Soviet scientists Radushkevich and Lukyanovich in 1952, they
are incredibly strong and stiff, with length-to-diameter ratios
of up to 100 million. They are grown upright in what is called a
forest, then pulled out into fibers and twisted into yarns. “The
nanotubes are no longer in the yarn axis, but are following
helical paths, just as you’d have with any yarn that you twist,”
Haines said. If you continue to twist the yarn under pressure,
it will actually form coils; you’ve probably discovered this phenomenon
while playing with your shoelaces. With the right
amount of tension on the ends of the yarn during the twisting
process, you can get neatly packed coils.
The dielectric in an electrochemical capacitor is an electrolyte,
a solution of charged ions in a liquid. “Because there’s
so much surface area on the surface of the nanotubes, the
ions can just come and hang out on the surface,” Haines said.
“When we compress the yarn, we’re actually getting rid of
surface area.” By pulling one strand (one electrode) and tightening
the twist, the ions on it pack closer together, increasing
the voltage. Since the ions all have the same sign, they repel
each other and are eager to escape. Even a small voltage on
the surface area of the nanotubes will collect a large charge—
much larger than the charge on their conventional parallel
plate counterparts. Thus, electrochemical capacitors have
earned the alternate name of “supercapacitors,” and their low
voltage means no electrocuted humans.
The most interesting application is the potential for embedding
the yarns into clothing. The group has already tracked
breathing, which Haines says is just the beginning. “You can
measure things like pulse, heart rate and all sorts of things
about the way the body is moving just by having different
yarns embedded in the textile,” Haines said. The biggest roadblock
to a commercial-scale use of energy-harvesting yarns is
the production cost of the carbon nanotubes. The search is on
for cheaper alternatives that have the same ability to host ions
from an electrolyte on an easily changeable surface area.
In the lab and in the fabrics, the electrolyte is some kind
of synthetic gel. But it turns out that seawater, with its high
salt concentration, also works well. Haines’ collaborators in
South Korea did indeed attach a balloon to one end of the
yarn and hold the other down to the seabed with a rock.
“They can see the voltage coming out of the yarn as the waves
are moving the balloon around,” Haines said. Harvesting the
mechanical energy of ocean waves has been an open challenge,
and one that these yarns may rise to meet—if scientists
succeed in finding a way to affordably produce them on the
industrial scale.
www.yalescientific.org
December 2017
Yale Scientific Magazine
27

Pesticides, Honey, and Dead Bees
|| global honey contamination with neonicotinoids ||
by Jiyoung Kang
art by Zihao Lin
As the weather gets colder,
most of us love bundling
up with a cup of hot tea
with honey. Not only do
bees provide us with delicious honey,
but they also pollinate about a third of
all food we eat. We admire bees as hard
workers, marvel at their waggle dance,
and thank them for honey and other pollinated
foods. However, their population has
been rapidly declining across the world due to threats
such as habitat loss, disease and pesticide use.
One class of pesticides known to be toxic to pollinators
is the neonicotinoids (termed “neonics”),
the most widely-used class of insecticides.
They affect the bees’ health, interfering
with their metabolism, learning
and growth. They even threaten the

health of queen bees, which can be severely detrimental to colony
population sizes. In a study recently published in Science, a team of
researchers at University of Neuchâtel and the botanical garden of
Neuchâtel found that most honey samples around the world are contaminated
with these dangerous neonics.
The project stemmed from an exhibition on bees organized by the
botanical garden of Neuchâtel in Switzerland. The director came up
with the idea of gathering global honey samples and asked visitors,
friends and colleagues who were travelling to bring back local honey.
Edward Mitchell and Alexandre Aebi, researchers at University of
Neuchâtel, saw the potential to use the university’s analytic capabilities
to do something more with this worldwide collection of honey—and
thus the collaboration began. Because of the controversy about pesticides
and pollinator populations and because of neonics’ wide use and
well-known effects on pollinators, they decided to construct a global
map of honey exposure to neonics.
Over one hundred colleagues, friends and relatives joined forces to
collect honey from every continent except Antarctica. The researchers
then selected and tested almost 200 samples for five different neonics.
Their results were shocking. The pesticides were found in 75% of all
samples, and 45% were contaminated with more than one of the five
tested compounds. The effects of exposure to this “cocktail” are still
not fully understood, but such combinations are suspected to be much
more lethal for bees than individual compounds alone. Additionally,
levels of neonics in nearly half of the samples exceeded the lowest
concentration at which they are known to be harmful to bees. The
detected levels were below the limit for human consumption according
to current EU regulations, although the long-term consequences
of consuming these “safe” honeys are still unknown.
According to the researchers, the significance of their work is several-fold.
“Many people will say that it is not surprising that there are pesticides
in honey, but we put a figure to this; we mapped it out,” Mitchell
said. Although there have been previous studies analyzing the pattern
of neonics and their impact on pollinators, this study is unique in that it
provides a global perspective. It was shocking, even for the researchers,
that such a high percentage of honey samples from all around the world
were contaminated with neonics.
Mitchell also believes that their work generates many new questions.
Although the neonicotinoid levels were below the limit set by regulations
on human consumption, the researchers cannot definitively say that it is
safe to eat contaminated honey. “We still don’t know how consuming
low concentrations of pesticide over a long period of time affects the
human body,” Mitchell said. Plus, more evidence is emerging that neonics
might have detrimental effects not only on non-target invertebrates
but also on vertebrates, which include humans.
