YSM Issue 96.1

Yale Scientific 

THE NATION’S OLDEST COLLEGE SCIENCE PUBLICATION • ESTABLISHED IN 1894 

MARCH 2023 

VOL. 96 NO. 1 • $6.99 

19 

A BOTANICAL 

MYSTERY 

12 

HELL PLANET 

WHY DOESN’T IMMUNOTHERAPY 

14 

WORK FOR EVERYONE? 

PLAQUE ATTACK 16 

A STARING SPELL 22

TABLE OF CONTENTS 

VOL. 96 ISSUE NO. 1 

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 

Sipping Up 

a One-Hundred-Year-Old Mystery 

Hanwen Zhang 

Since the Devonian period, xylem tissue arrangements in vascular plants have taken on a baffling variety of 

shapes before evolving to resemble the ones we see today. A group of Yale researchers have been working 

with scientists to reach the heart of the puzzle—and they’re pretty sure they have their answer. 

12 Hell Planet 

Brianna Fernandez 

Yale astronomers recently detected and characterized with cutting-edge precision a so-called "hell planet" 

55 Cancri e, an Earth-like planet that orbits near the very surface of its star, revealing new insights in 

processes of planetary system formation. 

14 Why Doesn’t Immunotherapy Work For 

Everyone? 

Abigail Jolteus & Emily Shang 

While many people positively respond to immunotherapy, there is still some resistance to this treatment. 

Researchers at the Yale School of Medicine have investigated why responses vary, specifically in patients 

with endometrial cancers, which could help improve the efficacy of immunotherapy for cancer patients. 

16 Plaque Attack 

Breanna Brownson & Connie Tian 

Yale researchers are currently investigating the efficacy of two Alzheimer’s drugs: aducanemab and 

lecanamab. This new generation of Alzheimer’s medication consists of monoclonal antibodies that target 

amyloid beta plaques in the brain to reduce cognitive decline. 

22 A Staring Spell 

Cindy Mei & Crystal Liu 

Previous studies of absence epilepsy have shown contradictory patterns in animal models and humans. In 

this study, researchers attributed such differences to experimental artifacts. They also identified different 

patterns of individual neurons during seizures, which could be promising therapeutic targets. 

2 Yale Scientific Magazine March 2023 www.yalescientific.org

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CAN WATER FREEZE IN A 

LIQUID STATE? 

& 

CAN A.I. DISTINGUISH ONE 

ARTIST FROM ANOTHER? 

By David Gaetano 

With the recent mania surrounding artificial intelligence 

(AI) and its capabilities both in creating art and identifying 

it, researchers are working to uncover hidden truths about 

Renaissance paintings. Experts believe they may have discovered 

concrete evidence of a previously unidentified Raphael painting. 

Professor of Visual Computing Hassan Ugail has developed AI 

technology capable of analyzing features of artwork imperceptible 

to the human eye. The AI system, known as a deep neural network, 

was trained for months in facial recognition and can compare 

aspects of a painting, including its texture and shading, to a 

database of previously analyzed pieces. 

This technology has been used to settle the long-disputed origins 

of the Brécy Tondo, a portrait of Mary and Jesus that possesses an 

uncanny resemblance to the Sistine Madonna, one of Raphael’s 

most famous paintings. While some experts believe the Tondo is 

a Victorian copy of the Raphael, Ugail’s technology says otherwise. 

With a similarity report of ninety-seven percent between the two 

pieces, this new evidence is hard to dispute. 

Although this technology has proved promising, it has sparked 

debate among experts. Those critical of the neural network’s ability 

believe that the technology is unable to consider the motivation 

behind the artwork—after all, would it be reasonable to conclude 

that Raphael created two nearly identical paintings? 

Ugail’s work provides a glimpse into what the future may hold 

for the field of art analysis. Though AI may not provide definitive 

answers to the Tondo’s origins, this technology shows just how 

diverse the applications of the neural network can be. ■ 

By Ignacio Ruiz-Sanchez 

The longstanding debate over which type of ice—cubed or 

crushed—is best to chill drinks is still largely undecided, 

but why are we limited to only two options? 

In a recent Science paper, researchers at the University College 

London (UCL) recently discovered medium-density amorphous 

ice (MDA), a form of ice with the same density as liquid water 

but that presents a glass-like appearance. Normally, when water 

freezes, the molecules crystallize into a hexagonal, solid structure, 

the most abundant form found on Earth. Since the early twentieth 

century, scientists have known about low-density and highdensity 

amorphous ice which both contain water molecules in a 

disordered arrangement. The former is created when water vapor 

freezes on a surface colder than -150 degrees Celsius, while the 

latter develops when normal ice is placed under high pressure 

at similar temperatures. Until now, however, medium-density 

structures were unknown. 

To produce MDA, the researchers used a ball mill tool to grind 

down standard crystallized ice. They placed the ice in a container 

that shook back and forth twenty times per second, exerting a 

pressure high enough to synthesize the unique structure. X-ray 

diffraction, which measures the crystallinity of solid structures 

as their electrons scatter X-rays, revealed that MDA had the same 

haphazard structure and density as liquid water. They discovered 

that this liquid was analogous to the water found in moons in 

our solar system, such as Jupiter’s Europa and Saturn’s Enceladus. 

Staying curious about the universe’s complicated relationship with 

water might ultimately unearth the possibility of life outside our 

little dome. ■ 


The Editor-in-Chief Speaks 

REDRAWING THE PERIMETER 

Science is accelerating faster than ever before. With recent innovations like 

ChatGPT reshaping the way in which we interact with the real and digital 

world, yesterday’s impossible is quickly becoming today’s norm. This 

rapidly expanding frontier highlights the integration of science into our 

daily lives, reminding us that research is rarely a pursuit for its own sake, but rather 

a deeply collaborative journey to better understand and improve human life and 

experience. Indeed, science is not an isolated singularity. It is—and will remain— 

an inextricable part of culture, politics, education, arts, and the humanities, woven 

into the very fabric of our society. 

In this issue, we examine how diverse disciplines contribute toward a 

dynamic, continuously evolving scientific and technological landscape. In 

physics, researchers have piloted rapidly firing lasers as a new way of diverting 

lightning compared to existing lightning rods (pg. 26). In neuroscience, new 

research questions the popular belief that oxytocin acts as a ‘love hormone,’ with 

implications for human socialization and conditions affecting bonding behavior 

(pg. 38). Our cover story explores how Yale research has uncovered the centuryold 

paleontological mystery of how the vascular system of ancient plants evolved 

to allow them to migrate from swamps and riverbanks to solid ground, leading the 

way for life to thrive on land (pg. 19). 

For the first time, the Yale Scientific has dedicated our special series of the year 

to redefining the boundaries between art, literature, and the sciences in a project 

titled “Perimeter,” inspired by Scientific American’s poetry column. Through 

creative non-fiction and scientific poetry, we hope to unite the precision and 

boundlessness of science with the beauty and imaginative potential of the written 

word. In issue 96.1, our Perimeter piece (pg. 39) is based on the discovery of ‘green 

pea galaxies’ using the new James Webb Space Telescope (pg. 30). The poem 

explores themes of personal growth and change as science has given us a greater 

capacity to ‘just look up’ than ever before. 

As always, I’d like to thank our masthead, student contributors, and mentors 

who make the Yale Scientific a reality. Thank you to Yale Departments, the Yale 

Science and Engineering Association, and the Yale Alumni Association for 

their continued support in helping us advance our mission of distilling complex 

scientific research into stories accessible to everyone. And, of course, I’m incredibly 

grateful to our readers and subscribers from around the world. Here’s to Volume 

96 and our upcoming year together! 

About the Art 

Alex Dong, Editor-in-Chief 

Researchers have identified key 

evolutionary characteristics of plant 

xylem that have allowed them to 

live on land and survive droughts. 

This cover illustration depicts the 

researchers surrounded by the 

wonders of plants as they uncover 

the mysteries behind their evolution. 

Catherine Kwon, Cover Artist 

MASTHEAD 

March 2023 VOL. 96 NO. 1 

EDITORIAL BOARD 

Editor-in-Chief 

Managing Editors 

News Editor 

Features Editor 

Special Sections Editor 

Articles Editor 

Online Editors 

Copy Editors 

Scope Editors 

PRODUCTION & DESIGN 

Production Manager 

Layout Editors 

Art Editor 

Cover Artist 

Photography Editor 

BUSINESS 

Publisher 

Operations Managers 

Subscriptions Manager 

Outreach Manager 

OUTREACH 

Synapse Presidents 

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Synapse Outreach Coordinators 

Synapse Events Coordinator 

WEB 

Web Managers 

Head of Social Media Team 

Social Media Coordinators 

STAFF 

Sanya Abbasey 

Luna Aguilar 

Ricardo Ahumada 

William Archacki 

Dinesh Bojja 

Risha Chakraborty 

Kelly Chen 

Leah Dayan 

Steven Dong 

Chris Esneault 

Erin Foley 

Mia Gawith 

Simona Hausleitner 

Tamasen Hayward 

Katherine He 

Miriam Huerta 

Sofia Jacobson 

Jenna Kim 

Catherine Kwon 

Charlotte Leakey 

Ximena Levya Peralta 

Yurou Liu 

Samantha Liu 

Helena Lyng-Olsen 

Kaley Mafong 

Georgio Maroun 

Cindy Mei 

Lee Ngatia Muita 

Lea Papa 

Hiren Parekh 

Himani Pattisam 

Emily Poag 

Madeleine Popofsky 

Tony Potchernikov 

Zara Ranglin 

Yusuf Rasheed 

Alex Roseman 

Ilora Roy 

Ignacio Ruiz-Sanchez 

Noora Said 

Alex Dong 

Madison Houck 

Sophia Li 

Sophia Burick 

Anavi Uppal 

Hannah Han 

Kayla Yup 

Krishna Dasari 

Mia Gawith 

Will Archacki 

Matthew Blair 

Jamie Seu 

Samantha Liu 

Anya Razmi 

Malia Kuo 

Ann-Marie Abunyewa 

Sydney Scott 

Kara Tao 

Catherine Kwon 

Jenny Wong 

Lucas Loman 

Dinara Bolat 

Tori Sodeinde 

Georgio Maroun 

Yusuf Rasheed 

Hannah Barsouk 

Sofia Jacobson 

Jessica Le 

Kaley Mafong 

Lawrence Zhao 

Anjali Dhanekula 

Abigail Jolteus 

Emily Shang 

Elizabeth Watson 

Keya Bajaj 

Eunsoo Hyun 

Jamie Seu 

Kiera Suh 

Yamato Takabe 

Joey Tan 

Kara Tao 

Connie Tian 

Van Anh Tran 

Sheel Trivedi 

Robin Tsai 

Sherry Wang 

Elise Wilkins 

Aiden Wright 

Elizabeth Wu 

Nathan Wu 

Johnny Yue 

Iffat Zarif 

Hanwen Zhang 

Lawrence Zhao 

Celina Zhao 

Matthew Zoerb 

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

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NEWS 

Biochemistry / Public Health 

LOST AMINO 

ACIDS 

EXPANDING THE 

GENETIC CODE 

BY JAMES HAN 

VERBAL 

AUTOPSIES HELP 

‘MAKE DEATHS 

COUNT’ 

GLOBAL EFFORTS IN 

MORTALITY SURVEILLANCE 

BY FAITH PENA 

IMAGE COURTESY OF PIXABAY 

IMAGE COURTESY OF WIKIMEDIA COMMONS 

Proteins, the molecular machines within a cell 

responsible for basic biological functions like 

maintaining structure and facilitating reactions, are 

made up of amino acids—a type of organic molecule with 

a specific domain that allows them to attach to one another 

like Lego blocks. Like the four bases of DNA which are 

common to all organisms on Earth, scientists have discovered 

twenty different amino acids, each with varying properties 

that allow for specific protein functions, that are conserved 

across all organisms, whether they are archaea, bacteria, or 

eukaryotes—the three domains of life. 

Recently, scientists have also discovered two other amino 

acids used by organisms to assemble proteins: selenocysteine 

and pyrrolysine. In a study published in the Journal of 

Biological Chemistry, a group of Yale researchers outlined 

a new family of enzymes that allows cells to integrate the 

latter amino acid into proteins. The authors were also able 

to pinpoint the time in evolutionary history in which the 

two families diverged, which they estimated to be before the 

three domains of life even emerged. 

“It’s quite amazing that cells can do so much with just 

twenty amino acids; by adding unnatural amino acids, 

we can expand the functions that proteins can have,” said 

Jeffery Tharp, the lead author of the study and a professor 

at the Indiana University School of Medicine. Studying 

the machinery cells use to add these noncanonical amino 

acids into proteins offers researchers powerful insights into 

engineering enzymes that can access the unique properties 

of other unnatural amino acids. ■ 

According to the World Health Organization, almost 

fifty percent of all deaths are unregistered. Autopsies 

aren’t performed in these cases, so the causes of 

these deaths go unrecorded. Ahmad Saleh MPH ’22, Ehsan 

Abualanain MPH ’22, and Madison Novosel MPH ’23 cofounded 

MakeDeathsCount (MDC) in response to these 

findings. What started as a project at the Yale School of Public 

Health has grown into a non-governmental organization 

(NGO) dedicated to increasing the amount and accuracy of 

causes of death (CoD) data globally through the logging of 

verbal autopsies (VAs). 

“In simple terms, a VA is a verbal interview of people close 

to the deceased about their symptoms to reach the same CoD 

as a typical autopsy,” Saleh said. “There are many preventable 

CoDs, but they are only preventable if the CoD is known.” 

MDC seeks to raise awareness of the insufficiency in the 

number of registered deaths and support NGOs who can 

conduct VAs in low- and middle-income countries where 

unregistered deaths are widespread. They currently work 

with HIS-Unit, a Syrian NGO, to pilot their first VA mortality 

surveillance project. Having reached their initial goal of six 

hundred interviews, MDC can analyze the data and supply 

mortality reports to the region. 

MDC is the only organization in the world focused on 

developing mortality surveillance, specifically through the 

use of VAs. Although the founders remain proud of this fact, it 

comes with plenty of challenges, and they are always looking 

for more support. They hope to expand their efforts globally 

with specific interests in Somalia, Colombia, and India. ■ 


Physics / Environmental Science 

NEWS 

RECOVERING 

LOST LIGHT 

SINGLE PHOTON DETECTOR 

AIMS TO UNVEIL NEW 

PHOTON STATISTICS 

BY STEVEN DONG 

ANIMAL 

ARCHITECTS 

HOW AN INTERCONNECTED 

ECOSYSTEM COULD HELP 

RESTORE FORESTS 

BY NEHA MIDDELA 

IMAGE COURTESY OF DR YIYU ZHOU 

IMAGE COURTESY OF FLICKR 

In quantum information science and quantum sensing, 

single-photon detectors play a crucial role in enabling 

various scientific breakthroughs and fundamental tests 

of quantum optics. While photon-number-revolving (PNR) 

detectors are considered the predominant tool for measuring 

light, PNR detectors today can typically only resolve up to ten 

photons at a time. 

To address this issue, the Tang Lab at Yale has developed an 

innovative on-chip detector that allows them to resolve up to 

one hundred photons with unparalleled accuracy, while also 

providing high-speed response times. With this new detector, 

they are able to uncover the statistical properties of photons 

from a true thermal light source—which emits light because of 

thermal radiation from its temperature, like an incandescent 

light bulb—at a level never seen before. 

However, creating the photon detector was a challenging 

process. The research involved complex chip fabrication 

processes, which included putting together multiple layers of 

semiconductors, superconductors, and optical circuits. Tang 

believes that this technology can be extremely powerful, and as 

quantum infrastructure continues to develop, he hopes that his 

photon detector can become accessible to regular researchers. 

With such promising results, what is the future of this 

technology? “In five or ten years, we could see the insertion of 

our detector technology in the commercial world,” Tang said. If 

researchers can leverage these advances in quantum technology 

to manufacture quantum devices in a more robust manner, 

Tang believes that it will play a remarkable role in making such 

devices more powerful than ever before. ■ 

In recent years, conservation and governmental 

organizations worldwide have devised new strategies 

for forest restoration, focusing on a variety of static 

metrics, including water flow and tree species composition. 

Yet existing research often misses a crucial, dynamic facet of 

these ecosystems that could be key to accelerating restoration 

efforts: seed dispersal by animals. A Yale-led team of 

researchers examining this process in the Barro Colorado 

Nature Monument in Panama has found that seed dispersal, 

particularly by large flightless animals, can greatly accelerate 

forest restoration efforts. 

Two factors made the Barro Colorado Nature Monument 

an ideal location for showcasing the beneficial effects of seed 

dispersal by animals—proximity to old growth forests and a 

ban on hunting since the 1970s, leading to a high population of 

large mammals. Additionally, since the Barro Colorado Nature 

Monument has been studied for over one hundred years, the 

researchers had a wealth of data about animal interactions in 

the area. “The areas we studied were next to large tracts of 

old growth forests with many dispersers, such as small birds, 

large birds, bats, and large flightless mammals,” said Sergio 

Estrada-Villegas, a lead author of the study. “This abundant 

community of animals was able to slowly go into these areas 

that were undergoing succession and regeneration and bring 

those seeds back into these areas.” 

