YSM Issue 97.1

Yale Scientific 

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

MARCH 2024 

VOL. 97 NO. 1 • $6.99 

AIRBORNE 

SECRETS 16 

SINK OR SWIM 

12 

TURNING THE TIDE 14 

19 

COSMIC TIME CAPSULES 

UNCHARTED RNA TERRITORY 

22

TABLE OF 

VOL. 97 ISSUE NO. 1 

COVER 

16 

A R T 

I C L E 

Airborne Mysteries 

Abigail Jolteus 

The environmental toll of Canada’s oil sands has escalated with recent groundbreaking research using 

aircraft-based measurements. Shockingly, total gas-phase organic carbon (TOC) emissions from 

Canadian oil operations were found to exceed industry-reported values by a staggering 6,300 percent. 

These findings thrust TOC into the spotlight as an important metric for a more holistic understanding 

of the oil industry’s environmental impacts, challenging conventional evaluation methods. 

12 Sink or Swim 

Anya Razmi 

Eighty percent of male infertile patients suffer from sperm motility issues. But because fertility genes 

don’t pass on to the next generation, finding out what causes low motility is surprisingly challenging. 

Researchers at Yale and Quaid-i-Azam University in Pakistan identified a defect in LRRC23—a protein 

component of sperm—that might be the key to unlocking one of the reasons behind male infertility. 

14 A New Immune Drug? 

Yossi Moff 

Bone marrow injury can leave patients dangerously susceptible to infection, without enough white 

blood cells to fight off pathogens. A Yale researcher has discovered new therapeutic potential for a drug 

known as A485 that uses a different pathway of activation, changing our understanding of immunity. 

19 Cosmic Time Capsules 

Diya Naik and Max Watzky 

Organic molecules are essential for life, but the question of how they formed in the galaxy has puzzled 

scientists for decades. A study examining the chemical makeup of samples from the asteroid Ryugu has 

provided fresh insights into this question. By focusing on polycyclic aromatic hydrocarbons, researchers 

have produced compelling evidence that these organic compounds originate in the frigid, energydepleted 

environments of molecular clouds. 

22 It's an RNA World Again 

Risha Chakraborty and Kenny Cheng 

Ribonucleic acids (RNA) have long been recognized as essential molecules within the cell for their roles in gene 

expression and defense against viral infections. However, recent discoveries have revealed RNA’s presence not 

only inside cells but also on their membranes. A team of researchers has turned their focus to neutrophils, the 

“firefighters” of the immune system, and uncovered an unexpected role of extracellular RNA in their function. 

2 Yale Scientific Magazine March 2024 www.yalescientific.org

CONTENTS 

More articles online at www.yalescientific.org & https://medium.com/the-scope-yale-scientific-magazines-online-blog 

4 

6 

25 

34 

Q&A 

NEWS 

FEATURES 

SPECIALS 

Can Nemo Count? • Alex Dong and Malia Kuo 

Can We Trace the Evolution of Sign Language? • Kelly Chen 

Life Out of Balance • Estella Wittstruck 

The Ripple Effect • Jiya Mody 

Mimicking Tumor Interactions • Nusaiba Islam 

Sssensitive Snakes • Lynna Thai 

Hitting the Pause Button • Sarah Li 

Identifying Ezekiel's Wheel • Faith Pena 

Giving Voice to the Voiceless • Aiden Wright 

I Am Alan Turing • Ximena Leyva Peralta 

Weathering the Storm • Samantha Liu 

Growing Smarter • Brandon Ngo 

Ditching Opioids • Megan Kernis 

AI vs. Superbugs • Madeleine Popofsky 

Massive, Mysterious Circles in Space • David Gaetano 

Woolly Questions • Hanwen Zhang 

Undergraduate Profile: Madhav Lavakare (YC '25) • Proud Ua-arak 

Alumni Profile: Emily Boring (YC '18) • Kenna Morgan 

Science in the Spotlight: Bridging Biology and Feminism • Genevieve Kim 

Science in the Spotlight: Word Wizards • Andrea Ortega 

Counterpoint: Mind Over Matter • Lee Ngatia Muita 

Crossroads: Biochemistry and Our Changing Climate • Yusuf Rasheed 

www.yalescientific.org 

March 2024 Yale Scientific Magazine 3

CAN WE TRACE THE 

EVOLUTION OF SIGN 

LANGUAGE? 

& 

CAN NEMO COUNT? 

By Alex Dong & Malia Kuo 

Had Nemo’s siblings survived, maybe there would’ve 

been a fight for dominance over his anemone. Alas, 

we’ll never know. 

Nemo and his family are anemonefish, also known as clownfish, 

characterized by their unique white bar patterning and territorial 

behavior over their host anemones. Notably, the thirty identified 

anemonefish species have a different number of bars on their 

bodies, ranging from zero to three. In a recent study published 

in the Journal of Experimental Biology, Japanese researchers from 

the Okinawa Institute of Science and Technology examined how 

anemonefish could use these bars to differentiate between species 

and identify potential intruders. Their question became, can 

anemonefish distinguish the number of bars on other individuals? 

The researchers presented —a species of 

anemonefish displaying three white bars—with four different 

fish models (zero, one, two, and three bars). attacked 

the three-bar model with a much higher frequency than any of 

the other models, suggesting that anemonefish count white bars 

to fend off primarily same-species competitors for their host 

anemone. These fish weren’t messing around: the alpha fish— 

the largest fish in the colony—battled eighty percent of threebarred 

fish for up to three seconds, and even stared down one 

intruder for eleven seconds. 

Coming next from Pixar: Fighting Nemo—Nemo engages in a 

scientifically accurate ninety-minute standoff against another 

three-barred clownfish. ■ 

By Kelly Chen 

The use of hand gestures for communication has a long 

history, dating as far back as 5 B.C.E. in ancient Greece. 

Despite having existed for a long time, gestural signals, 

which would eventually become sign languages (SLs), have 

historically been less well documented than oral languages due 

to challenges with recording visual gestures and the lack of 

widely used written systems for SL. 

To address this, researchers created a computer program to trace 

the history of nineteen contemporary SLs. Signs corresponding to 

the same set of core vocabulary words were taken from each of 

these languages as the input data. Phonetic parameters and patterns 

of the signs such as handedness (one- or two-handed signs), 

handshape, location of the sign, and movement were encoded as 

metadata to be used for comparison between the languages. 

Using this program, the researchers separated SLs into two 

independent language families by region: European and Asian. 

A lack of historical reports corroborated the hypothesis that 

these two SL families had little to no influence on each other in 

the past. Some SLs within the European SL family were grouped 

into subfamilies consistent with geopolitical history, namely 

the central European subfamily and the Eastern European 

subfamily with ties to the history of the Russian Empire and the 

Soviet Union. The Asian SL family consisted of two subfamilies: 

Japanese/Taiwan and Chinese/Hong Kong SL. As seen above, the 

use of computational phylogenetic methods only foreshadows 

the discovery of more connections across the linguistic history 

of sign language. ■ 


The Editor-in-Chief Speaks 

AT THE CROSSROADS 

Last summer, the Vol. 96 Managing Editors and I combed through the Yale 

Scientific archives on Crown Street and in Welsh Hall, flipping through hundreds of 

dust-covered magazines. As we cataloged 130 years of history—a project culminating 

in a new archival exhibit in the Benjamin Franklin Library—we unearthed a series 

of articles. Some of these included “Science Helps Develop an Emotional Art” 

(November 1927), “On The Relevance Of Philosophy To Mathematics And The 

Sciences” (January 1961), and “Science Courses for Humanities Majors” (November 

1962). All shared a common theme: an interest in mining the rich, complex, and, at 

times, contentious, relationship between STEM and the liberal arts. 