This study focused only on a subset of neonics—only five out of the
several hundred pesticide types used throughout the world. “So, there
is this big question mark about what else there is in honey, and not
just in honey but even in every food we eat,” Mitchell said. Although
their research cannot provide the answer, he believes it is important
to continue raising these questions and conducting more research on
the topic. “We should be more cautious about the way we develop and
use these pesticides and look for alternatives in case these pesticides
turn out not to be absolutely essential,” he said. Neonics are used to
coat seeds so that insects that later feed on the plants will be exposed
to the toxic compounds. Therefore, they are used preventively to minimize
future attacks, rather than as a direct response to a specific attack,
which is why Aebi believes that their necessity should be reevaluated.
ecology
FEATURE
There have already been cases in Switzerland in which a partial ban
on specific pesticides did not lead to yield losses in crops, contrary to
farmers’ worries.
Aebi has been a beekeeper for 15 years, in addition to being a biologist
and an anthropologist. He has experienced the changes in bee
population and honey first-hand. When the researchers first started
IMAGE COURTESY OF GUILLAUME PERRET
►Alexandre Aebi, one of the researchers behind this study, has
been a beekeeper for 15 years and has witnessed changes in bee
populations first-hand.
the project, they wanted to develop a technique to chemically analyze
the global collection of honey. They needed pure honey for their
protocol, so they could contaminate it with a known concentration of
neonics and calibrate their machines. Aebi recollected how he naively
thought that it would be easy, assuming that his honey was pure. It
turned out that his honey was contaminated with three molecules,
even though he has been taking care of his bees organically. “It is not
easy to keep the bees in purely harmless surroundings, because bees
can travel up to twelve kilometers to collect nectar,” he said. Despite
bans on neonics for certain crops, bees can still travel far away and be
affected by the pesticides in other farms or private gardens.
He has also heard from his beekeeping friends that not long ago, their
queen bees lived for around five years, but now the queens have to be
replaced every two years. When the queens are exposed to neonics,
they lose the ability to store spermatozoids, which decreases their ability
to produce new bees.
As such, the effects of neonics on bees are real and detrimental. The
researchers believe that political actions are crucial to minimize further
damage. A total ban on all neonics is in the works in France, and
partial bans are in effect throughout the EU, although their impacts are
yet unknown. More research must be initiated and funded to assess
such long-term consequences of pesticide exposure and regulations,
and to develop new alternatives and re-analyze the necessity of these
toxic compounds.
As a next step, the researchers would like to create maps for individual
countries or smaller regions, and possibly for different categories
of pesticides such as herbicides and fungicides. Aebi believes that
analyzing changes in wild bees and populations of other organisms
is also important. The researchers envision a future where both crop
yields and the environment are protected, with bees happily and safely
buzzing around, making honey.
www.yalescientific.org
December 2017
Yale Scientific Magazine
29

FEATURE
astronomy
MARS MIRRORS EARLY EARTH
MARS MIRRORS EARLY EARTH
Hydrothermal seafloor deposits on Mars send us back in time.
by: YULAN ZHANG | art by: EMMA WILSON
The search for the origin of life often leads deep
into the annals of Earth’s geological record. Based
on fossil evidence, scientists believe that early life
may have thrived in a hydrothermal seafloor environment
3.8 billion years ago; however, because
of Earth’s active plate tectonics, most geologic evidence
from this time period has been altered or
overwritten by younger, or more recent, geological
activity. A group of researchers led by Professor
Joseph R. Michalski from the University of
Hong Kong, however, recently uncovered strong
mineral evidence of contemporaneous hydrothermal
activity in the Eridania basin on Mars.
Since Mars and Earth share a similar early history,
these deposits could potentially lend insight
into conditions on early Earth. This research was
published July 2017 in Nature’s Communications.
Earth and Mars both formed about 4.6 billion
years ago, at the same time as the rest of the solar
system. Theoretical models combined with
chemical and geological evidence suggest that
their early environments were very similar; thus,
their early geological records are thought to hold
analogous information. Furthermore, whereas
Earth’s early geological record has been mostly
deformed or destroyed, Mars’ remains largely
pristine because Mars, unlike Earth, no longer
has active plate tectonics.
Earth’s interior is divided into three main layers:
the crust, the mantle, and the core. The crust
is the Earth’s surface, the core is the Earth’s center,
and the mantle is the thick layer of molten rock
in between. The theory of plate tectonics posits
that Earth’s crust is divided into several sections,
or plates, that push and rub against each other to
produce mountains, volcanoes, earthquakes, and
other geological phenomena. These movements
are driven by convection within the mantle, a
process of heat transfer that results in the creation
of a sort of cycling current. This process is
analogous to a pot of water on a stove: the burner
directly heats the water at the bottom of the
pot, causing it to rise. When this water reaches
the top, it loses some of its heat to the air, causing
it to cool and sink back to the bottom, where it
is heated again. This repeated process of heating,
rising, cooling, and then sinking creates a sort of
current inside the pot. The Earth’s mantle undergoes
a similar process, except instead of a stove, it
is heated by the Earth’s core.
One of the consequences of plate tectonics is
the constant recycling of oceanic crust. When
two plates push against each other, one of them
is sometimes pushed beneath the other, causing
it to sink and melt in the mantle. This process,
called subduction, is particularly prevalent in
oceanic crust. As a result, ancient oceanic crust
is often destroyed or altered over time, meaning
that clear geological records documenting the
emergence and early development of life are difficult
to find on Earth.