In the future, the scientists will expand their dataset in order 

to compare Barro Colorado with other sites and further test 

their hypothesis. Through these studies, they will examine the 

role of these animal architects in other sites in the neotropics. ■ 

www.yalescientific.org 

March 2023 Yale Scientific Magazine 7

FOCUS 

Ecology 

TURNING OVER 

A NEW LEAF 

How spongy mesophyll 

maintains its 

mechanical stability 

BY JENNY LIU 

PHOTOGRAPHY BY EMILY POAG 

Picture a leaf: the image that comes to mind may be a 

rounded, green shape with lines running through it. 

But how did the leaf come to be? This imagery may be 

intuitive, but the development of the leaf itself has long eluded 

scientists. However, an interdisciplinary team of Yale researchers 

composed of biologists and physicists recently determined how a 

unique and niche structure, the spongy mesophyll, plays a crucial 

role in developing the structure of the leaves. Specifically, they 

explored how the movement of plant cells follows a transition 

from spherical, tightly-packed cells in early development to 

loose, porous networks in later stages while maintaining their 

mechanical stability. 

The team chose to explore the spongy mesophyll, which is 

the tissue that exists between the leaf top and the leaf bottom, 

because of its important role in performing photosynthesis. From 

a biological perspective, this material is extremely important in 

carbon sequestration. As sunlight hits the top of the leaf, carbon 

from the atmosphere is absorbed through the bottom layer. Once 

those processes happen, the light and carbon dioxide molecules 

react with the chloroplasts in the cells of the spongy mesophyll. 

This, in turn, creates glucose for the plant to provide them with 

energy to continue to grow. “So, from a plant biology perspective, 

this tissue is super important because it’s like a combination of 

the lungs and the stomach of the plant,” said John D. Treado, a 

physicist and lead researcher of the project. 

However, instead of focusing on the biological function, 

this study instead pivoted toward how the spongy mesophyll 

maintains its mechanical integrity. Unlike animals, whose cells 

can move around while the animal is still developing, plants can 

develop only through cell division and cell growth with no mobile 

cells. From a physical perspective, plant cells have a fundamental 

constraint on how they are able to grow. Furthermore, the cells 

grow in a densely packed manner. However, observational images 

and computer simulations of the spongy mesophyll revealed that 

it actually grows in a different way. “The tissue looks basically 

like a sponge,” Treado said. There are rather large spaces between 

the cells, which makes the tissue very porous rather than densely 

packed. How could this be sustained? 

To figure out this question, the team created computer 

simulations and varied different parameters to see which 

simulations were most similar to the images they collected of 

the mesophyll. They implemented certain growth rules based on 

deformable polygons that can change their shape in response to 

different stressors placed on them. As more pressure was placed 

on the cells, the boundary relaxed and expanded in response, 

which is how the network of mesophyll cells grows while keeping 

its overall formation. They found that the robust generation 

of pore space was due to a unique balance of the parameters 

of cell growth, adhesion, stiffness, and tissue pressure. The 

lack of contact with other cell boundaries made growth and 

remodeling of the cell wall possible. Additionally, cells needed 

to use the cell-cell adhesive strength to build networks and make 

sure that those networks did not bend too much, but rather 

formed rigidly. Thirdly, the pressure inside the boundary must 

be constant throughout. All this demonstrates that a complex, 

unique tissue such as the spongy mesophyll can be assembled 

through simple mechanical rules. 

The significance of studying spongy mesophyll is rooted in 

its exciting applications for climate science and environmental 

engineering. Not only does this tissue allow plants to capture the 

energy they need to grow further through photosynthesis, but 

it also provides a key substance needed for other organisms to 

continue growing and provide more life—oxygen. “The reason 

the atmosphere is so oxygen-rich is because life evolved this 

ability, millions of years ago, to convert the carbon dioxide in the 

atmosphere to oxygen,” Treado said. “All of the other organisms 

that were evolving at the same time realized that they could 

breathe the oxygen that was created by the plant.” In the future, 

the spongy mesophyll has the potential to advance research on 

creating synthetic plant tissues to help with carbon sequestration. 

Perhaps, instead of only envisioning a leaf, scientists may be able 

to create one too. ■ 


Public Health 

FOCUS 

CAN YOU TAKE 

THE HEAT? 

The impact of 

rising temperatures 

on marginalized 

communities 

BY MATTHEW BLAIR 

PHOTOGRAPHY BY JENNY WONG 

Extreme heat is something we feel acutely. Not to be 

confused with a sunny day, extreme heat describes those 

times when it is insufferably hot outside, when the heat 

sits heavy and stale, and the mere task of existing outside becomes 

a feat of endurance. As the earth warms, extreme heat 

events become all the more intense. Without the proper resources, 

this heat can be dangerous, and, in some cases, deadly. 

An individual’s response to extreme heat is impacted by various 

factors, ranging from socioeconomic background to the specific 

street someone lives on. As such, some populations—especially 

historically marginalized groups—are more at risk in events of 

extreme heat. Mitchell Manware and fellow researchers at the Yale 

School of Public Health were left unsatisfied by prior attempts 

to quantify heat vulnerability, noting that they failed to create a 

holistic image of one’s actual risk. Thus, they created a new heat 

vulnerability index (HVI), which builds on past systems, but, 

importantly, also takes into account one’s race, ethnicity, and 

broader socioeconomic background. 

This improved HVI covers a complex amalgamation of 

variables, all aimed at more fully capturing not only who is most 

vulnerable to heat, but also why someone is vulnerable in the first 

place. “The HVI combines many different variables, each having 

evidence to support its association with heat-related outcomes,” 

said Manware, the first author of the research paper in which the 

HVI was presented. These variables include environmental factors 

such as the average summertime temperature and the percentage 

of land covered by non-green space, as well as social factors like 

the percentage of the population that is Hispanic or Latino, non- 

Hispanic African American or Black, elderly, unemployed, or 

English-proficient. As a result, this index is comprehensive in a 

way that a heat index has never been before. 

On a scale from ten to twenty-six, the HVI creates a standard 

of comparison for heat vulnerability, quantitatively capturing the 

unique vulnerability of census tracts across the country. “The HVI 

allows one to compare, say, New York City to Miami by including 

such a wide, diverse set of variables,” Manware said. 


By creating this standard of comparison—using a range of variables 

considering more than one’s geographic location—Manware and 

his colleagues have created a tool that shines a critical light on 

systemic, environmental racism stemming from America’s past. 

Environmental racism in the United States, tied to a long history 

of redlining and current disparities in public services, is the idea 

that different racial and ethnic groups are disproportionately 

exposed to various environmental hazards—identifying where 

these inequities are most prominent is an integral use of 

this index. 

“Individuals across the United States were assigned a heat 

vulnerability index score based on which census tract they lived 

in, allowing us to calculate an HVI average for eight race and 

ethnicity groups,” Manware said. “The non-Hispanic African 

American and Hispanic or Latino groups had the two highest 

average HVI scores, showing, again, in the whole United States, 

not just in one city or in one census tract, that these communities 

of color are disproportionately vulnerable to heat.” 

Developing this index was about not only identifying the 

problem, but also providing a starting point to inform and 

motivate climate activism. “Creating a website that was publicly 

available, and interactive, is a way to try and translate research 

into practice,” Manware said. “We didn’t want this paper just to sit 

and exist in some database: we wanted it to be seen and used by 

elected officials and regular citizens alike.” 

As the earth continues to warm, taking steps to combat climate 

change and mitigate its effects will become increasingly vital. The 

HVI is a remarkable tool that lays the groundwork for the equitable 

implementation of climate change policy. “Given the scale and the 

inevitability of climate change, it will take a collective effort to 

do what we can to mitigate its effects and adapt to the changes 

that have already happened,” Manware said. It will indeed take 

a collective effort to address climate change, and it can only be 

the hope that as climate change policy is implemented, there is 

a concern for the equitable distribution of resources to offset the 

history of environmental inequity in the United States. ■ 


FOCUS 

Computational Biology 

SMELL YOU 

LATER 

Can flies smell the 

motion of odors? 

BY MAYA KHURANA 

PHOTOGRAPHY BY JACOB LIAO 

What lies within an odor plume? For humans, a fleeting 

smell of something, perhaps accompanied by a flash 

of color. The plume is barely discernible, and there 

are mere seconds before it dissolves into indetectable wisps. But 

for flies, odor plumes contain a fountain of information that help 

them navigate the world. 

It has long been thought that flies use the wind as their primary 

directional cue when navigating turbulent odor plumes to 

identify the source of the scent. This theory has led to a widely 

recognized insect odor navigation model known as odor-elicited 

upwind motion, where flies use the direction of the wind to 

orient themselves upwind and move in their desired direction. 

However, Nirag Kadakia and his colleagues in the Emonet and 

Clark Labs at Yale University have found that these flies are able 

to determine the direction of the odor itself. Kadakia combined 

his experience in mathematical modeling with his interest in 

the experimental work at the Emonet Lab to study this insect 

olfactory model. “Olfaction is key for insects,” Kadakia said. “It’s 

their primary sense of finding food, finding potential mates, and 

fighting competitors.” In his research, Kadakia characterized 

what navigational algorithms these insects use to maneuver 

through their environments. “This is a tricky problem because 

odor landscapes are very complex,” Kadakia said. Odor scenes, 

as they are also known, are not continuous, but instead appear 

in bursts with periods of clean air in between. So, how do insects 

work around the complexities of these landscapes? 

To find out, Kadakia and his colleagues used optogenetic 

stimulation on genetically engineered blind flies. Essentially, 

they used light as a fictive odor—a fake stimulus—to make light 

behave as an odor signal, allowing the presence of wind to be 

eliminated as a variable. The flies were genetically blinded to 

ensure that they did not visually perceive the optical stimulation 

in any way. “We can deliver very precise ‘odor signals’ on the flies 

and make the signals move in certain directions,” Kadakia said. 

What his team found was that flies can sense the direction that 

the odor moves, and they react to it largely in the same way they 

would if it were a wind signal. Additionally, they found that the 

flies not only respond to odor motion cues but that they can sum 

different motion cues. “It’s possible that the wind can move in 

one direction and the odors can move in a different direction… 

Flies are able to combine these directions and go against [their] 

vector sum,” Kadakia said. Thus, flies are able to respond to the 

sum of these direction cues to optimize their navigation. 

Interestingly, these researchers uncovered a similarity 

between the odor detection algorithm and the visual detection 

algorithm. “I think the coolest way we were able to show that 

was by [using] illusory stimuli,” Kadakia said. These stimuli do 

not occur in nature, but they do have a motion component that 

the researchers were able to use to study the parallels between 

the two systems. “We broke up motion into these statistical 

properties, and using that we were able to show that [flies] can 

detect motion using the same algorithm [as the visual system],” 

Kadakia said. He was also able to manipulate the illusory stimuli 

to do something else: move opposite to their natural direction. 

“We can play odor plumes backward to reverse the odor motion,” 

Kadakia said. This allowed the researchers to study how flies 

respond when the odor motion has been changed but the rest 

of the environment, including the wind direction, has remained 

the same. What they found was that flies had much more trouble 

getting to the source of the odor in those scenarios. “That’s 

because they rely on the natural motion of the odor to navigate 

properly. When that is perturbed, their navigation success 

is affected,” Kadakia said. While this research has important 

implications for current models of the olfactory system, it also 

has a more widespread impact. “Understanding how insects 

navigate can also help us understand how they spread disease,” 

Kadakia said. 

This research has opened new channels for the world of 

computation modeling to explore. “I’m hoping the biggest impact 

will be a deeper understanding of how similar computations can 

be in olfaction and vision,” Kadakia said. Since so much research 

has been done on the visual capabilities of flies, it can guide the 

way for olfactory research going forward. Clearly, there is more 

to odor plumes than meets the (undiscerning, human) eye. ■ 


Computer Science 

FOCUS 

THE 

VIRTUALIZATION 

OF OUR PAST 

Using modern technology to 

reconstruct an ancient city 

BY YAMATO TAKABE 

IMAGE COURTESY OF SANYA ABASSEY 

When walking through a museum or examining 

historical texts at Beinecke Library, true understanding 

starts when you can visualize yourself living in these 

civilizations, immersed in the local culture and embracing their way 

of life. However, due to natural erosion and looting, it is becoming 

increasingly difficult to enjoy physical archeological sites. One of these 

sites is Dura-Europos. Founded around 300 BC and located along the 

Euphrates River in modern-day Syria, Dura-Europos was a critical 

site for cross-cultural trade. This site boasts the earliest evidence of a 

house church, and there are inscriptions and graffiti written in Greek, 

Latin, Persian, and Hebrew because of its proximity to the Roman and 

Persian Empires. 

The city came to the attention of Western scholars in the 1920s 

when British soldiers in the area came across some of the wall 

paintings from Dura-Europos. In the 1930s, Yale archaeologists were 

part of a Temple that excavated the site. As a result, Yale University 

has one of the largest collections of artifacts and documents from 

the ancient city housed in the Beinecke Rare Book and Manuscript 

Library, the Peabody Museum, and the Yale University Art Gallery. 

However, Dura-Europos cannot currently be investigated due to the 

Syrian Civil War. How can we walk through the ancient bustling town 

and experience day-to-day life without ever physically visiting the 

archeological site? The answer lies in a magical collaboration between 

the past and the present. 

In 2007, Holly Rushmeier, John C. Malone Professor of Computer 

Science, came across thousands of field photos of Dura-Europos in 

the Yale Art Gallery. “I was interested in apply[ing] computing for 

preservation and documentation of local cultural heritage and using 

the photos to craft a digital representation of the society,” Rushmeier 

said. However, she ran into an issue with the images as they were far 

too grainy and sparse for automatic 3D generation that many modern 

phones can accomplish. Also, there was too much cross-institutional 

material and international research. She needed help to somehow 

piece the photos together based on location and relevance to map out 

the city as a whole. Fortunately, Rushmeier met Anne Chen who was 

a fellow at the ARCHAIA program at Yale and had all the expertise 

needed. Chen, now an Assistant Professor of Art History and Visual 


Culture at Bard College, had experience studying both Roman and 

Persian empires and an interest in implementing Linked-open Data 

to the site’s research. 

Linked-open Data is a Wikilink-like concept that brings together 

data and resources from all over the world into one platform and 

connects them based on knowledge webs. A way to categorize the data 

is through “Urban Gazetteering”—classifying architectural structures 

and cataloging them by location so they can be distinguished 

online. This process works at a macro-level. It differentiates between 

settlements and improves keywording so specific buildings can be 

easily identified across the various settlements around the world. 

However, it does not yet work at the micro-level, as they still need to 

distinguish similar sites across the street from each other in the same 

city. Similarly, excavation reports were inconsistent, so connecting 

them proved to be a big challenge. They still needed historians, 

linguists, and archeologists in the area, as well as data scientists to work 

together to parse information while making it available and accurate 

across many languages. 

With any Wikidata or database project, using more data improves 

the accuracy of the entire workflow. In the future, Chen and Rushmeier 

plan to integrate artifacts in Damascus that have not yet been 

accounted for. They also plan to implement more of Yale’s database of 

Dura-Europos into Wikidata and potentially use computer vision or 

AI to categorize the data more efficiently and accurately. Furthermore, 

they plan to improve view spaces to increase accessibility for interested 

researchers and the public. By expanding the public interface, more 

researchers can exchange original findings and view different 

interpretations to translate them for modern understanding. 

Most importantly, both researchers aim to make the technology 

available to everyone. “Lots of locals were interested in the site, 

but there was no information available in Arabic despite the site 

being viewed as a textbook example in the US,” Chen said. Oral 

traditions have materialized around the site and thus the naming 

conventions of the buildings are all varied based on local language. 

It’s their goal to make the new Linked-Open Data translated for all 

local users, so anyone and everyone can virtually walk through the 

ancient Dura-Europos. ■ 


FOCUS 

Astrophysics 

HELL PLANET 

An exoplanet’s discovery could help map planetary 

formation and migration 

BY BRIANNA FERNANDEZ 

PLANET 

Imagine if Earth’s orbit shrunk to 1.5 

percent of its current radius. The Sun 

would swallow the sky, temperatures 

would soar to devastating heights, and 

Earth’s surface would be completely 

consumed by oceans of lava. A year, or a full 

rotation around the Sun, would pass in 17.5 

hours—but you wouldn’t see its completion, 

as you’d never survive on the scorching 

surface at a temperature of two thousand 

degrees Celsius. This world, a so-called 

“hell planet,” exists forty light years from 

Earth, but its fiery exterior and apocalyptic 

atmosphere are not what make this burning 

alien world interesting. 

