YSM Issue 94.3
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Yale Scientific
THE NATION’S OLDEST COLLEGE SCIENCE PUBLICATION • ESTABLISHED IN 1894
OCTOBER 2021
VOL. 94 NO. 3 • $6.99
19
A SHIFT IN THE
PSYCHEDELIC PARADIGM
THE SILENT MENTAL HEALTH
13
THREATS OF COVID-19
DECRYPTING DINOSAURS OF
16
THE EAST
BIRDS OF A FEATHER COLOR
22
TOGETHER
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TABLE OF CONTENTS
VOL. 94 ISSUE NO. 3
More articles online at www.yalescientific.org
& https://medium.com/the-scope-yale-scientific-magazines-online-blog
COVER
19
A R T
I C L E
A Shift in the Psychedelic Paradigm
Rayyan Darji and Anna Calame
New Yale research supports the therapeutic potential of psilocybin—a compound mired in decades
of controversy—to treat depression and other mental illnesses.
13 The Silent Mental Health Threats of
COVID-19
Shudipto Wahed
Yale researchers studied the impact of the COVID-19 pandemic on paranoia, gaining insights into its
origins in behavior and the brain.
16 Decrypting Dinosaurs of the East
Elisa Howard and Anavi Uppal
Millions of years ago, eastern North America was a landmass with its own flora and fauna. Did the
dinosaurs there evolve differently from those that lived elsewhere?
22 Birds of a Feather Color Together
Ryan Bose-Roy
Birds with non-iridescent blue feathers spontaneously make a nanostructure that can be used to
improve solar panels, paint pigments, and more, Yale researchers report.
6 NEWS
Building a Battery Future • Jordan Sahly • 10
Colder and Wiser • Van Anh Tran and Madison Houck • 12
22 FEATURES
The Mathematically Perfect Egg • Eunsoo Hyun • 25
Bioethics in the Age of COVID-19 • Risha Chakraborty and Justin Ye • 28
A Tech Clairvoyant for Paralyzed Voices • Alex Dong and Malia Kuo • 32
SPECIALS 31
Alumni Profile: Eric Y. Wang (YC ’21) • David Zhang • 35
Into the Newsroom: David Pogue ’85 • Dhruv Patel • 39
www.yalescientific.org
October 2021 Yale Scientific Magazine 3
CAN BRAINS BE
FOSSILIZED?
&
HOW WILL CLIMATE
CHANGE PROGRESS?
By Crystal Liu
Wildfires. Heatwaves. Strong precipitation and floods.
Extreme weather has been exceedingly common
this decade, destroying natural ecosystems and
claiming hundreds of lives. Global warming has contributed to
its increasing prevalence, according to a new report from the
Intergovernmental Panel for Climate Change (IPCC). And this
trend will continue in the foreseeable future.
"It is unequivocal that human influence has warmed the
atmosphere, ocean, and land," read the report's very first
finding. Skeptics of climate change prefer to blame natural
factors, arguing that there is no need to change human behavior.
But scientific evidence has ruled out this fantasy.
The goal of the Paris Agreement was to limit global warming well
below two degrees Celsius. Earth is now 1.1 degrees Celsius warmer
than it was in the 19th century. Under current policies, the difference
will rise to 2.7 degrees Celsius by the end of this century. If rapid
and massive measures are taken, however, a relatively cooler future
is possible. Adopting more eco-friendly measures, like afforestation
and the usage of cleaner energy sources, can cap warming at two
degrees Celsius in the late-twenty-first century.
But in an interview with the New York Times, Robert Kopp, a
climate scientist at Rutgers University, noted that we shouldn’t
view these standards as rigid. "It's not like we can draw a sharp
line where, if we stay at 1.5 degrees, we're safe, and at two
degrees or three degrees it's game over. But every extra bit of
warming increases the risks," Kopp said. ■
By Odessa Goldberg
If you consider yourself a pretty awesome human being
and your brain remarkably special, wouldn’t you want
your brain preserved and found 310 million years into the
future? Well, first you’d want to find yourself in a low-oxygen
environment at the time of your death. Then you’d want to
be covered in siderite, an iron carbonate. Your brain would
start to degrade, but have no fear: kaolinite would creep in
and form a perfect white mold of your brain in fifty years. And
after many, many years, rock would form around your brain
until you’d be found, studied, and lauded.
Fossils of brains are incredibly rare because lipid-rich brains
are quick to decay. But a fossil of the brain of a horseshoe crab,
Euproops danae, was recently discovered at the Yale Peabody
Museum of Natural History by researchers from the University
of New England, Harvard University, the Natural History
Museum in London, and Pomona College. The artifact was
originally sourced at Mazon Creek, a fossil site in Illinois.
Researchers compared this preserved brain with the brains of
modern horseshoe crabs and found that they were very similar.
They deduced that the organisms likely had similar behavior,
too. This fills a gap in the timeline of the central nervous systems
of euarthopods, one of the best-preserved invertebrate animals.
Finding a fossil of a brain like this is extraordinary: a product
of many processes going exactly the right way at the right time
in the right place. Before you theorize how you might fossilize
your own brain, pay homage to our horseshoe crab pioneer. ■
4 Yale Scientific Magazine October 2021 www.yalescientific.org
The Editor-in-Chief Speaks
THE SCIENCE OF TIME
TRAVEL
After one-and-a-half years of virtual Yale Scientific operations, this
September, we finally reunited. In-person meetings and workshops,
physical copies in residential college dining halls for everyone to peruse—
it’s all back. It has felt surreal, in the best possible way.
We’ve finally regained access to the YSM office, housed in a basement on Old
Campus, which we had been barred from throughout the pandemic as the building
was repurposed for quarantine housing. In the dim, slightly dusty space, we’ve dug
through stacks and stacks of old Yale Scientific magazines, dating all the way back
to the ’30s. A lot has changed throughout the decades—from cover aesthetics, to
the gender demographics of the editorial board, to the types of discoveries that
were considered innovative and important.
This issue highlights how scientific advances of today change our perceptions
of the past. In our cover article (p. 19), we discuss how new Yale research on the
therapeutic potential of psilocybin—the hallucinogenic chemical behind “magic
mushrooms”—adds to a long and contentious history of psychedelics research.
We question how long-standing biases might influence new AI algorithms (p.
28). We learn about microproteins that break our antiquated rules for defining
protein-encoding genes (p. 9). We even travel back to the start of our galaxy, as
new models help us understand matter accretion in black holes (p. 27)
Science, in this way, forms the bounds between the past and the future. And
where the future is concerned, I’m particularly inspired by two young scientists
and Yale undergraduates whose work we highlight in this issue. Chase Brownstein
’23 recently published a paper that looked deep into the past, investigating the
evolutionary history of eastern North American dinosaurs (p. 16). Meanwhile,
Eric Wang ’21 first-authored a paper on autoantibodies, key players in the response
to COVID-19 that might help inform future treatment pathways (p. 7 & p. 35).
I am incredibly proud, honored, and humbled to add to Yale Scientific’s long
history of science journalism with Issue 94.3 of our publication. I’m grateful to our
team, who I’ve had the privilege of meeting in-person this year, and to the years
and years of past teams whose labor has allowed our publication to endure. And,
of course, I’m incredibly grateful to our readers—whether you’ve been reading our
magazine for decades or just stumbled upon this issue for the first time.
About the Art
Isabella Li, Editor-in-Chief
This cover illustrates recent and
important strides made in the
field of psychiatry, where new
connections are being formed
between neuron and neuron,
treatment and disease.
Sophia Zhao, Cover Artist
MASTHEAD
October 2021 VOL. 94 NO. 3
EDITORIAL BOARD
Editor-in-Chief
Managing Editors
News Editor
Features Editor
Special Sections Editor
Articles Editor
Online Editors
Copy Editors
Scope Editors
Newsletter Editor
PRODUCTION & DESIGN
Production Manager
Layout Editors
Art Editor
Cover Artist
Photography Editor
BUSINESS
Publishers
Operations Manager
Advertising Manager
Subscriptions Manager
OUTREACH
Synapse Presidents
Synapse Vice Presidents
Synapse Outreach Coordinators
Synapse Events Coordinator
WEB
Web Manager
Web Developer
Web Publisher
Social Media Coordinator
Web Designer
SENIOR STAFF WRITERS
Rayyan Darji
Alex Dong
STAFF
Ann-Marie Abunyewa
Hannah Barsouk
Ryan Bose-Roy
Breanna Brownson
Sophia Burick
Anna Calame
Risha Chakraborty
Lauren Chong
Katherine Chou
Sarah Cook
Kassi Correia
Sophia David
Chris Esneault
Odessa Goldberg
Saachi Grewal
Hannah Han
Simona Hausleitner
Sydney Hirsch
Dhruv Patel
Anavi Uppal
Madison Houck
Elisa Howard
Eunsoo Hyun
Malia Kuo
Julia Levy
Gina Lee
Sophia Li
James Licato
Zi Lin
Crystal Liu
Jessica Liu
Angelica Lorenzo
Daniel Ma
Katherine Moon
Alex Nelson
Noor Nouaili
Gonna Nwakudu
Ethan Olim
Isabella Li
James Han
Hannah Ro
Jenny Tan
Cindy Kuang
Nithyashri Baskaran
Maria Fernanda Pacheco
Meili Gupta
Cathleen Liang
Alex Dong
Brianna Fernandez
Hannah Huang
Christina Hijiya
Tai Michaels
Beatriz Horta
Ishani Singh
AnMei Little
Catherine Zheng
Elaine Cheng
Sophia Zhao
Crystal Xu
Blake Bridge
Jared Gould
Brian Li
Sophia Zhuang
Lauren Chong
Alice Zhang
Sophia Li
Blake Bridge
Jared Gould
Athena Stenor
Anavi Uppal
Sophie Edelstein
Matt Tu
Brett Jennings
Eten Uket
Megan He
Siena Cizdziel
Sorah Park
Himani Pattisam
Jordan Sahly
Noora Said
Emily Shang
Yu Jun Shen
Anasthasia Shilov
Tori Sodeinde
Zeki Tan
Van Anh Tran
Shudipto Wahed
Sherry Wang
Norvin West
Nathan Wu
Justin Ye
Kayla Yup
David Zhang
Lana Zheng
The Yale Scientific Magazine (YSM) is published four times a year by Yale
Scientific Publications, Inc. Third class postage paid in New Haven, CT
06520. Non-profit postage permit number 01106 paid for May 19, 1927
under the act of August 1912. ISN:0091-287. We reserve the right to edit
any submissions, solicited or unsolicited, for publication. This magazine is
published by Yale College students, and Yale University is not responsible
for its contents. Perspectives expressed by authors do not necessarily reflect
the opinions of YSM. We retain the right to reprint contributions, both text
and graphics, in future issues as well as a non-exclusive right to reproduce
these in electronic form. The YSM welcomes comments and feedback. Letters
to the editor should be under two hundred words and should include the
author’s name and contact information. We reserve the right to edit letters
before publication. Please send questions and comments to yalescientific@
yale.edu. Special thanks to Yale Student Technology Collaborative.
NEWS
Environmental Studies
PERCEPTIONS OF
“NATURAL GAS”
THE INFLUENCE OF TERMINOLOGY AND
POLITICAL AFFILIATION
BY JAMES LICATO
IMAGE COURTESY OF FLICKR
Natural gas continues to be one of the most popular
energy sources across the world. The largest
component of natural gas is methane, a potent
greenhouse gas with twenty-five times the global warming
potential of carbon dioxide. Mining natural gas also results
in leaks that pollute the Earth’s atmosphere. However, the
American public perceives natural gas and renewable energy
sources, like wind and solar, similarly. This discrepancy
motivated Karine Lacroix and researchers from the Yale
Program on Climate Change Communication to study
the American public’s perception of natural gas based
on differing terminology, as well as the effect of political
affiliation on perception.
The researchers asked over three-thousand volunteers to take
a survey that questioned their perceptions of one of six energyrelated
terms: natural gas, methane gas, natural methane gas,
methane, fracked gas, and fossil gas. The team chose the terms
based on their prevalence in media and everyday conversation.
Lacroix and her team found that the term “natural gas”
was perceived most positively by a significant margin. Their
findings also suggest that there is a general lack of knowledge
about the ramifications of using natural gas. Partisanship
also affected term perception, with Republicans holding
more positive perceptions than Democrats.
Public opinion is an important driver for policy initiatives.
To more accurately portray the downsides of natural gas in
the public sphere, “climate communicators should refer to
[natural gas] as methane gas,” Lacroix explained. Lacroix
and her team look to continue their work in climate change
communication as greenhouse gas emissions rise. ■
TRACKING
MERCURY
POLLUTION
RIVERS ARE THE LARGEST CONTRIBUTOR TO
COASTAL OCEAN MERCURY POLLUTION
BY JESSICA LIU
IMAGE COURTESY OF WIKIMEDIA COMMONS
Seafood is tasty, but we are often hesitant to consume
it because of the ocean’s high mercury concentration.
Increased human activities have released mercury
into nearby rivers, where it naturally transforms to
methylmercury, a potent neurotoxin associated with lowered
intelligence, child developmental delays, and cardiovascular
impairments. Methylmercury also bioaccumulates in our
food web, making its health consequences long-lasting. Most
of our exposure to methylmercury comes from coastal fish
consumption. Thus, we could effectively minimize the health
risks of mercury intake by mitigating pollution at the source.
Previously, scientists believed that atmospheric deposition is the
most important contributor to coastal mercury. Yale postdoctoral
researcher Maodian Liu and colleagues recently challenged this
traditional view by developing a high spatial resolution dataset of
global riverine mercury export. They discovered that worldwide
riverine mercury export to coastal oceans is actually three-fold
that of atmospheric deposition, making it an unexpected driving
force of the global mercury cycle.
Riverine mercury measurement data has been scarce in the
past, resulting in large variations in export estimates between
different studies. “The greatest challenge is to verify the
reasonability of our estimates because our results are three times
the recommended value of the United Nations Environment
Programme,” Liu said. Nevertheless, Liu is confident in this
estimate since it matches empirical observation. Building off
this work, Liu and colleagues are developing a global model to
further quantify the spatial differences of river mercury cycling
in coastal oceans. Understanding the overlooked riverine process
will help policymakers better regulate mercury pollution issues,
targeting not only atmospheric but also aquatic releases. ■
6 Yale Scientific Magazine October 2021 www.yalescientific.org
Cellular Biology
NEWS
AN UNEXPECTED
REASON
FOR COVID
OUTCOMES
IMAGE COURTESY OF SMITHSONIAN INSTITUTION
THE PRESENCE AND ROLE OF
AUTOANTIBODIES IN PATIENTS WITH COVID-19
BY SOPHIA DAVID
As the COVID-19 pandemic rages on, researchers
have puzzled over several mysterious viral outcomes.
Infections are severe in some people yet mild or even
asymptomatic in others, and many have reported long COVID,
in which COVID-19 related health problems last four or more
weeks after infection. Yale undergraduate Eric Wang (YC ’21)
worked alongside members of the Ring and Iwasaki labs to
study the relationship between autoantibodies and COVID-19.
Generally, we consider antibodies to be illness protectors.
Autoantibodies, in contrast, may cause harm. “They are antibodies
that target proteins expressed by your body’s own cells,” Wang said.
They can trigger the killing of specific helpful immune cells and
disrupt general immune system communication.
Using samples from Yale New Haven Hospital patients and
healthcare workers, Wang and the research team tested blood
reactivity with 2,770 human extracellular secreted proteins.
They selected a few examples of autoantibodies and performed
in vitro signaling assays, later assessing their effect on disease
progression in mice. They found that autoantibodies targeted
cytokines, chemokines, and various cell surface protein
receptors, potentially altering disease trajectory.
“A lot of the symptoms and reasons people go to hospitals are
due not to the virus itself, but the body’s response to the virus.
For example, an overactive immune system has been implicated
in a lot of COVID-19 hospitalizations,” Wang said. These
autoantibodies may also be linked to long COVID symptoms.
With this new knowledge that autoantibodies may be risk
factors for more serious COVID-19 outcomes, physicians
may incorporate autoantibody screening in their practice. ■
Editor’s note: elsewhere in this issue, we profiled Wang. See pg. 35.
“HANDS UP,
WE’VE GOT YOU
SURROUNDED!”
IMAGE COURTESY OF NIAID
A PROTEIN THAT DISSOLVES BACTERIAL
MEMBRANES TO EXECUTE IMMUNITY
BY EMILY SHANG
Every society needs a group of superheroes. And as a
society of proteins, organic molecules, and nucleic
acids, cells are no different. To defend against pathogens,
certain proteins within the cell work vigilantly to secure
its safety. One group of these vigilantes hails from a set of
mysterious genes termed the apolipoprotein L (APOL) family.