Geological evidence suggests that Mars may
have once also had plate tectonics; however, due
to its relatively small size, this stopped long ago.
All planets radiate heat, meaning that they slowly
cool over time. Since Mars is much smaller in size
than Earth, it loses heat at a faster rate, similar
to how a cup of tea would cool faster than a pot
of soup. Since plate tectonics depends on convection,
which in turn depends on the presence
of a heat source, this heat loss means that Mars’
plate tectonics eventually shut down. Thus, Mars’
ancient geological record remains relatively undisturbed,
making it a valuable “Rosetta Stone”
for studying environmental conditions on early
Earth.
The Eridania basin is one of the oldest regions
of Mars’ crust. Previous research has shown that
it is composed of several smaller, connected
sub-basins that were once filled with water to a
depth of up to 1.5 km, making it the site of an
ancient sea. The Eridania basin contained more
water than all other Martian lakes combined, and
it would have had almost three times the volume
of the largest lake on Earth, the Caspian Sea.
Michalski’s group expanded upon these findings
by analyzing Eridania’s mineralogy using
data collected via high-resolution satellite imaging
and infrared spectroscopy. Infrared spectroscopy
uses infrared light, a type of light invisible to
30 Yale Scientific Magazine December 2017 www.yalescientific.org

astronomy
FEATURE
IMAGE COURTESY OF FLICKR
►The study determined that Eridania’s deposits had a hydrothermal
origin, meaning that they formed as a result of underwater volcanic
activity.
IMAGE COURTESY OF J. MICHALSKI ET. AL.
►Previous research has shown that the Eridania Basin is composed
of several sub-basins that were filled at most up to the 1,100 m
elevation line. This suggests that the parts of the lake were between
1-1.5 km deep.
IMAGE COURTSY OF WIKIMEDIA COMMONS
►The study used spectral data collected by NASA’s CRISM, an imaging
spectrometer that was built to search for mineralogical evidence of
water on Mars’ surface.
the human eye, to “look” at chemical compounds. This enables
scientists to see minerals in “colors” absents in visible light, allowing
them to identify the minerals. The infrared data used in
the study was collected through NASA’s CRISM (Compact Reconnaissance
Imaging Spectrometer for Mars), an instrument
on the Mars Reconnaissance Orbiter (MRO) that searches for
mineralogical evidence of past water on Mars’ surface. Satellite
images were used to help the researchers to contextualize their
results in terms of the planet’s actual geography to create a better
interpretation.
The researchers discovered that the Eridania basin contained
iron- and magnesium-rich clays. These substances are widespread
across Mars’ surface; however, the specific types and distribution
of clays present were unusual and sometimes matched
better with terrain on Earth’s seafloors than terrain on Mars.
In addition to clays, the researchers also found evidence of
carbonates, silica, and sulfides—compounds all formed through
hydrothermal activity, or underwater volcanism, on Earth. Using
a crater-counting function, the researchers also determined
that the deposits were about 3.8 billion years old, contemporaneous
with the oldest evidence of life on Earth.
Eridania’s clays may have formed through evaporation. However,
this would have resulted in the production of chemical
compounds not present in the deposits, making this hypothesis
unlikely. An alternative explanation for the deposits is air
fall—for instance, wind could have carried ash from a nearby
volcanic eruption into the basin. However, since no deposits of
similar age were found anywhere outside of the basin, this too
is implausible. Thus, the researchers concluded that the deposits
were most likely created in a hydrothermal context. This is
supported by the presence of large volumes of lava on the basin
floor, indicating that significant volcanic activity occurred at
some point during the basin’s history.
The Eridania basin is unique among other sites on Mars in its
ability to illuminate the conditions surrounding the origin of
life on Earth. Not only does it represent an ancient hydrothermal
environment, but it was also active around the same time
early life thrived on Earth. Michalski hopes that future studies
will continue investigating the details of his group’s current results.
He also hopes for a rover visit to the Eridania basin in the
future. “If we can visit it with a rover and obtain some physical
samples of the terrain, we would surely learn a lot about how
life originates, even if we don’t find direct evidence of life,” Michalski
said.
www.yalescientific.org
December 2017
Yale Scientific Magazine
31

FEATURE cell biology
BRILLIANT BACTERIA
Programing Bacteria to Make Materials
by MINDY LE || art by JASON YANG
In the past few decades, scientists have increasingly delved into
the field of synthetic biology. As its name suggests, synthetic biology
combines the realms of biology and engineering to produce systems
never before seen in nature. Often, these systems are inspired by
what is found in nature, but they proceed a step further by undergoing
“engineering” to become something more beneficial. In the
context of synthetic biology, engineering typically refers to the introduction
of foreign genetic material with “instructions” that tell the
organism of interest what to produce. However, synthetic biology is
not limited to simply expressing a biological product. In fact, scientists
have come up with a number of ways to engineer organisms to
do unexpected, beneficial things. For example, have you ever considered
designing bacteria that act as pressure sensors?
While such a physical device made up of microorganisms seems
difficult to imagine, researchers at Duke University have accomplished
just that. By engineering self-patterning bacteria that can
be printed on permeable, three-dimensional scaffolds, they generated
pressure sensors out of microbes. The sensors are domeshaped
and are made of both organic and inorganic materials,
namely gold nanoparticles applied onto the bacteria.