This planet, formally called 55 Cancri e, 

has an ultra-short period orbit, meaning that 

it essentially hugs its star as a full revolution 

takes under eighteen hours. The planet is 

known as a “super-Earth” since it is just 

larger than our home planet—except Earth 

orbits the Sun from a safe, habitable distance 

of ninety-three million miles rather than a 

shocking 1.4 million miles. Many extrasolar 

planets, or exoplanets, which orbit in close 

proximity to their stars are hot Jupiters: 

large, Jupiter-like planets that take under ten 

days to complete their orbits. Being so large 

and so close to their stars makes detection 

easy; the real challenge lies in detecting 

the smaller, Earth-like planets whose 

measurements are often drowned out by the 

noise from the stars they orbit. 

Armed with the EXtreme PREcision 

Spectrograph (EXPRES), an ultra-precise 

instrument that can make these difficult 

measurements, Yale astronomy researchers 

Debra Fischer and Andrew Szymkowiak are 

chasing otherwise elusive low-mass planets 

like 55 Cancri e. At first, astronomers thought 

the orbit was four times larger, as the blinkand-you’ll-miss-it 

nature of the orbit evaded 

proper study. But Harvard graduate student 

Rebekah Dawson accurately interpreted its 

signal, prompting recent Yale PhD graduate 

Lily Zhao to spearhead efforts to correctly 

characterize 55 Cancri e. By studying 

smaller planets of varying alignments and 

orbital distances, researchers can better 

understand how planetary systems form. 

But our current understanding is biased by 

our measurements of majority-large planets. 

Large, high-mass planets like those similar to 

Jupiter are easier to detect, so we have more 

data characterizing them, which is why we 

know the least about the smaller planets that 

make up the majority of planetary systems. 

EXPRESsing Precise Data 

EXPRES was developed by Fischer at 

Yale and installed at the Lowell Discovery 

Telescope at the Lowell Observatory in 

Flagstaff, Arizona. It uses the Doppler 

effect to detect planets based on the motion 

of their stars. As a planet orbits a star, it 

exerts a small gravitational effect. The star 

moves very slightly in response, shifting the 

frequency of its 

measured light. 

Scientists measure 

that Doppler 

shift using 

spectrographs, 

instruments that 

separate stars’ 

light into their 

component spectra. 

When the wavelengths 

of the spectra are bluer 

than expected, meaning 

they have shorter wavelengths, 

the star is being tugged toward us. 

Redder, or longer, wavelengths indicate 

movement away from us. These Doppler 

shifts can be described as changes in a star’s 

radial velocity, the measured motion of 

the star away from or toward an observer. 

Over time, radial velocity measurements 

can be used to determine properties of 

orbiting planets that are essential to their 

characterization, such as mass, orbital 

period, and distance from the star. 

Other instruments have detected 

thousands of exoplanets by the starlight they 

block as they pass between the star and its 

observer, but the resulting dimming from 

these transits only yields the radii of each 

planet. With the radial velocity method, 

researchers can also calculate how much 

it weighs. Using both mass and radius 

measurements allows them to determine 


Astrophysics 

FOCUS 

the planets’ densities. From this parameter, 

researchers can infer composition—in short, 

is it an ice planet or a rocky planet? 

However, radial velocity methods may 

produce data with large uncertainties due 

to instrumental interference, atmospheric 

effects, and intrinsic stellar variability, which 

could smother the near-imperceptible 

gravitational stellar effects caused by 

low-mass planets. EXPRES sought 

unprecedented radial velocity precision of 

a ten-centimeter-per-second Doppler shift, 

which is the motion that Earth induces on 

the sun as it orbits. 

When the project was first proposed, 

Fischer faced doubt from many 

prominent voices in the 

astronomy community, as 

they believed the stars’ 

large velocities would 

mask those of 

small planets. But 

she persevered. 

Today, EXPRES 

is able to detect 

Earth-sized 

planets at a 

precision of 

twenty to thirty 

centimeters 

per second, 

and other 

spectrographs have 

followed. “I think 

the performance of 

EXPRES emboldened the 

community to think, ‘Maybe 

we can get this precision,’ and it’s 

definitely worth doing,” Fischer said. 

And its precision will only keep 

improving. Newer spectrographs on 

bigger telescopes may push the precision 

to five to ten centimeters per second, and 

upcoming projects involving the James 

Webb Space Telescope and Habitable 

Worlds Observatory may provide the data 

to characterize hundreds more Earth-like 

planets. “They’ll be able to block out the light 

of the star, see the planets sitting around the 

star, and collect spectra of the atmospheres 

of those little pale blue dots. So this field will 

look back someday and laugh at how crude 

everything is right now,” Fischer said. 

55 Cancri e: A Hell of a Planet 

55 Cancri’s large, gaseous planets were 

among the first discovered outside our solar 


system, supporting the existence of multiplanet 

systems. Its large signal attracted 

astronomers as the study of exoplanets 

emerged in the late nineties. Using EXPRES 

data, Yale astronomers could detect and 

characterize the smaller planets in the 

system, uncovering more about planets with 

ultra-short orbital periods and the formation 

of their planetary systems, as EXPRES’ 

higher precision is especially valuable for 

understanding planetary architectures, or 

structures, of multi-planet systems. 

Knowing that Earth induces a tencentimeter-per-second 

shift on the Sun as 

it orbits, the EXPRES team modeled a tiny 

signal of just forty centimeters per second. 

The velocity signal is a function of the spin 

and angle of the star and indicates that 55 

Cancri e is a small planet that orbits its star 

along its equator. This signal would have 

been lost on most other spectrographs, 

highlighting the necessity of EXPRES’ 

precision in the search for low-mass planets 

such as super-Earths. 

55 Cancri e’s ultra-close orbit defies 

traditional models of planetary formation. 

Astronomers believe that small rocky planets 

form inside the ‘snowline’ of protoplanetary 

disks, which is the region within the dense 

gas surrounding a newly formed star (like the 

Sun) that is located near Mars in our Solar 

System. However, the current location of 55 

Cancri e is thought to be too hot for even 

rocky planet formation. Furthermore, its 

orbit doesn’t match the other known planets 

in the system. These clues suggest that the 

planet formed in a farther, cooler orbit and 

somehow migrated inward, altering its orbit 

as it neared the star’s equator. 

So how did it migrate in? Did 55 Cancri 

PHOTOGRAPHY BY DANIEL HAVLAT 

Dr. Andrew Szymkowiak next to a scale depiction of 

the spectrometer he helped construct. 

e gently spiral in and then find a parking 

spot relatively close to the star? Did it get 

gravitationally kicked in by other planets? 

Planet migration is a hotly debated topic 

in astronomical communities, and little is 

known. But the observation that this planet’s 

orbital plane is aligned with its stellar 

equator is consistent with a more gentle 

inward migration—which could occur as 

other material, dust, and gas exert a slow, 

dragging force on the planet—as opposed 

to a quick gravitational interaction, bringing 

researchers one step closer to understanding 

planetary migration and architectures. 

55 Cancri is particularly interesting 

because researchers already understand 

much about it, such as its five, tightly-packed 

orbiting planets, and now they are beginning 

to understand how planets in the system 

may have migrated. “Once we understand 

that as a sort of general principle, [that] it’s 

true that planetary systems are dynamically 

packed, then we can start to extrapolate 

about what that means for all of the worlds 

around the four hundred billion stars in the 

Milky Way galaxy. And then, the probability 

of life,” Fischer said. ■ 

A R T B Y B R E A N N A B R O W N S O N 

ABOUT THE AUTHOR BRIANNA FERNANDEZ 

BRIANNA FERNANDEZ is a senior in Pierson College studying Astronomy and Earth and Planetary 

Sciences. In addition to writing for YSM, they spent two years on the masthead as a copy editor and 

a layout editor. Outside of YSM, they research exoplanets and processes of planetary formation and 

advocate for incarceration-impacted individuals with the Yale Undergraduate Prison Project. 

THE AUTHOR WOULD LIKE TO THANK Emily Oldfield Debra Fischer and Andrew Szymkowiak for 

their time and enthusiasm in sharing their research. 

REFERENCES: 

Zhao, L.L., Kunovac, V., Brewer, J.M. et al. Measured spin–orbit alignment of ultra-short-period super- 

Earth 55 Cancri e. Nat Astron 7, 198–205 (2023). https://doi.org/10.1038/s41550-022-01837-2 

NASA Exoplanet Archive, operated by the California Institute of Technology under contract with the 

National Aeronautics and Space Administration under the Exoplanet Exploration Program. https:// 

exoplanetarchive.ipac.caltech.edu/overview/55%20cnc%20e#overview 


FOCUS 

Immunology 

Cancer subtype 

could be key 

WHY DOESN'T 

IMMUNOTHERAPY 

WORK FOR 

EVERYONE? 

BY ABIGAIL 

JOLTEUS & 

EMILY SHANG 

The cancer world 

is buzzing about 

immunotherapies. They promise to 

target cancer cells while avoiding healthy cells, 

a difficulty for many cancer treatments since 

cancer cells often originate from mutated 

healthy cells. So with six hundred thousand 

people in the United States still dying from 

cancer every year, why are these therapies 

either not working in patients or not offered to 

them? Immunotherapies have recently shown 

promising results—but only in a handful 

of cancer types—and even then, they seem 

to elicit different responses between cancer 

patients depending on individual variability. 

A new study completed in partnership 

between members of the Iwasaki Lab and 

the Santin Lab at the Yale School of Medicine 

analyzed data for endometrial cancer 

patients’ responses to immunotherapies. 

Immunotherapies are a type of cancer 

treatment that utilize the patient’s own 

immune system to fight cancer. Instead of 

using harsh substances such as chemotherapy 

or radiation to indiscriminately kill cancer 

cells, immunotherapy reactivates the body’s 

natural defense mechanisms to recognize 

and attack cancer cells. 

“Immunotherapy 

is this really exciting 

area of cancer treatment 

where we use antibodies or other kinds of 

drugs to manipulate the immune system into 

better targeting cancer and recognizing it as 

something that needs to be eliminated,” said 

Ryan Chow, an MD-PhD student at the Yale 

School of Medicine and first author of the study. 

A variety of different cancer immunotherapy 

approaches are actively being developed. Most 

clinical successes to date have been based on 

therapeutic antibodies that block specific 

proteins and receptors that allow cancer cells 

to evade the immune system. Other types of 

cancer immunotherapy include genetically 

modifying the patient’s existing immune cells 

to redirect them against tumors, as well as 

cancer vaccines that are analogous to those 

used for COVID-19 and other pathogens. 

“The idea of immunotherapy is that 

our immune system is very good at 

dealing with foreign pathogens, things 

like viruses or bacteria, but in a way, we 

can also think of tumors and cancers as 

being foreign because they have acquired 

alterations and mutations that make them 

different on a genetic level,” Chow said. 

While immunotherapies have improved 

survival rates for patients with certain cancer 

types, most patients do not respond to 

treatment. To date, the best response rates to 

immunotherapy have been seen in tumors 

with deficiencies in a DNA repair process 

called mismatch repair. Mismatch repairdeficient 

(MMRd) tumors characteristically 

accumulate very high levels of mutations, 

which in turn increases the probability 

that the immune system will successfully 

recognize the tumor as foreign. However, 

even among patients with highly-mutated 

tumors, less than half of patients will benefit 

from immunotherapy—a mystery that has 

long eluded scientists. 

“Though taking the brakes off the immune 

system can be really effective, when you do that 

there can be intense side effects such as organ 

failure, autoimmune diseases—this is not a 

drug without its problems,” said Tai Michaels 

'23, an undergraduate research assistant in the 

Iwasaki Lab and co-first author on the paper. 

Since the side effects of immunotherapy can 

be very severe, understanding why some 

patients are more or less likely to respond to 

treatment is key to maximizing the efficacy of 

immunotherapy while minimizing toxicity. 


Immunology 

FOCUS 

Two subtypes of tumors 

Yale researchers studied the effects 

of immunotherapy on patients with 

endometrial cancer, a type of cancer that 

starts in the lining of the uterus. The team 

looked at twenty-four participants with 

different molecular subtypes of endometrial 

cancer—either mutational MMRd tumors 

(mut-MMRd) or epigenetic tumors (epi- 

MMRd). Six of the patients were classified 

as having mut-MMRd, which means that 

the driving mechanism of the cancer is 

mutations in the MMR genes, and eighteen 

were classified as having epi-MMRd, which 

means the driving mechanism of the cancer 

is epigenetic changes that silence mismatch 

repair mechanisms. Epigenetic changes are 

reversible changes that alter the way cells 

‘read’ their DNA, but do not necessarily 

alter the DNA itself. 

All patients were administered an 

immunotherapy called pembrolizumab— 

an antibody that blocks the inhibitory 

immune receptor PD-1—to evaluate its 

efficacy. Normally, the PD-1 receptor acts 

as a safeguard to prevent immune cells 

from aberrantly attacking the body’s own 

cells. As tumors can take advantage of this 

inhibitory mechanism to evade elimination 

by the immune system, blocking this receptor 

through anti-PD-1 immunotherapy can 

unleash an immune response against tumors. 

The patients were treated with 

pembrolizumab every three weeks for up 

to two years. The researchers wanted to 

determine whether classifying patients 

by their mechanism of mismatch repair 

loss would allow them to better identify 

which patients are more likely to respond 

to anti-PD-1 immunotherapy. They 

observed that one hundred percent of the 

six mut-MMRd patients and forty-four 

percent of the eighteen epi-MMRd patients 

responded to the treatment, indicating 

that the mechanism of mismatch repair 

loss is indeed associated with the clinical 

effectiveness of anti-PD-1 immunotherapy. 

ART BY 

IVA KNEZEVIC 


“We used various sequencing techniques. 

Sequencing means trying to understand the 

DNA makeup of the cancer cells or looking at 

what kind of proteins or mRNA the immune 

cells are making, called [single-cell] RNA 

sequencing. By using a combination of the 

two, we were able to profile both the cancer 

and the immune cells in the same patients, so 

we can try to figure out after therapy, how the 

immune cells are reacting to certain types of 

cancer cells,” said Eric Song, an ophthalmology 

resident at the Yale School of Medicine and one 

of the lead senior authors on the paper. 

The researchers also looked at peripheral 

blood mononuclear cells (PBMC) from 

patients before and after pembrolizumab 

treatment using single-cell RNA sequencing 

and matched T-cell receptor repertoire 

sequencing—a method of tracking T cells, 

immune cells that attempt to recognize and 

kill cancerous cells, and their specificities. 

PBMC samples are composed of a variety 

of immune cells that circulate in the blood, 

including T cells and natural killer cells, two 

major cell types which can be involved in 

mounting anti-tumor immune responses. 

While the immune response in patients with 

mut-MMRd tumors was defined by T cells, 

that of patients with epi-MMRd tumors was 

instead characterized by natural killer cells. 

This led the researchers to conclude that the 

two molecular subtypes of endometrial cancer 

(mut-MMRd or epi-MMRd) are subject to 

different types of immune surveillance. This 

finding could, in turn, explain why patients 

with mut-MMRd tumors were more likely 

to respond to therapy, as the anti-PD-1 

immunotherapy pembrolizumab is usually 

thought to act on T cells. At the same time, the 

researchers also discovered that natural killer 

ABOUT THE 

AUTHORS 

cells from epi-MMRd patients demonstrated 

enhanced expression of many anti-tumor 

genes, suggesting that natural killer cells are 

the primary immune cells mediating antitumor 

responses in these patients. 

What's next? 

This study only analyzed twenty-four 

patients with one specific type of cancer, which 

raises the question of whether the conclusions 

would translate into a trend across other types 

of cancers and studies with larger patient 

cohorts. The researchers hope that the findings 

from this study could help inform further 

research on immunotherapies for various other 

cancers. Looking ahead, while this study was 

conducted on cancers with high mutational 

burdens, future studies could provide insight 

into cancers with variation in other factors— 

such as natural killer cell activation—and 

help improve the health outcomes of more 

cancer patients. “While mut-MMR patients 

had a uniformly high response rate, there was 

significant variation in response among epi- 

MMR patients which was not tied to mutational 

burden, suggesting that this was instead due to 

variation in other factors,” Michaels said. 

While Chow and Michaels worked together 

on data analysis and curation, Song and 

colleagues led the study conceptualization and 

data collection. Along with the Santin lab’s 

team, who designed and enrolled patients in 

the clinical trial, their contributions all came 

together in the end. “It’s such a big team effort; 

it’s not something that one person can do alone,” 

Chow said. As teams of scientists across the 

world continue in this vein, immunotherapies 

could continue to improve the health outcomes 

of more and more cancer patients. ■ 

ABIGAIL JOLTEUS 

EMILY SHANG 

ABIGAIL JOLTEUS is a sophomore in Berkeley College studying Ecology and Evolutionary Biology. In 

addition to writing for YSM, she is the web manager. Outside of YSM, Jolteus conducts research in the 

Konnikova Lab. 

EMILY SHANG is a Molecular Biophysics and Biochemistry major from the suburbs of Philadelphia. She 

has served as YSM’s website manager and staff writer since her first year. Outside of YSM, she’s interested 

in chess, the NYT mini, and fencing. 

THE AUTHORS WOULD LIKE TO THANK Tai Michaels, Ryan Chow, and Eric Song for their time and 

enthusiasm about their research. 