Since 1894, YSM has occupied a specialized niche—the intersection of science 

and the humanities. As a science magazine, we strive to unite the rigor of research 

methodologies with the imaginative ethos of storytelling to explore how science 

impacts society. As clinical and basic research becomes increasingly siloed, we 

recognize that an interdisciplinary approach is necessary to tackle and spread 

awareness about our world’s most pressing issues, from climate change to cancer. 

In the spirit of interdisciplinarity, our cover story synthesizes organic chemistry 

and environmental public policy to reveal the alarming rates of total gas-phase 

organic carbon emissions in Canada’s tar sands (pg. 16). In Features, we trace the 

winding journey of a 14,000-year-old woolly mammoth using isotopic dating and 

anthropological methods (pg. 32). In News, we delve into social medicine, analyzing 

the neurological effects of racism during pregnancy on infants (pg. 6) and the 

mental health crisis among Black youth in the US (pg. 10). Our theme culminates 

in our special series this year, “Crossroads,” in which we invite writers to sit in on 

interdisciplinary class offerings at Yale and interview the professors teaching them. 

In our first iteration of “Crossroads,” we glimpse into professor Karla Neugebauer’s 

classroom, where she teaches “Biochemistry and Our Changing Climate” (pg. 39). 

As we begin the new year, we aim to enrich our understanding of the societal 

impacts of science through our blog, Scope, and to launch a multimedia video series 

highlighting researchers pushing the frontiers of science. In addition, we will continue 

to reckon with our past by curating special exhibitions using our archival materials, 

diversifying our coverage, and challenging our historical and present biases. 

We would like to extend our sincerest thanks to all of our supporters and 

contributors, from our staff members and masthead to our subscribers. We are 

incredibly grateful, as always, for our long-standing partnerships with the Yale Science 

and Engineering Association, the Yale Alumni Association, and Yale Departments. 

The magazine you hold in your hands is the distillation of hundreds of hours of 

researching, interviewing, editing, writing, photographing, drawing, and designing. 

It is a labor of love, and we hope that you’ll join us by immersing yourselves in the 

wondrous intersection of science and the humanities. 

About the Art 

Hannah Han, Editor-in-Chief 

New research shows that Canada’s 

tar sands—infamous for being 

one of the most environmentally 

harmful sources of oil—are even 

worse than we thought. This piece 

highlights the devastating effects 

of this pollution: sticky black 

scars cutting across the vibrant 

landscape, and dark smoke 

obscuring the blue sky. 

Annli Zhu, Cover Artist 

MASTHEAD 

March 2024 VOL. 97 NO. 1 

EDITORIAL BOARD 

Editor-in-Chief 

Managing Editors 

News Editor 

Features Editor 

Special Sections Editor 

Articles Editor 

Online Editors 

Scope Editors 

Copy Editors 

Archivist 

PRODUCTION & DESIGN 

Production Manager 

Layout Editors 

Art Editor 

Cover Artist 

Photography Editor 

BUSINESS 

Publisher 

Operations Managers 

Subscriptions Manager 

Community Coordinator 

OUTREACH 

Synapse Presidents 

Synapse Vice President 

Synapse Outreach Coordinators 

Synapse Events Coordinator 

WEB 

Web Manager 

Head of Social Media Team 

Web Coordinator 

Web Developer 

Social Media Content Creator 

STAFF 

Ebru Ayyorgun 

Gabriela Berger 

Ryan Bose-Roy 

Andre Botero 

Risha Chakraborty 

Kelly Chen 

Yuanyu Chen 

Kenny Cheng 

Cara Chong 

Rayyan Darji 

Sara de Ángel 

Pempem Dorji 

Ian Gill 

Molly Hill 

Elisa Howard 

Nusaiba Islam 

Patricia Joseph 

Genevieve Kim 

Paul-Alexander Lejas 

Nyla Marcott 

Cullen Matthews 

Kenna Morgan 

Lee Ngatia Muita 

Diya Naik 

Brandon Ngo 

Kimberly Nguyen 

Nicole Isabel Oo 

Faith Pena 

Ethan Powell 

Yusuf Rasheed 

Ignacio Ruiz-Sanchez 

Sharna Saha 

Fareed Salmon 

Alondra Moreno Santana 

Hannah Han 

Sophia Burick 

Kayla Yup 

Mia Gawith 

William Archacki 

Keya Bajaj 

Evelyn Jiang 

Cindy Mei 

Lawrence Zhao 

Matthew Blair 

Lea Papa 

Katrin Marinova 

Yossi Moff 

Patrick Wahlig 

Matthew Blair 

Kara Tao 

Nina Yorou Liu 

Jiya Mody 

Madeleine Popofsky 

Luna Aguilar 

Annli Zhu 

Emily Poag 

Tori Sodeinde 

Gia-Bao Dam 

Megan Kernis 

Henry Chen 

Samantha Liu 

Hannah Barsouk 

Brandon Quach 

Jordan Thomas 

Sarah Li 

Sunny Vuong 

Michael Sarullo 

Abigail Jolteus 

Elizabeth Watson 

David Gaetano 

Henry Chen 

Sunny Vuong 

Jamie Seu 

Helen Shanefield 

Nikolai Stephens- 

Zumbaum 

Lynna Thai 

Melda Top 

Hien Tran 

Proud Ua-arak 

Qinyi Wang 

Max Watzky 

Elise Wilkins 

Estella Wittstruck 

Aiden Wright 

Nathan Wu 

Aaron Yu 

Johnny Yue 

Hanwen Zhang 

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

Scientific Publications, Inc. Third class postage paid in New Haven, CT 

06520. Non-profit postage permit number 01106 paid for May 19, 1927 

under the act of August 1912. ISN:0091-287. We reserve the right to edit 

any submissions, solicited or unsolicited, for publication. This magazine is 

published by Yale College students, and Yale University is not responsible 

for its contents. Perspectives expressed by authors do not necessarily reflect 

the opinions of YSM. We retain the right to reprint contributions, both text 

and graphics, in future issues as well as a non-exclusive right to reproduce 

these in electronic form. The YSM welcomes comments and feedback. Letters 

to the editor should be under two hundred words and should include the 

author’s name and contact information. We reserve the right to edit letters 

before publication. Please send questions and comments to yalescientific@ 

yale.edu. Special thanks to Yale Student Technology Collaborative.

NEWS 

Astronomy / Social Medicine 

LIFE OUT OF 

BALANCE 

THE TILTED PLANET 

PHENOMENON 

BY ESTELLA WITTSTRUCK 

THE RIPPLE 

EFFECT 

HOW SOCIAL STRESSORS 

IMPACT FETAL BRAIN 

DEVELOPMENT 

BY JIYA MODY 

IMAGE COURTESY OF TONYNETONE VIA FLICKR 

IMAGE COURTESY OF ANDRE FURTADO VIA PEXELS 

Scientists believe that when planetary systems first form, 

they are in a pristine, near-resonant state. Near-resonance 

describes when the orbits of multiple planets meet in set 

ratios and the planets regularly line up during their orbits. Nearresonant 

planets are expected to orbit in the same direction 

as their star’s rotation—an orientation known as alignment. 