Twenty years ago, the discovery of APOL1, which functions
outside of the cell to defend against extracellular parasites, led
scientists to believe that the other five APOL genes may defend
against intracellular pathogens since they lack a secretion signal.
Led by postdoctoral fellow Ryan Gaudet, the MacMicking lab
at Yale and collaborators unearthed the function of one of
these five genes, APOL3, which codes for a protein that attacks
Gram-negative bacteria such as Salmonella.
APOL3 interacts with another host defense protein,
guanylate binding protein (GBP1), which autonomously
binds to the sugar-rich surroundings of Gram-negative
bacteria. When GBP1 invites APOL3 to the inner membrane
of Gram-negative bacteria, APOL3 kills the pathogen by
dissolving the lipid membrane, essentially ripping apart the
bacterial membrane in the cytosol.
With great power comes great responsibility: APOL3 needs
to discriminate between self and non-self-membranes. APOL3
doesn’t surround lipids within the cytosol without specificity—
that would be dangerous. A key ingredient in host cell
membranes, cholesterol, is an inhibitor to APOL3 that prevents
self-destruction. “Cholesterol makes APOL3 less able to insert
its hydrophobic component into the membrane,” Gaudet said.
Gaudet is optimistic about the many avenues of exploration
for APOL3, including future work investigating the protein’s
role in vivo. ■
www.yalescientific.org
October 2021 Yale Scientific Magazine 7
NEWS
Astronomy
THE
ATMOSPHERES OF
MARS AND TITAN
New research may aid in
space exploration
BY ETHAN OLIM
IMAGE COURTESY OF NASA
Scientists have long been interested in predicting
weather on Earth, but in recent decades, tools developed
for climate science at home have increasingly been
applied to studies of extraterrestrial atmospheres. Inspired
by puzzling patterns in Martian dust storms, researchers at
Yale recently investigated the effects of annular modes of
variability—climate patterns that repeat every few weeks to a
month, independently of the cycle of seasons—on Mars and
Titan, a moon of Saturn.
Joseph Michael Battalio, a postdoctoral associate in Yale’s
Department of Earth and Planetary Sciences, noticed a few
years ago that certain patterns of Martian dust activity seemed
to repeat approximately every twenty sols (Martian days).
This length of time didn’t match the behavior of any known
Martian storm instigator but was quite similar to that of the
annular modes Battalio had previously studied on Earth. This
led him to look for the effects of these modes on Mars.
Supporting this hypothesis, Mars has many other
atmospheric similarities to Earth: it rotates at a nearly identical
speed (one sol is approximately twenty-four hours and thirtynine
minutes) and exhibits similar prevailing winds.
When Battalio began analyzing data from Mars, fluctuations
in atmospheric eddy kinetic energy—a quantity associated
with storms—and shifts in atmospheric mass showed cyclic
behavior that was clearly due to annular modes.
Similar results were also found on Titan, the largest moon
of Saturn and a body of particular interest due to stable
liquids and hydrocarbons on its surface. The moon is studied
via the Titan Atmospheric Model (TAM), a numerical
climate model created by Yale professor Juan Lora. “TAM
enables us to generate realistic simulations of Titan’s global
circulation,” Battalio said. These pronounced effects of
annular modes on Mars and Titan may suggest the ubiquity
of annular modes in terrestrial atmospheres.
This research makes great contributions to our
understanding of extraterrestrial atmospheric dynamics and
may aid our exploration of Mars. Martian dust storms are
notoriously brutal, and occasionally prove lethal to solarpowered
missions, but this research could help protect future
landers. “[Annular modes on Mars] impact the overall climate
and dust storm activity… [and] Mars’s modes may even
enable us to generate predictions of dust activity,” Battalio
said. Activity from annular modes on Mars tends to reliably
foreshadow dust activity, so accurate current observations of
the atmosphere allow prediction of storms in a few days’ time.
Looking forward, Battalio has received a grant from NASA
to continue investigating atmospheric variations on planets
and moons. He plans to look further into modes on Mars
and Titan, particularly as they relate to weather events.
For instance, Titan’s methane storms are currently not
well understood, but they pose a potential hazard to future
landers such as NASA’s Dragonfly. Other bodies, such as
Venus—which has atmospheric patterns similar to Titan’s—
and Jupiter are also on the docket. Finally, his research into
annular modes could prove useful to the study of exoplanets,
helping to provide baseline atmospheric understanding so
that more irregular winds can be spotted.
Battalio and Lora have broken new ground in extraterrestrial
atmospheric science, and their work has countless
applications—on Earth, in our solar neighborhood, and
lightyears away. ■
8 Yale Scientific Magazine October 2021
www.yalescientific.org
Biochemistry
NEWS
UNCOVERING
THE ROLE OF A
MICROPROTEIN
The NoBody protein changes
all the rules
BY HANNAH BARSOUK
PHOTOGRAPHY BY HANNAH BARSOUK
Sarah Slavoff (left) and Zhenkun Na in front of the Advanced Biosciences
Center at Yale’s West Campus.
Researchers Sarah Slavoff and Zhenkun Na of Yale’s
Department of Chemistry are standing up for the little
guy.
More than a hundred years in the making, the Human Genome
Project was born from our need to understand the little parts of
ourselves. With our entire genome sequenced at the turn of the
century, researchers began picking proteins to study as if from a lineup
during gym class. Insulin, flaunting its pharmaceutical applications,
was chosen first. A blood clotting factor went second. Around twenty
thousand picks later, lil’ old NoBody (NBDY) microprotein is ready
for its time in the limelight. Microproteins have and will continue to be
master regulators in cells, even if they’re not winning popularity contests.
Sarah Slavoff entered the field of proteomics—the study of the
proteins that make up life—asking all the right questions but
none of the popular ones. She began working to fill the gaps in our
knowledge of what she calls “the dark matter of the genome” during
her postdoctoral fellowship at Harvard. Like many others taking a
protein-based approach to gene discovery, Slavoff sought to separate
the junk from jewel. And while it would be nice if regions of our DNA
could scream to us, “Hey, I’m important!”, natural selection hasn’t quite
worked that kink out yet. Instead, researchers relied on a strict set of
rules when identifying new protein-coding gene sequences:
1. They must begin with a specific three-letter sequence (AUG)
known as a start codon.
2. A single mammalian transcript encodes one protein.
3. The protein must be longer than a hundred amino acids.
Slavoff ’s proteomic experiments, however, began producing tens
of thousands of potential results that were discounted because they
broke one or more of these rules. “Biology is just as messy and
beautiful as you would expect it to be,” Slavoff noted a decade later.
Through ribosome profiling and bioinformatics approaches, her lab
has discovered exceptions to identifying protein-coding genes. “All
of these rules are actually broken. And they’re not just broken in rare
exceptions, they’re broken very widely,” Slavoff said. After adjusting
experimental parameters to account for this inconsistency, the
floodgates were opened: in the world of proteomics, the mavericks
and outcasts now shared a table at lunch with the jocks and socialites.
In an effort led by postdoctoral fellow Zhenkun Na, the lab further
justified that these “new” proteins aren’t just sitting around. In fact, they
might be serving some of the most important functions in cells. Enter:
NoBody, a microprotein that is a mere sixty-eight amino acids long.
One unique property of NoBody is its ability to behave like a fluid,
forming liquid droplets in cells. While in this droplet state, certain
modifications to NoBody, such as the addition of chemical groups
known as phosphates, cause the dissociation of membrane-less
organelles known as processing bodies, or P-bodies. Small like the
proteins that regulate it, the complexity of P-bodies’ anatomy is not
to be underestimated. They serve as storage sites for enzymes that
function in the processing and breakdown of RNA. Thus, NoBody’s
mood at any given moment—in other words, its phosphorylation
state—can make the difference between whether or not certain RNA
sequences, and the proteins they encode for, are produced by the cell.
What’s even more astounding is that NoBody can regulate P-body
dynamics seemingly without formal or consistent structure. It is not
made of folded sequences such as alpha helices or beta sheets, which
are some of the defining features of secondary structure in typical
proteins. NoBody is just one of many “intrinsically disordered”
microproteins with the power of order over our cells. The very
existence of microproteins challenges everything we know about
what proteins look like, what they do, and where to look for them.
One proteomics database, OpenProt.org, predicts the existence
of over forty thousand microproteins and other proteins missing
from our modern understanding of the human proteome. As of
today, characterized proteins in the human body make up only
half that number. With each one of these unfilled links potentially
representing a new function, location, or structure in the cell, we
should take a long, hard think before choosing the next protein
from our lineup. “It took us over a hundred years to build up and
annotate the human genome right. We don’t have another hundred
years to figure out what these things are doing,” Slavoff said. ■
www.yalescientific.org
October 2021 Yale Scientific Magazine 9
NEWS
Chemistry
BUILDING
A BATTERY
FUTURE
Sodium batteries in
a lithium-dominated
world
BY JORDAN SAHLY
IMAGE COURTESY OF WIKIMEDIA COMMONS
Every day around the world, modern luxuries are plugged in,
charged, and drained—and the cycle begins anew. Critical
to this energy dependence is the lithium-ion battery, the
electrochemical backbone behind cell phones, laptops, electric
cars, and most other battery-powered devices. In the US alone,
electronics consume some two thousand metric tons of lithium
annually, of which over fifty percent arrives as imports from other
countries such as China, Chile, and Australia.
Yiren Zhong, a postdoctoral associate in Yale’s Department of
Chemistry, understands the need to find a substitute for lithiumion
batteries. “We all know that lithium is a very very limited
resource, not only in the Earth’s crust but also in the oceans, in the
lakes,” Zhong said. Resource scarcity and related environmental
concerns have inspired chemists—including Zhong—to look
for candidates no further than a row down in the periodic table.
One promising candidate is sodium, an alkali metal like lithium.
Sodium and lithium have many similar qualities due to periodic
trends, with the notable difference that sodium is larger in atomic
size and has less electric potential overall. However, sodium is
also far more abundant naturally on Earth. Would this periodic
similarity make sodium a prime candidate for battery production?
This is what Zhong set out to study with his research, published in
August of 2021 in the Journal of the American Chemical Society.
Despite its natural abundance, sodium has a long way to go
before it can replace lithium as a primary battery component. There
are pros and cons for sodium metal as an electrode. Compared to
lithium, sodium has good reversibility—the ability to return the
electrochemical reaction to its original reactants, meaning that
batteries with good reversibility can be recharged and reused.
However, sodium also cannot be charged or discharged very quickly.
Intrinsic elemental properties stand in the way of sodium’s potential.
Zhong’s research group investigated these properties through rigorous
experiments testing sodium batteries at varying power levels, then
examining the electrode’s physical and chemical structure after
both charging and discharging. The research team performed the
experiments at high currents, which were closer to those of lithium
batteries, and at far lower currents for comparison. When the sodium
electrode was discharged at the higher currents, it performed with only
zero to sixty percent Coulombic efficiency—the ability of a battery to
output the usable electrons, or electricity, that it produces.
An interesting physical reaction indicated a key elemental difference
between lithium and sodium. When built through charging, sodium
metal electrodes naturally form in dendritic structures, which
are long, thin columns of metal that become porous, microscopic
forests on the surface of the electrode. On electrodes charged at high
current densities, these dendritic structures form with non-metallic
impurities. When discharged at high current densities, these impure
porous surfaces reduce the reversibility of the battery overall by
allowing fast-moving current to react unevenly—especially at the base
of the electrode—causing electrode erosion and eventual electrical
disconnection. Thus, the low performance of sodium batteries likely
stems from their elemental characteristics, namely their atomic size:
electrodes made from sodium metal have more spread-out dendritic
structures due to the larger atomic size. This creates the porous surface
that allows for erosion of the electrode foundation layer at high
currents, like waves washing away the base of a sandcastle.
Zhong’s findings, however, also suggest a favorable future for sodium.
At low power levels, the sodium battery did not decay and performed
favorably with Coulombic efficiencies as high as 99.5 percent. At these
low current densities, sodium batteries may demonstrate commercial
usefulness in technologies like short-range transportation tools.
Having observed sodium’s intrinsic characteristic limiting
its potential in batteries, Zhong’s group laid the foundation
for future sodium battery technology. One of his newest ideas
involves the electrode shape itself. “My current thinking
is trying to use a three-dimensional electrode,” Zhong said.
He theorized that a three-dimensional electrode may reduce
local current density across a larger surface area, which could
improve the electrochemical reaction in the battery.
As our society’s energy dependence grows each year, more
environmentally friendly batteries become a necessity rather than
a goal. “We need to develop a battery future,” Zhong said. “By
the year 2050, I would envision that sodium would be one of the
major components in the battery market.” Sodium metal has the
potential to help build a sustainable battery future, and thanks to
the continued work of innovative chemists, that future is in reach. ■
10 Yale Scientific Magazine October 2021 www.yalescientific.org
IMAGE COURTESY OF WIKIMEDIA COMMONS
In scientific experimentation, some information is more attainable
than others, by nature of the method of retrieval. For instance,
clinicians can easily gather blood pressure and other laboratory
values; aptly, this type of data is called easy-to-obtain information
(EI). However, other data may be too expensive, time-consuming,
or both to collect on a larger scale. Flow cytometry, a laser-based
technique to measure the chemical and physical properties of cells,
is an example of this type of hard-to-obtain information (HI). To
circumvent these limitations, a team of Yale researchers, including
graduate student Matthew Amodio and associate professor Smita
Krishnaswamy, developed a model called the Feature Mapping
Generative Adversarial Network (FMGAN) that allows for the
accurate prediction of HI given EI. Their methodology is novel—
in fact, Krishnaswamy’s lab pioneered all of the frameworks used
throughout the study, even those used as comparators to the FMGAN.
The most recent study applied the neural network model in two
contexts. One generated RNA sequences of cells perturbed with
drugs, a form of HI, via the chemical structure of the compound,
a form of EI. The second predicted the flow cytometry data (HI) of
COVID-19 patients using clinical measurements (EI).
The FMGAN’s predictive capabilities come from the addition of
a condition-embedding network. This network transforms the EI
into representations called manifolds that are easier to visualize,
reduce redundancy, and thus simplify data extrapolation. “The
condition-embedding network translates the data from how it
exists naturally to a form more easily used by our model, which it
gradually learns how to do,” Amodio said. The manifold structure
is preferable to the alternative form of data representation in
ambient space, as its smooth structure produces outputs that move
uniformly with changes in input. This point is especially relevant
in the context of Krishnaswamy’s work with chemical structure
and RNA sequencing—small modifications to certain portions of
the input can determine molecular function, so it is important to
maintain such consistency in the magnitudes of movements.
Further, the scientists introduced stochastic mapping, a measure of
randomness, into the model. “The drugs do not produce a single result
every time,” Amodio said. “The cell measurements change even in
applying the same drug to the same system. There are lots of sources of
randomness with respect to the data we looked at. Thus, it makes sense
www.yalescientific.org
PREDICTING
INACCESSIBLE
INFORMATION
A neural network
to improve data
acquisition
BY SYDNEY HIRSCH
Computational Biology
NEWS
to use models that include randomness to accurately represent that.”
In other words, stochastic mapping was another deliberate addition to
their neural network that further increased prediction reliability.
In applying the FMGAN to predict the RNA sequencing data of
cells treated with drugs, the team performed four experiments. In
the first two, they provided the model with preprocessed data and
good manifold coordinates; the purpose was simply to show that
information could be generated from the data. After demonstrating
the FMGAN’s success under these conditions, the researchers
executed two more challenging experiments that required the full
capabilities of the network in creating its own manifold coordinates.
One tested the condition of drug chemical structure in the form
of simplified molecular-input line-entry system (SMILES) strings,
a specialized notation system. The other instead looked at image
representations of said chemical structure. The latter performed
better than the former, likely due to the more advanced architecture
of the images compared to the strings. Both, however, demonstrated
the efficacy of the FMGAN and its condition-embedding network.
To demonstrate the breadth of the FMGAN’s applications, the
researchers also tested its ability to predict future flow cytometry
information from COVID-19 patients’ clinical measurements
upon entering the ICU. During experimentation, researchers took
both clinical and flow cytometry measurements from all study
participants. They omitted the data of fourteen patients, training the
neural network model on the remaining 115. Ultimately, the FMGAN
was able to use clinical measurements to generate flow cytometry
predictions for the never-before-seen patients. In practice, this data
gives clinicians insight into a patient’s immune function and is a
predictor of mortality. Instantaneous and accurate determination of
this HI would allow physicians to craft optimal courses of treatment.