REFERENCES: 

Chow, R. D., Michaels, T., Bellone, S., Hartwich, T. M. P., Bonazzoli, E., Iwasaki, A., Song, E., & Santin, A. 

D. (2022). Distinct Mechanisms of Mismatch-Repair Deficiency Delineate Two Modes of Response to 

Anti–PD-1 Immunotherapy in Endometrial Carcinoma. Cancer Discovery, 13(2), 312–331. https://doi. 

org/10.1158/2159-8290.cd-22-0686 


FOCUS 

Pharmacology 

Computational Biology 

Plaque Attack 

New class of drugs joins the battle 

against Alzheimer’s disease 

By Breanna Brownson and Connie Tian 

Art by Sophia Zhao 


Pharmacology 

FOCUS 

Alzheimer’s disease (AD) is a 

progressive and devastating disease 

that affects more than six million 

Americans. This neurodegenerative disease 

is characterized by the deterioration of 

memory, cognition, and behavior to a 

greater extent than the memory loss 

typically associated with aging. AD involves 

the buildup of abnormal protein in the 

brain, forming beta-amyloid plaques and 

tau tangles. These protein aggregates are 

believed to cause the malfunctioning of 

neurons and the loss of neural connections 

that ultimately result in AD. 

In Alzheimer’s, the first areas of the brain 

to be affected are usually the hippocampus 

and the entorhinal cortex, both of which are 

crucial to memory formation. Over time, 

neuronal death can affect additional parts 

of the brain, causing brain tissue to shrink. 

Symptoms of the disease at different stages 

can vary, ranging from difficulty handling 

money to not recognizing loved ones or 

even forgetting how to eat, eventually 

progressing to total body shutdown. Given 

the immense toll of Alzheimer’s on both 

patients and their loved ones, research 

focused on treating AD has the potential to 

transform the lives of millions. 

Scientists do not fully understand what 

exactly causes neurodegeneration and 

cognitive decline. Thus, it is unlikely that 

a single drug could successfully treat all 

patients living with Alzheimer’s. Based on 

current knowledge that the brain produces 

less acetylcholine—an important brain 

chemical for memory and thinking—as the 

disease progresses, several cholinesterase 

inhibitors have been approved by the US 

Food and Drug Administration (FDA) to 

help manage symptoms in patients. These 

drugs, such as galantamine, rivastigmine, 

and donepezil, prevent the breakdown of 

acetylcholine and temporarily improve a 

patient’s quality of life. These drugs were 

the only available treatments until recently, 

in 2021, when the FDA approved the first 

AD drug—aducanumab—that targeted the 

underlying cause of the disease. 

With this development, scientists 

are now advancing the landscape of 

Alzheimer’s disease treatment with this 

new class of drugs that attack the disease 

at its source rather than just ameliorating 

symptoms. Recent clinical trials at Yale are 

studying monoclonal antibodies that target 

amyloid plaques. 

Drug Contender #1: Aducanemab 

Anita Huttner, director of the Yale 

Alzheimer’s Disease Neuropathology Core, 

obtained the first pathological evidence 

substantiating the impact of aducanumab 

to reduce amyloid plaque neuropathology 

in an AD patient. Aducanumab is a human 

antibody, or immunotherapy, that targets 

the protein beta-amyloid. Currently, 

aducanumab is sold under the brand name 

Aduhelm to treat patients with early-stage 

AD or mild cognitive impairment. The 

researchers hypothesized that healthy donors 

with no cognitive effects likely possessed 

immune systems that could successfully resist 

AD, so they used a process known as ‘reverse 

translational medicine’ to harvest antibodies 

from healthy donors and turn them into 

therapeutic antibodies. 

In a recent study published in Acta 

Neuropathologica, Huttner analyzed an 

eighty-four-year-old woman with moderate 

dementia who received thirty-two monthly 

doses of aducanumab before passing away 

in hospice. The patient was included in a 

multicenter trial of aducanumab organized 

by Huttner’s colleague Christopher van Dyck 

at the Alzheimer’s Disease Research Unit 

at Yale, which enrolled patients with earlystage 

Alzheimer’s disease and tracked their 

disease progression over time with amyloid 

positron emission tomography (PET) scans 

and cognitive tests. To determine the effects 

of aducanumab, Huttner analyzed the data 

collected over the course of the patient’s time 

in the study and from their final autopsy. 

Huttner’s autopsy of the patient who 

recently passed confirmed that aducanumab 

successfully reduced the size of amyloid 

plaques in the patient’s brain. “The results 

were very surprising,” Huttner said. “The 

effects were very significant. The antibody ate 

away at the fluffy periphery of the amyloid 

plaques, leaving a dense core behind.” 

This data corroborated the amyloid 

PET scans collected over the course 

of the patient’s treatment and 

provided substantial evidence 

supporting the therapeutic 

effects of aducanumab. As 

aducanumab has completed 

a phase three study in early 

AD patients, Huttner’s 

studies are a reason 

for optimism. 

However, Huttner cautions that there is 

still much work to do. “Keep in mind that the 

ultimate goal is not just to remove plaques, 

but also to prevent cognitive decline,” she 

said. The autopsy results show that amyloid 

plaques were decreased in the recently 

deceased patient, but they do not reveal 

the mechanism of the antibody’s action 

or why amyloid plaques lead to cognitive 

decline. Still, Huttner is enthusiastic 

about this first stepping stone towards 

better understanding AD pathology and 

developing an effective treatment. 

Drug Contender #2: Lecanemab 

van Dyck, director and founder of Yale’s 

Alzheimer’s Disease Research Unit, has 

been researching the ability of another drug, 

lecanemab, to slow cognitive decline in 

patients with early-stage Alzheimer’s disease. 

Following the recent publication of the phase 

III clinical trial results in the New England 

Journal of Medicine, the FDA granted the 

treatment accelerated approval. 

Lecanemab is an antibody that works by 

binding to amyloid beta protofibrils, which 

are small soluble protein strands that come 

together to form the larger insoluble protein 

fibers that form harmful beta-amyloid plaques. 

Lecanemab is thought to clear protofibrils 

from the brain, slowing the progression of 

Alzheimer’s disease. By reducing toxic forms 

of amyloid plaque buildup, lecanemab also 

decreases the number of abnormal tau tangles 

in the brain. “The difference between this and 

the originally approved drugs 

[for Alzheimer’s] back 

in the '90s is that 

those were 



FOCUS 

Pharmacology 

symptomatic 

therapies,” 

van Dyck said. 

“They were compensating 

for neurodegeneration rather than 

slowing it.” 

In a trial consisting of 1,795 participants, 

van Dyck and other investigators found that 

lecanemab reduced amyloid plaque in the 

brains of patients with early-stage AD, as 

well as led to significantly less cognitive and 

functional decline than a placebo for the 

eighteen months that the treatment was taken. 

When looking towards the future for 

lecanemab, van Dyck is excited to research 

the efficacy of lecanemab when given to 

participants with elevated brain amyloid 

who don’t yet have symptoms in the AHEAD 

Phase III clinical trial funded by the National 

Institutes of Health. “It’s all about going earlier,” 

van Dyck said. “Imagine how much time we 

might save somebody [with Alzheimer’s] with 

intervention before symptoms begin that 

then continues for several years of treatment. 

That’s very much the hope.” 

van Dyck credits a mixture of personal 

and intellectual motivating factors for 

his involvement in Alzheimer’s research. 

“I remember going to my grandparents’ 

fiftieth wedding anniversary when I was in 

college. I hadn’t seen them for two or three 

years, and when I said, ‘Hey, grandad!’ he 

responded, ‘Who are you?’” van Dyck said. 

van Dyck has spent his career studying 

degenerative diseases like Alzheimer’s 

from a patient-oriented standpoint. “I 

trained initially in psychiatry and really 

gravitated towards older patients with these 

cognitive disorders that were like a puzzle 

to diagnose,” van Dyck said. “Right out of 

residency and fellowship, I founded Yale’s 

Alzheimer’s Research Unit. At that time, 

no other researchers were interested in 

Alzheimer’s disease, so we had to build it 

from the ground up.” 

Fast forward to the present, 

van Dyck is now leading a 

massive research unit with studies 

ranging from neuroimaging 

investigations of AD to therapeutics 

trials, as has been the case with 

lecanemab. Pharmaceutical company 

Eisai is partnering with Biogen Inc. for 

the manufacture and sale of lecanemab as 

Leqembi, a drug delivered via intravenous 

infusion once every two weeks. 

The Verdict? 

Aducanumab and lecanemab are both 

antibodies targeting toxic aggregated forms of 

beta-amyloid proteins in the brains of patients 

with AD. Both exhibit promising results 

in their ability to reduce amyloid plaques 

in their clinical trials, but some patients 

in both drug trials have experienced side 

effects such as brain swelling and bleeding. 

Since amyloid protein is also deposited in 

vessel walls, its clearance by antibodies may 

compromise the blood-brain barrier, leading 

to temporary swelling. Sometimes, the 

swelling can cause small vessels to rupture 

leading to microhemorrhages in the brain. 

Larger hemorrhages are rare and unusual, 

and considering the fact that there are no 

existing treatments for patients with AD that 

actively target the disease itself rather than 

ABOUT THE 

AUTHORS 

just managing symptoms, the benefit-to-risk 

ratio may be favorable. 

van Dyck emphasized that both 

aducanumab and particularly lecanemab 

are are already being used as treatments 

for AD based on the success of these trials. 

“Most experts view lecanemab as the first 

unequivocally positive disease-modifying 

therapy for AD,” van Dyck said. He described 

lecanemab’s development as relatively smooth, 

contrasting it against that of aducanamab. “Its 

trials were fraught with complications and 

unfortunate circumstances,” van Dyck said. 

These issues included having to adjust dosages 

mid-study and having to prematurely halt the 

trials for presumed futility. 

Although the last decade of AD research 

has largely focused on the amyloid beta 

protein, the disease is much more complicated 

than plaques accumulating in the brain—there 

are many types of dementia and causes of 

cognitive decline. “The amyloid story is just one 

aspect of understanding Alzheimer’s disease,” 

Huttner said. It remains uncertain whether 

focusing on amyloid beta plaques is the best 

trajectory due to the complexity of the disease. 

Regardless, we are at the point where we can 

start analyzing the effects of aducanumab and 

lecanemab. The information from these trials 

has the potential to inform a new class of drugs 

and a new way of understanding Alzheimer’s 

disease pathology. ■ 

BREANNA BROWNSON 

CONNIE TIAN 

BREANNA BROWNSON is a sophomore in Morse College majoring in Molecular, Cellular, and 

Developmental Biology. Outside of YSM, Breanna serves as Vice President of United Against Inequities 

in Disease. She enjoys dancing and choreographing for Danceworks and Peristalsis, as well as playing with 

her cat, Mauna Loa. 

CONNIE TIAN is a senior in Hopper College majoring in Molecular, Cellular, and Developmental 

Biology. She currently conducts research in the DiMaio Lab at the Yale School of Medicine, focusing 

on engineering genetically expressible, small transmembrane proteins to facilitate the degradation of 

disease-relevant transmembrane proteins. Outside of YSM, she is involved in the Yale Club Soccer team, 

Community Health Educators, and Yale Undergraduate Science Olympiad. 

THE AUTHORS WOULD LIKE TO THANK Christopher van Dyck and Anita Huttner for taking the time 

to discuss their research in depth and for sharing additional resources that aided in the writing of this 

article. 

FURTHER READING: 

Plowey, E. D., Bussiere, T., Rajagovindan, R., Sebalusky, J., Hamann, S., von Hehn, C., Castrillo-Viguera, C., 

Sandrock, A., Budd Haeberlein, S., van Dyck, C. H., Huttner, A. (2022). Alzheimer disease neuropathology 

in a patient previously treated with aducanumab. Acta Neuropathologica, 144(1), 143–153. https://doi. 

org/10.1007/s00401-022-02433-4 

van Dyck, C. H., Swanson, C. J., Aisen, P., Bateman, R. J., Chen, C., Gee, M., Kanekiyo, M., Li, D., Reyderman, 

L., Cohen, S., Froelich, L., Katayama, S., Sabbagh, M., Vellas, B., Watson, D., Dhadda, S., Irizarry, M., Kramer, 

L. D., Iwatsubo, T. (2023). Lecanemab in early alzheimer’s disease. New England Journal of Medicine, 388(1), 

9–21. https://doi.org/10.1056/nejmoa2212948 


Ecology & Evolutionary Biology 

FOCUS 

Sipping Up a 

One-Hundred-Year-Old 

Mystery 

Discovering 

the drivers 

behind plant 

xylem tissue 

evolution 

By Hanwen Zhang 

Art by Courtney Johnson 

Like any great puzzle, the initial setup seemed deceptively simple. 

What two botanists noted at the 1920 Royal Society of Edinburgh 

meeting was just that: larger plants had more complex vascular 

systems. The bigger the plant, the more shapes its bundles of xylem 

and phloem would take on to exchange water with its root systems. 

Yet, as with all unsolved mysteries, the pair of scientists could not 

explain why this relationship existed. The scientific world would go 

on to assume that increasing vascular tissue complexity was nothing 

more than a morphological quirk of plant size, not considering that 

there might be an evolutionary layer to the problem. 

A recent study published in Science from the Brodersen Lab at the 

Yale School of the Environment might just have fit the pieces together. 

Through simulations, modeling, and paleobotany, they uncovered how 

certain vascular tissue arrangements could have offered the 

earliest plants a survival advantage as they migrated from 

the comforts of their watery habitats onto dry land. One 

century and two years later, we have an answer. 



FOCUS 


A Balancing Act 

The earliest forebears 

of plants today were 

likely a small and scraggly 

bunch—most fossil reconstructions give 

them the look of tiny, mushroom-like hairs 

rather than anything that remotely resembles 

a fern. But they faced many of the same 

challenges as their present-day descendants: 

accessing light, finding enough carbon, 

weathering droughts. At its heart, the struggle 

for survival is also about photosynthesis. 

“One of the core parts of how plants work 

is that they exchange water for carbon,” said 

Jonathan Wilson, professor of environmental 

studies at Haverford College and an author 

of the study. To acquire atmospheric carbon, 

plants must open their stomata. These tiny 

pores on the undersides of leaves release 

precious water vapor in exchange for the 

carbon dioxide in their environment. What 

follows is usually a tightrope walk of delicate 

tradeoffs: keep water sources steady, and you 

slowly deplete your carbon reserve; open a 

stoma too wide or for too long, and you might 

die from drought. 

There’s another catch: 

opening stomata also runs 

the risk of succumbing 

to another kind of slow, 

languishing death. In 

extremely dry 

surroundings, the 

atmosphere can 

pull from the plant’s 

exposed water 

reserves harder 

than usual. Water 

molecules would 

normally 

follow like 

a chain or 

rope, tugged along by 

hydrogen bonds. 

Yet in some 

instances, 

these hydrogen bonds 

can break to cause what 

Wilson explained as a 

‘cavitation’: a bubble of 

air within the vascular 

tissue. Like a clogged artery, 

the consequences are often 

fatal. This ‘embolism’ blocks the 

xylem, which is responsible for transporting 

water from the roots to the leaves, leading 

the obstructed parts to waste and wither 

away. Left unsolved, it only worsens. “These 

gas bubbles can spread through the vascular 

system where connections exist, which 

means that the connectivity of the vascular 

network becomes a key feature of drought 

tolerance,” said Craig Brodersen, professor 

at the Yale School of the Environment and 

principal investigator of the study. 

While some vascular plants—namely, 

trees—can either grow new xylem or 

dissolve the air bubble, this is not always 

an available option. “The tricky part about 

this is [that] in a lot of places, water stressinduced 

embolism is a limiting factor in 

plant growth,” Wilson said. 

Piecing It Together 

During their search through the early fossil 

records, the researchers noticed a stunning 

variety of patterns: there were xylem tissue 

cross sections that appeared like neat circular 

bundles, three-lobed stars, tapered lines, and, 

in other cases, haphazard U-shaped streaks of 

paint. “We see this diversity of arrangements 

early on in plant evolution, and then quickly 

that […] diversity gets kind of winnowed 

down a little bit,” Wilson said. 

By the time nature finished dry running 

its designs, most surviving species seemed to 

have undergone a sudden spike in vascular 

system complexity. Xylem cells arranged in 

the form of narrow, curled arcs or warped 

asterisks had somehow taken the place of the 

contiguously bunched circles. Something 

was afoot. 

Making sense of this problem required 

turning to a mix of math and microscopy. 

Some researchers including Wilson 

imaged fossilized plant stems from four 

hundred million years ago with electron 

microscopy. Another group simulated 

the evolutionary changes in the 

primordial xylem arrangement 

by incrementally adding nodes 

and branches to create complex, 

spiraling shapes that could approximate 

the kinds found in the fossil record. Others 

conducted experimental drought trials on 

currently existing plants to gather data for 

their models. 