However, orbits often aren’t perfectly aligned. Malena Rice 

GSAS ’22, an assistant professor of astronomy at Yale, researched 

a group of near-resonant planets to better understand why so 

many planetary systems have misaligned, sideways, or backward 

orbits. “The fact that we have all these weird, wacky planets 

means we can study other kinds of systems as we’re working 

toward understanding how our solar system fits into a broader 

picture,” Rice said. 

Rice examined the tilts of orbits in near-resonant systems 

through the Stellar Obliquities in Long-period Exoplanet Systems 

survey, founded by Rice as a PhD student. With telescopes, 

Rice and an international team of collaborators recorded the 

properties of large planet TOI-2202 b. Despite TOI-2202 b being 

in a near-resonant system, its orbit was still tilted by twenty 

degrees, likely from interacting with other celestial bodies. The 

reason for this dramatic tilt is unknown, but discoveries like this 

help scientists get closer to the answer. While TOI-2202 b is the 

most tilted example to date, several other near-resonant systems 

demonstrate a similar slant. “A lot of planetary systems are being 

tilted a little bit; there’s this low-level dynamical disturbance 

that is regularly occurring,” Rice said. “Understanding their 

properties helps us to engage with how amazing the laws of the 

universe are on a broad scale.” ■ 

A 

groundbreaking study conducted by a team of researchers 

from Yale and Columbia University found that a pregnant 

woman’s experience of discrimination and acculturation, 

or assimilation to a new culture, can leave a lasting imprint on their 

infant’s brain, altering key emotional processing centers. 

The collaboration between Yale’s Multi-modal Imaging, 

Neuroinformatics, & Data Science Laboratory and Columbia’s Early 

Neuroimaging, Neuroimmune, and Neuropsychology Lab examined 

the experiences of Latina women in New York City’s Washington 

Heights neighborhood. By measuring brain activity with a technique 

known as functional magnetic resonance imaging, the study examined 

changes in functional connectivity—how parts of the brain interact with 

each other—in infants. The study found that negative experiences during 

pregnancy, including discrimination, acculturation, stress, anxiety, and 

depression, have distinct effects. Infants from mothers facing higher 

discrimination levels exhibited weaker connectivity in the amygdala (the 

brain’s emotional processing center) and stronger connectivity in the 

fusiform cortex (the facial processing site). Acculturation was associated 

with weaker connectivity in both areas among infants. 

The findings have important implications for healthcare 

professionals, particularly in prenatal care. Dustin Scheinost GSAS 

’13, an associate professor of radiology and biomedical imaging at 

Yale and the senior author of the study, emphasized the importance 

of screening for acculturation to improve maternal and newborn 

outcomes. The results, he explained, underscore the need for 

broader societal awareness of the long-lasting physical impacts of 

discriminatory experiences. “How we treat each other is pretty 

important,” Schienost said. This study adds to the mountain of 

evidence showing that discrimination harms not only the person 

experiencing it, but also future generations—a powerful argument 

for working toward a more just and inclusive world. ■ 


Biology / Mathematical Ecology 

NEWS 

MIMICKING 

TUMOR 

INTERACTIONS 

A NEW PATH 

TOWARD PERSONALIZED 

CANCER THERAPY 

BY NUSAIBA ISLAM 

SSSENSITIVE 

SNAKES 

HUNTING WITH PRECISE 

INFRARED SENSORS 

BY LYNNA THAI 

IMAGE COURTESY OF WEINING ZHONG VIA FLICKR 

IMAGE COURTESY OF GEOFF GALLICE VIA FLICKR 

In a world where cancer claims millions of lives every year, a 

pioneering study by Yale’s Krishnaswamy lab in collaboration 

with the University College London Cancer Institute shines a 

beacon of hope by introducing a novel method that personalizes 

cancer therapy based on a patient’s unique genetic profile. 

Their study employed patient-derived organoids (PDOs) and 

cancer-associated fibroblasts (CAFs) to replicate the tumor’s 

environment in the lab. PDOs are small, lab-created structures 

that simulate the complexity of real tumors, while CAFs are cells 

within tumors that aid cancer growth. By employing heavy metal 

labels for molecular analysis and a unique data analysis system 

named “Trellis,” the team tracked each cell’s drug response, 

identifying those resistant to chemotherapy for targeted 

future treatments. 

Alexander Tong GSAS ’20 and ’21, a former graduate student 

in the Krishnaswamy lab and an author of the study, emphasized 

the potential of this approach. “The closer we can get our models 

to the tumor microenvironment, the closer we can get to treating 

patients individually,” Tong said. 

This research represents a significant shift from the one-sizefits-all 

approach to cancer treatment, focusing instead on the 

specific genetic landscape of each patient’s tumor. It is a crucial 

step forward in combating drug resistance and boosting the 

effectiveness of cancer therapies. 

In the future, the team aims to refine its methodology by 

developing sophisticated algorithms to accurately predict 

treatment outcomes for diverse patient profiles, drug 

combinations, and therapeutic strategies. This computational 

innovation could greatly reduce the reliance on extensive 

data collection, leading to more efficient treatment plans and 

optimizing the path toward individualized cancer care. ■ 

In the gloomy hours of the night, a hungry pit viper 

finds itself in search of a meal. Despite the darkness, 

the snake’s ability to locate its prey is strong and precise 

without visual cues. How is this possible? The viper utilizes a 

unique sensory system—a thermal imaging pit organ where 

neurons embedded in a tissue at the back of the pit can detect 

temperature changes as small as one milli-Kelvin, exposing 

all of the snake’s nearby food options. 

In a recent study published in Proceedings of the National 

Academy of Sciences, Yale physicists Isabella Graf and 

Benjamin Machta were interested in understanding how 

these sensory organs could detect such small temperature 

changes. Using statistical physics concepts and information 

theory, the researchers constructed a simple mathematical 

model that describes the basic parameters of infrared sensing. 

“Our model focuses on how information in temperaturesensitive 

ion channels is aggregated into a collective neural 

response,” Graf said. “We have a mathematical equation for 

how these channels influence voltage dynamics in single 

neurons. We use rather simple dynamic equations that don’t 

depend on space, but just on time.” 

Many biological sensory systems can detect small changes, 

meaning that the scientists’ model may have applications 

outside of the pit viper study. There are numerous examples 

where it’s important to recognize the use of a feedback system 

for sensory adaptation—for instance, in bacteria like E. coli, 

which can sense and move towards certain chemicals in 

their environment. The researchers aim to answer questions 

of how collective sensory organs can detect what individual 

senses can’t catch on their own—a striking example of 

biological innovation. ■ 



FOCUS 

Reproductive Health 

HITTING 

THE PAUSE 

BUTTON 

How Freezing Ovarian 

Tissue Delays Menopause 

BY SARAH LI 

PHOTOGRAPH COURTESY OF THERAPY FOR WOMEN 

Every night, six thousand women experience an internally staged 

rebellion. Waves of heat engulf them, and their skin prickles 

with discomfort. Mood swings become their unwelcome 

companions—a rollercoaster ride of emotions that they can’t control. 

Menopause’s arrival reshapes a woman’s world in unexpected ways. 

Researchers at Yale have pioneered a groundbreaking method to 

potentially delay or eliminate menopause and its unwanted symptoms. 

Kutluk Oktay, a reproductive endocrinology and infertility specialist at 

Yale, led a collaboration between physicians and data scientists aimed 

at modeling the delay of menopause. Their efforts could pioneer a path 

toward innovative interventions that may revolutionize women’s health 

and reproductive options. 