In a study published in early October, the researchers engineered
a specific strain of Escherichia coli (E. coli), a bacterium commonly
used in biological research, to produce a protein that composes the
pressure sensor. “The main motivation is to demonstrate the following
principle: living cells can be engineered to form self-organized
2D or 3D structures, which in turn can be used to assemble structured
materials with well-defined physical properties,” said Lingchong
You, the head researcher on the study and a biomedical engineering
professor at Duke University.
The team chose to develop pressure sensors based on previous work
at Harvard and MIT, where bacteria were engineered and applied onto
pre-patterned, 2D surfaces to make electrically conductive biofilm
switches that were controlled by an external electrode and supplemented
with inorganic nanoparticles for conductivity. “Pressure sensing
happens to be a function we used to demonstrate the idea above,” You
said. “Our work represents a fundamentally new strategy to assemble
32 Yale Scientific Magazine December 2017 www.yalescientific.org

structured materials with well-defined physical properties.”
To engineer a genetic circuit in E. coli that produced the pressure
sensor’s scaffolding material, the researchers introduced foreign
plasmids into the bacteria. Plasmids are circular pieces of DNA that
carry a set of instructions telling the bacteria what to do. In this experiment,
the foreign plasmids instructed the bacteria to produce a
protein called curli, which acts as the building block to assemble the
pressure sensor’s dome-like structure.
Following plasmid introduction, the researchers laid out a scaffolding
design with a permeable membrane template—outlined using a
modified inkjet printer—underneath growth media. The membrane
provided structural support for both bacterial growth and the later
addition of gold nanoparticles. After constructing the membrane support,
a liquid culture of the bacteria was applied over the membrane.
Individual bacterial colonies grew into the dome-like shapes, which
researchers could control by adjusting the pore size and hydrophobicity
(the extent of water-repulsion) of the membrane.
To complete the pressure sensor, gold nanoparticles were overlaid
onto the bacterial colony domes after the colonies were fixed into
place. The researchers hypothesized that the viscoelasticity—or resistance
to shear stress and distortion—of the organic curli matrix, combined
with the conductivity of the gold nanoparticles, could contribute
to a functional organic-inorganic hybrid pressure sensor.
Indeed, this is what they observed. When two bacterial domes were
moved to face each other and a constant electrical voltage was applied
to the edge of a dome, the contact between both domes allowed electrical
current to flow. One way to visualize this is by imagining that each
bacterial dome is someone’s face. Just like the spark of a first kiss, when
the two bacterial domes make contact, an electrical current is produced.
Importantly, the strength of the current reflected the strength of the
externally applied pressure. After further testing this relationship, both
verifying and modeling the association, the researchers established that
the bacterial domes could act as robust pressure sensors.
The investigation is a key step toward improving our understanding
of how to program spatial patterns in cell populations, a topic
within synthetic biology that has often been neglected. While this
neglect is partially due to the difficulty of modeling spatiotemporal
patterns over just temporal ones, other concerns include the difficulty
of demonstrating such dynamics experimentally. In this investigation,
the researchers not only addressed such concerns but also took a step
beyond previous work by introducing the programming of self-organization.
Here, the engineered bacteria were able to grow into their
desired structure without any pre-patterning.
What do these bacterial pressure sensors hold for the future? “There
are many opportunities and we’re currently pursuing some of these.
We can imagine the generation of hybrid materials with other properties
that can be used for diverse applications, including environmental
cleanup and medicine,” You said.
Additionally, the researchers discussed the possibility of using curli
to form other structures with different inorganic materials introduced.
For example, if the gold nanoparticles were replaced with catalytic
metal nanoparticles, catalytic structures could be built for many chemical
and physical applications. Likewise, the curli protein itself could
be replaced by other organic molecules to produce materials such as
hydrogels. There is also the possibility of using other organisms, such
as yeast, to create different pattern formations.
The future of this technology holds much promise. “I expect that the
research in this direction will need to simultaneously address two related
►An artist’s rendition of nanoparticles in a cell
cell biology
FEATURE
IMAGE COURTESY OF UNIVERSITY OF TORONTO
issues. One is to push the limit in terms of the diversity of materials that
can be generated by living cells. The other is to generate specific types of
materials for specific applications,” You added. Moving forward, their
team hopes to expand on this work. “As the next step, we’re focusing
on two directions: the generation of different kinds of spatial patterns,
which remains a fundamental challenge in synthetic biology, and the
implementation of different types of hybrid living materials,” You said.
Here at Yale, researchers at the Yale Microbial Sciences Institute are
also employing synthetic biology to make new materials. One such
scientist is Nikhil Malvankar, an assistant professor in the Yale Department
of Molecular Biophysics & Biochemistry. Malvankar’s laboratory
focuses on engineering soil bacteria that produce pili, a naturally conductive,
filamentous protein that functions similarly to copper wires.
His group aims to uncover the mechanisms of electron movement
within these filaments, which act as nanoscale “wires” with tunable
conductivity, to better understand how this system works at the molecular
level and then to apply this knowledge to improve other bacterial
systems. “The long term goals are to use synthetic biology for designing
biomaterials and bioelectronics devices that will complement
and extend current semiconducting technology,” Malvankar said.
Regarding the growing potential of synthetic biology, Malvankar
highlights critical points to consider when working with microorganisms.
“Bacteria are very adaptable organisms and employ multiple
components and redundant pathways for cellular processes.
Furthermore, bacteria can only function in limited environmental
conditions such as physiological pH and aqueous environment,”
Malvankar said. He also provided ideas for improving the bacterial
pressure sensors. “In the future, it should be feasible to use living
cells rather than fixed cells and also avoid expensive and toxic gold
nanoparticles and use all-organic, biological systems.”