The findings teased out a surprising 

advantage: xylem tissue arrangements that 

were more structurally complex fared better 

under drought stress. In the narrower, thinner 

groupings of vascular tissue, each xylem cell 

was surrounded by fewer neighbors and 

therefore less prone to embolism. Highly 

lobed, intricate xylem tissues offered fewer 

paths through which the embolism could 

spread. The simulation results suggested that 

advantageous xylem tissue arrangements 

could have potentially decreased plant 

mortality two-fold. 

A Glimpse Into The Past 

The intimate association between 

xylem shape and drought resistance 

reveals telling insight about the past. The 

team drew upon a wide range of species 

for their analysis, sampling everything 

from lycophytes—a plant lineage that had 

once spawned one-hundred-foot trees in 

cold swamps three hundred million years 

ago whose modern descendants are low 

creepers—to everyday ferns. 

Comparing the xylem shapes between 

past and present specimens showed an 

evolutionary trajectory shaped by an arc 

of drought resistance. Statistical analyses 

determined that the least droughtresistant 

xylem arrangements were found 

entirely among extinct Paleozoic species; 

even configurations that were fairly 

common among plants at the time are 

hardly seen today. 

“These plants [worked] very, very well 

for their environment. But we also find that 

some early land plants had vascular systems 

that would have allowed […] relatively mild 

drought events to harm them,” Wilson said. 

Xylem cells in sampled modern-day ferns 

have at most three neighbors. Among their 

Paleozoic predecessors, that number would 

have hovered closer to around four or five. 

In other words, the study suggests that some 

constant, evolutionary pressure has continued 

to shape xylem tissue arrangement. 

Species in reliably moist environments 

varied widely in their xylem arrangement. 

Only in xeric conditions—where drought is 

a constant, daily threat—did the researchers 



FOCUS 

come across plants with consistently 

resilient xylem arrangements. 

The findings dispel the age-old 

assumption of size and its inevitable 

complexity. The shapes of xylem tissue were 

not biological oddities or products of some 

unexplainable physiological rule of thumb. 

“There’s lots of different arrangements of a 

vascular system that could support larger 

plants,” Wilson said. “[But] the fact that 

we don’t see a uniform distribution of these 

strategies in plants [is] telling us that there’s 

an environmental selection on top of it.” 

The study instead suggests that there were 

real evolutionary advantages for having 

differently shaped xylems, and that xylem 

tissue shapes continue to be sculpted by 

the complex interplay of environmental 

factors: water supply, soil moisture, and 

atmospheric humidity. 

The project also gives us a window into 

an evolutionary period where even the 

slimmest of advantages must have made 

a difference. “Nobody had really looked 

at [xylem tissue] from this kind of ecophysiological 

perspective before,” Wilson 

said. Plants arrived on land anywhere 

from five hundred to seven hundred 

millions of years ago, but the first vascular 

organisms—most of the plants we readily 

recognize today—wouldn’t appear until a 

few hundred million years later. That leap 

from mossy bryophytes to stemmed plants 

posed formidable challenges: the earliest 

vascular organisms would have had to develop 

new modes of transporting water that went 

against the forces of gravity. The researchers 

also noticed that xylem tissue diversification 

coincided with the Devonian period, a time in 

which scarce levels of atmospheric CO 2 

would 

have forced these plants to negotiate the razorthin 

margins of survival even more rigorously 

than before. For the first vascular pioneers, the 

terrestrial world was an unforgiving one. 

“The main takeaway is that plants developed 

this complex inner plumbing, and it protected 

them from drought, and allowed them to 

colonize and spread on the land surface,” 

Wilson said. “We wouldn’t have vegetation 

on land, if plants hadn’t […] figured out these 

particular evolutionary strategies.” 

Towards The Future 

The team’s findings have immediate 

importance. Unlocking the secrets of 

xylem arrangement and water uptake 


could allow the agriculture industry to 

develop plants better prepared for an 

increasingly erratic climate. “We believe 

that by understanding how the earliest 

plants overcame the limitations of living 

on land. We can also better understand 

how plants will respond to drought in 

the future,” Brodersen said. 

But the sprawling, rich history of 

plant evolution cannot be distilled into a 

single study. The findings offer no more 

than a slice of the roughly 320,000 plant 

species that have since made themselves 

at home on this planet. Wilson expressed 

potential interest in comparing the water 

uptake processes found among their 

specimens of study to those of flowerbearing 

angiosperms, which connect 

ABOUT THE AUTHORS 

IMAGE COURTESY OF SCIENCE PHOTO LIBRARY 

A colored scanning electron micrograph of a dicotyledon rootlet cross-section. 

their xylem cells with special structures 

called pits. 

The researchers hope that their work 

offers just a start to decoding other 

evolutionary puzzles, too. Xylem tissue 

is, after all, only one trait among a vast 

selection of others. “I think everybody is 

in this collaboration is quite interested in 

thinking about interesting evolutionary 

novelties in plants,” Wilson said. 

For now, though, they close the onehundred-year-old 

puzzle with a fourhundred-million-year-old 

story. Plants 

effectively terraformed early Earth, 

but also changed themselves. They tell 

a story about the power to shape and 

be shaped, all the while tucking their 

heritage and history within themselves.■ 

HANWEN ZHANG 

HANWEN ZHANG is a junior in Benjamin Franklin College majoring in Ecology & Evolutionary 

Biology and English. He currently works with the Coughlan Lab, where he is phenotyping 

drought responses among the Mimulus flower genus. 

THE AUTHOR WOULD LIKE TO THANK Craig Broderson and Jonathan Wilson for their invaluable 

insight into their research. 


Bouda, Martin, et al. “Hydraulic Failure as a Primary Driver of Xylem Network Evolution in Early Vascular 

Plants.” Science, vol. 378, no. 6620, 2022, pp. 642–646., https://doi.org/10.1126/science.add2910. 


FOCUS 

Neuroscience 

A STARING SPELL 

THE MYSTERIOUS MECHANISMS 

OF ABSENCE SEIZURES 

BY CINDY MEI & CRYSTAL LIU 

ART BY AVA HOFFMAN 

It comes without warning: all motion halts 

and activity stills. Moments later, the 

world returns between blinks, all memory 

of the lost time gone. These staring spells are 

the hallmarks of absence seizures, which are 

brief episodes of unresponsiveness and loss 

of consciousness. Epilepsy, a neurological 

disorder that affects nearly seventy million 

people worldwide, is characterized by the 

occurrence of recurring seizures due to 

abnormal electrical activity in the brain. 

Absence epilepsy primarily presents in 

children, comprising ten percent of childhood 

seizures. They can occur up to several hundred 

times a day and prevent normal engagement 

in school and social interactions. Knowledge 

about absence seizures has evolved 

considerably with the help of neuroimaging 

techniques and computational methods. 

However, there are still many questions on 

the mechanisms by which absence seizures 

occur that Hal Blumenfeld, Yale School of 

Medicine professor of neurology and director 

of the Yale Clinical Neuroscience Imaging 

Center, and his lab seek to answer. “For 

years, we’ve worked on trying to understand 

the basic cellular mechanisms of what goes 

wrong during loss of consciousness in 

absence seizures because that’s been a puzzle,” 

Blumenfeld said. 

The Puzzle of Absence Seizures 

It is now understood that absence 

seizures are caused by abnormal rhythmic 

activity in the corticothalamic network, 

an interconnected circuit in the brain that 

regulates attention and cognitive processing. 

But some of the unexplained phenomena that 

Blumenfeld and his lab encountered were 

discrepancies in brain activity during absence 

seizures between children and animal models. 

Common techniques used to map seizures 

include functional magnetic resonance 

imaging (fMRI), a technique that maps 

the flow of oxygenated blood 

in the brain utilizing 

its different 

magnetic 

properties 

from 

deoxygenated blood, as well as 

electroencephalograms (EEGs), which 

measure electrical activity generated by 

neurons in the 

brain. 


Neuroscience 

FOCUS 

During absence seizures in children, the 

cerebral cortex typically shows a decrease 

in blood-oxygen-level-dependent (BOLD) 

signal on fMRIs and a repetitive spikewave 

discharge (SWD) pattern on EEGs. 

SWDs are the defining electrographic 

characteristic of absence seizures. However, 

previous experiments in animal models 

showed confusing results: studies instead 

observed an increase in cerebral fMRI 

signal which did not resemble the decreases 

seen in children. 

There were also major discrepancies in 

behavioral response between children and 

animal models during absence seizures. 

“Absence seizures interrupt an individual’s 

ability to respond normally to the 

environment, whether it’s something that’s 

simple and repetitive, like tapping on a 

button, or more challenging like responding 

to a specific stimulus,” Blumenfeld said. 

However, previous attempts to characterize 

such changes in animals failed because 

behavioral activities suppressed or 

interrupted seizures. “The problem is that 

nobody had ever tested absence seizures in 

an animal model where animals were 

in a state where the seizures wouldn’t 

be interrupted… the tasks that 

were used were very exciting for 

the animals,” Blumenfeld said. 

The pursuit to understand 

these discrepancies drove a 

five-year-long project led 

by Cian McCafferty, then 

a postdoctoral student 

in Blumenfeld’s lab and 

current lecturer and 

principal investigator in the 

Department of Anatomy 

and Neuroscience at 

University College Cork. 


Validating an Animal 

Model 

In their study 

published in Nature 

Communications, 

McCafferty and 

colleagues used a 

common model for 

absence epilepsy: 

genetic absence 

epilepsy rats 

of Strasbourg 

(GAERS). “As a 

rat model, the 

“We finally had a model that 

” 

behavior can be more easily interrogated 

than a mouse model. They are less prone 

to impulsive or hyper-aggressive behavior 

[than mice],” McCafferty said. 

Previously, fMRI scans of absence 

seizures had only been done on 

anesthetized animals, as the cold and loud 

fMRI machine generates a distressing 

environment. In this study, researchers 

were able to habituate the rats to the 

machine and record fMRI without 

anesthesia. “[McCafferty] would wrap 

them up like a little child, almost like 

swaddling a baby, to make them very 

comfortable,” Blumenfeld said. “And 

he would train them until they’re very 

calm and habituate them. So they’re at 

the point that they would be able to not 

move without any drugs or anesthesia 

and sit still for long enough to do an 

MRI scan… just like children do.” Unlike 

measurements from anesthetized rodents, 

a decrease in blood flow accompanied 

absence seizures in these rats, just like in 

children. The researchers then determined 

that previously reported increases in blood 

PHOTOGRAPH COURTESY OF HAL BLUMENFELD 

Cian McCafferty at his 'rig' in the lab where he conducted the majority of this work 

we could trust. 

flow were due to anesthesia rather than a 

characteristic of the seizure itself. 

Besides a new method for fMRI scans, 

this study also developed two behavioral 

tests that did not disrupt absence seizures. 

In one task, rats were trained to respond 

about once a minute to eighty decibel (dB) 

sound signals, around the volume of a noisy 

restaurant, by licking a sensor to receive a 

sugary water reward. However, this intensity 

kept the rats aroused and inhibited seizures. 

So, researchers lowered the intensity to 

forty-five dB, or average room noise, every 

few minutes, or upon detection of an SWD 

(signaling seizure onset)—whichever came 

sooner. This change allowed for seizures to 

occur and interrupt behavior. On average, 

rats responded to 88.2 percent of all sound 

signals before seizures but only 0.4 percent 

during seizures. 

In the other task, researchers trained 

rats to spontaneously lick at a spout by 

giving sugar rewards at random intervals. 

The average rate of licking decreased 

during SWDs, indicating that activity was 

interrupted. Licking recovered within a 


few seconds after SWDs ended. However, 

five percent of all seizures were “spared,” 

meaning that rats demonstrated at least 

one lick during SWDs. No rats responded to 

sound signals during a seizure as an auditory 

response was a more demanding task. These 

behavioral changes are consistent with 

observations in humans. “Just like children, 

the rats had a decrease of fMRI activity in 

their cortex and these changes in behavior. 

We finally had a model that we could trust,” 

Blumenfeld said. 

Measuring Neuronal Activity 

Once the model was validated, the group 

turned to investigating the underlying 

causes of absence seizures on the cellular 

level. In EEGs, they found for the first time 

an overall decrease in neuronal firing both 

at the surface and deep in the brain, which 

Blumenfeld hypothesized was most likely 

responsible for the loss of consciousness. 

They also discovered a decrease in neuronal 

activity a few seconds before SWDs started 

and a transiently higher activity at seizure 

initiation before the overall decrease again. 

In addition, they found that neuronal 

patterns were more rhythmic during 

seizures. During normal function, neurons 

encode information in varied firing 

signals. The increase in rhythmicity and 

loss of irregular firing, then, indicates that 

important signaling is lost. 

After discovering these changes in 

neuronal firing, the researchers went 

on to characterize individual neurons 

and discovered four different patterns of 

neuronal firing that contribute to the overall 

physiology of an absence seizure SWD. The 

majority of neurons decreased in firing, 

contributing to the overall lower activity. 

However, there are groups of neurons that 

show increased firing, some that have no 

change in firing, and some that display a 

transient increase in firing just before the 

seizure begins. “We think that the different 

neurons might be playing different roles in 

the seizure initiation and maintenance— 

in particular, the group of neurons with 

abnormal transient increase in firing might 

be critical for triggering the onset of the 

seizure. And identifying these can be very 

exciting to try to prevent the seizures from 

getting started,” Blumenfeld said. 

This study also reported systematic 

neuronal and behavioral changes forty to 

eighty seconds prior to seizure initiation, 

“We think that different neurons might be 

playing different roles in seizure initation 

and maintenance [...] identifying these 

can be very exciting to try to prevent 

the seizures from getting started. 

consistent with the directions of changes 

at seizure onset. Still, McCafferty remains 

cautious with these findings. “These 

changes are quite preliminary. One thing 

that would be interesting to see is whether 

those trajectories of behavior and EEG 

happen at other times when it doesn’t 

lead to a seizure,” McCafferty said. 

Toward Targeted Therapeutics 

McCafferty is interested in one day 

using these findings to predict and inhibit 

seizures. While there is still a long way to 

go from identifying a trend to establishing 

reliable predictive power, he believes 

that pre-onset changes may inform an 

algorithm to predict seizures in children 

with absence epilepsy. “Other people have 

suggested things that happen in a shorter 

period before the seizure starts that could 

lead to the seizure,” McCafferty said. There 

is robust evidence that sensory stimuli 

can prevent seizures and, in some cases, 

ABOUT THE AUTHORS 

” 

even stop them at an early stage. It may 

be possible to devise portable devices 

that detect neuronal changes and prevent 

an anticipated seizure or restore partial 

functionality after seizure onset. 

At the same time, Blumenfeld’s lab 

is working to determine the different 

neuronal cell types, including their genetic 

identities and how different groups 

connect to one another. These efforts 

will help develop targeted therapeutics 

for absence seizures. “Prior to relatively 

recently, it looked like things were going 

wrong in the whole brain all at the same 

time [during an absence seizure], so it’s 

really hard to figure out how to fix that. 

But if it turns out that there are only 

some neurons that you need to target to 

fix, that could facilitate the development 

of more targeted therapies,” McCafferty 

said. Maybe one day, equipped with 

targeted therapies and devices to stop 

seizures, scientists can eradicate these 

staring spells. ■ 

CRYSTAL LIU is a sophomore in Pierson College majoring in Molecular, Cellular and 

Developmental biology. Besides writing for YSM, she is part of a plant molecular biology lab, 

Chinese Undergraduate Students at Yale, and Club Jump Rope. 

CINDY MEI is a sophomore in Hopper College majoring in Neuroscience. In addition to writing 

for YSM, she is part of Yale Math Competitions, Yale DEMOS, and epilepsy research at the Yale 

School of Medicine. 

THE AUTHORS WOULD LIKE TO THANK Cian McCafferty and Hal Blumenfeld for their time 

and enthusiasm about their research. 


CRYSTAL LIU 

CINDY MEI 

McCafferty, C., Gruenbaum, B. F., Tung, R., Li, J.-J., Zheng, X., Salvino, P., Vincent, P., Kratochvil, 

Z., Ryu, J. H., Khalaf, A., Swift, K., Akbari, R., Islam, W., Antwi, P., Johnson, E. A., Vitkovskiy, P., 

Sampognaro, J., Freedman, I. G., Kundishora, A., … Blumenfeld, H. (2023). Decreased but diverse 

activity of cortical and thalamic neurons in consciousness-impairing rodent absence seizures. 

Nature Communications, 14(1). https://doi.org/10.1038/s41467-022-35535-4 


Materials Science 

FEATURE 

MAGIC MUSHROOMS 

3D PRINTING LIVING FUNGI 

People constantly anthropomorphize objects. We look at a chair 

with two buttons and a line and see a face. We bump into our 

dresser and apologize as if it had feelings. At the end of the day, we 

know they are not alive, but new research conducted by researchers 

at Eidgenössische Technische Hochschule (ETH) Zürich and Delft 

University of Technology could soon change this assumption. 

Professor Kunal Masania of Delft University of Technology and 

Professor Andre Studart of ETH Zürich, along with their colleagues, 

have created a 3D-printed material out of living fungi that has 

the ability to self-heal. “The most frustrating thing about making 

structural materials is that you are really limited by the design 

complexity that you can come up with, and biological materials don’t 

have that problem,” Masania said. 