Oktay was the first physician and reproductive surgeon to research and 

complete an ovarian transplant for cancer patients using cryo-banked 

ovarian tissue. He began wondering if his research on preserving fertility 

in cancer patients could be expanded to benefit a larger population. 

Cancer patients often lose their eggs due to chemotherapy, pushing 

them to develop premature menopause. During the procedure, Oktay 

removes a section of ovarian tissue and freezes it, preserving fertility and 

effectively delaying this premature response. No treatment is currently 

available to delay menopause and extend the natural fertility period in 

healthy women, but Oktay suspected ovarian tissue freezing could be a 

successful approach. Because this study would take decades to conduct 

experimentally, Oktay turned to mathematical modeling to begin his 

research. By altering the variable inputs of a previously developed model 

that determines the feasibility of follicle behavior in the human ovary, a 

new modeling system for his research was born. 

“The human ovarian cortex’s primordial follicles (PFs) [are] the key 

to predicting the onset of menopause,” Oktay explained. In women, 

menopause has been biologically determined to occur after the 

depletion of PFs in the ovaries. This is a natural process that starts before 

puberty begins. Using this information and past research as guidance, 

the team put together a model predicting the delay of menopause. They 

considered four main parameters: age of ovarian tissue harvest (twentyone 

to forty years old), amount of ovarian cortex harvested, whether or 

not the transplantation procedure was done in a single step or multiple 

fractions (one or three transplants), and percentage of post-freezing PF 

survival (forty percent is ‘average’, eighty percent is ‘improved’, and one 

hundred percent is hypothetical). 

So, what did the model reveal? First, it confirmed Oktay’s suspicions 

that this procedure could be applied to healthy women. Next, it affirmed 

the impacts of the four parameters on the success of menopause 

delay. The model also suggested that for most women under forty, the 

procedure can postpone menopause, with procedures performed earlier 

in life delaying menopause for longer. The model further found that with 

an increase in the amount of tissue harvested in most women, the delay 

period also increased. Three separate cortex transplantation procedures 

resulted in greater menopause delay than one procedure, and the group 

reported that more procedures would further the delay of menopause. 

However, each additional procedure yields a smaller marginal increase 

in the delay. As expected, the larger the percentage of viable PF in the 

tissue after thawing, the longer menopause can be delayed. 

From these modeled results, the team believes the ovarian 

transplantation procedure is suitable for healthy women to extend 

their fertility period, delaying menopause. In cases where all favorable 

parameters are maximized, the extent to which menopause is delayed 

could surpass the natural lifespan. This means that some women with 

ideal conditions may never experience menopause. Though this may 

seem like a dream, some critics argue that the procedure is working 

against natural biological processes and stress that there could be serious 

consequences for trying to disrupt this natural cycle. The main concern 

is that with an extended estrogen-producing cycle, there is an increased 

risk of breast cancer—an association already observed among women 

who naturally have delayed menopause. “Delaying menopause to sixty 

is well within [the age of] naturally occurring menopause,” Oktay said. 

“You have to do the cost-benefit analysis.” Though there is a risk, it is 

likely outweighed by the improved quality of life afforded by extra 

menopause-free decades. 

Mathematical modeling offers us a glimpse into the future, but all 

models have their limitations. Looking to expand their work, the team 

hopes to apply their research to a clinical setting. With the world of 

medicine becoming more focused on improving quality of life and 

beating the biological clock, this cryopreservation procedure could 

bring icy relief to millions. ■ 


Paleontology 

FOCUS 

IDENTIFYING 

EZEKIEL’S WHEEL 

Honoring the Legacy 

of a Fossil Hunter 

BY FAITH PENA 

PHOTO COURTESY OF PAUL-ALEXANDER LEJAS 

Imagine walking into your friend’s house and finding that 

it’s filled with fossils. Well, that’s exactly what Derek Briggs, 

a professor of earth and planetary sciences and curator of 

invertebrate fossils at the Yale Peabody Museum, encountered 

during his first visit to Samuel J. Ciurca, Jr.’s house some twenty 

years ago. “His entire house was full of eurypterids, such that 

there was hardly anywhere to sit down, which was amazing,” 

Briggs said. Ciurca was a chemist with Kodak in Rochester, 

New York, and a dedicated fossil collector who specialized in 

eurypterids, which are commonly known as sea scorpions. 

One of Ciurca’s most prominent discoveries was a mysterious 

fossil he nicknamed Ezekiel’s Wheel. Ciurca discovered this 

fossil alongside eurypterids in a quarry in southern Ontario. 

Despite his experience, neither he nor others could figure out 

which genus or species Ezekiel’s Wheel belonged to. As a result 

of interactions with Briggs and his group, many thousands of 

Ciurca’s fossils ended up at the Yale Peabody Museum and have 

been studied by Yale students. One of those students, Nicolás 

Mongiardino Koch GSAS ’21, worked with Briggs to resolve 

the nature of Ezekiel’s Wheel. Their success illustrates the 

importance of working with gifted fossil collectors to acquire 

important material for advancing science. 

Even though Ciurca was not a professional paleontologist, 

his approach to fossil collecting was scientific in the way that 

he kept careful notes of the fossils and localities he visited. His 

paleontological exploits focused on western New York and 

southern Ontario, Canada, where a sequence of Silurian rocks 

called the Bertie Group is located. The Silurian period is a 

geologic period of the Paleozoic Era that occurred more than four 

hundred million years ago. Ciurca amassed extensive collections 

from the Bertie Group and became an authority in these rocks 

and the fossils they contain. In the early 2000s, Yale acquired a 

large number of specimens from Ciurca, amounting to over ten 

thousand eurypterids. However, within this collection was the 

unusual specimen that Ciurca called Ezekiel’s Wheel. “The 

fossil itself consists of radiating layers of tubes, and it vaguely 

looks like a wheel,” Briggs said. The wheel-like shape fascinated 

Ciurca, and he wrote on the slab with the most preserved 

version of the specimen: “the most beautiful fossil ever found.” 

Briggs taught a course titled “Extraordinary Glimpses of 

Past Life,’’ where students studied the processes involved 

in preserving exceptional fossils and completed a research 

project as part of the assessment. In 2015, Mongiardino Koch 

was given specimens of Ezekiel’s Wheel for his project and 

made important progress in interpreting its identity. Ciurca 

continued to add fossils to his collection until he died in 2021. 

In the meantime, Yale placed Ciurca’s fossils on temporary 

display at the Peabody Museum, and Briggs and his group wrote 

several papers with him. Upon his death, Ciurca bequeathed 

many additional fossils to Yale, including new examples of 

Ezekiel’s Wheel. With this collection, Briggs and Mongiardino 

Koch were finally able to solve the mystery. A combination of 

careful study of the anatomy and microstructure of the fossils 

and an analysis of its relationships with other fossil species— 

also known as phylogeny—showed that Ezekiel’s Wheel is 

related to a group of tiny pseudocolonial animals called 

cephalodiscids. Today, cephalodiscids are attached to rocks 

on the seabed. Ezekiel’s Wheel, however, is unique among 

cephalodiscids because it has a large float supporting a series 

of radiating tubes, each of which houses a tiny organism. “We 

increased the known range of form of cephalodiscids, living 

and fossil, and added to the number of known fossils in the 

Bertie Group associated with eurypterids,’’ Briggs said. The 

information reveals a new kind of organization that existed 

420 million years ago in the history of marine life. 