Through this set of experiments, Krishnaswamy and her team
demonstrated the efficacy of their novel FMGAN neural network
model through its applications in drug discovery and clinical
inference. However, the FMGAN program is not limited to
these spaces—its architecture is not hardwired to address these
structures specifically and can be generalized to other data. This
area of quantitative computational biology is underexplored, but
breakthroughs have the potential to transform how scientists
leverage the information they have readily available. ■
October 2021 Yale Scientific Magazine 11
NEWS
Immunology
COLDER AND
WISER
The impacts of aging on
thermoregulation
BY VAN ANH TRAN
AND MADISON HOUCK
ART BY BREANNA BROWNSON
Babies don’t shiver when they’re cold—at least for the first six
months of their lives. Instead, they keep warm through a
mechanism called non-shivering thermogenesis, in which a
special type of fat called brown adipose tissue generates heat. But as
babies grow older, thermogenesis is no longer their primary means
of keeping warm. According to a study by researchers at multiple
centers, including Yale, age-related changes in thermoregulatory
control arise from changes in the body’s immune system. The
authors discovered that aging impairs a specific kind of immune cell
called type 2 innate lymphoid cells (ILC2s), which are important for
the maintenance of healthy adipose (fat) tissue.
We have two types of fat in our bodies: white adipose tissue
(WAT) and brown adipose tissue (BAT). Aging is marked by a
decline in brown adipose tissue and a shift in the distribution of
white adipose tissue. As we grow older, we have an increase in white
adipose tissue in our trunk and abdomen. This visceral adipose
tissue is subject to enhanced inflammation and insulin resistance,
which increases the risk of obesity among the elderly.
There also exists a third type of body fat midway between
white and brown adipose tissue: beige adipose tissue, which
arises from white fat parent cells but possesses similar features
to brown fat cells. Beige adipose tissue also responds to cold
exposure via energy expenditure and heat production.
The scientists looked into ILC2s because of their role in visceral
adipose tissue “browning,” the production of beige fat cells. They
compared the immune compartment differences between young
and old mice models and found that there was an almost complete
loss of ILC2s in the visceral adipose tissue of older mice.
ILC2s are tissue-specific immune cells, meaning they stay
within the visceral adipose tissue after their generation in the bone
marrow. ILC2 development depends on the proliferation of IL-
33, which belongs to a class of small cell-signaling proteins that
regulate our immune systems. The research team found that IL-33
was produced in different cellular locations in the adipose tissue
of young versus old mice. This switch in cellular source led them
to believe that there is less IL-33 available to develop ILC2s. Less
ILC2s means less browning, and thus a weakened cold tolerance.
The authors hypothesized that if they could supplement IL-33
in old mice, the resulting ILC2 development would restore healthy
cold response. They examined this through the “cold challenge”
method, during which mice were placed alone in cages that were
kept at around forty degrees Fahrenheit. Experimenters checked
on the mice twice a day to monitor mortality rates, then took
adipose tissue samples from mice that survived for two straight
days to look for signs of a healthy cold response.
So, can IL-33 alone fix the immune system of older mice? In short, it
can’t. Actually, mice with supplemented IL-33 had a higher mortality
rate than did other old mice in the cold challenge. Their response
to cold and temperature regulation was still entirely dysfunctional.
Faced with totally unanticipated results, the researchers came to
realize that maybe the problem wasn’t with IL-33 at all: it was with
the ILC2s themselves. Using RNA sequencing, they discovered that
ILC2s of old mice are pathogenic. Simultaneously, there are very
few healthy ILC2s left to offset these negative effects. While the
researchers were unable to determine the exact mechanism of old
ILC2 lethality, it certainly seems to be a double-edged sword that
leads to the dysfunction of the thermogenic response.
The research team tried one last experiment. ILC2s from
young, healthy mice were directly transplanted into older mice.
Only then did the thermogenic response increase and mortality
rates in the cold challenge decrease.
These results caution us that attempting to “fix” an immune
pathway can be tricky—we don’t know if we could be causing more
problems than we solve. “With age, the immune system has already
changed, and we need to be careful how we manipulate it to restore
the health of the elderly,” said principle investigator Vishwa Deep
Dixit, Waldemar Von Zedtwitz Professor of Comparative Medicine
and of Immunobiology at Yale, in an interview with YaleNews.
Fully understanding how to repair the immune system could be
a game changer for the elderly or people with immune deficiencies.
“Immune cells play a role beyond just pathogen defense and help
maintain normal metabolic functions of life,” Dixit told YaleNews.
These other functions include cold response and regulation of fat.
Armed with more knowledge of why the immune system stops
working, researchers like Dixit can continue to work towards solutions
that will lead to a healthier population in more ways than one. ■
12 Yale Scientific Magazine October 2021 www.yalescientific.org
THE
SILENT
Psychology
MENTAL
FOCUS
HEALTH THREATS OF
Your feelings
of paranoia
are not
all that
uncommon
During the Great Depression in 1929, immigrant workers
became scapegoats for economic hardship, accused of taking
jobs away from native-born Americans. After the tragedy of
9/11, many people grew fearful that their lifelong Muslim
neighbors could somehow be implicated in the terrorist attacks. Such
crises have historically caused individuals to see others as a threat. Drastic
changes tend to make people more paranoid.
This trend continues with the COVID-19 pandemic. Toilet paper stock
quickly ran out as shoppers rushed to acquire household supplies as if in
a post-apocalyptic frenzy. Asian Americans experienced an exponential
increase in hate crimes due to fringe conspiracy theories regarding the
origin of the SARS-CoV-2 virus. Differing opinions on mask-wearing
have turned into heated, politicized debates. Everyone seemed to share a
heightened sense of apprehension about the future.
Yale Cognitive Research Scientist Praveen Suthaharan, Associate Professor
of Psychiatry Philip Corlett, and their team recently published a study in
Nature Human Behavior about the effects of the COVID-19 pandemic on
individuals’ paranoia. To these researchers, the widespread uncertainty
caused by the pandemic provided an unprecedented opportunity to track
the impact of an unfolding crisis on human beliefs.
www.yalescientific.org
BY SHUDIPTO
N. WAHED
ART BY
KATHERINE
MOON
PHOTOGRAPHY
BY HANNAH
HUANG
October 2021 Yale Scientific Magazine 13
FOCUS
Psychology
PHOTOGRAPH BY HANNAH HUANG
Praveen Suthaharan, a member of the Corlett Lab, poses underneath a series of brain artwork.
A Pandemic of Paranoia
Constantly wearing a mask to protect
each other from a virus we cannot even see
with our own eyes, against a disease that
is in many cases asymptomatic, can
be overwhelming—enough to
put anyone on edge. Previously
mundane activities, like going
to the grocery store or
visiting grandparents,
now draw concerns: just
by doing them, one could contract
or transmit a potentially fatal disease.
The study’s authors saw that paranoia
significantly increased throughout the
duration of the COVID-19 pandemic,
with self-reported paranoia levels
peaking as states drew closer to
reopening. Overall effects on other
mental illnesses were also negative. “We
have all experienced challenges since
the onset of the pandemic, and we also
noticed this in our data: that over time,
depression and anxiety increased during
the lockdown,” Corlett said.
Ensuring that the general public
remains calm and willing to work
together is essential to overcoming a
crisis such as the COVID-19 pandemic,
especially in efforts like vaccination
and social distancing. While many have
argued for and against the merits of
mandatory lockdowns, this study’s data
demonstrate that divergence in statelevel
response correlated with differential
increases in paranoia—both selfreported
and measured via laboratory
tasks. Vigorous, proactive lockdown
policies were associated with less
paranoia when compared to
lax lockdown policies. One
may similarly expect to
see different outcomes
based on states’ varying
mask mandates, Corlett posited.
To Mask or Unmask
Over a year into the pandemic, wearing
a mask while around others should
seem like a no-brainer. Masks are cheap,
effective, and easy to wear. Suthaharan’s
team was interested in understanding
why so many people were and are still
opposed to wearing a mask, despite the
seemingly clear cost-benefit analysis for
doing so. “It’s similar to when you see a
patient smoking a cigarette outside of
the hospital,” Corlett said. “We wanted
to understand why people engage in
behaviors risky for their health.”
In their study, the researchers found
that paranoia was highest during
reopening in states that required maskwearing.
This supports the notion that, in
social settings, humans are “conditional
cooperators”—we tend to follow rules
as long as we perceive others doing the
same. As soon as this is no longer true,
we tend to stop following these rules. As
the data suggested, when there was a mask
mandate but people saw others without a
mask, that raised confusion and paranoia.
In fact, individuals with paranoia were
far more reluctant to wear masks and
reported wearing them significantly less.
Suthaharan wanted to know whether
mask mandates themselves
could have contributed to the
increased mental health
issues experienced
during the pandemic.
To that end, his team
performed a type of analysis
called “difference-in-differences,”
which allowed them to infer causal
relationships by comparing changes
in paranoia levels in states that
implemented a mask mandate to
states that did not, or only recommended
it. The analysis revealed that mandated
mask-wearing was associated with a forty
percent increase in paranoia levels.
These results could be connected
to a lack of clarity in public health
messaging, Corlett conjectured. Early
in the pandemic, health organizations
such as the CDC and WHO did not
fully support masking, even claiming
inefficacy at times. Later, emerging
evidence supported a reversal in opinion,
which in turn led to mask shortages and
induced worries among people who were
now unsure about whether they would
be able to get masks.
The uncertainty and paranoia caused
by mask mandates possibly led to distrust
of public health organizations as maskwearing
became a politicized topic. “In no
other time in history have we experienced
a pandemic this problematic, and instead
of dealing with it as a community of likeminded
people, what we’ve done is double
down on our differences,” Corlett said.
All in This Together
If there is any comfort
to be taken by those
who have experienced
mental
health
difficulties since the
14 Yale Scientific Magazine October 2021 www.yalescientific.org
Psychology
FOCUS
start of the pandemic, it is that nobody
is alone in their struggle. With this
collective aspect in mind, Suthaharan
and his team were keen to study grouplevel
cognition to see if characteristics
and experiences shared by a population
affected mask-wearing or paranoia.
Using an index of cultural tightness and
looseness, developed by psychologists
at the University of Maryland, to
measure a state’s
cultural tolerance
for rulebreaking,
the
researchers
found that
stricter states that
mandated mask-wearing
experienced the lowest rates of
mask-wearing. Individuals in
culturally tight states
may have grown
paranoid seeing
others without masks,
leading to overall lower levels of maskwearing
in these states. Fear of social
reprisal due to anti-mask sentiments
may have further driven their paranoia.
Many of those who were hesitant to
wear a mask were also hesitant to receive
a COVID-19 vaccine, with unproven
conspiracy theories circulating about its
development and its usage in government
surveillance. The research team found that
paranoia was significantly correlated with
belief in these specific conspiracy theories,
as well as belief in other theories, such as
that prominent Hollywood entertainers
are involved in child trafficking.
These results demonstrate that our
surrounding culture and environment
can substantially affect mental health.
“It was very interesting and informative
to show that group-level characteristics
such as rule-following and cultural
tightness impacted peoples’ behaviors
and beliefs,” Corlett said.
Cognitive Origins
The Corlett lab has been interested
in studying the origin and neural
mechanisms of paranoia for several
years—even before the pandemic.
Notably, within the field of psychiatry,
there are mixed opinions regarding the
origins of paranoia in the mind and
www.yalescientific.org
brain. Some believe that the brain has a
distinct module for dealing with social
relationships and that problems with this
part of the brain cause paranoia. Corlett,
on the other hand, contends that the
same reward mechanisms in our brains
that tell us whether we like things, such
as different types of food or even money,
are implicated in paranoia. To him, we
do not differently process positive or
negative feelings towards something in
social versus nonsocial settings.
In this study, the authors conducted two
types of experiments to assess paranoia:
social and nonsocial. In the nonsocial
task, participants were instructed to
choose between three cards that each had
a different probability of being “correct.”
They were also told that the underlying
probabilities would change, but not how
often or when. A paranoid individual
would likely switch their choices more
frequently, even after positive feedback
(“win-switching”), incorrectly attributing
probabilistic errors to a shift in underlying
probabilities. In the social task, instead
of using cards, individuals were
told they could collaborate with
one of three individuals
who would either help or
hurt them.
The researchers found that
the win-switching frequency in the
nonsocial task was indeed significantly
correlated with paranoia, validating that
performance on the task was an accurate
measure of one’s paranoia levels. More
importantly, they also found that there
was no difference in behavior between
the social and nonsocial tasks, suggesting
that Corlett’s theory may offer a more
ABOUT THE AUTHOR
valid and accurate understanding of
paranoia’s origin.
Interestingly, participants in this study
performed the same tasks before and
during the pandemic, yet yielded starkly
different outcomes in each condition.
This may shed light on the replication
problem in psychological research,
where many published findings cannot
be reproduced by other researchers. It is
possible that some of these findings could
be merely artifacts of changing real-world
conditions between replication attempts.
But even so, this study suggests that realworld
changes can have profound impacts
on individual behavior in laboratory tasks.
An Informed Future
This study could have many implications
for the field of psychiatry, and the
authors hope that its insights into human
psychology will help those struggling with
mental illness. They also hope that their
research will affect positive change for the
ongoing COVID-19 pandemic. Given
how paranoia affects individual
responses to worldwide crises, this
study’s results could help guide
future decision-making and
inform effective communication
between the public, governments,
and other organizations.
“Conducting online research during
a pandemic was a challenge, but also
inspiring,” Corlett said. “It is unusual to
be so connected to real-world events and
to study them as they unfold, and for our
data to have implications for how the
situation could be handled differently
now, and in the future.” ■
SHUDIPTO N. WAHED
SHUDIPTO WAHED is a sophomore in Benjamin Franklin from Pittsburgh, Pennsylvania interested in
studying Molecular Biophysics & Biochemistry. Shudipto conducts research on protein engineering in
the Ring Lab at the Yale School of Medicine. Outside of YSM, Shudipto is a senator for the Yale College
Council and an analyst in the Yale Student Investment Group.
THE AUTHOR WOULD LIKE TO THANK Professor Philip Corlett for his time and enthusiasm.
FURTHER READING
Reed, E. J., Uddenberg, S., Suthaharan, P., Mathys, C. D., Taylor, J. R., Groman, S. M., & Corlett, P. R. (2020).
Paranoia as a deficit in non-social belief updating. ELife, 9.
Suthaharan, P., Reed, E. J., Leptourgos, P., Kenney, J. G., Uddenberg, S., Mathys, C. D., ... & Corlett, P.
R. (2021). Paranoia and belief updating during the COVID-19 crisis. Nature Human Behaviour, 5(9),
1190-1202.
October 2021 Yale Scientific Magazine 15
FOCUS
Paleontology
Millions of
years ago,
long before
any of us existed, dinosaurs
roamed the Earth. What might
have stood where you are right now?
Maybe a T. rex or a Triceratops?
If you are somewhere in eastern North
America, the dinosaurs that lived near
you long ago might be unique. Chase
Brownstein, a Yale College junior
pursuing the Ecology and Evolutionary
Biology major, recently conducted
research showing that eastern North
American dinosaurs were probably very
different from the famous species of the
American West. His work sheds light
on the possibility of multiple paths to
evolutionary success.
Dinosaur Island
During the Mesozoic Era, when
dinosaurs like the T. rex existed, the
Earth looked very different from how it
does today. Surrounded by oceans and
seaways, eastern North America was
isolated from the rest of the world for
about thirty million years, constituting
an island landmass named Appalachia.
But since the 1800s paleontologists have
largely neglected the study of what kinds
of life once inhabited Appalachia.
When organisms evolve on an
isolated landmass, it’s considered more
likely for them to develop in ways that
differ substantially from their relatives
elsewhere. This has caused researchers
like Brownstein to ask: was this true for
dinosaurs isolated in Appalachia, and if
so, what unique characteristics did they
have? Poor fossil-forming conditions
and other factors, however, have made
this question difficult to answer.
Firstly, Appalachia has smaller
mountain ranges compared to western
North America. This means that the
shorter rivers created by these mountains
don’t flow as far and therefore cannot
accumulate as much sediment as their
longer counterparts in the West. This
Art by Zi Lin
accumulation of sediment is what
creates fossil-forming regions. Shorter
rivers generate fewer of these regions;
thus, fewer fossils formed on Appalachia
to begin with, making it difficult to
know what kinds of dinosaurs lived
there. Additionally, the fossils that
did form had a high chance of being
destroyed later by glaciers. The same
glaciers that carved out the Great Lakes
dug up much of the fossil-containing
sediment in eastern North America.