Fungi contain mycelia, which are rootlike structures that grow 

underneath mushrooms and absorb nutrients from the soil. More 

importantly, mycelia can form a complex signaling network. The 

researchers mixed individual cells of this mycelia from the fungi 

Ganoderma lucidum into an ink called a hydrogel, which can 

then be fed into a 3D printer and used to create different types 

of structures. “When you let the structure grow, all these cells 

reconnect and form all of the signaling networks they had as a 

living organism before,” Masania said. 

This signaling network is what gives the material its remarkable 

regenerative and growing abilities. But how does it work? The answer 

lies with hyphae—elongated cells in mycelia that catch nutrients from 

the environment and expel waste. This process creates a chemical 

gradient that tells the organism where nutrients and space are, and 

thus where to grow. “That is really something special that you cannot 

do any other way, even with 3D printing,” Masania said. 

Currently, the material can heal gaps up to three millimeters across. 

However, the fungi on its own has been 

shown to fill gaps of ten millimeters or 

more in larger organisms, so there is 

room to improve. That improvement 

would come with more advanced 

work on the biological component 

of the material. 

The material’s lifespan is 

dependent on three factors: 

sugar, water, and space. But 

even without one of these 

requirements, the material 


BY MADELEINE POPOFSKY 

ART BY KARA TAO 

will not die—instead, it will go dormant. It is extremely resilient and 

can later be reactivated with the return of the missing requirement. 

The mycelia network was even able to survive accidental 

contamination in the lab, showing that it is strong as 

well as forgiving to researchers. 

This fungi material can be used for 

robotics—specifically soft robots, which are 

made of malleable skins as opposed to firm 

metal. Soft robotics is a relatively new field 

with exciting medical and industrial applications 

since they have increased range of motion and 

flexibility. The researchers created a robotic grasper 

that could pick up items and a rolling mechanism 

that would allow a robot to move. “It can protect 

the robot from the environment, but it can also 

protect the environment from the robot, and 

then it’s regenerative, so if it is damaged 

it will repair itself,” Masania said. 

Potentially even more exciting 

than the material’s regenerative 

properties is the potential to 

harness the mycelia’s chemical 

signaling mechanism in conjunction 

with artificial intelligence, which is 

the subject of the lab’s future research. 

By placing electrodes on the material, the 

action potential (a change of voltage across a membrane) produced 

by the chemical signaling can be recorded, similar to those created by 

neurons in our brains. The goal is to separate the chemical signaling 

caused by the normal biological processes of the organism and those 

specifically caused by environmental triggers. 

By separating out the signals caused by environmental triggers 

such as fungi growth from its sensing of nutrients, the researchers 

would be able to use these signals to collect environmental data, 

such as the locations of such nutrient sources. Moreover, they 

could play back these signals to the organism to gain control of 

its functions. For instance, researchers could replicate the signal 

for nutrients in a certain part of the material, causing the mycelia 

to grow in certain directions—essentially brainwashing a living 

organism to do their bidding. 

Your fridge may not have feelings just yet, but a world full of soft 

robots with self-healing, growing, living skin may be on the horizon. ■ 


FEATURE 

Physics 

CATCHING LIGHTNING 

RAPID-FIRE LASERS DIVERT LIGHTNING STRIKES 

For the first time, scientists have successfully used lasers 

to divert lightning in real-world experiments. During the 

summer of 2021, a team of around twenty-five scientists used 

a rapid-firing laser to redirect lightning, moving it more than fifty 

meters. Their results will pave the way toward improved lightning 

protection for airports, launchpads, and other large infrastructures. 

During storms, charges accumulate in clouds. When this buildup 

becomes too large, there is a rapid discharge of electricity, 

called lightning. Classical metal Franklin lightning rods provide 

a preferential channel for the discharge to reach the ground. This 

way, they guide lightning away from houses and small structures. 

“They protect roughly an area with a radius corresponding to their 

length,” said Aurélien Houard, a researcher at École Polytechnique 

in France and the leading author of the Nature paper detailing the 

team’s results. However, Franklin rods rarely protect areas with a 

radius greater than thirty meters. “What we want with the laser is 

to increase the range of protection,” Houard said. 

Much like a Franklin rod, lasers create a preferential channel for 

lightning. The difference is that they do so using air rather than 

metal. When a high-intensity laser is fired rapidly enough, it heats 

up the air in its path and transforms it into plasma by turning the 

gas particles into charges. This phenomenon creates a tunnel with 

very high conductivity through which lightning can travel. The 

biggest advantage is that lasers can reach higher in the sky than any 

metal rod and can point in multiple directions. 

Guiding lightning with lasers was first achieved in the lab over 

twenty years ago. But diverting lightning by two meters in a 

controlled laboratory setting is child’s play compared to doing it 

over tens of meters in an unpredictable storm. Calculations and 

simulations showed that only rapid-firing lasers would reproduce 

the lab results in the real world. “Although it worked on paper, 

we had to convince someone to build that laser up for us,” said 

Jean-Pierre Wolf, professor of physics at the University of Geneva. 

“When I was at Yale [on sabbatical] in 2000, I was already talking 

about lightning control with lasers. It’s been a very long-term 

project.” It was only six years ago that new laser technology and 

funding sources came together to create a laser capable of firing 

at the necessary one thousand pulses per second at an intensity of 

roughly one terawatt, or one million million watts. 

French, Swiss, and German scientists came together in a highly 

collaborative research team determined to show the capabilities 

of the laser. They chose a telecoms tower at the top of Säntis 

Mountain in Switzerland, a location with a high rate of lightning 

strikes, equipped with multiple sensors for accurate lightning 

measurements. During six hours of operating the laser in 

thunderstorms, they recorded four successful lightning redirection 

events. Out of these, only one happened in good enough conditions 

to be recorded by high-speed cameras. The footage showed that the 

lightning strike followed the plasma conductive channel created by 

the laser over a fifty-meter distance. 

Working with lightning in the field is challenging because of 

its unpredictability. On top of that, the research team couldn’t 

use the laser at all times. “When the air traffic was very heavy, 

in the morning, for instance, we weren’t allowed to shoot,” Wolf 

said. “We were lucky to have four events where the laser was on, 

and everything was operating correctly.” Ideally, the research 

team would have tested the different wavelengths the laser can 

emit: infrared, visible green, or ultraviolet. But due to their time 

constraints, the team only tested infrared radiation. 

Ultraviolet light ionizes the air more easily but does not travel 

as well through the air, while infrared radiation has the opposite 

characteristics. Both Houard and Wolf are optimistic that green light 

would be the best option. “We would also need to better characterize 

the ability of the plasma to trigger and guide lightning. All of these 

parameters are not very well known,” Houard said. After all, this 

project was only a demonstration experiment. “We would need 

much more experimental characterization before we can really claim 

that we can protect a large area with this [system].” 

Despite the promise of increased lightning protection, it could 

be anywhere between five and fifteen years before this project 

comes to fruition. Scientists are essential for these first steps of 

characterization and optimization, but it will be an engineering 

challenge to create compact and cost-effective laser-based 

technology for lightning protection in the future.■ 

BY XIMENA LEVYA PERALTA 

ART BY KARA TAO 


Environmental Science 

FEATURE 

CLIMATE CHECKMATE 

BY KELLY CHEN 

AIR POLLUTION HINDERS CHESS PLAYERS’ PERFORMANCES 

When the World Chess Championships occur, everything is 

accounted for—the weight of the chess pieces, the matte 

of the chess board, the indoor noise levels, the number of 

arbiters and broadcasters—ensuring that the best chess players in the 

world can play at the top of their game. But scientists have discovered 

a confounding factor that competitions don’t account for, something 

that people can’t even see: air quality. Many studies have already 

been performed to corroborate the negative impacts of outdoor air 

pollution on the human mind, but new research suggests that the 

buildings we spend our days in may not actually keep out these 

harmful particles. Steffen Künn and Nico Pestel from Maastricht 

University as well as Juan Palacios, Head of Research at MIT’s 

Sustainable Urbanization Lab, have studied just how badly indoor 

air pollution can hinder strategic decision-making by looking at the 

game of chess. Chess is a game of constant strategic decision-making 

where all players are gathered in one location, making it an ideal way 

to explore the impacts of air pollution on people’s cognitive abilities. 

The data included over thirty thousand chess moves from three 

different chess tournaments in Germany from 2017 to 2019. Players 

in the tournament were given a total of 110 minutes to make the 

first forty moves, with additional time for moves past the fortieth 

move. Air quality data measured the concentration of PM 2.5 , or fine 

particulate matter with a diameter smaller than 2.5 micrometers, 

from three sensors installed in the tournament venue. PM 2.5 can 

enter the lungs and bloodstream when inhaled, leading to harmful 

effects on the body. 

Each chess move was analyzed independently by an artificial 

intelligence chess engine for optimality and errors based on the 

configuration of the chessboard. Overall, it was found that when 

chess players are exposed to high levels of air pollution, they make 

more erroneous moves. Other confounding variables such as time 

of day, temperature, traffic jams, indoor carbon dioxide levels, and 

the impact of the opponent’s errors on the observed player were 

explored to ensure that there were no other factors that could have 

caused these effects. 

The researchers also found that air pollution has an increased 

effect on chess players when they are under stricter time pressure. 

In an evenly matched game, the last moves they make become the 

most crucial for the players, but also the most time-intensive. “Air 

pollution hits the hardest on cognition when good moves are needed 

the most,” Palacios said. Strategic decision-making is highly utilized 

in chess, but also in everyday life and careers. From managers to 

workers to students where day-to-day work requires intense cognitive 

thinking and decision-making, it’s concerning that their decisions 

could be negatively influenced by environmental factors, especially 

when these decisions could result in long-term consequences. 

This study is one of the first to explore indoor air quality and 

the effects it has on cognitive thinking, and there is great potential 

for future research in this area. “We are still in the infancy of 

understanding what the costs are of indoor air problems,” Palacios 

said. A federal report done by the Governmental Accountability 

Office found that forty-one percent of public school districts in the 

United States need to update or replace the heating, ventilation, and 

air conditioning (HVAC) systems in over half of their schools. If 

skilled chess players are led to erroneous decisions because of indoor 

air pollution, we can only imagine how poorly ventilated education 

buildings are affecting the learning of students worldwide. 

Unsurprisingly, worsening outdoor air pollution is correlated 

with worsening indoor air pollution. More research is necessary to 

examine how we can construct and upgrade buildings to protect us 

from harmful particulate matter. “[We need] better understanding 

of the indoor environmental conditions on humans and [we need 

to use this understanding] to protect us against climate change and 

environmental hazards in the United States and beyond,” Palacios 

said. We could be getting close to the climate endgame—hopefully, a 

victorious checkmate is still in sight. ■ 

ART BY 

HANNAH SHI 



FEATURE 


TINY TRANSFORMERS 

DESIGNING SHAPESHIFTING ROBOT WORKERS 

BY LEE NGATIA MUITA 

Fans of the cult classic film franchise 

Terminator remember the iconic 

scene where the evil robot T-1000 

easily passes through a metal grate 

by partially turning into liquid. Well, 

machines can do that now, and they 

don’t have to be evil! Researchers from 

Sun Yat-Sen University, The Chinese 

University of Hong Kong, and Carnegie 

Mellon University have created a robot 

that can turn from solid into liquid and 

vice versa, at will. 

The scientists drew inspiration for this 

innovation from the most mysterious of 

places: the ocean. The unassuming sea 

cucumber has a remarkable ability to 

rapidly change its stiffness to adapt to 

its environment. To do so, the animal 

internally manipulates the millions of tiny 

fibers embedded within its tissues to link 

together in a tight mesh for hardening, 

and unlink for softening. 

The sea cucumber employs this tactic 

in many ways, including stiffening to 

navigate hostile environments that would 

otherwise pierce and tear soft tissue, and 

softening to move through obstacles and 

fit into efficient hiding spots. Scientists 

were especially inspired by the sea 

cucumber’s ability to fit through tight 

spaces and sought to develop this process 

for use in machinery. 

In order to replicate this ability, 

scientists used magnetoactive liquidsolid 

phase transitional matter, which is 

a magnetic substance that can quickly 

switch between liquid and solid states. 

Since the process of changing states 

between solid and liquid is tied to 

temperature, the scientists had to find a 

metal that melted and froze at relatively 

warm temperatures. They chose gallium, 

which is a nonmagnetic metal that melts 

at 29.8 degrees Celsius. This means that it 

is a solid at room temperature and exhibits 

the strength typical of a solid metal, but it 

melts when held in your hand for a while. 

Once they had fast-transition matter, they 

had to turn it into a responsive machine. 

This next step was done by embedding 

ferromagnetic neodymium-iron-boron 

microparticles into the internal structure 

of gallium. These micromagnets were 

held in fixed positions by the strong solid 

matrix of gallium so they all synchronized 

appropriately with the magnetic field. 

This process produced a gallium alloy 

that could respond to magnetic fields 

and enabled the researchers to control 

its movement. These magnets and the 

physical properties of gallium contribute 

to most of the functionality of the shapeshifting 

robots. 

In its solid state, the shape-shifting 

machine is very responsive to magnets and 

can easily be controlled by manipulating 

the magnetic field around it. These 

properties allow the machine to move 

through a given path, jump over obstacles 

and move up to speeds of 1.5 meters per 

second. When the machine encounters a 

space too narrow for a solid, it turns into a 

liquid through internal heating that melts 

the gallium. 

This heating is achieved by manipulating 

the magnetic field around the machine to 

cause its micromagnets to form a specific 

pattern that induces a current within the 

metal. This current encounters resistance 

as it flows through the robot, causing it 

to produce enough heat and raising the 

temperature to about thirty-five degrees 

Celsius, which is above the melting 

point of gallium. This process, known 

as electromagnetic induction, enabled 

scientists to dictate when and where the 

material changed from solid to liquid. 

As a liquid, the properties of the alloy 

notably change. It no longer responds as 

well to magnets because the solid matrix 

holding and aligning the micromagnets 

falls apart during melting. As a result, the 

micro-magnets respond independently 

to the magnetic field and to each other, 



FEATURE 

creating many shifting incohesive 

magnetic alignments within the material, 

reducing the complexity of the material’s 

mobility. Nonetheless, while it loses its 

ability to jump, the liquid still responds 

enough to magnets that it can split into 

smaller blobs, elongate, reshape itself, and 

merge from smaller parts, just like water. 

In order to turn back into a solid, the 

matter simply cools to room temperature 

and solidifies. You may wonder why 

scientists can’t cool the material the same 

way they heated it up, but cooling using an 

electric current is difficult unless special 

thermoelectric materials are used, which 

would interfere with the functionality of 

the liquid-solid machine. Nonetheless, 

senior author and mechanical 

engineering professor Carmel Majidi of 

Carnegie Mellon University is working 

with another group to implement similar 

functionality, so they may eventually be 

able to dictate when it solidifies as well. 

A shape-shifting machine sounds great 

for escaping through the bars of a prison 

cell, but these malleable machines have 

tangible real-life applications as well. 

“The medical sector has the greatest 

potential to benefit from applying this 

technology,” Majidi said. The scientists 

demonstrated these applications by using 

the machine to remove a foreign object 

from a model stomach. In real life, a 

person would swallow the machine as a 

pill, and it would be guided to the foreign 

object using a magnet. At this point, it 

would change into a liquid and envelop 

the object in a process similar to a white 

blood cell consuming harmful cells. It 

would then solidify to trap the object 

and carry it out under the guidance of a 

magnetic field. Since the body is warm, 

scientists would add compatible metals 

such as bismuth or iron to the alloy in 

order to raise the melting point above the 

average body temperature. 

The machine could also be used for 

drug delivery: it could be inserted into the 

body as a solid containing the medicine 

to be delivered and guided to a specific 

location. Once there, it would melt and 

release the medicine before solidifying 

and exiting. 

Furthermore, the machine could be used 

in the assembly of circuits by carrying 

tiny components to specific points in 

the circuit, changing to liquid around 

the connectors, and then solidifying to 

form a firm weld that conducts electricity 

through the component. In addition, the 

material can act as a universal screw for 

construction by pouring the 

liquid machine into a screw hole 

and using a magnet to guide 

and fit it snugly into every 

crevice, before solidifying and 

fixing itself as the perfect screw. 

Moreover, the machines could be 

used in the remote repair of most 

engineering structures. Imagine a 

future where you need only drop 

a pin-shaped machine inside a 

malfunctioning 

computer to 

allow a hardware specialist working from 

home to diagnose and repair your device 

in mere moments. 

These applications are possible because 

the machine, in its solid state, is designed 

to carry up to ten thousand times its 

own weight, which was demonstrated as 

the machine lifted and supported a twohundred-gram 

weight. The ability to bear 

this weight is more than sufficient when 

applied to the minuscule scale that the 

machines are expected to operate on, and 

more weight can be supported by using 

swarms of these machines to carry heavier 

loads through weight distribution. 