All in all, the identification of Ciurca’s Ezekiel’s Wheel 

is one example of how fossil collectors can make an impact 

on paleontology and evolutionary biology. Fossils that are 

difficult to interpret may spend some time sitting in museum 

drawers, but new specimens and methods will eventually reveal 

their secrets and add to our knowledge of the history of life on 

our planet. ■ 



FOCUS 

Social Medicine 

GIVING VOICE TO 

THE VOICELESS 

The Black Youth 

Mental Health Crisis 

BY AIDEN WRIGHT 

IMAGE COURTESY OF AMANDA CALHOUN 

In October 2021, experts in youth mental health declared 

the mental health crisis among children and young adults 

a national emergency. At the time, Amanda Calhoun ’11, 

now Chief Resident of the Yale Albert J. Solnit Integrated Adult/ 

Child Psychiatry program, was focused on studying the status of 

mental health outcomes for one group in particular: Black youth. 

Recent studies have revealed that Black youth face rising suicide 

rates. Calhoun noted that previous psychiatric research has also 

focused on how external factors like poverty, stigma towards 

mental health, and lack of education inhibit Black youth’s ability 

to access mental health care. However, Calhoun’s concerns went 

in a different direction. “As a psychiatry fellow, I couldn’t stop 

thinking about the medical racism Black youth and families 

face when they do access care,” Calhoun said. With this critical 

observation, Calhoun established the Black Youth Mental Health 

Clinical Case Conference Series at Yale. 

The case conference series, which began in January and concludes 

in June, seeks to interrogate real cases of anti-Black medical racism. 

At the center of every event lies a desire to humanize Black youth. 

One way Calhoun achieves this is through storytelling. “I wanted 

everyone to be able to relate to the struggle this child was having 

no matter what their background is,” Calhoun said. “I want people 

to feel like these children are in the room with us.” At the first case 

conference, Calhoun shared the compelling story of Christina, a 

young Black girl who was admitted to the hospital due to “out of 

control” behavior. During her stay, Christina’s already precarious 

situation was exacerbated by incidents of racism from her 

predominantly white medical team. 

Importantly, narratives like Christina’s illuminate how medical 

racism manifests itself. When white medical providers comment 

that Christina’s hair is “wild” or refer to her as the “Tasmanian 

devil,” they invoke a history of anti-Black medical racism. By sharing 

narratives like Christina’s, the case conference series emphasizes an 

important point: her story is not unique. 

Anti-Black racism is deeply embedded in the American 

medical system, and without a concerted effort, Black youth 

seeking mental health care will continue to be victimized. 

Notably, the cases discussed in the conference series are 

anonymized to ensure medical providers do not face 

retaliation. Calhoun herself is no stranger to the backlash 

that can arise from speaking out against medical racism. In 

2021, after giving the keynote speech at the White Coats for 

Black Lives demonstration at the Yale School of Medicine, 

Calhoun was the target of multiple death threats. “The death 

threats were not the most difficult part of being an activist. 

[…] What’s more difficult is getting people to stand up against 

racism,” Calhoun said. This encapsulates the ethos of the case 

conference series: to not only raise awareness but also to find 

solutions to medical racism. 

Another integral feature of the case conference series is the 

commentary of three expert discussants. Though the conference 

delves into issues of mental health, not all of the expert 

discussants are required to have a background in psychiatry. 

“We try to pull from diverse backgrounds,” Calhoun explained. 

“Most children will never see a child psychiatrist, […] but 

they will see their teacher, maybe their counselor, maybe their 

religious leader.” By inviting experts who hail from a variety of 

disciplines, the conference takes an interdisciplinary approach, 

harnessing diverse perspectives to tackle a complex issue. The 

conference is also designed to reflect this same diversity of 

thought in the audience; it is free to register, open to the public, 

and has a hybrid format to encourage attendance. 

In the future, Calhoun hopes the conference will be even more 

widely attended and lead to tangible initiatives and solutions. 

She also plans to consolidate all of the insights and discussions 

from the case conference series into a book that can be used as 

a reference for healthcare professionals. “It feels gratifying to 

take these stories and write [them] on paper. It feels like giving 

voice to the voiceless and giving space to stories that have been 

silenced,” Calhoun said. “There’s a lot of racist behavior in the 

medical system, and it needs to change, and one of the ways to 

do that is to start calling it out.” ■ 


Social Technology 

FOCUS 

I AM ALAN 

TURING 

How Opera Uses AI to 

Tell Turing’s Story 

BY XIMENA LEYVA PERALTA 

IMAGE COURTESY OF JEAN-FRANÇOIS MONETTE 

C 

omposer Matthew Suttor and the team of artists and 

programmers behind the experimental opera I AM ALAN 

TURING have welcomed artificial intelligence (AI) as a 

collaborator. The opera’s libretto blends human-generated and 

machine-generated lyrics and dialogues to explore the life and ideas 

of brilliant computer scientist Alan Turing. Supported by Yale’s Center 

for Collaborative Arts and Media (CCAM), the project presents a new 

model for creating opera in the information age and explores what it 

means to be human in light of AI. 

Suttor, program manager at CCAM and senior lecturer in Theater 

and Performance Studies at Yale, was amazed by Turing’s insights on AI 

while exploring the archive at King’s College, Cambridge, a few years 

ago. In his 1951 lecture “Intelligent Machinery, A Heretical Theory,” 

Turing argued that it is possible to construct machines that closely 

simulate human behavior. Yet, humans should not be afraid of being 

replaced. “There would be plenty to do, trying to understand what the 

machines were trying to say,” Turing wrote. 

Renowned for his work on deciphering Nazi codes during World War 

II, Turing laid the groundwork for modern computing and AI. In 1936, 

he introduced the first theoretical description of a computer, the Turing 

machine. In 1950, he proposed the Turing test, which gauges how well a 

machine can think like a human. If a human cannot distinguish between 

the answers of a machine and another human, then the machine has 

passed the test. 

Suttor first proposed the opera to a group of collaborators in 2019. 

“Right from the very beginning, there was this idea of the opera being 

some kind of Turing test for the audience, so it had this meta kind of 

framework,” Suttor said. It was then that Smita Krishnaswamy, associate 

professor of genetics and computer science at Yale, introduced Suttor 

and his team to representatives of OpenAI. 

At the time, GPT-2 was OpenAI’s latest large language model (LLM)— 

an AI trained to understand and generate natural language—but it lacked 

chat capabilities like its famous successor, ChatGPT. With assistance 

from Yale University Library’s Digital Humanities Lab, Suttor’s team 

created an interface to interact with GPT-2. Through Zoom calls in 2020, 

the team trained the model on various large text datasets and fine-tuned 


it using Turing’s writings. They then posed direct yet philosophically 

profound questions to the model, such as “Can computers think?” They 

experimented with different settings of temperature—the randomness 

of the output—and the number of characters produced, and they almost 

immediately obtained interesting answers. 

The team embraced the AI as an artistic collaborator. “Asking 

questions is also a form of training,” Suttor said. “Interacting with an 

LLM forces you to ask better questions.” Discussing the AI’s outputs was 

extremely valuable for the team from a pedagogical point of view and 

was a powerful exercise in collaboration. 