Finally, it’s difficult to even access the
fossils that did survive the glaciers, as the
eastern coast of North America is much
more densely populated than the West.
Most of the land is privately owned.
“Nobody wants you to make a giant hole
in their backyard,” Brownstein said.
Many of the major fossil discoveries
that are now in museums like the Yale
16 Yale Scientific Magazine October 2021 www.yalescientific.org
Paleontology
FOCUS
DECRYPTING
DINOSAURS
Uncovering records of eastern North
American tyrannosaurs
of
the
East
By Elisa Howard and Anavi Uppal
Peabody
Museum
of Natural
H i s t o r y
w e r e
therefore
made in the
19th century, when
populations were less dense and
eastern fossils more accessible.
Uncovering Clues
New Jersey State Museum. The fossil
revealed distinct anatomical features
distinguishing Dryptosaurus from other
tyrannosaurs like the T. rex. In particular,
Dryptosaurus had an elongated skull and
hands ranking among the proportionally
largest for any dinosaur. Furthermore,
it had massive claws reaching up to six
inches long and an unusually shaped
foot with three bones.
While at the Peabody Museum,
Brownstein noticed that the foot
of a tyrannosauroid found in the
Merchantville Formation in Delaware
displayed similar features to that
of Dryptosaurus. To investigate, he
used the Tree Analysis Using New
Technology (TNT) program to
conduct a phylogenetic analysis of
the Merchantville tyrannosauroid
In 2015, while browsing collections at
the Yale Peabody Museum, Brownstein
elucidated connections between two
different tyrannosaurs—Dryptosaurus
and the Merchantville tyrannosauroid—
to answer the question of whether
distinct dinosaur species evolved on the
once-isolated eastern North America.
“This research is the culmination of
several years of work into the question of
eastern North American biogeography,”
Brownstein said.
In 1866, West Jersey Marl Company
workers discovered the enormous fossil
of a dinosaur that lived approximately
sixty-seven million years ago in
modern-day New Jersey. Yale Professor
of Paleontology Othniel Charles Marsh
named the dinosaur Dryptosaurus in
1877. Brownstein had the opportunity
to study the Dryptosaurus fossil at the
www.yalescientific.org
IMAGE COURTESY OF WIKIMEDIA COMMONS
Dryptosaurus had an elongated skull and hands, ranking among the proportionally largest for any dinosaur.
October 2021 Yale Scientific Magazine 17
FOCUS
Paleontology
and Dryptosaurus. The program
incorporated the skeletal features of
the two dinosaur species to determine
evolutionary relationships.
From this computational analysis,
Brownstein discovered that the
Merchantville tyrannosauroid and
Dryptosaurus evolved from a common
ancestor and are part of the same clade.
That clade, known as Dryptosauridae,
is a distinct group of tyrannosaurs
that existed solely in Appalachia. For
over a century, paleontologists have
hypothesized the existence of a distinct
set of tyrannosauroids native to the
once-isolated eastern North America.
With Brownstein’s research, we now have
evidence supporting that hypothesis.
Though factors such as poor fossil
records still constitute obstacles to
our knowledge of the dinosaurs that
inhabited the east, Brownstein’s research
underscores the rise of anatomical
differences in the dinosaurs of eastern
and western North America. In a broader
context, such discoveries highlight the
profound interplay between geographical
isolation and the evolution of species.
Searching for History
Evolutionary biologists and
paleontologists often develop “just-so
stories,” speculative explanations for the
origins of a biological trait. The term
comes from Rudyard Kipling’s 1902 “Just
So Stories for Little Children.” The book
includes a collection of animal tales such
as “How the Rhinoceros Got His Skin,”
in which the rhinoceros developed
wrinkles after rubbing against a tree. In
the context of dinosaurs, there are many
speculative hypotheses that tyrannosaurs
evolved a specialized skull, superior
sight, or other specific traits to achieve
supremacy. The T. rex—the “King of the
Dinosaurs” that lived in western North
America—boasted hallmark features of
dinosaur superiority, such as a gigantic
skull, forceful jaw, powerful hindlimbs,
and muscular physique. Yet, whether
those features are indeed necessary for
biological success remains up for debate.
The eastern North American
Dryptosaurus, for example, differed from
the T. rex and other tyrannosaurs: it
had larger hands, extensive claws, and a
distinctive unit of foot bones. “Eastern
North American tyrannosaurs were
really big, were probably predators,
and had a different set of features than
western North American tyrannosaurs,”
Brownstein said. “This may cause us to
rethink the hypothesis that there was
only one way that tyrannosaurs got so big
and successful.” In this way, Brownstein’s
discoveries point towards the possibility
that tyrannosaurs achieved success
through the evolution of differing features.
As Brownstein emphasized, his
research raises broader questions of
evolution that demand further research
and contemplation—the prevailing one
among them being: how many paths
could there be to evolutionary success?
To find out more about eastern North
American dinosaurs, the next step would
be to discover a more complete skeleton
of these species. Currently, research is
limited to the fossils that have already
been found, which do not include the body
part that paleontologists consider to be
the most informative: the skull. However,
looking at living things today could also
shed light on the nature of extinct species.
Analyzing the characteristics of dinosaur
descendants can sometimes help us learn
more about their ancestors.
Behind the Discoveries
Brownstein—who has an impressive
research history, having published about
twenty peer-reviewed articles in journals
including Royal Society Open Science,
the Journal of Paleontology, Scientific
Reports, and the Zoological Journal of the
Linnean Society—intends to go forward
ABOUT THE AUTHORS
with other research while he waits for
more fossil discoveries. He is currently
studying fishes with Yale Professor and
Chair of Ecology and Evolutionary
Biology Thomas Near.
Brownstein said that he was fortunate
to have access to fossil collections like
those at the Peabody Museum and
described his appreciation for those who
have provided support and advice in his
research endeavors. “I have been very
fortunate to have people who gave me a
chance,” Brownstein said.
Brownstein has a genuine passion
for the field of research. “I have always
been really fascinated with nature, time,
what lived before, and how we got here,”
he said. Research simply makes him
happy. “If I want to do something that
I enjoy, I will do research, write, and
study things,” he said. Based on this
passion, Brownstein described science
in the larger context of the human desire
for exploration. “It is a human thing to
constantly explore. The urge to discover
is a motivator in science, and it’s a
beautiful thing,” he said.
Just like we push the boundaries of
our universe with space travel, we are
now pushing the boundaries of time
by uncovering our planet’s incredible
history. In Brownstein’s case, we now
understand that the geographical
isolation of eastern North America over
the course of thirty million years likely
provided the means for the evolution of
distinct dinosaur species.
As we continue to uncover our planet’s
incredible history, what will we discover
next? ■
ELISA HOWARD AND ANAVI UPPAL
ELISA HOWARD is a sophomore neuroscience major in Berkeley College. In addition to writing for YSM,
she volunteers at CT Hospice and Yale Community Kitchen, constructs 3D-printed limb devices through
Yale e-ENABLE, and helps organize blood drives for the American Red Cross at Yale. During the summer,
she researches neural repair in the Strittmatter Lab at the Yale School of Medicine.
ANAVI UPPAL is a sophomore astrophysics major in Pierson College. In addition to writing for YSM, she
is one of Synapse’s outreach coordinators, and she teaches science to elementary schoolers through Yale
Demos. She’s also a fall social media intern at NASA Ames Research Center.
THE AUTHORS WOULD LIKE TO THANK Chase Brownstein for his time and enthusiasm about his
research.
FURTHER READING
Doran Brownstein, C. (2021). Dinosaurs from the Santonian–Campanian Atlantic coastline substantiate
phylogenetic signatures of vicariance in Cretaceous North America. Royal Society Open Science, 8(8),
210127. https://doi.org/10.1098/rsos.210127
Marsh, O. C. (1896). The Dinosaurs of North America. Govt. Print. Off.
18 Yale Scientific Magazine October 2021 www.yalescientific.org
On a cold November day in 1957,
Laika made history as she rode
into orbit on a Soviet spaceship,
withstanding tremendous
acceleration to become the
first living being to circle the Earth. Laika wasn’t
a trained astronaut—she was a dog, a former
stray from the streets of Moscow chosen for
this historic, but ultimately fatal, mission.
In the name of science, humans have
since launched hundreds of different animals
into space. Now, however, scientists are
sending mice on a very different kind of
trip—one that doesn’t require them to leave
the laboratory, much less the Earth.
Rather, they’re on a mushroom trip.
Neuroscience
FOCUS
Could
shrooms
shake up
the future of
psychiatry?
BY ANNA
CALAME AND
RAYYAN DARJI
ART BY
ELAINE CHENG
A SHIFT IN THE
PSYCHEDELIC
PARADIGM
IMAGE COURTESY OF PIXABAY
www.yalescientific.org
October 2021 Yale Scientific Magazine 19
FOCUS
Neuroscience
Research into the neurological effects of
psilocybin, the hallucinogenic compound
found in so-called “magic mushrooms,”
has experienced a powerful revival in
recent years. Psilocybin is a serotonergic
psychedelic, meaning that it has a high
affinity for serotonin receptors and
produces altered states of consciousness,
including positive mood. Clinicians and
academics have long been interested
in the potential of these substances as
therapies for neuropsychiatric disorders,
including depression and addiction, but
their clinical implementation has faced
considerable challenges.
The frontal cortex’s neuroplasticity,
or its ability to adapt over time, has
proven fundamental to the efficacy of
antidepressant therapies. Results of
previous studies suggested a potential
relationship between psychedelics and
neuroplasticity, but the particulars
remained unknown. To address some
of these uncertainties, researchers from
Yale School of Medicine’s Department of
Psychiatry examined psilocybin’s effect on
the brain and demonstrated psilocybininduced
structural neuroplasticity at
cellular resolution for both short and
long timescales.
Structural and Behavioral Effects of
Psilocybin
Psilocybin has a centuries-long
tradition of medicinal and spiritual use,
particularly among Indigenous peoples.
Despite this, however, psilocybin has not
been extensively studied in the context
of Western medicine, leaving many
questions about its neurological functions
unanswered. “Psychedelic compounds like
psilocybin produce temporary psychedelic
experiences that last for four to six hours,
but it’s a mystery as to how those shortterm
actions translate to longer-lasting
therapeutic effects on mental illnesses,” said
Alex Kwan, associate professor of Psychiatry
and Neuroscience at Yale and senior author
of the paper. By studying how psilocybin
affects neuron structure, researchers could
bridge this gap and offer a structural
explanation behind its well-observed
lasting therapeutic effects, which include
a substantial reduction in depression and
anxiety symptoms according to early but
promising clinical trials.
20 Yale Scientific Magazine October 2021
In this study, the researchers
administered various doses of psilocybin
to mice and evaluated the neurological
effects through a series of tests.
“One of our focuses is on neuronal
structure. We used two-photon
imaging, a fluorescence
imaging technique used
for live tissues, and
confocal imaging, an
optical laser imaging
technique with high
resolution, to see the
structural changes
caused by singledose
psilocybin,”
said Ling-Xiao
Shao, first author
of the paper and
a postdoctoral
associate researcher
in Kwan’s lab. The
researchers used the twophoton
imaging technique to
longitudinally track the dendritic
spines—protrusions from the membranes
of dendrites, the branch-like appendages
of neurons that receive communications
from other cells—in neurons within
the mice’s medial frontal cortex. These
spines play a vital role in receiving and
processing electrical impulses.
The study’s results suggest that a
single dose of psilocybin was sufficient
to enhance the formation of dendritic
spines in the medial frontal cortex of
the mouse, increase spine head width,
and boost spine protrusion length. A
month after administration of psilocybin,
approximately a third of psilocybininduced
new dendritic spines remained.
These results are especially promising for
potential therapeutic use, as conditions
like depression are associated with a
loss of synapses in the frontal cortex
region. Psilocybin’s stimulation of lasting
dendritic growth may offer a solution.
While imaging neural modifications
clarifies the physical effects of
psilocybin, it does not fully account
for the functional outcomes of the
compound. To understand the impact
of these structural changes on behavior,
the researchers applied footshocks to
the mice and assessed if single-dose
psilocybin improved their ability to
escape stressful conditions. The results
demonstrated
that mice exposed to psilocybin exhibited
healthier stress-response behavior.
While this study provides compelling
evidence in support of the enduring
actions of psilocybin in the brain, it is
still unclear whether the compound’s
therapeutic potential can be isolated from
its hallucinogenic effects. Kwan and Shao’s
study found that suppressing psilocybin’s
hallucinogenic effects by knocking out
a key serotonin receptor, 5-HT2A, did
not interfere with the therapeutically
promising changes in neuron structure.
However, further research is needed to
determine if this separation of function is
possible in humans.
The Rise (and Fall) of Psychedelic
Psychiatry
Kwan and Shao’s recent foray
into the world of hallucinogens is
representative of a larger, ongoing
renaissance in psychedelic research
after decades of fluctuating acclaim and
condemnation. When Swiss researcher
Albert Hofmann first discovered LSD’s
potent hallucinogenic effects in the
early 1940s, he was not alone in his
excitement about the drug’s psychiatric
potential. Hundreds of academic
www.yalescientific.org
Neuroscience
FOCUS
articles expounding psychedelics’
effects appeared in medical journals
throughout the 1950s. So began a brief
and initially promising affair between
psychedelics and clinical psychiatry
in the United States. Various
clinics and institutions, including
Harvard, devoted significant
resources to researching
the therapeutic potential
of psilocybin and LSD.
Psychedelic researchers,
such as Timothy Leary and
Richard Alpert, became
household names.
However, growing
backlash against the
free-loving, acid-tripping
counterculture of the
1960s—facilitated by
psychedelics’ association
with anti-war dissidence—began
to turn the political tide. In 1965,
the passage of the Drug Abuse Control
Amendments Bill banned the unlicensed
individual manufacturing and sale
of hallucinogenic drugs, signaling
a strengthened political and legal
resistance to hallucinogens and ringing
a death knell for psilocybin. In 1970,
the Controlled Substances Act explicitly
designated psilocybin a Schedule I
drug, the most restrictive classification,
indicating a high potential for abuse and
no accepted medical use. In so doing,
the Act not only subjected psilocybin to
extremely prohibitive regulations, but
also heavily stigmatized its use, taking
the wind out of the sails of psilocybin
research for years.
By Kwan’s own recollection, the
landscape of psychedelic research was
nearly barren even just a decade ago.
“Reading from other labs who were
studying this fifteen years ago, the culture
was very different, very restrictive,” Kwan
said. “There were no suppliers of these
compounds…there were only a few
labs who would [synthesize psychedelic
compounds] in the United States.”
The Psychedelic Revival
In recent years, however, the research
landscape has shifted. With greater
knowledge of how drugs function on a
molecular level, further research into
www.yalescientific.org
the science of addiction, and growing
recognition of the failures of the War on
Drugs, popular conceptions of drug use are
shifting. While much of the mainstream
drug debate focuses on recreational use,
these changing perspectives have opened
up the academic and clinical fields as well.
Kwan and Shao’s study adds to a growing
body of research into the therapeutic
potential of psilocybin and other
psychedelics to treat mental disorders.
As a compound used in conjunction with
psychotherapy, psilocybin has a number
of uniquely appealing characteristics—it’s
non-addictive, has low risk of overdose,
and may require less frequent dosing than
selective serotonin reuptake inhibitors, the
most common class of antidepressants.
Financial support for research
from activist organizations, academic
institutions, and commercial entities has
accompanied this growing recognition
of psilocybin’s potential. Echoing the
academic enthusiasm of the 1950s,
centers dedicated to the study of
psychedelic drugs have opened at a
number of research institutions in recent
years, among them Johns Hopkins,
Massachusetts General Hospital, and
New York University. Promising clinical
psilocybin trials in the U.S. led the FDA
to designate psilocybin a “breakthrough
therapy” in 2018, indicating significant
institutional optimism about the
drug’s therapeutic potential. Kwan and
Shao’s own study reflects the growing
acceptance of psychedelic research, given
its publication in Neuron, a prestigious
peer-reviewed research journal.
Even in today’s more liberal
environment, however, obstacles remain
ABOUT THE AUTHORS
for those interested in conducting
research with psychedelics. “Even
though the public perception is changing
quickly, the funding is still slow,” Kwan
explained. “We had a pilot grant from
Yale, but [this research] is not funded
right now at the federal level, so it’s
tricky.” The National Institutes of Health
has abstained from funding psychedelic
research, even as commercial interest in
psychedelic psychiatry grows.
Moreover, while Kwan and Shao are
optimistic about the therapeutic potential
of psilocybin, they caution against framing
psychedelics as a panacea for mental
illness. Noting “the possibility of adverse
effects,” Kwan described particular risks
for people with a history of psychosis or
cardiovascular issues. “There’s a lot of
hype in terms of what these compounds
can do, but they’re definitely not going to
be a solve-all,” Kwan cautioned.