With all of these applications and more, the future of synthetic
biology is very exciting. “In the current state of synthetic biology
and bioengineering, one fundamental question is what things we
can actually fabricate using living things. I hope to see different
examples emerging from the community, which can further stimulate
our imagination,” You said.
www.yalescientific.org
December 2017
Yale Scientific Magazine
33

COUNTERPOINT
A FALSE FIXATION ON NITROGEN
►BY GENEVIEVE SERTIC
Understanding forest regrowth is crucial to predicting and
mitigating environmental damage, and with over half of the word’s
tropical forests currently recovering from human land use, insight
into forest regrowth mechanisms is more important than ever.
To accurately model and fully leverage the potential of regrowing
forests to act as carbon sinks for climate-changing atmospheric
carbon dioxide, we must comprehend the mechanisms that augment
and limit the growth rates of these recovering forests.
Trees need a variety of resources to grow, and their growth is limited
by the scarcest of these resources. Often, this limiting resource is
nitrogen. Nitrogen becomes available to plants when nitrogenfixing
bacteria on a host plant’s roots convert nitrogen in the air into
a plant-usable form available to both the host (called a nitrogenfixing
plant) and its neighbors. This has led many researchers who
study forest regrowth to posit that more nitrogen-fixing trees leads
to more overall forest growth. However, a team of researchers
from Columbia University, the University of Connecticut, and
Rice University recently called this conclusion into question. They
found that in moist Costa Rican tropical forests, areas with more
nitrogen-fixing trees actually had a lower growth rate than did those
IMAGE COURTESY OF WIKIMEDIA COMMONS
►The primary nitrogen-fixing tree examined was Pentaclethra macroloba,
a tree native to moist tropical forests such as those noted in the study.
with fewer nitrogen-fixing trees. The results of this study call for a
reevaluation of the influence of nitrogen fixers on the forest around
them.
In order to test whether nitrogen fixers augmented forest growth,
the researchers searched for connections between the presence
of nitrogen-fixing trees and growth of surrounding trees. In onehectare
plot areas, they compared the number of nitrogen-fixing
trees with both annual tree growth and the growth of the fixer’s
neighboring trees. Surprisingly, in both cases, the researchers
observed a negative trend that suggested that more nitrogen fixers
lead to slower forest growth.
The researchers proposed several possible explanations for these
unexpected results. While nitrogen-fixing trees provide usable
nitrogen to the trees around them, they may crowd out their nonfixing
neighbors. Fixing-trees have high growth and survival rates,
as well as high nutrient demands. Their resource consumption and
the shade they produce may inhibit neighboring trees from growing.
Additionally, nitrogen may not be the limiting factor in the growth
of these neighboring trees—in fact, the limiting resource may be
something that the presence of nitrogen-fixing trees is making even
scarcer.
The results from this research run counter to several similar
studies. Two studies on regenerating moist tropical forests in Brazil
and Panama found that the number of nitrogen-fixing trees was
positively correlated with total biomass accumulation. Why do the
results conflict? A difference in the ages of forests and genera of trees
may contribute to the disparity, but the researchers believe that the
disparity is more likely due to differences in baseline soil nutrient
availability between the sites analyzed in the studies.
Benton Taylor, PhD student at Columbia University and first
author of the paper, highlighted the implications of the study for
Earth systems modelers and their assumptions on the effect of
nitrogen-fixing trees on growth and atmospheric carbon dioxide
levels. “If modelers assume that places with high nitrogen-fixer
abundances will have high nitrogen inputs and, thus, have high rates
of growth and carbon sequestration, the results of their models may
be misleading,” Taylor said. He further noted that, although several
pieces of evidence suggest that the study’s results may be typical,
the questions of when and through what ecological factors nitrogen
fixers have an effect on forest growth remain unanswered. These are
the questions Taylor plans to pursue.
Forest regrowth is having and will continue to have a pivotal effect
on the world’s climate. Climate predictions and climate mitigation
both hinge on a better understanding of forest regrowth and
the mechanisms through which it may be augmented. The nowprevalent
regrowth of tropical forests ought to serve as a focus for
curbing climate change—but it’s clear that fixing nitrogen won’t
necessarily fix everything.
34 Yale Scientific Magazine December 2017 www.yalescientific.org

INN VATI N
STATION
Optimal Leaps in Optimizing Fat Burn
►BY HANNA MANDL
Society’s embrace of dietary interventions and increased
physical activity ensues to relieve obesity as a global health
threat, but such interventions can only go so far. Dieting and
exercise have seemingly helped athletes and those who wish
to shed a few extra pounds, but the market lacks an affordable,
accessible and accurate technology to monitor progress in
body fat loss. Consider bringing a ten-thousand-dollar mass
spectrometer—the necessary machinery to collect fat loss
data, comparable in size to an office printer—to the gym.
It may seem extreme to go to such lengths to measure fat
burning, but until now, there was little else to rely on.
New research curtails these concerns. Investigators at ETH
Zurich and the University Hospital Zurich have recently
developed a real-time breath acetone sensor to detect fat
burning through a person’s exhalations during physical
exercise. Andreas Güntner, a co-author of the study and a
postdoctoral researcher in the lab run by professor Sotiris
Pratsinis, explains that the group targeted acetone because
it is the most volatile byproduct of body fat burning, or
lipolysis. During body lipolysis, byproducts like acetone
move into the bloodstream and eventually find their way
to the pulmonary alveoli in the lungs, where they can be
released from the body via exhalation.