The opera’s title originated from one of their earliest conversations 

with GPT-2. When asked to produce lyrics for a “sexy” song about 

Turing, the AI came up with “I’m a Turing machine, Baby.” The AI is 

so integrated into the opera that even Suttor and his team cannot tell 

machine-generated text apart from human-generated text. 

Beyond the libretto, the opera incorporates AI and aspects of Turing’s 

work in other areas. Some AI-generated images of Turing, Suttor, and his 

team are used throughout the production. GPT-2 was also used to write 

code snippets for creating animations featured during the performance. 

Even Turing’s later works on mathematical biology come into play. 

Based on Turing’s diagrams of spiral patterns in sunflower seeds, Suttor 

created unique harmonic progressions by tracing equivalent spirals onto 

the circle of fifths, a method of organizing pitches in music theory. These 

progressions underpin much of the opera. 

Suttor and his team recently presented a work-in-progress 

performance of I AM ALAN TURING at the CCAM as part of the 

Machine as Medium Symposium: Matter and Spirit. The event explored 

how AI and creativity intersect and give rise to new approaches to 

timeless questions about human existence. 

In its current form, the opera spans eight music pieces across various 

genres, but there’s still more work to be done. Suttor is excited to see how 

the project continues to evolve through workshops and collaborations 

between humans and machines. In light of the latest AI surge, I AM 

ALAN TURING serves as a testament to Turing’s enduring influence 

and the boundless possibilities when art and technology converge to 

explore the essence of humanity. ■ 


FOCUS 

Genetics 

SINK 

SWIM 

When sperm lose their ability to 

swim, the chances of conception 

take a dip as well. Around eighty 

percent of male patients with infertility have 

defects in their sperm motility, which refers 

to the sperm’s ability to move effectively 

and ultimately reach and fertilize an egg. 

Yet pinpointing the exact causes of these 

defects is surprisingly difficult. 

In a recent study, researchers from the 

Yale School of Medicine and Quaid-i- 

Azam University in Pakistan collaborated 

to tackle this problem. “The majority of 

the mutations of these kinds of fertility 

OR 

A New Explanation for Male Infertility 

BY ANYA RAZMI 

ART BY LUNA AGUILAR 

genes are really hard to identify because, 

by nature, infertility genes or mutations 

affecting fertility don’t pass on to the next 

generation,” said Jean-Ju Chung, a senior 

author on the study. 

Pakistani colleagues on Chung’s team 

collected blood and semen samples from the 

members of a family with hereditary male 

infertility caused by low sperm motility. 

Because the samples had similar genetics, 

it was easier to isolate which mutation 

was specifically tied to infertility. Using 

a type of DNA sequencing called whole 

exome sequencing, the scientists were able 

to identify a gene mutation that caused a 

defect in a protein component of sperm 

called leucine-rich repeat-containing 23 

(LRRC23). LRRC23 was truncated, meaning 

the protein was cut short. 

This left scientists with a question: 

how exactly might this defective protein 

cause infertility? 

Demystifying the Role of LRRC23 

Using CRISPR/Cas9, a gene-editing 

technology that allows researchers to 

target specific DNA sequences, the team 

was able to reproduce the human mutation 

in mice. Then, they studied sperm cells 

from the animals via a computer-assisted 

sperm analyzer to measure sperm motility. 

Live sperm cells were recorded using a 

video camera and their movement was 

tracked using special software which 

calculated the velocity and path of each 

cell. The data showed exactly what the 

scientists expected: the sperm could not 

swim properly, and the mice were infertile. 

“Biology is intricate and everything should 

be coordinated,” Chung said. Therefore, 

a structural defect in a single protein can 

affect the entire movement of the sperm. 

Sperm swim using flagella—small, hairlike 

structures that beat back and forth 

to generate cell movement. Flagella are 

composed of nine sets of microtubules: 


Genetics 

FOCUS 

hollow, tubular structures that run 

along the flagellum. These microtubules 

are connected in the core of flagella by 

T-shaped multiprotein complexes called 

radial spokes. Made up of “head” and 

“stalk” components, radial spokes are 

essential for controlling how the cilia and 

flagella beat—and by extension, controlling 

how sperm move. 

The researchers demonstrated that 

the protein LRRC23 is a crucial head 

component of a specific radial spoke, radial 

spoke 3 (RS3). Chung’s team collaborated 

with the Zhang lab in Yale’s Department 

of Molecular Biophysics and Biochemistry 

to use a technique called cryo-electron 

tomography, a powerful imaging tool that 

bombards frozen samples with electrons to 

create high-resolution, three-dimensional 

representations of molecular structures. 

The advantage of cryo-electron tomography 

is that live samples can be observed on a 

highly magnified scale. “This technique is 

now the leading technique in structural 

biology,” Chung said. 

Chung’s team was able to visualize the 

structure of sperm with and without 

the genetic mutation. In samples where 

LRRC23 was defective, the entire head 

region of RS3 was missing. This affected 

how the microtubules in sperm cilia and 

flagella interacted, leading to decreased 

sperm motility. 

Flipping the Script on LRRC23 

Before this study, scientists thought that 

LRRC23 was a stalk protein rather than 

a head protein. Indeed, it was believed 

that LRRC23 was a homolog of the RS2 

stalk protein RSP15—in other words, 

researchers thought LRRC23 and RSP15 

shared a common ancestor and therefore 

might have similar functions. The 

problem, Chung’s team realized, was 

that RSP15 is a protein found in a type 

of algae called Chlamydomonas—and 

RS3 in Chlamydomonas doesn’t have a 

head component. 

To put this long-held notion to the test, 

the scientists used biochemical analyses to 

track the evolution of LRRC23 and observe 

its interactions with other proteins. If 

LRRC23 were indeed a stalk protein, it 

would have been expected to interact with 

other known stalk proteins. Instead, it 

only interacted with head proteins. 

“We actually found out that LRRC34, not 


LRRC23, looked like a mammalian RSP15 

homolog, which conflicts with the major 

paradigm in the field,” Chung said. She 

and her team concluded that LRRC23 

must be a head protein—specifically, a 

head component of RS3. This critical 

discovery gives researchers new insights 

into the structure and function of LRRC23. 

The journey to this finding was not 

without obstacles. Halfway through the 

study, another research team published 

an article making similar connections 

between the gene Chung’s team was 

studying and male infertility. “It was 

disappointing in the moment,” Chung 

said. But Jae Yeon Hwang, the first 

author of the study, didn’t give up. 

He encouraged the team to continue 

studying LRRC23, and they ultimately 

discovered the protein’s role as a head 

rather than stalk protein. “We were able 

to make a different conclusion which 

turned out to be validated at multiple 

levels, including evolution, genetics, 

biochemistry, and structure,” Chung said. 

“It was a comprehensive and satisfying story 

as a scientist and highlights the power of 

interdisciplinary collaboration.” 

But the story doesn’t end here. The 

team plans on pushing their work up to 

the atomic resolution. “Our next step 

is doing a proteomic study to really 

figure out the molecular composition 

and architecture of the radial spoke 

protein,” Chung said. This entails a 

comprehensive examination of all the 

proteins present in a biological sample, 

which will give researchers even more 

information about how exactly LRRC23 

dysfunction causes male infertility. 

ABOUT THE AUTHOR 

Clinical Implications 

For Chung, the most satisfying part of her 

research is its potential translation into clinical 

practice. “This study in particular is linked 

to real, human patients,” she said. Identifying 

genes that reduce sperm motility will allow 

couples to be more informed about their 

fertility journeys. With a comprehensive, 

compiled list of genes causing fertility defects, 

clinics can conduct genetic screening to 

inform clients of their chances of conception. 