In the meantime, though, Kwan and
Shao intend to remain an integral part
of this research. The results of their
study offer fertile ground for further
exploration of psilocybin. After observing
the neurological changes induced by
psilocybin, Kwan and Shao are eager
to address new questions regarding
the particular molecular signals, brain
receptors, and neural cell types involved.
Five decades on from the initial
criminalization of psilocybin, the
psychedelic research landscape again
appears bright. While we may not be
“turning on, tuning in, and dropping
out” any time soon, researchers like
Kwan and Shao remind us that the future
of psychiatry may well be psychedelic
after all. ■
ANNA CALAME AND RAYYAN DARJI
ANNA CALAME is a junior in Davenport College studying the history of science, medicine, and public
health. Outside of her work with the YSM, Anna is involved with Yale UAID, YaleBleeds, and the club
tennis team.
RAYYAN DARJI is a sophomore in Grace Hopper interested in studying neuroscience on the pre-med
track. In addition to writing for YSM, Rayyan is involved with the Yale Muslim Students Association,
Alzheimer’s Buddies, and YNEURO.
THE AUTHORS WOULD LIKE TO THANK Alex Kwan and Ling-Xiao Shao for discussing their research
process and findings with them, and the research team would like to acknowledge the non-profit
Usona Institute for providing psilocybin for research.
FURTHER READING
Shao, L.X., Liao, C., Gregg, I., Davoudian, P.A., Savalia, N.K., Delagarza, K., & Kwan, A.C. (2021). Psilocybin
induces rapid and persistent growth of dendritic spines in frontal cortex in vivo. Neuron, 109(16).
October 2021 Yale Scientific Magazine 21
FOCUS
Ornithology
BIRDS OF A FEATHER
COLOR TOGETHER
BY RYAN BOSE-ROY
ART BY ANASTHASIA SHILOV
Studying the structure of bird feathers
could revolutionize engineering
From the bright red-necked tanager to the deep blue crowned pigeon, over ten-thousand
species of birds share the planet with us. Throughout history, their colorful feathers
have flickered ubiquitously into fashion and culture. But where do bird feathers get
their colors from? What makes cardinals red and blue jays blue?
The search for answers to these questions has led to novel discoveries in nanophotonics
and soft-matter physics. A recent Yale study on how birds make blue feathers—led by Vinod
Saranathan, Ornithologist and Applied Physicist at Yale-NUS, and Richard Prum, William
Robertson Coe Professor of Ornithology at Yale—opens new avenues in many line of research,
from understanding the physics of cell biology to creating more efficient solar panels.
22 Yale Scientific Magazine October 2021
www.yalescientific.org
Ornithology
FOCUS
Prum, who is also head curator of
vertebrate zoology at the Yale Peabody
Museum, explores the relationship
between the phenotypic diversity of bird
species and their evolutionary history.
“I was interested in paleontological
discoveries in bird feathers, and also a
sideline on pigmentation and coloration,
and before you know it those two worlds
connected,” he said.
How Bird Feathers Have Color
In some birds, feather colors are
produced by pigments, like brown
melanins and orange carotenoids. In many
other birds, however, colors are produced
by the intrinsic structure of the feather.
In these “structurally colored” feathers,
light is scattered off proteins coating
secondary feather barbs—microscopic
comb-like fronts that doubly extend out
from the stiff center of a feather and then
stock together into a vane.
Some structural colors are iridescent:
light bounces off at different angles on
a feather’s surface creating positive and
negative overlap, resulting in a feather
whose color changes depending on the
direction from which you look at it.
Peacocks have iridescent feathers, and
they change from blue to turquoise as the
bird moves around. However, blue jays,
blue grosbeaks, and several other birds
have non-iridescent feathers: they always
look blue, no matter what direction you
look at them. And they never fade. “Birds
that were collected one-hundred years
ago look just as lifelike as if they were
collected today,” Saranthan said.
The barbs of non-iridescent birds’
feathers are made of a protein called
β-keratin, which forms nanostructures
interspaced by pockets of air that evenly
scatter different wavelengths of incoming
light, creating a pure single color.
These structures grow by a process called
phase separation, which also happens
when you pour soda into a glass. In the
pressurized soda can, the carbon dioxide
and water are thoroughly mixed. When
the can is opened, the pressure changes,
and carbon dioxide rises from the liquid
in the form of bubbles, which form foam
on the sides of the glass. Drop a coin in the
glass and you’ll see bubbles form on the
surface of the coin as well; bubbles need
nucleation sites, or central hubs, to form
www.yalescientific.org
and grow over time. At the nanoscale,
this is what generally happens in bird
feathers, except that while carbon dioxide
forms spherical bubbles, β-keratin in bird
feathers forms a variety of shapes.
Previously, using scattering patterns from
super-high intensity X-rays, Prum and
Saranathan had identified structures made
from keratin fibrils in the surface patterns
within feathers of every single bird in the
ornithology collection of Yale’s Peabody
Museum. “There are two types of structures
we thought were generated,” Saranathan
said. “One looked like swiss cheese, or
bubbles in a beer foam. The other one
looked like nano-spaghetti—you get this
random jumble of keratin fibrils in the air.”
However, while perusing the feathers
of different bird species, Saranathan and
Prum found something that, as Saranathan
puts it, “looked very funky.” In the leafbird
species, found only in Asia, iridescent colors
were not produced in the secondary feather
barbs, but in the primary feather branches.
“That was really a clue that something
new was going on here,” Saranathan says.
Rather than the swiss-cheese or nanospaghetti
subunits lining the surface of
the feather, the building blocks formed by
β-keratin took the shape of a new, complex
topological structure called a single gyroid.
Gyroids: A Game-Changer
A gyroid is an example of what
mathematicians call a minimal surface,
a shape that takes the least amount of
surface necessary to span a given region
of space. Structures with high-surface
area-to-volume ratios, like a human
brain, consist of lumps and folds and have
a high degree of average curvature. At
any given location on the gyroid surface,
however, the positive bumps
and negative depressions even
out to zero, yielding a mean
curvature of zero.
Gyroids are minimal
surfaces that are triply
periodic, meaning that a small piece
on the surface can be repeated in three
independent directions to assemble the
entire surface. What gives the gyroid its
characteristic shape is that it has no planes
of reflectional symmetry and no straight
lines at any point along its surface. Any
point along its surface lies in a region that
looks something like a saddle.
Ten years ago, Saranathan had
conducted X-ray analysis on iridescent
green butterflies and found these
same single gyroid structures. Though
these structures have been modeled by
scientists and mathematicians since the
1970s, Saranathan’s butterfly discovery
was the first time they had ever been
positively identified in nature.
The single gyroids that Saranathan and
Prum identified in birds and butterflies
represent a game-changer for several
reasons. For one, single gyroids are
structurally distinct from the far more
common double gyroid structures,
which consist of two interlocking gyroid
surfaces enmeshed together. Unlike the
double gyroid, the single gyroid has
both a full electronic bandgap as well
as a full optical bandgap, which means
that it completely traps all directions
and polarization states of light and easily
excites electrons to a conductive state.
This gives single gyroids better electronic
(conductive) and optical (reflective)
properties than double gyroids. Thus,
they could be an incredibly useful tool
in solar cells for sequestering light and
turning it into electricity.
Additionally, Saranathan and Prum’s
discovery could open up new ways
of directly synthesizing single gyroid
nanostructures, which could serve as
a powerful optical tool for a variety of
disciplines. Currently there is no way
for engineers to make the single gyroid
directly. Saranathan and Prum explained
that soft-matter engineers instead embed
Lego-like molecules with hydrophobic
and hydrophilic components in solution,
where they locally reorder into a double
gyroid structure. Engineers
then chemically
degrade
one of
October 2021 Yale Scientific Magazine 23
FOCUS
Ornithology
IMAGE COURTESY OF VINODKUMAR SARANATHAN
Dr. Vinodkumar Saranathan with models of a double gyroid (left) and single gyroid (right).
these components, backfill the empty
space with gold, and burn away the
remaining organic complement. This
process leaves a single gyroid made
of gold, which can then be used as a
template to form single gyroids from
other materials.
Inherent limits in this double gyroid
etching process make it impossible to
synthesize single gyroids larger than fifty
nanometers in unit size. Unfortunately,
single gyroids that interact effectively
with light are around five-hundred
nanometers. Researchers have yet to
find a way to synthesize one of that size.
Both butterflies and birds, however, have
figured out the process.
Making Single Gyroids
Saranathan used X-ray analysis to observe
the β-keratin structures in other species
that are sister species to single gyroid
leafbirds. He found swathes of keratin
nano-spaghetti, assembled through
phase separation. Prum noted that it is
highly likely that two species diverged
from a common ancestor by way of the
nanostructure formed, keeping the same
general formation process.
Crystal structures produce more
saturated colors. For that reason,
Saranathan suggested that keratin
structures resembling single gyroids were
preferred by some female leafbirds over
those resembling nano-spaghetti.
Nevertheless, these birds somehow form
single gyroid crystals without ostensibly
having to form a double gyroid first.
“The way they are making this is new to
science, period,” Saranathan said. “New
to biology, new to engineering, new to
physics.” Birds’ spontaneous self-assembly
of these structures illuminates the exciting
potential for humans to recreate this selfassembly
in the laboratory.
Single gyroids and their discovery in
living systems represent a breakthrough
in a vast number of scientific disciplines.
The optical structures used by birds to
make colors can also be used to better
manipulate the flow of light. This makes
them highly applicable in solar cell
technology. A structural approach to
creating color, rather than one based off
pigments, could inspire the development
of sustainable and less toxic paints,
tiles, textiles, and cosmetics that resist
fading over time, too. Furthermore, the
formation of networks and gel matrices
from large liquid-like particles, similar
to how keratin forms single gyroids,
is a process nearly ubiquitous in cell
biology. A better understanding of single
gyroid synthesis could lend insight into
organelle-less phase separation—a
widely growing area of interest in cell
biology—soft-condensed matter physics,
and physiological systems.
In an age where nanotechnological
structures in computer chips and rapiddiagnostic
tools are designed to optimally
control the flow of electrons and light,
learning from self-assembled structures
like single gyroids could open up whole
new areas of research. “This is an example
of why I think bird-watching science
matters,” Prum said. “That tension
between irregularity and specificity is
something that I really enjoy, and this
research is a great example of the way in
which that works together.” ■
Curiously, butterflies make single
gyroids the same way researchers do—
only somehow, they’re able to make them
ten-times larger than engineers can.
But “the birds,” Saranthan said, “are
completely revolutionary.” In contrast
to butterflies, there’s no templating.
Birds like the blue jay seem to make
single gyroids spontaneously by phase
separation, as if they dropped a quarter
in a glass of soda and single gyroids
assembled on the coin’s surface.
To ascertain the spontaneous generation
of single gyroids by phase separation,
24 Yale Scientific Magazine October 2021
ABOUT THE AUTHOR
RYAN BOSE-ROY
RYAN BOSE-ROY is a sophomore in Trumbull majoring in Biomedical Engineering and “something else,
we’ll figure out what it is.” In addition to writing for YSM, Ryan works the Trumbull buttery shift on
Sunday nights, where he delights in making quesadillas and regaling customers with stand-up bits while
taking their orders.
THE AUTHOR WOULD LIKE TO THANK Dr. Prum and Dr. Saranathan for their time and willingness to
be interviewed for the article. At the request of Dr. Saranathan (and at the author’s own discretion), the
author would like to acknowledge the Yale Peabody Museum for its existence.
FURTHER READING
Saranathan, V., Narayanan, S., Sandy, A., Dufresne, E. R., & Prum, R. O. (2021). Evolution of single gyroid
photonic crystals in Bird Feathers. Proceedings of the National Academy of Sciences, 118(23). https://doi.
org/10.1073/pnas.2101357118
www.yalescientific.org
Mathematics
THE MATHEMATICALLY
FEATURE
PERFECT EGG
BY EUNSOO HYUN
ART BY SAACHI GREWAL
Over millennia, the egg has evolved to become one of the
most adaptable shapes in nature: strong, small enough
for safe delivery, and capable of surviving in extreme
conditions. This distinctive shape has long been a subject of
fascination among researchers. “[We are investigating] whether
some mathematical laws were designed first and nature was
created in accordance to them, or vice versa,” said Valeriy
Narushin, a researcher at Vita-Market Ltd and the Research
Institute for Environment Treatment in Ukraine. Narushin’s
recent work on developing a universal mathematical formula
for egg shape demonstrates a collaboration between biologists,
engineers, and scientists, united by a common desire to crack
the mystery of this unique natural phenomenon.
There are four main categories of egg shapes: circular,
elliptical, oval, and pyriform. The most commonly recognized
egg shape, which we encounter in chicken eggs, is the oval. “As
for me personally, I like pyriform, or speaking in mathematical
language, conical eggs. These are laid by some species of
waders and guillemots,” Narushin said. Pyriform, in contrast
to the oval, is a more unconventional “pear-like” or pointed
shape. There are many hypotheses as to why certain types of
eggs evolved this way, ranging from their structural integrity
to their ability to fit into nests efficiently, but there is no clear
explanation yet as to why some eggs converged to a pyriform
shape over time.
At first glance, it may seem quite straightforward to map the
shape of an egg using mathematical equations. However, while
these equations are very good at creating idealized egg shapes that
can be used in art and architecture, they fall short when it comes
to tracing a real egg. Thus, the challenge was to deduce a universal
mathematical formula that corresponds to all types of egg shapes
and is easily transferable between geometrical figures.
www.yalescientific.org
The researchers successfully developed a more complex,
universal formula based on measurements of the egg length,
maximum breadth, vertical axis shift, and diameter at one
quarter of the egg length. This formula allows them to
theoretically describe any avian egg, keeping in mind that
small discrepancies are to be expected due to the diversity of
eggs as a natural object. Importantly, the formula can describe
the shape of any of the four egg types—a feat that has never
before been achieved to this level of accuracy.
In the process of collecting data for this study, the researchers
also furthered a more comprehensive project aimed towards
sustainable and nondestructive methods of egg evaluation.
“Elaboration of non-destructive methods for testing eggs is the
basic goal of our research group, which we call the ‘Eggy-team,’”
Narushin said. The researchers used images instead of actual
eggs whenever possible and did not handle any endangered or
wild bird eggs. This is part of a long-term goal: the development
of non-invasive research methods can improve poultry
management and environmental conservation efforts.
But why the obsession with eggs? “According to Professor
Tim Birkhead, [eggs] are the most perfect things on the Earth.
And we fully agree with him. From ancient times, eggs were
used as cult objects in art, architecture... etc. And of course,
an egg is an excellent food used in more than ten-thousand
recipes,” Narushin said.
The study of eggs has far-reaching impacts. In the food
industry, egg density and the ratio of egg weight to surface area
are crucial in considering egg freshness, shell thickness, storage
conditions, and incubation success. “If you know a geometrical
formula of a given egg, it’s rather simple to recalculate all these
parameters (curvature, a longitudinal length and others) with
equations of the integral geometry,” Narushin said.
The egg also provides a source of architectural inspiration.
“The egg profile has several advantages for architects due to its
harmonic shape, relative strength, and minimal consumptions
of building materials,” Narushin said. “Famous egg
constructions include The National Centre for the Performing
Arts in Beijing and the Gherkin in London.” From food science
to art, the egg has an influence far beyond what its humble
appearance may suggest.
Now that this universal formula has been found, what lies
in the future of oomorphology? “The first [investigation] is
based on deducing universal formulae for calculating volumes
and surface areas of different egg types, and their ingression
into the principles of mathematical evolution,” Narushin said.
“The second one is related to the study of shell mathematical
secrets. Why is the shell relatively thick in some species and
thin in others? Hope we can propose some results very soon.”
So the study of eggs continues, one formula at a time. ■
October 2021 Yale Scientific Magazine 25
FEATURE
Chemistry
THE FUTURE OF
CARBON CAPTURE
BY SARAH COOK
ART BY MALIA KUO
These days, it’s hard to escape the reality of climate change
in daily life. Carbon dioxide is one of the main greenhouse
gas drivers of climate change: according to the EPA, 6,558
tons of the gas were emitted in the United States in 2019 alone.
But what if there was a way to ‘harness’ this carbon dioxide and
instead transform it into usable energy? Enter: carbon capture.
Researchers from the US Department of Energy’s Pacific
Northwest National Laboratory (PNNL) recently discovered a
new method of integrated carbon capture that converts carbon
dioxide into methane, a main component
of natural gas. The reactants of this
method include waste carbon
dioxide, a 2-EEMPA solvent, and
renewably sourced hydrogen.