Detecting acetone in exhaled breaths is not very simple,
however. “It is rather challenging to accurately detect
acetone in breath as it occurs at trace level concentrations—
typically parts per million—among more than 800 chemical
species,” Güntner said. To solve this, the researchers decided
to coat the sensor with a highly porous film of tungsten
trioxide doped with silicon atoms. The highly porous nature
of this film allows for easy diffusion of gas molecules and
offers a large surface area for sensing acetone at various
concentrations. The researchers used silicon to stabilize the
tungsten trioxide because the resulting chemical compound
is highly sensitive, selective and stable, allowing for the
sensor to detect acetone exclusively.
To test the sensor, the team collaborated with pulmonary
specialists including the Director of the Department of
Pulmonology, Malcolm Kohler, at the University Hospital
Zurich. Twenty volunteers completed three thirty-minute
sessions of moderate cycling on an ergometer to stimulate
lipolysis, followed by a resting period. During and after the
periods of exercise, the researchers measured breath acetone
profiles by asking the volunteers to blow into a tube that was
fixed to the acetone sensor.
“We observed large variations from person to person,”
Güntner said. “While some volunteers showed increasing
breath acetone concentrations—indicating enhanced body
fat burn—already after a short work-out, it took some others
almost ninety minutes of training.” These results were confirmed
by mass spectrometry and not only indicated that the sensor
could successfully detect acetone as a marker of lipolysis,
but interestingly also provided insight into each volunteer’s
individual metabolic state. Parallel blood measurements of
the biomarker beta-hydroxybutyrate—a standard method
for monitoring body fat metabolism—agreed with the data
collected by the acetone breath sensor, ensuring that the acetone
sensor measurements were indeed accurate.
Alongside these results, the small size and low cost of this
acetone breath sensor prove it to be advantageous over other
similar instruments. According to Güntner, the chip is the
size of a one-cent euro coin (comparable in size to a US
dime) and is fabricated from low-cost components, making
it ideal for integration into a device that can be used at home
or at the gym. Current systems used to measure breath
acetone include indirect calorimetry and mass spectrometric
techniques—methods which are complex, lack portability
and cost thousands of dollars. Portable breath acetone tests
are already available for use, but existing models are either
inaccurate, not reusable, or incapable of detecting acetone
in real-time.
While the researchers refine their prototype breath
acetone sensor, health and fitness fans can look forward to a
new method of personalizing and optimizing their training
routines. The researchers are optimistic about the future
of their one-size-fits-all sensor. “I believe this device could
be quite attractive for athletes to optimize their training
regimens and personal fueling tactics,” Güntner said. “But
also for those who would like to guide dieting toward
effective fat loss.”
www.yalescientific.org
December 2017
Yale Scientific Magazine
35

UNDERGRADUATE PROFILE
ALEXANDER EPSTEIN (SY ‘18)
PEERING INTO THE MIND OF A FUTURE LEADER IN SCIENCE
►BY ALICE WU
Growing up five blocks away from the Museum of Natural History
in New York, current senior Alexander Epstein (SY ’18) was constantly
roaming around its exhibitions from a young age. As a child,
he never stopped absorbing new information. Many of the museum’s
teachings surprised him, jump-starting his interest in science;
in particular, he was fascinated with the Vertebrae Evolution Hall
at the museum. “It can prompt you to rethink your entire view of
life,” Epstein said. For example, he discovered there that fish are not
a valid evolutionary group: salmon are more closely related to humans
than to sharks, so there can’t be an evolutionary group that
includes salmon and sharks, but not humans. “As a kid, this made
me rethink a lot of how I felt about the world. It got me into science
again and again,” Epstein said.
During high school, Epstein developed interests in other subjects
as well; he especially enjoyed his history and English classes. He
was on the robotics team and helped build a 120-pound metal robot
to compete in various events. At Yale, Epstein chose to hone in
on his passions by double-majoring in Chemistry and Molecular,
Cellular, and Developmental Biology (MCDB). He feels that Yale is
a great place to study science because it cultivates a nurturing environment,
especially in the upper-level courses. Aside from schoolwork,
Epstein is a Cell Biology peer tutor and was the former Elementary
Curriculum Coordinator for the MathCounts Outreach
program, which aimed to make math accessible to students in New
IMAGE COURTESY OF ALEXANDER EPSTEIN
►Epstein posing next to two giant plush microbes in his lab around
Christmas-time last year.
Haven public schools. Moreover, Epstein is incredibly passionate
about his academic interests, having dedicated his past three summers
to cell biology research.
Epstein began conducting scientific research in high school,
where he worked at a private company near New York City. “In
spite of every failure I had—because research is ninety-nine percent
failure—I still enjoyed it,” Epstein said. As a result, Epstein
was compelled to continue pursuing research at Yale, where he ultimately
ended up working in the lab of MCDB Professor Thomas
Pollard.
Epstein’s research in Professor Pollard’s lab focuses on the actin
filament cytoskeleton, which holds the shape of the cell together.
Actin filaments are composed of protein building blocks that assemble
together into long rods. Like Lego bricks, they can be assembled
into a wide variety of different structures, each of which
serves a special function inside the cell. Epstein is currently studying
the Arp2/3 complex, a protein-based machine that builds huge
branched networks of actin, pushing the front of a cell forward as
it moves and helping the cell to take in nutrients through a process
called endocytosis. He is exploring how the protein complex is regulated,
so that these branched networks are assembled at the right
time and in the right place, supporting successful endocytosis.