Further, they can tell couples if their future 

children might have a risk of being infertile 

when they grow up. 

“By human nature, [couples] not only want 

to get treated, they also want to understand 

why they can’t conceive,” Chung said. Once 

couples have a better scientific understanding 

of why they might be infertile, it becomes 

easier to suggest treatment or new options 

for conception. 

There is still hope for patients with defective 

LRRC23 proteins. A technique called 

intracytoplasmic sperm injection can be 

used on men who have low sperm motility. 

Intracytoplasmic sperm injection is a type 

of in vitro fertilization in which a healthcare 

provider chooses a healthy-looking sperm 

and uses a needle to inject this sperm directly 

into an egg. Then, the resulting embryo is 

transferred to the uterus of the female partner. 

“The success rate may be low, but they 

can still conceive,” Chung said. “The 

process can be mentally, physically, and 

emotionally painful for women.” Chung 

hopes that her team’s work will lead to a 

better understanding of the regulatory 

mechanisms behind low sperm motility— 

and to better chances for conception. ■ 

ANYA RAZMI 

Anya Razmi is a senior in Pierson majoring in English with a Concentration in Writing. In addition 

to writing for YSM, she is a content designer, a Writing Partner, an Academic Strategies mentor, 

an editor for the literary magazine The Foundationalist, and is working to create a novel menstrual 

product with the startup Sprxng. 

THE AUTHOR WOULD LIKE TO THANK Dr. Jean-Ju Chang for her time and dedication to her work. 

REFERENCES: 

Hwang, J. Y., Chai, P., Nawaz, S., Choi, J., Lopez-Giraldez, F., Hussain, S., Bilguvar, K., Mane, S., 

Lifton, R. P., Ahmad, W., Zhang, K., & Chung, J.-J. (2023). LRRC23 truncation impairs radial 

spoke 3 head assembly and sperm motility underlying male infertility. eLife, 12. https://doi. 

org/10.7554/elife.90095.3 


FOCUS 

Immunology 

A NEW IMMUNE 

DRUG? 

HOW STRESS, 

WHITE BLOOD CELLS, 

AND IMMUNITY 

INTERSECT IN A485 

BY YOSSI MOFF 

ART BY CARA CHONG 

Our bodies are constantly under siege 

by dangerous pathogens. Thankfully, 

our biological systems have 

developed immune defenses to fight off these 

pathogens and stave off illness. White blood 

cells, which are produced by bone marrow, lie 

at the center of our immune system. Without 

them, we cannot fight off disease. For patients 

with bone marrow damage, however, this 

shield is compromised. 

Currently, there are a few ways to fight off 

disease in spite of injured bone marrow, such 

as antibiotics, immunoglobulin therapy, and 

drug treatments to stimulate white blood cell 

production. In many cases, though, these 

treatments fall short. Thanks to recent work 

by Nikolai Jaschke, a postdoctoral researcher 

in the Wang lab at Yale, that might change. 

Jaschke discovered new therapeutic potential 

in a synthetic molecule called A485, which 

was originally developed by a pharmaceutical 

company named AbbVie in 2017. He 

theorized that A485, which previously 

demonstrated potential anti-tumor effects, 

may have more effects than what its original 

characterization suggested—among them, 

a mechanism to combat infection in people 

with injured bone marrow. 

Putting A485 to the Test 

Produced by bone marrow, white blood 

cells enter the bloodstream and tissues, where 

they can rally against pathogens to protect 

from infection. If bone marrow is injured or 

experiences failure, it is unable to produce 

sufficient numbers of white blood cells. A 

severely low white blood cell count leads to an 

increased risk of infection and complication. 

Currently, patients who exhibit bone 

marrow failure are treated with granulocyte 

colony-stimulating factor (G-CSF). G-CSF is 

naturally produced by the body to stimulate 

the production of neutrophil granulocytes, 

the white blood cells that form the front line 

of defense against infection. G-CSF has also 

been developed into a drug administered 

to counteract a drop in white blood cells, 

known as neutropenia. However, some 

patients treated with G-CSF following bone 

marrow injury may still develop neutropenia 

and subsequent infection. This complication 

is known as acute neutropenic fever and is 

currently hard to tackle therapeutically. 

Enter Jaschke and his research on A485. 

Previously published research on A485 by 

AbbVie had shown that A485 could inhibit a 

histone acetyltransferase domain. Mutations 

in this domain are often associated with 

leukemia, a cancer characterized by the 

uncontrolled release of blood cells. Thus, 

Jaschke posited that A485, by temporarily 

inhibiting this leukemia-inducing region, 


Immunology 

FOCUS 

may be able to trigger the release of white 

blood cells. 

Now, this hypothesis had to be tested. 

First, Jaschke demonstrated that A485 

increases neutrophil mobilization into the 

bloodstream. Specifically, he found that 

mice treated with both G-CSF and A485 had 

significantly greater neutrophil mobilization 

than mice treated with just G-CSF or A485 

alone. However, while the effects of G-CSF 

are more prolonged (white blood cell counts 

remain at higher levels for a long time), only 

twelve hours after the injection of A485, 

the white blood cell count dropped back to 

pre-administration levels.. This rapid return 

to baseline levels reduces the likelihood of 

side effects and enables greater precision in 

treatment administration. “What we showed 

was that this increase in white blood cells 

is sufficient to clear a substantial amount of 

bacteria from the blood. And of course, if 

you clear a lot of the pathogen that is trying 

to destroy your tissues and compromise your 

health, you will ultimately end up in a better 

place than another mouse or a patient that 

didn’t receive this therapy,” Jaschke said. 

The researchers then took their work a 

step further. Bone marrow injury can 

often affect cancer patients undergoing 

chemotherapy. Chemotherapy targets are 

rapidly proliferating cell types, including 

those in the bone marrow. Thus, bone 

marrow injury often emerges as a side effect 

of the primary purpose of killing cancerous 

cells when administering chemotherapy. 

To simulate the bone marrow 

injury of chemotherapy-treated 

cancer patients, Jaschke used a mouse 

model of chemotherapy-induced bone 

injury. They infected the mice with a 

bacterium called Listeria monocytogenes, 

causing a systemic infection of the bacteria 

in the mice. Following infection, the mice 

were treated either with A485 or an empty 

control after the point of infection. They 

found that a significantly higher percentage 

of A485-treated mice survived the infection 

compared to the control group, despite both 

having initially low white blood cell counts. 

The “Stress” Axis 

Though the researchers’ results 

revealed the powerful effects of A485, the 

mechanism behind its activity remained a 

mystery. After many different experiments, 

Jaschke found that A485 treatment greatly 

increased levels of corticosterone, the 


mouse corollary to human cortisol. Thus, 

he reasoned, A485 must work through the 

hypothalamic-pituitary-adrenal axis, or 

“stress” axis. The hypothalamic-pituitaryadrenal 

axis is a set of endocrine pathways 

associated with the production and 

circulation of various stress hormones, 

including cortisol. But Jaschke found 

something unexpected—A485 activity 

did not rely upon corticosterone at all. 

Instead, intermediary molecules like 

adrenocorticotropic hormone (ACTH) 

helped facilitate the effects of A485. Based 

on these findings, Jaschke and his team 

proposed that ACTH must be more 

than simply an intermediate, opening 

new doors of research into additional 

functions of ACTH. 