While traditional carbon
capture methods usually boil
the carbon dioxide out (the
capture step) before shipping
it elsewhere to be converted into
methane (the conversion step), this
new process simply passes the carbon
dioxide over a catalyst and mixes it
with hydrogen, all in one chamber,
completing the conversion at one site.
“Rather than just doing the wasteful
regeneration [of carbon dioxide],
we’re just doing the conversion at the
same time,” Heldebrant said.
And best of all? This method presents
the lowest price of carbon capture so far.
The 2-EEMPA solvent used in the method
has been in development for fourteen years
with corporations such as Florida Corporation, GE Global
Research, and University Partners, with twenty-million dollars
of Fluor Corporation funding. Unlike traditional solvents,
2-EEMPA has a low water content and can more easily dissolve
carbon dioxide, while requiring less overall energy to complete
the conversion process. Previous methods required high
temperatures to push the equilibrium in favor of the conversion,
but 2-EEMPA simply allows the chemicals involved to facilitate
the conversion to methane, necessitating only about half of the
typically required temperature and pressure.
Because of this ability to reduce the amount of energy used in
the conversion of carbon dioxide to methane, using 2-EEMPA
UNLOCKING CHEAP CONVERSION
OF CARBON DIOXIDE TO METHANE
in power plants could decrease the price of carbon capture by
nineteen percent. “Right now, everybody talks about wanting
to do carbon capture, but there is a high cost,” Heldebrant said.
Current commercial technology can capture carbon dioxide at
$58.30 per metric ton, but this new method costs only $47.10
per metric ton. This method therefore reduces total capital
investment by thirty-two percent and the minimum selling
price for natural gas by twelve percent.
It’s important to note that while this new process produces
methane, which is itself a harmful greenhouse
gas, synthetic methane’s carbon neutrality
and household and industrial uses still
make it an improvement over other
forms of methane. Furthermore,
Heldebrant’s project was funded
in California, where the new lowcarbon
fuel standard prohibits the use
of methane derived from fossil fuels
in a few years. This makes Heldebrant’s
research even more vital for companies
currently relying on producing natural gas.
“Ultimately in the long term, we would love
to see everything go to renewables, but at
least right now, we would much rather see
something that’s carbon-neutral as opposed
to carbon-positive just pulling the methane
out of the ground,” Heldebrant said.
Compared to previous methods, this
method’s low price creates financial incentives
for carbon capture, but it also creates a potential
problem of oversaturation of the methane
marketplace once the method becomes large-scale. “If
we’re only going to be making methane, you’re going to disrupt
the entire methane marketplace, and then that basically means
there’s no longer an economic driver to do it,” Heldebrant said.
In the future, PNNL hopes they can find new substances to
which they can convert waste carbon dioxide, such as dimethyl
ether (a type of diesel additive), cyclic carbonate (a type of
electrolyte solvent in batteries), and polymer carbon dioxide.
The work to pioneer carbon capture technology at such low
costs has been decades in the making, but this new research
has finally shown that cheap carbon capture technology is not
only feasible, but also has the potential to become a beneficial
driver of the economy and environment. ■
26 Yale Scientific Magazine October 2021 www.yalescientific.org
Astronomy
THE LIVES OF BLACK
FEATURE
HOLES AND GALAXIES
NEW MODELS FOR ALL SCALES OF MOTION
BY DANIEL MA ART BY SORAH PARK
How do supermassive black holes swallow up matter and help
drive the galaxies of our universe? This fundamental question
in astrophysics has yet to be fully answered, but it strikes at
the heart of our creation and existence. Supermassive black holes,
present in most galaxies, play a key role in galaxy evolution through
their gravity, but nobody knows exactly how. In particular, the way
these supermassive black holes accrete matter has been uncertain. For
example, quasars—active galactic nuclei powered by supermassive
black holes—are so powerful that they can outshine their entire host
galaxies and be seen billions of light-years away. But how can so much
gas accrete so rapidly as to sufficiently power these quasars?
Earlier this year, Daniel Anglés-Alcázar’s research group at the
University of Connecticut made groundbreaking success in modeling
black hole-galaxy interactions, finding a viable mechanism for
black hole gas accretion and quasar luminosity. This
model is unique in its use of novel mathematical
techniques, dubbed “Lagrangian Hyper-refinement,”
to accurately represent the flow of gas into a black
hole on both small and large scales at once.
Previously, researchers had to make simplified
guesses as to how black hole accretion would
influence their galactic models, as the galactic
models didn’t have the necessary resolution to
incorporate existing black hole accretion models.
This was a major limitation, considering how much the
black holes’ mass could influence surrounding structures. But Anglés-
Alcázar’s new model is able to do the equivalent of “adding more pixels to
an image in the region where you want to zoom in,” he said, dynamically
generating more gas circulation elements wherever the black hole is at
any given moment to increase the resolution. Hence, even though the
model begins on a multi-galactic scale, one can zoom in a million times
at its center and see activity on the scale of only a few light-years.
The model’s results have been very promising. The presence of
large asymmetries in galaxy shapes was found to be crucial to the
accretion process. As a galaxy rotates, its asymmetrical parts,
such as spiral arms, exert a constant gravitational pull on
rotating gas. This makes the gas slow down, fall into smaller
orbits, and eventually fall into the black hole. The model
produced fractal-like generations of such spiral arms
from the galaxy scale down to the accretion disk scale,
supporting this theory’s application on all scales.
Most impressively, under some conditions, the inflow
of gas into the black hole was found to be large enough
to explain luminous quasars. In other words, gas was
www.yalescientific.org
entering the black
hole fast enough
to account for the
quasar’s energy
output. “This was
the first time that
a single simulation
covering the whole
range of scales had been
able to show that effect,”
Anglés-Alcázar said.
When the researchers studied
the few quasars near enough to
the Earth to observe in detail, they
obtained results that resembled the
model’s. Additionally, the model shows
that, surprisingly, even supermassive black
holes can move substantially over time, and
galaxies change their shapes by the interactions
between their arms and migrating central black holes.
But an even bigger surprise was that the model, with certain
starting conditions, also showed that galaxies often go into and out
of active phases over time. Dormant supermassive black holes—such
as our own galaxy’s Sagittarius A*, which doesn’t accrete much matter
at the moment—can become active again after several million years by
similar steps as described previously. The process, however, occurs at a
much lower level, with galactic features slowing gas down and
making it fall inward. These results greatly enhanced the
team’s confidence in the model, as they not only matched
known statistics on the frequency of dormant versus active
black holes, but also showed that the model could cover
two different situations despite being made for only one.
Anglés-Alcázar is very optimistic about his model’s
future. “We can do these kinds of experiments on dwarf
galaxies or on galaxies more like our own Milky Way, or
the same galaxy but at an earlier phase, or even the very early
universe, back when the first galaxies were forming,” he said. Anglés-
Alcázar also wishes to make the model even more accurate by
including the effects of black holes’ strong winds and relativistic jets.
The door is wide open to new discoveries. And
each discovery is another crucial step towards
understanding our world. “In order to
understand galaxies, we have to first understand
black holes,” Anglés-Alcázar said. ■
October 2021 Yale Scientific Magazine 27
FEATURE
Computational Biology
BIOETHICS IN THE
AGE OF COVID-19
LAUNDERING BIAS AND
SAVING LIVES THROUGH AI
BY RISHA CHAKRABORTY
AND JUSTIN YE
Over the past year and a half,
our hospitals, overwhelmed by
COVID-19 patients desperate
for oxygen, have been debilitated by
staff and resource shortages. While
many called for vaccines as a hopeful
cure-all, some recognized a faster
alternative: efficient and deliberate
distribution of hospital resources.
Fourth-year PhD candidate Amogh
Hiremath and Professor of Biomedical
Engineering Anant Madabhushi at
Case Western Reserve University were
among the bioengineers who confronted
this problem. “It’s particularly heartwrenching,
as a father myself, to
see pediatric wards filled up… kids
[who] require critical surgeries just
don’t have a bed,” Madabhushi said.
Recognizing that delayed or inaccurate
risk assessments could prove fatal,
Hiremath and Madabhushi developed
CIAIN (integrated clinical and AI
imaging nomogram), the first deeplearning
algorithm to predict the
severity of COVID-19 patients’
prognoses based on patient CT lung
scans as well as clinical factors.
Artificial intelligence, at its core,
endeavors to mimic processes within a
human brain. Similar to how humans
take lessons from past experiences and
apply them to novel situations, computers
“learn” information from a training set
and apply it to a testing set. In the case
of a prediction algorithm like CIAIN,
computers are initially fed information
ART BY NOORA SAID
from existing patient data to correlate
features of CT scans and clinical test
results with patient prognoses. Once
the algorithm is trained, it can then be
applied to novel patient information—
the testing group—and give prognoses
with a high degree of precision. CIAIN
is the “first prediction algorithm
to use a deep learning approach
in combination with clinical
parameters,” Hiremath said.
This makes it more accurate than
algorithms using imaging alone.
Another major advantage of
CIAIN lies in its speed of
deployability: given that
accessing medical datasets
is relatively difficult
compared to obtaining
a set of natural images,
Hiremath and Madabhushi
used roughly one-thousand
patient scans from hospitals
in Cleveland, Ohio and
China to train, fine-tune,
and test their model. And
notably, CIAIN is the
first algorithm designed
for COVID-19.
Given that their
paper only examined
unvaccinated patients,
Madabhushi and Hiremath
now want to investigate
if they can find the risk of
hospitalization for vaccinated
individuals. “As we hear
about new breakthrough infections, the
question is if we need to run the analysis
retrospectively on patients who have been
vaccinated,” Madabhushi said. However,
while it is one thing to create predictive
algorithms retrospectively, it is another
to apply such algorithms to novel patient
data without prior physician evaluation.
A prospective study—a study that follows
patients before their ultimate outcomes
are known—would employ a dualpronged
approach. First, the researchers
would evaluate the algorithm in the pilot
phase of a prospective non-interventional
trial, where radiologists would upload
a CT scan and the algorithm would
generate a risk score for a patient. In a
few months, if the tool performed well,
the study could then transition into a
prospective interventional form, and the
researchers could propose the algorithm
to the FDA for clinical approval.
Despite anticipating the usage of CIAIN
in the emergency room, Madabhushi was
careful to emphasize the limited role
28 Yale Scientific Magazine October 2021 www.yalescientific.org
Computational Biology
FEATURE
even very advanced algorithms can play
in clinical settings. The vast majority of
AI algorithms in the foreseeable future
are intended to be decision support tools;
they merely augment and complement the
physician’s interpretation by aggregating
data and prognosticating patient
outcomes more accurately. Ultimately,
only physicians interact with patients
and thus are the best individuals to make
treatment decisions. Madabhushi likened
the role bioengineers like himself and
Hiremath play in healthcare to the role
aircraft engineers play in improving
functionalities on the console of an
airplane. Ultimately, the physicians are
the pilots in the cockpit.
No discussion on novel AI technology
is complete without considering
possible biases in the model and the
effects of such biases. Imagine an
algorithm trying to classify whether
or not an object is ice cream. If, in
training the algorithm, one only feeds
it images of vanilla ice cream in a cone,
the algorithm is likely to reject images
of any other flavor, since it is not used
to classifying anything but vanilla ice
cream cones as ice cream. Simply put,
algorithms are biased if the correlations
they have learned from a certain
training set (vanilla ice cream cones)
can’t be extrapolated to the testing set
(ice cream of all types).
While this example may be
innocuous, biases in models used
in healthcare can have life-ordeath
consequences. This year, the
American Society of Nephrology
finally updated their model for
calculating glomerular filtration
rate, which was originally
based on assumptions derived
from Caucasian patients.
Their old model was
found to make inaccurate
calculations for African
Americans, culminating in
frequent misdiagnoses of
chronic kidney disease.
Even if AI just provides a
single data point for physicians
to use in decision-making,
AI predictions are often given
precedence over other data points
“The future of AI in healthcare
”
seems clear, but its implementation
remains challenging.
due to the complex methodology by which
models aggregate information. Hence,
ensuring that AI predictions are as accurate
and unbiased as possible is crucial.
Even without prompting, Madabhushi
and Hiremath highlighted the methods
by which they attempted to avoid
introducing biases to CIAIN. “We
were very deliberate and purposeful
in making sure the data was collected
from a few different sites,” Madabhushi
said. Diversifying the source of data
generalized the algorithm and also
reduced the likelihood of a “leakage
problem,” a known biasing factor
AI models face when data is poorly
separated between the training set and
testing set. The resulting overlap means
the algorithm will learn the training set
well and accurately classify the testing
set, but will demonstrate poor accuracy
in classifying a new “validation”
testing set because it hasn’t learned
enough variation. Both Hiremath and
Madabhushi expressed the need for
further validation to verify CIAIN is
sufficiently generalizable.
While generalizing models might
help decrease bias, it is not a fixall.
With African American patients
three-times more likely to die from
COVID-19 than Caucasian patients,
an algorithm trained on a mixed-race
group may fail to accurately predict
prognoses for either group. Scientists
must integrate how social determinants
of health—including ethnicity, race,
and socioeconomic status—play a role
in disease manifestation and prognosis.
“While we haven’t explicitly explored
these factors with our methodology and
platform yet, it is definitely something
we want to look at,” Madabhushi said,
who is of the strong belief that scientists
need to get away from the idea that “one
model fits all.” In fact, Madabhushi
and Hiremath have compared the
accuracy of models specific to different
ethnic groups for breast, uterine, and
prostate cancer—in each case, the
model designed for the subpopulation
yielded more accurate predictions than
a more general model. Madabhushi
expresses hope that “[scientists] will get
to the point where there is a buffet of
models and a physician can selectively
invoke a model based on the ethnicity
or other attributes of their patient.
Otherwise, we are doing a disservice to
underrepresented populations.”
In theory, the future of AI in
healthcare seems clear: scientists must
identify differences among populations
and incorporate them into increasingly
population-specific algorithms. But its
implementation remains challenging:
one of the biggest hindrances
scientists face is a lack of data from
underrepresented populations. Until
this data can become readily available
via drastic institutional and structural
change, it is up to scientists like
Hiremath “to improve the current
prediction models in a step-by-step
manner, improve the biases that are
involved, and create a usable product.”
As AI becomes increasingly ubiquitous
in healthcare, there are fears that biased
and over-generalized algorithms are
being put into practice faster than
refined and population-specialized
algorithms are being created. We
must remember that the personalized
aspect of medicine—the conversations,
interactions, and human observations—
are just as, if not more, important than
an algorithm’s score. AI can be a fantastic
passenger-seat navigator to a physician
driver. But society must be careful not to
let AI take the wheel, lest the tool meant
to improve patients’ survival endangers
it instead. ■
www.yalescientific.org
October 2021 Yale Scientific Magazine 29
FEATURE
Computational Biology
CIRCA DIEM: OPENING THE AI BLACK BOX
NEW RESEARCH INTO CIRCADIAN RHYTHMS
ALSO REVEALS THE INNER WORKINGS OF AI
BY SIMONA HAUSLEITNER AND KATHERINE CHOU
ART BY KASSI CORREIA
The fact that the Earth rotates
around its axis once every
86,400 seconds seems like a
faraway explanation for the passage of
time, but what if this simple concept
actually relates to the most important
physiological and behavioral processes
in our bodies? Our internal circadian
rhythm is a twenty-four-hour biological
clock that influences everything from
our sleep cycle and metabolism to our
immune system and susceptibility
to disease. Understanding the gene
expression that underlies such a
fundamental adaptation for life poses
many challenges for scientists, but
modern artificial intelligence (AI)
algorithms and machine learning
(ML) models provide new avenues into
exploring such scientific questions.
A team of researchers at the Earlham
Institute in Norwich, England recently
conducted a study to increase the
transparency of how ML systems work,
while also shining light onto the most
advanced computational system we
know of: the human brain.
Circadian rhythms depend on many
factors, including environmental
stimuli like light and temperature. This
is one of the reasons why changing
time zones can cause us to experience
jet lag—a misalignment between our
body’s expectation of the day-night
cycle and the changing cues presented
by a new geographical location. It has
been experimentally determined that
these circadian rhythms are controlled
by the expression of specific genes
that oscillate between on-off states
during the twenty-four-hour intervals.
However, past efforts to detect this
circadian rhythmicity have required
the generation of long, high-resolution
time-series datasets, an effort that
is expensive, inefficient, and timeconsuming.
To work with such large
amounts of data, the researchers took a
new approach, involving a combination
of AI and ML algorithms, to predict
circadian gene expression.