Deservedly, Epstein has received recognition for his hard work.
He was awarded the Beckman Scholarship as a sophomore in recognition
of his research background and scientific promise. Each
Beckman Scholar is given financial support to continue their research
over the course of one academic year and two summers.
Epstein was also awarded the Goldwater Scholarship in his junior
year, which recognizes his commitment to research and potential
for being a future leader in his field. The scholarship is one of the
oldest and most prestigious undergraduate awards for students in
STEM fields and provides a substantial scholarship.
Despite his numerous accolades, Epstein is most proud of the
knowledge that he has attained at Yale. “I went in knowing a little
bit of biology and not very much of math and physics—I didn’t
know multivariable calculus—and now I’m taking abstract algebra,
physical chemistry, and have some understanding of quantum mechanics.
What I could do then versus what I can do now… This difference
is what I’m most proud of,” Epstein said.
Next year, Epstein plans on finding a fellowship that will enable
him to do research at Cambridge. He is interested in studying the
structure of protein aggregates, or misfolded proteins clumped together,
which contribute to Alzheimer’s Disease. This type of research
would involve many techniques that Epstein has never performed
before, which he views as a great learning opportunity.
Much like the cells that he has studied at Yale, Epstein is always
moving forward.
36 Yale Scientific Magazine December 2017 www.yalescientific.org

ALUMNI PROFILE
ESTHER CHOO (JE ’94, MD ’01)
USING SOCIAL MEDIA TO PROMOTE SOCIAL EQUITY
►BY GRACE CHEN
When Esther Choo posted a chain of tweets about her interactions
with racist patients in the emergency room, she never expected it to receive
tens of thousands of retweets and over a hundred thousand favorites.
One responding tweet reads, “We’ve got a lot of white nationalists in
Oregon. So a few times a year, a patient in the ER refuses treatment from
me because of my race.” Another says, “Sometimes I just look at them,
my kin in 99.9% of our genetic code, and fail to believe they don’t see
our shared humanity.” The enormous response to Choo’s tweets is bittersweet;
while her words clearly resonated with many, they also demonstrated
how deeply discrimination continues to plague society.
Choo has been using Twitter for almost a decade. Besides her personal
account, Choo also promotes @FemInEM, an organization dedicated to
women in emergency medicine, and @WomenDocs4Hmnty, a group of
women physicians serving those affected by humanitarian crises. “Over
time, I’ve actually started to view it as part of my personal and professional
obligation,” Choo said. “Going on Twitter and talking about some
of these really tough topics is part of my identity now.”
Beyond Twitter, Choo works with organizations like FemInEM and
Physician Mothers Group (PMG). She is a senior advisor to FemInEM,
which addresses the issues holding women back in medicine and what
can be done to overcome these gender disparities. PMG, a group of
70,000 physician mothers across country, has a research arm that studies
how to best support women throughout their careers. Choo also recently
co-founded a company called Equity Quotient, which measures and
addresses the culture of gender equity within healthcare organizations.
Before obtaining her medical degree from the Yale School of Medicine
in 2001, Choo graduated from Yale College in 1994 with a degree
in English. She returned to school and earned a Master’s in Public
Health in 2009 from Oregon Health and Science University (OHSU),
where she is now an associate professor.
Choo believes getting an MPH was the best decision she ever made.
She recognized her interest in health disparities after working in several
safety-net hospitals, which provide care for economically disadvantaged
populations. Her research background now helps her address
how to take care of society’s most vulnerable patients. “I understand
data much better,” Choo said, “When I’m talking about a problem, I’m
able to communicate it better. Then when I work a shift and I’m curious
about things like ‘why do we do that?’, as a researcher, I can turn
that into a research project.”
According to Choo, the biggest obstacle in fighting discrimination in
medicine is that society does not yet fully understand the problem itself.
“I honestly think we’re a bit stuck on characterizing the problem,” she
says. “If you look at the medical literature, there has been a surge of data
IMAGE COURTESY OF ESTHER CHOO
►Esther Choo (JE ‘94, MD ‘01) uses her expertise in public health and
her social media presence to fight the discrimination she witnesses
in healthcare.
coming out about the existence of the inequities experienced by physicians
based on race, ethnicity, gender, and more, but there’s still incomplete
data about the nature of problem. We all thought we could jump in
and fix the problem, but to have solutions we need to understand it first.”
Choo’s advice is twofold: first, not to be blind-sided by discrimination
and second, to foster conversation by calling it out when it happens.
“As we move up to positions of influence, we need to realize it’s
our responsibility to change the landscape of medicine for the next generation,”
she said. Joe Robertson, the president of OHSU, demonstrated
this last December when he released a statement saying that hate-speech
and requests for specific physicians based solely on ethnicity would not
be tolerated. Choo thinks the importance of this statement was not an
immediate change of behavior but the solidification of OHSU’s culture.
Many institutions lack such an explicit statement.