“The materials required to produce a 

machine are about as costly as a kitchen 

magnet,” Majidi said. This affordability 

has the potential of reducing surgery 

costs when manufactured and applied 

en masse. With more research being 

conducted focusing on the development of 

nanomachines, we can expect even more 

interesting, quality-of-life improvements 

through inventions like this one. ■ 

ART BY COURTNEY JOHNSON 



FEATURE 

Astrophysics 

GREEN PEAS IN SPACE 

BY ROBIN TSAI AND LUCY ZHA | ART BY HANNAH BARSOUK 

HOW TINY GALAXIES 

HELPED REMODEL THE 

UNIVERSE’S HISTORY 

You gaze up at the sky on a clear 

night. The stars, too numerous to 

count, appear as nothing more 

than little specks. Together, however, they 

keep the universe lit up like fireflies in the 

dark. For astronomers, these stars and 

galaxies serve as lampposts throughout 

the universe’s history and evolution. But 

about thirteen billion years in the past, 

there was a “dark age” without visible 

galaxies, stars, or any kind of light which 

has puzzled astronomers. Scientists aren’t 

sure how reionization—the epoch of highenergy 

radiation that ended this cosmic 

dark age—occurred. Recently, however, 

two astronomers, James Rhoads of NASA’s 

Goddard Space Flight Center and Sangeeta 

Malhotra of Arizona State University, 

presented findings that could revolutionize 

our understanding of this dark era. 

Before we can talk about reionization, 

however, we must take a few steps back to 

the Big Bang. The universe began with an 

explosion from an infinitely dense point, 

then stretched and continued to grow to as 

large as it is right now. Immediately following 

the Big Bang was an era of pure brightness: 

a hot soup of electrons, quarks, and photons. 

When the universe expanded enough for 

this soup to cool down, hydrogen atoms 

formed from the protons and electrons in 

an era known as the recombination epoch. 

This thick, dense fog of neutral hydrogen 

continuously absorbed light within it, thus 

ushering in the universe’s dark age. 

Then, something amazing happened. 

“One might naively expect for the neutral 

hydrogen to just sit there, but sometime 

in the late 1960s [we discovered] that the 

gas between galaxies is ionized today, and 

has been for at least the last 10 billion 

years,” Rhoads said. The neutral hydrogen 

did not stay neutral forever: it reionized. 


Astrophysics 

FEATURE 

Cosmic objects—such as galaxies, 

stars, or clouds—send out a spectrum of 

wavelengths, from infrared light, to visible 

light that brightens up the night sky, to 

ionizing X-rays. These spectra are largely 

determined by the objects’ chemical 

compositions and their corresponding 

emission lines. As such, these spectra 

are a “signature” of these cosmic objects, 

allowing them to be classified based 

on their light’s properties. Add a bit 

of redshift—wherein these photons’ 

wavelengths are stretched by the source’s 

speed away from us or by the universe’s 

expansion—and you also get information 

about the object’s age. In particular, 

because of the universe’s expansion, the 

further away an object is from us, the 

faster it is moving away from us. The faster 

it is moving away from us, the redder its 

spectrum is. Because light takes time to 

travel, redshifted galaxies must be older. 

To figure out what kind of galaxies drove 

the harsh radiation of reionization, we 

must find two qualities of a galaxy: the 

redshift and the spectrum. The problem? 

These galaxies are faint—extremely faint. It 

wasn’t until recently, with the launch of the 

James Webb Space Telescope (JWST), that 

astronomers were finally able to see these 

faint galaxies at high redshifts. 

But there’s one more elephant in the room: 

what drove the sudden reionization? Neutral 

hydrogen gas left alone in a tank cannot 

suddenly ionize; there must be some driver 

for the process to occur. Now, armed with 

a powerful enough telescope, astronomers 

could finally answer their question about 

reionization. Cue Rhoads and Malhotra, 

who noticed something peculiar about the 

JWST data they were analyzing. 

Six months after its launch, JWST sent 

back images that contained the answer to 

this puzzle. Focused on a galaxy cluster 

named SMACS 0723, Rhoads and Malhotra 

noticed that three of the galaxies closely 

resembled some local galaxies—galaxies 

that were billions of years separated from the 

trio. These were the Green Pea galaxies, aptly 

named for their greenish hue and minuscule 

size. “We [saw] that they were small, their 

galaxy population was young [at their 

redshift]… what you see in these galaxies 

is that their spectra are dominated by these 

huge [emission] lines,” Malhotra said. 

"I think the JWST is 

going to revolutionize 

[our understanding of 

reionization]." 

Malhotra and Rhoads found that these 

emission lines were created by light 

elements, as opposed to heavy elements 

which require eons to form. Galaxies with 

light elements generate stars at an alarming 

rate, sending out wave after wave of harsh 

electromagnetic radiation. These properties 

are unexpected for local galaxies, but it made 

sense that these galaxies would appear at the 

epoch of reionization. “We’d have expected 

that these Green Peas were analogs of these 

high-redshift galaxies, but we hadn’t tested 

that. So we were so excited when it actually 

happened!” Malhotra said. Astronomers 

had hoped that the Green Pea galaxies, 

which are well-understood, would somehow 

appear at the epoch of reionization, so 

it came with great excitement that their 

predictions were accurate. 

There is little doubt that more groundbreaking 

headway will be made. As more 

discoveries are made with JWST data, 

it is likely that we will see more objects 

like the galaxies analyzed in Rhoads’ 

and Malhotra’s study, and we may finally 

find the key to the end of the universe’s 

dark age. “I think the JWST is going 

to revolutionize [our understanding of 

reionization],” Malhotra said. 

As for Rhoads and Malhotra, their 

plans going forward remain similar. 

They have worked in this field for many 

years and expect to continue working 

towards uncovering more about the highredshift 

universe. Working with both 

ground-based telescopes and JWST, the 

two astronomers expect to build a more 

quantitative evidence base surrounding 

reionization-era galaxies. And since 

distant galaxies are harder to study, Rhoads 

and Malhotra plan to closely analyze our 

local Green Pea analogs. They will garner a 

greater understanding of the high-redshift 

galaxies’ properties by studying local 

galaxies instead. 

The journey to understand the end 

of the universe’s dark age has been 

arduous, but also highly rewarding. Just 

as our universe exited its dark age, our 

knowledge about it has as well. “It’s been 

quite a fun thing to do! We’re looking at 

images, finding new things, making new 

discoveries, and forming a community," 

Malhotra said. "This definitely represents 

the fun part of science.” ■ 

IMAGE COURTESY OF NASA 

This photograph, taken by the James Webb Space Telescope, shows the galaxy cluster SMACS J0723.3-7327, 

wherein the trio of galaxies was found. 



FEATURE 

Genetics 

TURNING 

BACK 

THE CLOCK 

USING EPIGENETICS TO REVERSE AGING 

BY RISHA CHAKRABORTY 

Humanity has been obsessed with 

ending mortality for millennia. 

From famous historical 

conquests to find the Fountain of Youth to 

the contemporary race to find medicines 

combating heart disease, cancers, and 

neurodegeneration, scientists and 

philosophers alike are driven by the 

motivation to turn back the clock. Aging 

is a fundamental, natural process of 

life—all living organisms grow old and 

eventually die, and since the advent 

of molecular biology, scientists have 

attempted to figure out why. 

Professor David Sinclair of Harvard 

University is a pioneer in the field 

of aging. From his discovery of the 

anti-aging molecule resveratrol to his 

successful restoration of eyesight for 

old and glaucomatous mice, Sinclair 

and his lab are making notable leaps in 

understanding and even reversing aging. 

One of the members of Sinclair’s team, 

postdoctoral fellow Jae-Hyun Yang, 

spearheaded an article published in Cell 

early this year studying one of the lab’s 

greatest contributions to the field of aging. 

They suggested that a loss of epigenetic 

information—changes in the chemical 

modification and packaging of our DNA 

and proteins within the nucleus—causes 

aging. Yang identified possible molecular 

mechanisms of aging and accordingly, a 

possible target for therapies that could 

one day reverse aging. 

Prior to joining Sinclair’s lab, Yang 

was interested in studying epigenetic 

modifications that activated muscle 

genes during mouse embryonic cell 

differentiation, the process in which 

naive cells acquire a specific identity, as 

in whether they should be an eye cell, or a 

liver cell, or a muscle cell. Upon learning 

more about the fields of epigenetics and 

cell fate decision while obtaining his PhD, 

he was drawn to combining his interests 

and harnessing epigenetic mechanisms to 

study the process of aging. Differentiation 

is characterized by the accumulation 

of epigenetic information, while aging 

is characterized by the opposite. The 

team’s paper marks the success of a literal 

decade-long project to prove that loss 

of cell-specific epigenetic information 

contributes to aging. 

“The difference between the epigenome 

and genome is similar to that of the 

software and hardware of a computer,” 

Yang said. Ultimately, the computer 

hardware—the amount of storage it 

has, its processing ability, its graphics 

elements—is similar to the genome of an 

ART BY LUCY SUN 

| 

organism: at its core, the organism is 

determined by the sequence of nucleotides 

in its DNA. However, the computer can’t 

actually do anything useful without 

software—applications that make the 

computer function the way it does. 

This is similar to the epigenome of an 

organism—by turning certain genes on 

and off at different points in their lifetime, 

epigenetic changes are capable of giving 

individual cells their identity, allowing 

them to become different types of cells. 

When DNA is damaged, the process of 

preserving the lost genetic information 

causes the loss of the original epigenetic 

information. Yang hypothesized that 

The difference between the epigenome and 

genome is similar to that of the software 

and hardware of a computer. 


Genetics 

FEATURE 

the accumulation of this epigenetic 

information loss is what ultimately 

constitutes aging. 

To test this hypothesis, Yang developed 

a genetically-altered mouse called ICE 

(Inducible Changes to the Epigenome), 

to which epigenetic information loss 

could be introduced without genetic 

information loss. After inducing 

epigenetic information loss in ICE mice, 

Yang observed hallmarks of aging, 

including an increased frailty index 

(constituting body weight, grip strength, 

mobility, vision, and hearing), reduced 

bone density, damage to kidney cells, 

loss of melanocyte stem cells in skin 

contributing to fur graying, cognitive 

decline, and impaired muscle function. 

He found that many developmental 

processes that determine cell identity 

were altered in ICE-induced cells and 

mice. Regions of DNA that were far apart 

and originally should not have been able 

to impact each other did in fact bind and 

communicate, which caused cells to lose 

their identity. Specifically, he showed that 

muscle cells tended to behave more like 

immune cells after ICE treatment. 

Next, Yang wanted to test if he 

could reverse the physiological 

effects he saw in his ICE mice. 

Knowing that gene-expression 

factors called the Yamanaka 

factors —Oct4, Sox2, Klf4, 

and Myc (OSKM)— 

alleviate the symptoms 

of aging mice, Yang 

wondered if treating his 

induced ICE mice with 

the Yamanaka factors, 

except Myc, would reverse 

features of aging. In fact, 

he found that treating 

cells or mice with OSK 

restored age-associated 

gene expression, epigenetic 

marks, and turned back the 

epigenetic aging clock. Yang 

hypothesized that there may 

actually be some copy of the 

epigenome in the cell that can 

be restored upon treatment with 

Yamanaka factors to reverse aging. 

“It’s hard to target aging, as a treatment, 

because aging is not defined as a disease. 

But [Yamanaka factors] can be used for 

multiple different age-associated diseases. 

Currently, we can target different tissues 

and other projects in the lab are targeting 

eyes, muscles, and kidneys,” Yang said. 

“I hope we can eventually target aging 

as a whole, but for now we are targeting 

specific diseases and tissues. I’m 

interested in finding safer and cheaper 

methods that could replace [Yamanaka 

factors], so we can have the same effect 

without using gene therapy.” 

Moving forward, Yang is interested in 

exploring some of the specific epigenetic 

factors that may be relocated after 

DNA damage, causing DNA cross-talk 

issues and contributing to epigenetic 

information loss. Yang is eager to find 

ways to make these 

p r o t e i n s 

function 

more faithfully with the goal of preventing 

the aberrant cross-talk between farapart 

DNA and the loss of cell specificity 

contributing to the progression of aging. 

Yang and his fellow researchers in the 

Sinclair lab have their work cut out for 

them. From identifying single cell— 

as opposed to bulk tissue—epigenetic 

changes to testing the results of this 

paper on human cells, tissues, and 

organoids, their work aims to determine 

the most crucial factors contributing to 

the universal process of aging, enabling 

us to gain a deeper understanding of 

why, despite our differences, humanity 

is united in mortality. With their 

advancements directly contributing to 

possible treatments for all the diseases 

whose greatest risk factor is aging, we 

are inching closer than ever before 

toward a world in which we may 

indeed live longer and 

healthier lives. ■ 



UNDERGRADUATE PROFILE 

GRAYSON WAGNER 

YC ’23 

BY ELISE WILKINS 

Grayson Wagner (YC ’23) knew from a young age that 

she wanted to be an engineer. She grew up admiring her 

father’s work as an industrial engineer, and by her junior 

year of high school, she had decided on biomedical engineering. 

Wary that many students switch majors during college, Wagner 

wasn’t sure if she would stick with it. However, she has delved 

deeply into the realm of biomedical engineering, while adding a 

second major in mechanical engineering. 

In 2020, Grayson founded Yale’s inaugural e-NABLE chapter—a 

volunteer group that uses 3D printing to construct upper-limb 

prostheses for those in need. The e-NABLE club allows Wagner 

to use her two majors for a humanitarian purpose. She established 

the chapter with the help of Vincent Wilczynski, the Deputy 

Dean of the School of Engineering and Applied Sciences. She 

originally learned about the organization during her senior year 

of high school and wanted to bring it to Yale. “I’ve shadowed at 

a lot of clinics, [and] I’ve seen a lot of patients. I’ve gotten that 

experience, and it’s a really interesting field. A lot of people don’t 

know about [prosthetics], about the fabrication, the assembly, and 

the difference it can make for people,” Wagner said. 

The e-NABLE club began work soon after its founding. The 

group received a request from a father hoping for a prosthetic 

arm that his daughter, Emily, could use to hold her bow while 

playing the cello. When starting projects, the group consults a 

database that contains about twenty basic prosthetic designs, 

including ones for upper-limb prostheses beginning at the wrist, 

elbow, shoulder, and even fingers. The team can then download 

the design that is best suited for their goal and use computeraided 

design software, such as SolidWorks or Onshape, to upload 

the design and make their changes. Once satisfied, the prototype 

can be 3D printed and assembled. 

A notable aspect of designing prostheses in this manner is that 

the files for each design are transferable. Wagner explained that 

while Emily was filming a commercial in Arizona, her prosthesis 

broke mid-shoot, but e-NABLE design head Zubin Kremer Guha 

(YC ‘24) was able to send the files to Arizona where the device 

could be reprinted. Wagner loved working with Guha and the other 

design head for the project, Audrey Whitmer (YC ‘23). “It was 

exciting seeing two 

different passionate 

engineers come 

together and create 

one cohesive device 

for Emily. They 

did a fantastic job,” 

Wagner said. 

The prostheses 

made by e-NABLE 

PHOTOGRAPHY BY DANIEL HAVLAT are not intended to 

PHOTOGRAPHY BY DANIEL HAVLAT 

replace traditional prostheses since the volunteers are not certified 

prosthetists or orthotists. However, as Emily’s story shows, there 

are many benefits to making specialized prosthetics that are 

not meant for everyday use. “You can make these really specific 

adaptive features that are harder to do and less accessible in a 

clinical setting,” Wagner said. 

Wagner’s passion for biomedical engineering extends to her 

research with John Geibel, a professor of cellular and molecular 

physiology and vice chairman of the Department of Surgery at Yale. 

With Geibel, Wagner works on bioprinting, which uses similar 

techniques to 3D printing but relies on biomaterials such as living 

cells to build complex structures. Bioprinting has the potential 

to greatly impact the future of manufacturing bioengineered 

tissues and organs. Wagner, who has many interests within this 

field, published a review paper in Pharmaceutics in December 

2022 on the use of hydrogels—networks of polymer chains with 

great capacity to hold water—in bioprinting, and she has recently 

submitted another review about bioprinting’s applications to 

bone tissue. Wagner further shares her love for engineering as the 

president of Tau Beta Pi, the engineering honor society. She also 

enjoys connecting with friends outside of the engineering sphere 

as a member of the Yale Climbing Team. 

For the rest of the semester, Wagner plans to savor her last 

moments with her biomedical engineering class, and she looks 

forward to continuing her work in tissue engineering and medical 

device design after graduation. “I’m excited to move on to my next 

phase, working with companies that are taking bioprinting and 

tissue engineering from the bench to the bedside,” Wagner said. ■ 


ALUMNI PROFILE 

DAVID QUAMMEN 

YC ’70 

BY SANTIAGO CALDERON 

David Quammen (YC ‘70) gestured behind him to a large 

glass tank on the floor of his office. “Over there is a 

rescue python that shares this office with me. He’s lived 

here for four years. His name is Boots,” he said, with a note of 

pride. The same love of nature that prompted Quammen to 

catch snakes and bugs as a boy continues to be a major influence 

in his work as a science non-fiction writer. Throughout his 

long career, Quammen has written numerous essays and books 

on the natural world and the forces that drive it, including a 

monthly column in Outside magazine that he has continued for 

fifteen years, numerous pieces for National Geographic, and a 

book on COVID-19 titled Breathless. 