Hussien Mohsen, a researcher in the
Gerstein Lab at Yale who was not involved
in the study, further explained the
intersection between artificial intelligence
and gene expression research. Mohsen
focuses on interpretable machine learning
for cancer genomics—a field where, as
in the circadian rhythm field, there has
been increasing interest in deep learning
algorithms (a subset of machine learning)
in recent years. According to Mohsen,
this is particularly due to technological
advancements, which allow us to generate
the immense archive of data that lies at the
heart of deep learning. “Interpretability
of machine learning has become way
more popular with deep learning for
that particular reason: because you have
enormous amounts of data,” Mohsen
said. “The models become so incredibly
complex that we need to simplify them—
our human cognition can't really follow
what's going on.”
When it
comes to applying
these data analysis
tools to the field of
biology, scientists must
ensure that AI techniques
are simultaneously
efficient and reliable so
that the results generated can be applied
to the whole population being studied.
In computing, the “black box” refers
to systems that are considered only in
terms of their inputs and outputs, with
no real understanding of their inner
workings. As powerful as AI algorithms
are for navigating increasingly complex
issues, this lack of transparency raises
concerns for future research: how
is the model transforming data into
results? How are the ML algorithms
making decisions based only on pattern
identification? And if there are any
issues, how would we know?
To this end, in their study of circadian
rhythms, the Earlham Institute researchers
formulated an approach involving three
key elements: 1) developing ML models
that quantify the best transcriptomic
timepoints for sampling large gene
sequencing datasets while reducing the
overall number of timepoints required;
2) redefining the field by using only
DNA sequence features rather than
transcriptome time point information; and
30 Yale Scientific Magazine October 2021 www.yalescientific.org
Computational Biology
FEATURE
IMAGE COURTESY OF NATIONAL HUMAN GENOME RESEARCH INSTITUTE
The circadian rhythm, also known as the body’s
“biological clock,” is endogenous (originates
from within an organism), but also influenced
by environmental variables, including light,
temperature, and geographical location.
3) decoding the “black box” of ML models
to explain the mechanism of how AI is
used to predict circadian clock function.
In order to effectively analyze the
expression of circadian rhythms, the
researchers chose the small flowering
plant Arabidopsis thaliana as a model
organism. Arabidopsis was the first plant
to have its entire genome sequenced, and
because some of its regulatory elements
were already known, the researchers used
that pre-existing knowledge to validate
their ML predictions. This allowed them
to understand how their ML model was
reaching its predictions, thereby decoding
the mystery of the AI black box.
When there are tens of thousands,
even millions, of data points, how do
we understand that data and extract
their patterns and trends? Mohsen
explained that we learn by finding
parameters that capture what patterns
exist—the more sophisticated the data,
the more parameters we need. But using
more parameters necessitates a greater
understanding of what each does.
“There are multiple approaches and even
definitions of what interpretability is,”
he said. Fundamentally, though, “it is
just learning how the prediction process
works or which input features are
corresponding to a specific prediction.”
The Earlham Institute researchers
used MetaCycle—a tool for detecting
circadian signals in transcriptomic
data—to analyze a dataset of Arabidopsis
genomic transcripts. Using this
information, the researchers trained
a series of ML classifiers to predict
if a transcript was circadian or noncircadian.
They found that the AI was
not just using gene expression levels,
but also timepoints for its predictions.
However, these predictions were not
always one-hundred percent accurate,
and the researchers thus set out to
ascertain the optimal sampling strategy
and number of timepoints needed.
Circadian gene expression rhythms
follow diverse patterns, but all share a
twenty-four-hour periodicity. Having
fewer timepoints is more efficient, but leads
to concerns over loss of information and
accuracy. The researchers aimed to find the
optimal balance between a low number of
transcriptomic timepoints and improved
accuracy, so they started with a twelve
timepoint ML model and sequentially
reduced it to three timepoints.
The explainablity aspect of their
model comes with understanding how
the model was making its predictions.
The researchers needed to see which
k-mers (short sequences of DNA) were
the most influential in impacting the
ML model's predictions, and found that
the most accurate predictions resulted
from a k-mer length of six.
“[Machine learning] has
already reshaped a significant
part of how we study the
biology of disease.
”
Overall, the study showed the
possibility for reducing the number of
transcriptomic timepoints while still
maintaining accuracy in predicting
circadian rhythmicity. Since creating
datasets takes significant time and
resources, a reduction in sampling could
have important long-term impacts in
increasing efficiency.
The findings of this study have major
implications for the future of biomedical
science and AI: recent studies have
shown that disruption of clock genes
is associated with sleep disorders,
heightened susceptibility to infections,
Alzheimer’s disease, and metabolic
syndrome. “[Machine learning] has
already reshaped a significant part of
how we study the biology of disease,”
Mohsen said. “I very much see AI playing
a larger role in drug development and in
terms of the way we study biology.”
More recently, Mohsen and the Earlham
Institute researchers have shifted to a
new focus: advancing the clarity of how
and why these powerful algorithms
are providing the predictions that they
do. As scientists explore foundational
questions of how human physiology
works, understanding the powerful tools
used in probing those questions is just
as crucial. According to Mohsen, having
unexplainable AI poses “a huge risk
in medicine and elsewhere” due to its
prevalence in everyday life, including face
recognition, surveillance, and biohealth.
In illuminating the “black box” for
ML models that predict circadian
rhythms, research merging transparent
AI and genomics opens possibilities for
understanding the rapidly-developing
technology in our hands. Ultimately, this
has implications for precision medicine,
novel drug development, and decoding
the genetic basis of disease in the future. ■
www.yalescientific.org
October 2021 Yale Scientific Magazine 31
A NEW TECH CLAIRVOYANT FO
FEATURE
Neuroscience
A NEUROPROSTHESIS THAT TRANSLATES BRAIN ACTIVITY TO
BY ALEX DONG & MALIA KUO
He had not been able to speak
for sixteen years. At the age of
twenty, the patient, known as
BRAVO-1, experienced a severe stroke
resulting in paralysis and anarthria,
the loss of the ability to articulate
speech. But now, after the implantation
of a novel neuroprosthesis, BRAVO-1
can communicate efficiently with the
world—using only his brainwaves.
Edward Chang, neurosurgeon and
Chair of Neurological Surgery at the
University of California San Francisco
(UCSF), spearheaded this decades-long
effort to successfully decode words and
sentences from neural activity.
Chang’s journey with the brain started
during his time in medical school
at UCSF, where with brain mapping
techniques he observed surgeries
where the patients were actually awake.
“It dawned on me that there was a
huge, huge need to better understand
how the human brain works to treat
neurological conditions that we don’t
necessarily have cures for yet,” Chang
said. “I decided to go into neurosurgery
because it not only allowed me to work
IMAGES COURTESY OF PIXABAY
directly with the brain, but also take
care of patients in a way that’s hard to
do in other fields.”
In addition to practicing, Chang
conducts research as co-director of
the Center for Neural Engineering and
Prostheses, which is a collaborative
organization between UCSF and UC
Berkeley that focuses on developing
biomedical technology to help people
with neurological disabilities like
paralysis and speech disorders.
Over the last decade, Chang’s lab
intently studied the region of the brain
that controls the vocal tract. “What we
found was a map of the different parts of
the vocal tract and kinematic properties
that give rise to speech,” Chang said.
This neural code for every consonant
and vowel is composed of elemental
movements, such as the tongue moving
forward, that are very precise and highly
coordinated. With this newfound
knowledge, they sought to create a
device that could translate brain activity
into words. Thus, over the past decade,
Chang and his research group have
been working on a “neuroprosthesis”—a
device that can record and decode the
participant’s brain activity, then display
their “speech” on screen.
Helping to lead these efforts is postdoctoral
researcher David Moses,
whose interest in programming,
bioengineering, and their intersection
with medicine and neuroprosthetics
led him to the Chang lab. Thus began
the BRAVO (BCI—brain computer
interface—Restoration of Arm and
Voice) clinical trial, in which Chang and
his team enrolled their first participant,
BRAVO-1, to begin testing the potential
speech neuroprosthesis.
The neural implant, composed of 128
electrodes that record neural activity
from the surface of the brain, was
implanted in BRAVO-1 over the brain
region that controls the vocal tract.
Unlike the telepathic transmission
commonly depicted in sci-fi movies,
this technology relies on the patient
trying to engage in speech: the implant
detects these signals, which are then
analyzed. “This isn’t like mind reading
or any internal monologue… it has to
be controlled by volitional attempts
to speak,” Moses said. Alongside the
development of the hardware, Chang’s
research group primarily focused on
creating and programming the software
behind this new device.
In February of 2019, they implanted
the device in the patient’s sensorimotor
complex, which controls speech. Two
months later, BRAVO-1 began to attend
fifty data-recording sessions over a span
of eighty-one weeks. “[BRAVO-1] is an
incredible person and truly a pioneer.
Even though we had a lot of proof of
principle, there’s a lot of reasons it might
not have worked,” Chang said.
One such concern was that after the
patient had not spoken for over fifteen
years, there was no telling how much
information about his speech attempts
would be represented in the expected
part of his brain. During each session,
the participant performed many trials of
two different tasks: an isolated-word task
and a sentence task. Twenty-two hours of
data were collected from over 9,800 trials
of the former task, which involved the
participant’s attempts to say one word
from a predefined set of fifty common
English vocabulary words. In addition,
250 trials of the sentence task, in which
32 Yale Scientific Magazine October 2021 www.yalescientific.org
Neuroscience
FEATURE
R PARALYZED VOICES
SPEECH
the participant attempted to produce
word sequences from the same set, were
also performed. Both tasks helped the
researchers train, fine-tune, improve,
and evaluate their computational models.
Finally, the conversational variant of the
sentence task was implemented, in hopes
of demonstrating a real-time sentencedecoding
process. The participant was
first visually prompted with a question
or statement onscreen. Then, he tried to
speak in response to the prompt from a
predefined set of fifty common English
vocabulary words. The electrode arrays
in the implant detected and collected
the brain signals, which were then
sent and processed in real-time to the
computational processing system.
In the system, first, a speech detection
model identifies when the participant
www.yalescientific.org
has been attempting to speak. This
algorithm specifically detects the
onsets and offsets of the participant’s
word production attempts directly
from brain activity, limiting the
temporal window of relevant signals
analyzed in the later steps. Next, a word
classification algorithm predicts the
probability that each of the fifty words
has been attempted. However, this is
not as simple as identifying one signal
associated with one word. “There isn’t
one particular part of my brain that
only lights up when I’m saying just that
word,” Moses said. Instead, when we
pronounce certain words, our brain
relays signals to our vocal tract, which
then performs certain articulatory
gestures such as opening our mouths.
Thus, the brain activity processed by
the neural implant is not necessarily
limited to certain words or phrases,
but rather depends on the pattern of
articulations associated with each word.
A third algorithm yields the
probabilities for the next word in a
sentence given the previous ones. This
language model is based on English
linguistic structure; for instance, “I
am very good” is more likely to be said
than “I am very going.” Finally, the
predicted word or sentence is displayed
onscreen as feedback, demonstrating
the newfound possibility of “speech” for
the paralyzed patient.
Chang’s system better resembles
real-time speech in terms of accuracy
of communication and rapid pace,
achieving a median rate of 15.2 words per
minute decoded and a median word error
rate of 25.6 percent. The research team’s
next steps include replicating these
results in more than one participant: as
long as the patient is cognitively intact
and can attempt to produce speech,
this neuroprosthesis could potentially
be useful for people with a variety of
injuries or disabilities, interpreting
their brain waves and allowing them to
communicate once more.
However, while this device is certainly
ground-breaking, there are still some
limitations with the current system. “It
seems very unlikely that we could just
expand this current form to a thousand
words,” Moses said. The team intends
to keep working on modifications or
alternative approaches to their initial proofof-concept
to expand the neuroprothesis’
potential. The ultimate vision is some
kind of brain-computer interface that
is convenient, portable, and minimally
intrusive, with the ability to decode words
and sentences quickly, facilitating accurate
communication with the outside world.
“Now that we even have this initial
proof of concept, and this first shred of
evidence that this is feasible, it’s really
quite motivating to see how far we can
go with it,” Moses said. The researchers
describe this project as a unique
opportunity to tangibly help paralyzed
people reconnect and communicate with
the outside world, which the team finds
incredibly rewarding and is committed
towards pursuing. Ultimately, Chang
and his research team hope to restore the
individual’s voice—thereby reaffirming
both the patients’ autonomy and
fundamental connection to humanity. ■
A R T B Y J E S S I C A L I U
October 2021 Yale Scientific Magazine 33
UNDERGRADUATE PROFILE
ANNA B ALBRIGHT
YC ’23
BY SOPHIA BURICK
For Anna Albright (YC ’23), caring about our climate is a
way of life. It all began in her high school environmental
science class. As she learned about worrying phenomena
like the greenhouse gas effect and its feedback loops that melt
our ice caps, she couldn’t help but feel deeply frightened. “The
only way I could fight this feeling, fight the fear, was to think,
I have to be a part of the solution,” Albright said.
So, she got to work. Even before she
arrived at Yale, she threw herself
into climate activism.
She testified at the
Massachusetts State
Senate, spoke at
an MIT climate
summit, and
helped draft
the City of
Cambridge’s
climate goals.
At Yale, she
has made
it a mission
to continue
this work,
exploring her
activism in a
new dimension:
capital allocation.
Early on, Anna
discovered a great
interest in a rapidly
growing area of finance
called environmental, social, and
IMAGE COURTESY OF LAUREN CHONG
governance (ESG)-based investing. ESG- based
investing is centered around the idea that an investor should
weigh a company’s achievement of environmentally stable,
socially responsible, and internally ethical practices before
deciding to invest. Albright believes widespread implementation
of ESG holds great potential to galvanize fast and effective
positive change for our climate. “Trillions of dollars—tens of
trillions of dollars—move through the financial system each
year,” Albright said. “Even if you can get a portion of that to go
to better places, or you change the incentives around where it
goes, or you even change the standard morals or ethics about
what you can invest in—that really has an impact.”
She began her work promoting ESG at Yale with the Yale
Student Investment Group (YSIG). She was one of only
three girls in her YSIG class and, to her knowledge, the only
Environmental Studies major in the group. “My goal is definitely
two things,” she said. “Number one is to make sustainability
central to investment strategy and financial strategy. And
number two is to make these spaces more accepting spaces
for people who face a stigma about entering the industry.” She
became a YSIG board member her sophomore year, and has
been remarkably successful over the last few years in actualizing
both of her missions. With the help of another board member,
she made ESG a required component of every soft pitch given
in the group, and she’s proud to report the group’s newest
applicant class is fifty percent women. Next summer,
Albright will work as an ESG analyst for J.P. Morgan,
bringing her passion for sustainability in finance
to the corporate world.
Last fall, at the height of the pandemic,
Albright was inspired by an Intro to
Marketing course at the School of
Management to apply for a job unlike
anything she’d done before: a social
media manager position for the Yale
School of Public Health Instagram page.
“When I saw this job come up, I was
really excited, because I felt like there
was a lot of latent opportunity there that
Yale had not harnessed,” she said. Before
her arrival, the page featured mostly
student profiles and campus photos and
had less than two-thousand followers.
Albright knew the account could be so much
more—a place for the public to gain knowledge in
an accessible and fun way. “One, they were hungry
for information about Covid,” she said. “And two, they
were hungry for fun, digestible internet content. That’s
all they wanted.” With the help of her boss, Kayla Steinberg,
Albright began to radically change the account. They creatively
communicated essential information about public health during
the pandemic using trending memes and art that captured the
attention of thousands of Instagram users.
In the last year, the account’s reach has skyrocketed to over
fifteen-thousand followers, and they’ve received attention from
some uber-famous public figures. “Ariana Grande reposted one
of the posts, which was huge,” she said. In another instance, her
work (partially) inspired a student’s future. “A student tweeted,
‘I just decided I’m going to Yale School of Public Health. Not
going to lie, their memes had something to do with it,’” she said.
If there’s one running theme in Albright’s work at Yale and
beyond, it’s her passion for cutting through the apathy that so
often plagues society, from climate change to a global pandemic.
“The hardest step is getting past the apathy,” she said. “And when
you can do that, you can change people’s minds.” ■
34 Yale Scientific Magazine October 2021 www.yalescientific.org
ALUMNI PROFILE
ERIC Y. WANG
YC ’21
BY DAVID ZHANG
PHOTOS BY ALEX DONG
For Eric Y. Wang (YC ’21), photography has always been about
seeing things you would normally miss in daily life. And
throughout his four-year research career at Yale, Wang always
approached scientific problems the same way, looking for things other
people would normally miss. The approach has led him to countless
successes. Earlier this year, Wang was first author in a Nature paper on
autoantibodies and is now on his way to a MD/PhD at Weill Cornell.