Being an activist can be frustrating, but Choo has identified the
things that inspire her to persevere, such as her children and her
Christian faith. She also draws inspiration from the responsibility she
carries as an alumna of an elite institution. “The minute you walk into
Yale, you’re given a position of incredible privilege that almost nobody
else gets,” she says. “My friends were the type of people who recognized
this privilege and didn’t take it for granted. Every minute since
has been about how we pay back.”
www.yalescientific.org
December 2017
Yale Scientific Magazine
37

FEATURE
science in the spotlight
SCIENCE IN THE SPOTLIGHT
BOOK REVIEW: HOW TO TAME A FOX (AND BUILD A DOG)
►BY MIRIAM ROSS
How does an animal transform from a violent hunter into a loyal
companion in the space of just a few generations? Or, put more simply:
what defines a dog? American evolutionary biologist Lee Dugatkin and
Russian geneticist Lyudmila Trut explain the mystery in their new book,
How to Tame a Fox (and Build a Dog). The authors paint a thrilling
portrait of the longest-running experiment in animal behavior: an
attempt to recreate domestication of silver foxes. The conception and
details of the project are placed in the historical context of the Soviet
Union under Stalin and beyond, making the story a mix of scientific
discovery, folk tale and spy novel.
Dmitri Belyaev, the Russian scientist who devised the experiment,
selected silver foxes from commercial fur farms scattered throughout
Russia and gradually turned them into pets. Belyaev’s method was easy:
select the tamest fox pups, breed them, and repeat. The domestication
of wolves was estimated to have taken 15,000 years, but Belyaev’s team
observed changes within only a few generations. To date, they have
bred 56 generations and counting. The first foxes snarled and lunged at
the researchers, who approached wearing thick gloves. Now, the foxes
race towards people, lobbying for pats and nuzzling their caretakers.
Interestingly, these tamer foxes physically resemble dogs more than
their wild predecessors. Their ears are floppy, their fur is piebald, and
their tails wag wildly. New work aims to understand the genetic changes
behind this transformation.
The research setting itself is dramatic, located in freezing Siberia.
SPOTLIGHT
Dugatkin and Trut inspire a continual
sense of awe, relaying multiple anecdotes
of the workers’ strength and devotion.
One research project required midnight
blood samples from the foxes. Shifts
lasted three weeks, with temperatures
below -40°F, yet none of the workers
complained, despite having multiple
children at home to care for. Trut
remembers their attitude as “if it was for
science, let’s do it.” Yet, perhaps the most
surprising of the novel’s traits was its
successful evocation of “fear of missing
out,” otherwise known as “FOMO,” in the
reader. Not only was the story gripping and the book hard to put down,
but one feels nearly ready to head to Siberia and meet the foxes—despite
the freezing cold weather!
Tightly-woven, accessible, and engaging, How to Tame a Fox has
received praise from across the board. By incorporating the social
and historical context of the experiment, the authors make the book a
compelling read. Ultimately, the book investigates the interplay of genes,
evolution, and environment on behavior: a new take on the age-old
debate of nature versus nurture. This fantastic and entertaining story is a
relevant reminder of the wonders research can uncover.
BOOK REVIEW: LIFE 3.0: BEING HUMAN IN THE AGE OF ARTIFICIAL INTELLIGENCE
►BY LUKAS COREY
Intelligence is simply the ability to solve complex tasks—or so says
Max Tegmark, founder of the Future of Life Institute and author of the
new book Life 3.0: Being Human in an Age of Artificial Intelligence. By
his definition, what separates our problem-solving and thinking abilities
from those of a supercomputer or a calculator? Are we already inferior to
chess-playing computers and statistical models? And most importantly,
what makes us human, if not our superior intelligence? Tegmark poses
and addresses these questions as he seeks to answer both what it means to
maintain our humanity as we develop AI technology and why this issue
is important.
According to Tegmark, Life 1.0 was primarily comprised of bacteria
working towards replication and survival, and Life 2.0 consisted of animals
pursuing goals beyond survival by manipulating their environment. The
first two versions were limited by living creatures’ inability to modify
themselves, but Life 3.0 does not have the same constraint, Tegmark
writes—calling it the “master of its own destiny.” The implications of
computers with an awareness of their own abilities and the cognition
for self-improvement are massive. For one, as he describes, intelligence
is power, and it could be dangerous to give machines with no inherent
ethical mind a position of power. Even though these machines would
theoretically be under human control, artificial intelligence involves
determining the subtasks relevant to successfully completing a larger task,
and with no way to predict these subtasks, it may be impossible to program
a moral, legal and practical mindset into
these machines.
However, Tegmark remains
overwhelmingly optimistic, explaining
that technology is responsible for nearly all
the improvement in quality of life since the
stone age and it will undoubtedly continue
to be moving forward. In bite-sized
chunks of easily-digestible computing
and philosophical concepts, Tegmark
convincingly illustrates the necessity
for further evaluation of our goals as
a society and further planning for AI’s
incorporation into our world—a discussion that Tegmark says may be the
most important conversation of our time.
As either an introduction into the complexity of artificial intelligence
or a further exploration of its potential and moral implicativons, Life 3.0
serves as a magnificent guide with a series of examples and shameless
illustrations. Despite these easily-manageable explanations, Tegmark
never shies away from an issue due to its complexity. Regardless of one’s
field of study or profession, the reader is forced to consider how AI may
impact one’s life and what preparation is required. It may be wise, or
possibly even intelligent, to pick up a copy on the way home today.
38 Yale Scientific Magazine December 2017 www.yalescientific.org

Research: Expectations vs. Reality
►BY EMMA HEALY
cartoon
FEATURE
CONGRATULATIONS
to the
Yale Science & Engineering Association
for winning the
Outstanding SIG Award
from the AYA Board of Governors!

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