Quammen’s journey to becoming a non-fiction author began 

with a love of nature and writing that transitioned seamlessly 

into his studies at Yale. In the summer between his junior and 

senior years, Quammen traveled to a troubled neighborhood 

in Chicago to work as a community organizer. That experience 

inspired his first book, To Walk the Line, which he wrote on 

yellow legal pads in his dorm room and published in 1970 

after his mentor, Pulitzer Prize-winning novelist Robert Penn 

Warren, recommended it to an editor. 

After finishing his education at Yale with an English degree 

and spending two years at Oxford on a Rhodes Scholarship 

studying the works of William Faulkner, Quammen decided he 

wanted a change of scenery. “I was tired of ivy-covered walls, 

I was tired of being in school, and I was tired of being in elite 

institutions. [...] As I thought of it then, I wanted to live closer 

to the ground,” Quammen said. Using the profits from the 

publication of his first book, he bought a Volkswagen bus and 

packed it with Penguin paperbacks, an electric typewriter from 

his parents, and a fishing rod, before driving to Montana. Not 

foreseeing how long he would spend there, he ended up staying 

for a lifetime. He worked for thirteen years before he published 

his second book, writing in the mornings while working as a 

bartender and a fishing guide to cover 

his living expenses. 

While he was in Montana, Quammen 

reconnected with the natural world. 

“[My interest in the natural world] 

reawakened now that I was in a place 

that had mountains and wildlife 

and rivers filled with trout and 

snow,” Quammen said. Meanwhile, 

he became fascinated with 

Darwin’s works and with scientific 

writing in general. In 1980, after 

pitching an article on the benefits 

of mosquitoes to an editor of Outside 

magazine, he began writing its monthly 

PHOTOGRAPHY BY RONAN DONOVAN 


nature column. In the 

process, Quammen’s 

focus transitioned 

from novels 

and essays on 

natural history 

to science 

writing about 

theoretical 

ecology and 

the history of 

evolutionary 

thinking. “As 

passionately 

interested in 

and impressed 

by William 

Faulkner and 

his novels as I was, 

I became that interested in 

and impressed by Charles Darwin,” Quammen said. This focus 

on non-fiction writing led him to pursue a successful career 

writing about Ebola, molecular phylogenetics, and a biography 

of Darwin himself. 

The vast amount of Quammen’s research is conducted 

through two avenues: extensive reading of scientific journal 

articles and interviews with experts (he conducted ninetyfive 

Zoom interviews for Breathless), with occasional field 

visits. His next book, to be published in May 2023, is drawn 

from a collection of conservation-related pieces originally 

published in National Geographic, titled The Heartbeat of the 

Wild. After that, he will resume work on a book on cancer as 

an evolutionary phenomenon. The novel contains a number 

of counterintuitive cases, such as devil facial tumor disease 

(DFTD), a cancer affecting Tasmanian devils. Cancers are 

almost never transmitted between individuals, instead arising 

due to time, genetic mutations, or environmental factors. 

However, DFTD is a transmissible cancer that spreads through 

bites, indicating that cancer is an evolutionary phenomenon 

and that tumors can adapt over time. This interplay between 

evolution and cancer fascinates Quammen, and he is excited to 

conduct more research. 

Quammen is looking forward to whatever comes his way, but 

is experienced enough to know that life is unexpected. “Life 

doesn’t follow your plans. [...] You gravitate toward things that 

a) interest you and engage your passions, but b) allow you 

to pay for food and shelter,” Quammen said. He still lives in 

Bozeman, Montana with his wife, an assortment of dogs and 

cats, and, of course, Boots. ■ 

PHOTOGRAPHY BY CHARLIE HAMILTON JAMES 


HOW FAR THE LIGHT REACHES 

BY WILLIAM ARCHACKI 

SCIENCE 

I N 

IMAGE COURTESY OF UNSPLASH 

You’ve probably seen it in nature documentaries: a translucent fish 

meanders through the darkness, searching for scraps of food in 

the wasteland of the deep ocean. The screen sparkles with flakes of 

decaying matter that drift above the ocean floor, to be consumed by sparse 

communities of microbes and strange, gelatinous creatures. The narrator 

explains that the deep ocean has an average temperature of just four degrees 

Celsius and that the water is under such pressure that it could crush anything 

but a few specialized vehicles. 

More than two-thirds of the Earth’s surface is water, and our 

understanding of the organisms that live in its depths remains severely 

limited. But to Sabrina Imbler, a science journalist and former New York 

Times reporting fellow, the mystery of the murky waters is no cause 

for unease. Rather, as Imbler shows in their new collection of essays, 

How Far the Light Reaches: A Life in Ten Sea Creatures, the networks of 

resiliency that populate Earth’s waters provide a glimpse of the beauty 

that can flourish amid turbulence and oppression. 

Each essay in the collection examines one creature and a corresponding 

piece of Imbler’s identity, drawing parallels between the unique ecology of 

the sea and Imbler’s lived experience. In the collection’s opening essay, Imbler 

notes that goldfish can grow to be long-lived, far-traveling giants when 

freed from the confinement of fishbowls. Interweaving poignant adolescent 

memories within the exposition of goldfish biology, Imbler suggests that a 

person’s identity, too, may flourish when freed from constraints. As Imbler 

recounts the process of defining their queer, mixed-race identity, they show 

that nature serves as a model for personal authenticity. 

When the spotlight turns to the yeti crab, a tiny crustacean that ekes out an 

existence in the heated waters of hydrothermal vents, Imbler questions the 

notion that living in Earth’s most inhospitable environments is a matter of 

mere survival. The yeti crab is an eternal dancer, waving its pincers in circles 

continuously to harvest microbes on its hairlike filaments, living in a place 

scientists long thought impossible. “I prefer to think of it not as a last resort 

but as a radical act of choosing what nourishes you,” Imbler writes. 

The unexpected triumph of the yeti crab comes interspersed with Imbler’s 

memories of the queer, mixed-race communities they have found hidden 

in American cities. Imbler touches upon the struggles they have faced 

grappling with racism, sexism, gentrification, fetishization, and other forms 

of intolerance in contemporary America. Movingly, Imbler reflects on 

resilient aquatic populations as symbols of solace and hope. 

Imbler’s sprawling exploration of the creatures that inhabit the sea 

questions the way our definitions of normality restrict us. An examination 

of hybrid fish in one essay becomes a critique of the impulse to categorize 

nature’s disorder. For Imbler, the vast and beautiful world of sea creatures 

offers a call for a deepened understanding of our most authentic identities— 

abnormal, confounding, and gelatinous as they may seem. ■ 


THE ELEPHANT WHISPERERS 

BY VICTOR NGUYEN 

In a village in Tamil Nadu, the southernmost state in India, a marriage 

ceremony is taking place. Elderly elephant caretakers Bomman and Bellie 

revel in their newly formed union wearing vibrant, ceremonial wreaths. 

But the most extraordinary sight is their groomsman and bridesmaid: 

elephants Raghu and Ammu who celebrate their marriage alongside them. 

The recently released Netflix documentary, The Elephant Whisperers, explores 

the interdependence between elephants and humans and gives insight into 

the possibilities of cross-species connections. 

In the film, Bomman and Bellie first meet when the Indian forestry department 

assigns them to the same elephant sanctuary. Their connection flourishes 

through their combined efforts to take care of Raghu and Ammu, a pair of 

injured elephants. Through an arduous recovery process, the pair nurse Raghu 

and Ammu back to health. Stories similar to Raghu and Ammu are becoming 

more common as elephants and humans come into close contact due to crop 

raiding, which occurs when elephants eat crops grown by farmers. According 

to a review article published in Frontiers in Ecology and Evolution in 2019, 

four hundred people and one hundred elephants are killed in these incidents 

each year, which is why sanctuaries like the one run by Bellie and Bomman are 

pivotal in creating separate safe spaces for both parties. 

Beyond just rehabilitating displaced elephants, the sanctuary also serves as 

a place of healing and hope for Bellie and Bomman. Raghu reminds Bellie of 

her daughter who passed away; when Bellie mourns her loss, Raghu wipes 

her tears with his trunk. For Bomman, caring for Raghu and Ammu connects 

him to his rich ancestral heritage, since Bomman’s father and grandfather 

were elephant caregivers. These heartfelt anecdotes reveal how it's possible to 

foster strong familial ties through human-animal interactions. 

Though this story may seem idealistic, it is important to acknowledge where 

the lines between narrative and reality lie. Critics of the documentary assert that 

the practices portrayed in the film are not compliant with wildlife rehabilitation 

standards. They argue that true rehabilitation requires animals to be reintroduced 

to nature after recovery, rather than being incorporated into human practices. 

According to the Asian Elephant Specialist Group, effective recovery is an 

T H E 

SPOTLIGHT 

intensive process consisting of three steps: planning, rehabilitation, and postrelease 

monitoring. During rehabilitation, caretakers focus on the elephants’ 

ability to reintegrate, and after their release into the wild, the elephants are 

monitored to ensure successful assimilation. While the recovery of Raghu and 

Ammu may not have followed these standards, it must be acknowledged that 

without the help of Bellie and Bomman, they would have suffered more. 

With its 2023 Oscar nomination, The Elephant Whisperers brings to light 

the importance of human interactions with nature and how this relationship 

can be mutually beneficial when approached in a mindful manner. This 

dialogue is vital in a world where human habitation increasingly crosses over 

into animal territory. After all, how we interact with our environment and 

animal neighbors is a choice that impacts us all. ■ 

IMAGE COURTESY OF PIXABAY 



COUNTERPOINT 

Does the ‘Love Hormone’ 

Oxytocin Really Lead to 

TRUE LOVE? 

Derived from the Greek phrase for ‘quick birth,’ 

oxytocin—initially discovered as a ‘contraction 

hormone’ in 1909 by physiologist Sir Henry 

H. Dale—has historically been touted as a miracle 

pregnancy hormone due to its efficient labor-inducing 

abilities. Produced in the hypothalamus and released 

into the bloodstream by the pituitary gland, oxytocin 

aids in both childbirth and postpartum lactation, and is 

commonly used by obstetricians and gynecologists. 

In popular culture, however, oxytocin has been viewed 

quite differently. Through the influence of marketing 

strategies, oxytocin has become associated with the 

development of love. Commonly referred to as the ‘love 

hormone’ or ‘liquid trust,’ oxytocin products are sold 

by numerous companies that claim to have benefits for 

consumers’ outward trustworthiness and ability to form 

lasting, loving relationships. These claims were founded 

on numerous scientific studies conducted through the 

1990s on prairie voles—a species of rodent known for 

their lifelong monogamous mating patterns. These 

studies suggested that the hormone played a significant 

role in the development of their mating relationships 

and parental behaviors. 

Later studies from the 2000s and early 2010s also 

showed that oxytocin levels increase when people hug, 

experience gentle touch, or engage in consensual sexual 

interactions, while cortisol levels, associated with stress, 

decrease. Validated by these studies, oxytocin’s supposedly 

unmatched ability to promote love and bonding between 

people has been the main focus of ‘love hormone’ 

companies over the last twenty years. However, a recent 

study by Kristen Berendzen, Ruchira Sharma, and their 

colleagues at the University of California, San Francisco 

has uncovered inaccuracies and possible exaggerations 

in our understanding of this hormone. 

In their paper published in Neuron in January, the 

researchers revealed that oxytocin may not be the 

determining factor in yielding mating and parental 

relationships in prairie voles. The researchers used 

CRISPR gene targeting technology, a gene editing tool 

capable of manipulating precise DNA sequences, to 

produce oxytocin receptor (Oxtr)-null prairie voles. 

These Oxtr null voles lacked function in their oxytocin 

By Lea Papa 

IMAGE COURTESY OF STOCKSNAP 

receptors and were therefore unable to support oxytocin 

signaling. When these Oxtr null prairie voles were tested 

against control Oxtr prairie voles with intact oxytocin 

signaling abilities, the scientists found that the Oxtr 

null voles were still able to develop certain behaviors 

that previous studies had suggested were the result of 

oxytocin signaling in the brain. 

Unexpectedly, even without the presence of oxytocin 

signaling, the Oxtr null prairie voles formed social 

attachments, mated normally, and presented typical 

parental behaviors. All of these behaviors were shown 

to have developed to the level—or mostly to the level, 

in a few cases—of those in control voles. Both male 

and female voles made mating connections and 

showed a preference for their mate over animals of the 

opposite sex. Female voles gave birth to healthy babies 

and nursed their pups to weaning, and parent voles 

displayed a similar intensive care for their children as 

regular voles did. 

The study also revealed some variation in prairie 

vole behavior which may be attributed to the changes 

in oxytocin signaling induced by the researchers, even 

though the social behavior observed in Oxtr and Oxtr 

null voles was mostly the same. The most notable of 

these differences was that Oxtr null voles showed less 

aggression than regular voles towards voles of the 

opposite sex who were not their mate. In addition, Oxtr 

null female voles were found to produce litters with fewer 

surviving pups at weaning. These observations suggested 

that the importance of oxytocin in social attachment is 

much less than was previously believed. 

Together, these findings indicate that oxytocin 

may play a different, more complex role in bonding, 

parenting, and social interaction than what was once 

believed. The groundbreaking results of this study, 

however, are not sufficient to fully understand the 

nuances of oxytocin and its properties. Subsequent 

oxytocin studies in a variety of species and populations 

will be necessary to decode this new mystery of the 

famous ‘love hormone.’ In any case, companies profiting 

from oxytocin product sales may have to find a new way 

to play on their consumers’ relationship insecurities— 

one that doesn’t involve their star hormone. ■ 


BY SAMANTHA LIU 

We start as seething plasma, like the mid-June afternoon 

when we rolled open the car sunroof to scream 

karaoke lyrics at the neighborhood police. We are 

seventeen and deathless then, the universe white-slick as our 

hands outstretched beneath the sun. When our high school 

valedictorian declares our futures blindingly bright, we throw our 

graduation caps into the sky and fill the football field with green 

pea galaxies of boundlessness. 

We end as cosmic blackout on I-287, ouroboric in the way a thick 

fog can block a vehicle’s headlight. When I drive down this October 

highway, the only galaxies I see are suffocated by suburban light 

pollution and this blanket of hydrogen / hanging over the universe. 

The astronomers call it intergalactic, distant bodies and hazy lives 

of my hometown friends four months and twenty states away, 

and all I can think about is how adulthood is a dying star, all my 

potential narrowing and flickering out, when— 

supermassive black hole swirling welcomed gravity swallowed 

harsh radiation tore apart a ‘fog’ violence gnashes the clouds 

billow-black pulled back when sudden luminosity furious & 

brilliant & starlight reddening reddening redshift reionization 

reionization reionization 

—Eventually, this dark age ended. When the clouds clear, we find 

ourselves surrounded by ionizing radiation. Lit green by fledgling 

stars, these are Peter Pan galaxies, rebirthing us as lone protons 

and electrons. Which is to say we are for the 

first time unbounded—whole, charged, 

free. And I wonder what it would take for 

us, too, to carve out a pea of possibility 

in our own hearts. To survive harder 

and shine brighter, while hurtling 

lightyears away from where we 

came. To create our own 

constellations. Maybe, when 

the fog lifts, rendering 

stars and galaxies visible 

for the first time, it’s 

just us discovering 

the radiance that 

was there all 

along. 

PERI 

COSMIC 

DAWN OVER I-287 

Artist’s Statement: 

There is no shortage of poetry about 

astronomy. As early as the founding 

of civilization, we have searched for 

romanticized meanings in our cosmos— 

we are all made of stardust, or we all see the 

same night sky, or it’s written in the stars— 

and tried to create art from it. What struck 

me, then, about Shannon Hall’s Nature 

article was not only the beautiful language 

and metaphors she used to describe our 

galaxies. Hall took the science of discovery— 

of hydrogen reionization and rest-optical 

spectra—and wove it into a story, a real 

story, about our universe’s genesis. And this 

story is not so different from our own lives. 

As the universe transformed from “seething 

plasma” to “cosmic blackout,” I thought 

back to my life half a year ago—at home 

for October break, two months into college, 

and already feeling that nebulous cloud of 

adulthood settling over my future. So when 

Hall wrote about discovering these “Peter 

Pan galaxies” which not only uncloaked us 

from darkness, but also continue to 

light the skies today, I thought that 

was beautifully poetic. We don’t 

need to romanticize the stars, and 

we don’t need to invent far-flung 

metaphors. All the stories and 

all the meaning we 

need—it’s right 

there above us, 

if only science 

teaches us to 

look. ■ 

METER KARA 

ART BY 

TAO 



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Yale Scientific 

for writing, production, web, 

business or outreach? 

Learn more at 

yalescientific.org/get-involved 

AD_YALE_SC_ENG_Half_winter_2023.qxp_8 1/31/23 7:55 AM Page 1 

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YSM Issue 96.1

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