Coming into Yale, Wang knew he wanted to pursue both research
and photography. Having done both in high school, Wang immediately
joined a lab as well as the Yale Daily News (YDN) during his first year.
Although his very first research project didn’t go as planned, Wang
used these experiences as valuable learning moments. “It was a good
experience because in science, things are bound to go wrong, even
in the best projects, and having that early experience of things not
working reinforced my desire to do research,” Wang said. “The fact
that I still wanted to do research after going through this experience
probably means I am really interested in it.”
During his sophomore year, Wang joined Aaron Ring’s (YC
’08) lab, hoping to have the opportunity to take on
his own project. “For me, what I
really wanted from a lab was
the ability to lead my own
project and take on
something for myself,”
Wang said. With
the support and
encouragement
of Ring, Wang
quickly translated
his passion for
research into
meaningful work,
taking charge
of a project that
would later become
the foundation for his
autoantibody publication.
Wang would spend two years
tirelessly developing novel technology capable of detecting
autoantibodies, something seen in many autoimmune diseases as
well as in patients with COVID-19.
When COVID-19 forced all the labs to close, Wang was able to make
the most out of his situation, remotely analyzing his screened COVID-19
patient samples, which eventually led to his publication. “Eric had a
totally fearless and gung-ho mindset where he got completely absorbed
in an interesting scientific question and was willing to take any approach
he could to address that question,” Ring said.
Wang’s drive was not only seen in the laboratory, but also in
the photojournalism work he did for YDN. Wang quickly rose
www.yalescientific.org
through the ranks, from contributing photographer his first
semester to photo editor by the beginning of his sophomore year.
For Wang, photojournalism was a completely different type of
photography than what he was
used to. “I came from a really
quiet suburb. Our [high]
school didn’t really
have a newspaper, so I
never really had that
exposure,” Wang
said. Nonetheless,
Wang used
photojournalism as
one of his ways to
stay connected to the
Yale community. Wang
documented a diverse
array of events at Yale,
from the opening of Benjamin
Franklin and Pauli Murray Colleges to the protests against a
shooting that involved the Yale Police Department in 2019. “It
was really cool seeing your photos being spread online,” Wang
said. “This was particularly true in the case of protests.
Photos from protests can be very powerful and moving and
can call people to action.”
Although photography and research might not
immediately seem to involve overlapping skills, the ability
to see the things others normally wouldn’t has helped
Wang get to where he is today in both of his passions.
When asked about his future plans and why
specifically he chose to pursue a MD/PhD, Wang
mentioned the unique perspective he will gain on human
diseases as a physician scientist. “When you talk about
things in science, you don’t really talk about the patients as
much. It’s very easy to get disconnected from what actually
matters—which for me is being able to help patients,” he said.
Research-wise, Wang hopes to continue growing as a scientist,
formulating important scientific questions and ideas so that one
day, he can start his own lab. Wang also hopes to continue his
love for photography and to take advantage of all the unique
features that New York has to offer through street photography.
His biggest advice for aspiring scientists? “Not to stress about
things like publications…it’s much more important to focus on
developing yourself as a scientist,” he said. Living by that advice,
Wang has been able to broaden his scientific knowledge and gain
a unique way of thinking that has helped him find success. ■
Editor’s note: Elsewhere in this issue, we covered Wang’s research
paper. See pg. 7.
October 2021 Yale Scientific Magazine 35
BREAKING BOUNDARIES
BY CHRISTOPHER ESNEAULT
Lying in my bed on a Saturday morning, I hesitantly opened my laptop to begin
watching David Attenborough’s latest documentary, Breaking Boundaries: The
Science of Our Planet. I say “hesitantly” because, while I am a huge proponent of
sustainable living and learning about how climate change affects us, I’m honestly not
a big documentary guy. While I have, no doubt, seen my fair share of An Inconvenient
Truth-esque films, sooner or later, they all begin to meld into one big, urgent,
overwhelming, ominous mess. However, after watching this riveting documentary, I
can say with full confidence that if you are someone who wants to learn more about the
ways in which humans have, quite literally, broken the boundaries of Earth’s climate,
biospheres, oceans, and atmosphere, then this is the perfect Netflix quick-fix for you.
Taking a much more climate-forward approach to education than his past
documentaries, David Attenborough starts off by introducing Swedish climate
scientist Johan Rockström. Rockström and his colleagues gained fame within the
scientific community recently when they hypothesized that there are nine boundaries
humans need to respect in order to keep Earth sustainable for human life. While we
currently live within the safe zones for five of the boundaries (freshwater use, ocean
acidification, aerosol pollution, ozone layer depletion, and novel pollutants like nuclear
waste), we have already surpassed four of the boundaries: climate change, land use,
biodiversity integrity, and biogeochemical flows of nitrogen and phosphorus.
The effects of crossing these boundaries can be seen most significantly by
the melting of the ice poles. However, scientists in the documentary also point
out that an increase in drought, wildfires, flooding, and even the onset of the
COVID-19 pandemic can all be tied back to our unsustainable living habits.
Their perspectives show us that this planetary crisis is a metaphorical
asteroid coming to Earth. We are reaching a point where ignorance of this
issue is simply unacceptable. Healthcare services have become overwhelmed,
entire ecosystems face collapse, and novel zoonotic diseases have been
transmitted to humans, all because of the climate disaster. If humans do not
act with responsibility and purpose, our planet will soon be uninhabitable.
After hearing about this incredibly overwhelming climate crisis, where do
you begin to tackle this problem on an individual level?
Watching this documentary is definitely a start. You can also join a club on
campus. If you’re interested in assuming a leadership role, think about applying
to be a Residential College Sustainability Liaison. When eating in the dining
halls, maybe swap out your cheeseburger for tofu tenders every so often, since
transitioning to a more plant-based diet is one of the single most important
ways you can reduce your carbon footprint. When possible, buy your clothes
second-hand, and walk or bike around. Continue to educate yourself about the
problems facing our planet and vote for environmentally conscious politicians.
With these actions in mind, we must now begin to act with a unified
purpose, in search of—as David Attenborough puts it—the perfect home. ■
TOP PHOTOGRAPH COURTESY OF HOUSE OF LORDS
BOTTOM PHOTOGRAPH COURTESY OF GERARD SIMMONS
SCIENCE IN TH
36 Yale Scientific Magazine October 2021
www.yalescientific.org
FUZZ BY MARY ROACH
BY NORVIN WEST JR.
PHOTOGRAPH COURTESY OF SCIENCE PHOTO LIBRARY
Animals—they are the lovable beings that are generally seen as allies to
humans, bringing joy and perspective to our lives. But what happens
when there is trouble in paradise—when animals and humans begin
to have conflict? And does nature handle it, or do we take it into our own
hands? Mary Roach, in her new book Fuzz: When Nature Breaks The Law,
analyzes this issue from a humorous and first-person point of view.
Roach demonstrates a beautiful case of nature facilitating cohabitation
between animals and humans in Aspen, Colorado. We’ve all seen animals
snooping for food, but according to Roach, the bears of this mountainous
town take it to another level. Here, residents don’t just find bears dumpsterdiving;
they find bears snatching food off dinner tables and hiding in the
rooms of houses. There is hope for the future though: laid-back bears, like
an infamous one nicknamed “Fat Albert,” are favored by natural selection
because they calmly carry out their food operations in such a suave manner
that homeowners can tolerate it. They are therefore more likely to get away,
survive, and pass on their calm temperaments to their offspring.
Roach finds a contrasting example in India’s more lethal, man-eating leopards.
Expert animal handlers have tried relocating them, but particularly aggressive
species are even more dangerous after being moved. Moreover, relocation would
likely create a dilemma over whether it is ethical to remove animals from their
natural habitats. To address this ostensibly unsolvable problem, scientists attempt
to control the density of these populations, rather than remove them altogether.
Elsewhere, Roach writes, humans are using molecular biology and
chemistry to alter the animals around them. Aaron Shiels, a wildlife
biologist, is working on an escape-proof habitat for mice, which would be
genetically modified to only produce male offspring. This would be done
with CRISPR technology, which targets a gene and cuts it out or replaces it.
In isolation, Shiels’s work would eventually lead to a less dense population
of mice. Additionally, a few US cities are trying a contraceptive on rats
called Contra-Pest, which uses 4-vinylcyclohexen diepoxide and triptolide,
two components that impact the reproductive viability of certain species.
People can also shift their mindsets when it comes to wildlife. On an individual
level, perceiving interactions with nature as an inherent part of life rather than
a burden could give people peace of mind. Perhaps we should remove ourselves
from animals’ natural habitats rather than the other way around. According to
Roach, people have invaded Bengali forests and turned elephant habitats into
their own, forcing the elephants to aggressively come into villages looking for
refuge. Indeed, sometimes we as people are our own worst enemies, villains to
the very animals we love and cherish. We mustn’t maliciously take advantage
of our manpower and intellect, but rather use it to facilitate human-animal
coexistence in a way that is mutually beneficial. ■
E SPOTLIGHT
www.yalescientific.org
October 2021 Yale Scientific Magazine 37
COUNTERPOINT
WHAT MAKES A HABITABLE PLANET?
BY NATHAN WU
IMAGE COURTESY OF PIXABAY
We all know how the story goes. A mysterious
spaceship is detected in the atmosphere. Humans
try to communicate with the aliens on it. Aliens are
hostile and attempt to conquer Earth. Pandemonium ensues.
The “alien invasion” trope and extraterrestrial beings in
general have been parts of movies, books, and other media for
decades, from H. G. Wells’s The War of the Worlds to the cult
classic film Independence Day to everyone’s favorite quarantine
video game, Among Us. The idea of encountering aliens has
captured our imaginations. However, in scientific communities,
the search for extraterrestrial life has yet to find success.
Traditionally, scientists have looked towards planets with
conditions like ours in their search for life. Whether a planet
has appropriate conditions for liquid water has been a primary
concern. These planets can neither be too close nor too far
from the star they orbit: this famed “Goldilocks” region is
usually considered to be the habitable zone for a star. An
additional constraint is that the models used to predict the
bounds of this region assume a small, rocky planet with an
Earth-like atmosphere filled with nitrogen gas, oxygen gas,
and carbon dioxide. However, two recent studies tell us that
we may not be looking in the right places.
Nikku Madhusudhan and his team at the University of
Cambridge proposed a new type of potentially habitable planet.
These planets, known as “Hycean worlds,” are composed of massive
oceans with surrounding atmospheres made mostly of hydrogen
gas. Madhusudhan’s team first explored the range of masses and
radii that Hycean worlds can take on and then determined the
range of temperatures (and, by extension, distances from various
stars) that allow for habitable Hycean surfaces.
Madhusudhan’s team found that Hycean planets offer several
advantages over Earth-like ones when it comes to the search for
life. Hycean worlds can be much larger than rocky, terrestrial
ones, and their thick atmospheres provide insulation that allows
for liquid water far away from a star: some “Cold Hycean”
planets may not need any stellar irradiation at all, with their
only heat source being internal. The increased range of sizes
and distances from a star that Hycean planets have could mean
that scientists can broaden their search for extraterrestrial life.
Meanwhile, Noah Tuchow and Jason Wright of Penn State
questioned the habitability of planets in the traditionally
defined habitable zone. They noted that, while the traditional
definition considers whether liquid water could exist under
current conditions, a planet’s habitability is dependent on
whether it has existed in the habitable zone ever since life there
began. Planets currently observed in a star’s habitable zone may
have entered the zone relatively recently, either due to changes
in a star’s luminosity or planetary migration. These “belatedly
habitable” planets are unlikely to gain the ability to host life: if
Venus somehow took Earth’s spot in our solar system, entering
the “habitable zone,” it would never regain liquid water.
Identifying the “belatedness” of a planet’s habitability is a
difficult task. It requires knowledge of both a star’s life history
as well as when and how planetary formation occurs. However,
while no simple model can tell us which planets we can ignore,
Tuchow and Wright’s research will guide future extraterrestrial
exploration. Considering belated habitability for planets may
change how we approach future mission design, as many planets
found in habitable zones will merely be belatedly habitable.
These two studies are challenging our traditional ideas of
what makes a planet habitable. Our current definition of the
habitable zone, centered around the possibility of finding
liquid water on Earth-like planets, ignores other types of
potentially habitable planets and fails to consider the impact
of stellar history on habitability. These studies teach us that
our initial conceptions about science are often false: life in
the universe need not look like life on Earth. Our current
definition for “habitable zone” may be less useful than we once
thought, and it may be time to reconsider it. Perhaps applying
a new definition will help us find those aliens we’ve fantasized
about for so long—let’s just hope they aren’t as hostile as those
in all the movies. ■
38 Yale Scientific Magazine October 2021 www.yalescientific.org
INTO THE NEWSROOM:
DAVID POGUE ’85
By Dhruv Patel
IMAGE COURTESY OF DAVID POGUE
David Pogue (YC ’85) is not your average CBS Sunday
Morning science and technology correspondent. He’s
written or co-written more than 120 books, given
five TED Talks, and has hosted twenty NOVA science specials
on PBS. All of this makes him uniquely qualified to provide
insight into what it’s like to communicate with the larger
public through media.
After graduating summa cum laude from Yale with a degree
in music, Pogue conducted and arranged Broadway musicals
for ten years. But on the side, he taught computer lessons.
Over a decade, his hundreds of hours of teaching clients—
including celebrities—how to use computers gave him a good
sense of what the average adult can grasp and how quickly they
can grasp it, a skill that would prove useful later in his career.
Pogue also wrote technology review articles on the side. An
impressed outgoing tech columnist at the New York Times
recommended Pogue to fill his position, where he remained
from 2000 to 2013. Pogue got his first break into covering science
and the environment when he was approached about hosting a
NOVA science special on PBS while at a talk he was giving. “We
had fun working together, so I started doing more shows for
them. The areas that they let me cover began to expand: first it
was tech, then it was tech and science, then it was tech, science,
and environment. So I gradually started doing more stories
on plastic in the ocean, and fracking, and the environment. It
gradually became part of my portfolio,” Pogue said.
Pogue is now a CBS Sunday Morning science and technology
correspondent. What he loves particularly about this position is the
creative control and liberty he has when presenting a story. “Being
able to choose my own story ideas, the ability to write my own script,
the ability to comment on the story as it’s being edited—these are all
luxuries you don’t get in other television,” Pogue said.
To cater science for the audience at home, Pogue relies on
his experience teaching computer lessons and writing books,
six of which have been of the popular For Dummies series. “I
like to imagine that it’s me from twenty years ago—before I
had gotten into the world of science and technology—in the
audience,” Pogue said. Keeping that thought in mind, Pogue is
cautious not to under-explain a concept. “I would much rather
be accused of over-explaining than shooting over the heads
of the audience. If the latter happens, the audience learned
nothing and the segment can be considered a failure.”
In Pogue’s mind, explaining key concepts, regardless of how
trivial they may seem, is a win-win situation: it allows those who
already know the concepts to feel smug about their knowledge,
but it also allows those who didn’t know this concept to learn
something new. This approach of building a segment while
keeping the audience’s perspective in mind, including their
ability to understand certain ideas, allows Pogue and his team to
effectively and adeptly convey scientific information to viewers.
Pogue acknowledges that there is still room for science
writers and reporters to improve. We are, after all, living in a
world where more and more people are becoming hesitant to
accept scientific findings. According to Pogue, there are two
causes of this suspicion. One is that recent scientific findings
are new and unfamiliar to many people; the second is that
modern science phenomena cannot be seen or observed by the
naked eye (e.g., the transmission of the COVID-19 virus from
person to person). As Pogue explains, the way to overcome
this fear is by relentlessly explaining the facts and significance
of these new findings with humor and entertainment value.
Importantly, Pogue mentions that science reporters and writers
must maintain empathy as well—because a person’s mind will
not be changed by facts, but by empathy and understanding.
As one of his favorite sayings goes, “People don’t care what you
know—unless they know that you care.”
Pogue doesn’t have a specific plan on what he’d like to do in the
future. He likes it when life presents a new opportunity. After
all, he didn’t plan anything that has happened in his career; he
simply said yes to the opportunities presented to him.
As for his advice to today’s scientific writers, Pogue mentioned the
necessity of pursuing your passion, trusting that things will turn out
all right. “Don’t wait. Don’t think that because you’re young, you can’t
do or become or start whatever you want,” Pogue said. ■
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October 2021 Yale Scientific Magazine 39
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