Jaschke had begun his work on A485 

in Germany, performing the bulk of the 

research there. Upon joining the Wang 

lab at Yale, Jaschke was able to complete 

his infection models and fully address his 

hypothesis. “There were a lot of things that 

could not be done in Germany; a lot of the 

conceptual framework was substantially 

rejiggered. It became a very different story 

in [Jaschke’s] time here,” said Andrew 

Wang, the principal investigator of the 

lab and an associate professor of internal 

medicine at the Yale School of Medicine. 

The Wang lab focuses on how a patient's 

state of mind affects how they manifest 

disease and respond to treatments. A big 

mystery for Wang and his lab is why white 

blood cells are released upon feelings 

of stress—there is no tissue damage or 

infection, so what are the white cells being 

mobilized for? While this big question 

remains largely unanswered, Jaschke’s work 

revealed a direct correlation between white 


blood cells and the stress pathways of our 

body. He showed that white blood cells 

rely upon an aspect of the stress axis to be 

released and mobilized against the disease. 

A New Immune Drug? 

Jaschke considered his findings curious 

but also warned the public against 

jumping to any conclusions. “This is an 

interesting observation, but it doesn’t 

mean that this has any therapeutic 

relevance for humans,” Jaschke said. He 

emphasized the need for extensive further 

testing before any clinical treatments 

could be made with A485, especially 

given the limitations of his research. For 

instance, the study exclusively used L. 

monocytogenes for infection models; the 

results of this one infection model cannot 

automatically be generalized to the whole 

range of harmful human infections. Also, 

the researchers knew the precise disease 

type and its time of onset in the mice, 

which is rarely the case in real-world 

clinical practice. 

Ambitions of A485 entering the clinical 

scene as a drug to recruit white blood 

cells to fight disease remain. But Jaschke 

knows that the next steps are largely out 

of his hands. “For me personally, I’ve done 

the work I wanted to do. [...] If there is an 

interest from a larger scale to really screen 

it in the clinics, it would be great,” Jaschke 

said. The next crucial step for A485 is to 

become an approved drug in clinical trials, 

beginning with more mouse models and 

eventually evaluations for safety in humans. 

If successful, patients battling infection 

with an injured bone marrow could look to 

A485 for hope. ■ 

YOSSI MOFF 

YOSSI MOFF is a first-year student in Saybrook College. Currently undecided, he is planning to 

pursue the Molecular, Cellular, and Developmental Biology major. In addition to writing for YSM, 

Yossi recently became one of its copy editors. Yossi is involved with the Slifka Center for Jewish 

Life and is an avid intramural sports participant. 

THE AUTHOR WOULD LIKE TO THANK Nikolai Jaschke and Andrew Wang for sharing their 

expertise and enthusiasm in their field. 

REFERENCES: 

Jaschke, N. P., Breining, D., Hofmann, M., Pählig, S., Baschant, U., Oertel, R., Traikov, S., Grinenko, 

T., Saettini, F., Biondi, A., Stylianou, M., Bringmann, H., Zhang, C., Yoshida, T. M., Weidner, H., 

Poller, W. C., Swirski, F. K., Göbel, A., Hofbauer, L. C.,…Rachner, T. D. (2024). Small-molecule 

CBP/p300 histone acetyltransferase inhibition mobilizes leukocytes from the bone marrow 

via the endocrine stress response. Immunity, 57(2), 364–378. e9. https://doi.org/10.1016/j. 

immuni.2024.01.005 


FOCUS 

Environmental Computational Engineering Biology 

AIRBORNE MYSTERIES 

Challenging Air Pollution Estimates Across Canada’s Oil Sands 

By abigail jolteus 

Art by Kara Tao 


Environmental Engineering 

FOCUS 

Oil production is estimated to be 

responsible for around fifteen 

percent of total global energy- 

related emissions. From extraction to 

refining to consumption, various stages of 

oil production are heavily associated with air 

pollution. But our ability to estimate organic 

carbon emissions from these processes 

may be threatened by the emergence of 

more unconventional oil sources in recent 

decades. Two of these sources, heavy oil and 

bitumen deposits, are projected to account 

for about forty percent of oil production by 

the year 2040. 

In a recent paper published in Science, 

a team of researchers from Yale and 

Environment and Climate Change Canada, 

a department of the Canadian government, 

examined the magnitude and impact of 

traditionally unmonitored gases on total 

organic carbon emissions. 

Addressing Overlooked Air Pollutants 

Organic carbon emissions, or gaseous 

organic compounds, refer to substances 

containing carbon and hydrogen that are 

released into the atmosphere. Historically, 

studies on carbon emissions have focused 

on volatile organic compounds (VOCs), 

a subset of organic carbon emissions that 

have short- and long-term adverse effects on 

human health and the environment. “These 

compounds pose both environmental and 

human health risks,” said Lexie Gardner 

(YC ’23), a co-author of the study and 

environmental engineer at CDM Smith. 

Short-term health effects include respiratory 

irritation, headaches, dizziness, and fatigue, 

while more long-term effects include cancer, 

organ damage, and neurological effects. 

While certain subsets are typically the 

focus of monitoring and industry reporting, 

many types of emissions go unmonitored— 

including emissions that still contribute 

greatly to air pollution. These compounds 

include intermediate-volatility organic 

compounds (IVOCs) and semivolatile 

organic compounds (SVOCs). Their 

volatility, or tendency to evaporate at a given 

temperature, influences their emissions 

and abundance in the atmosphere, though 

they all undergo chemical reactions in the 

atmosphere that affect air quality. Up until 

now, they have largely gone unmonitored 

compared to VOCs. “There are opportunities 

for improvement in emissions reporting,” 

said Drew Gentner, an associate professor of 

chemical and environmental engineering at 


Yale and senior author of the study. 

Studying unmonitored gases is 

particularly important because the reported 

concentration of emissions helps dictate 

policy on environmental regulations. Air 

pollution contributes to the worsening 

effects of climate change, which has direct 

ramifications on legislation. “Organic 

carbon emissions encompass a wide range 

of species with a diverse range of sizes and 

functionalities,” said Megan He (YC '22), 

the lead author of the study and a current 

graduate student at Harvard University. “For 

typical research and reporting purposes, 

it is hard to measure all of these individual 

species together,” He said. 

Underreporting by Canadian Oil Sands 

Operations 

Oil sands are a critical contributor to 

the majority of Canadian oil production, 

particularly in the Athabasca oil sands 

regions in northern Alberta, which make 

up about two-thirds of Canadian oil 

production. Oil sands provide a substantial 

source of unconventional petroleum, 

which refers to compounds of hydrogens 

and carbons (hydrocarbons) extracted 

from unconventional sources, such as tight 

reservoirs and oil sands themselves. Special 

extraction and processing techniques 

are used to extract these compounds 

from unconventional sources compared 

to conventional ones. Oil sands, often 

incorrectly known as tar sands, are composed 

of bitumen—a heavier version of crude oil— 

sand, and clay. The bitumen is separated 

from the sand and the clay and is then refined 

into various petroleum products. However, 

the extraction and processing techniques 

pose several environmental challenges, one 

of which is their impact on air quality. 

The researchers were interested in using 

new measurements to quantify the total 

carbon emissions and compare those values 

to estimates reported by the industry on the 

Athabasca oil sands. They performed both 

airborne measurements and supplementary 

laboratory experiments. 

The first experiment they did was to 

collect air samples and later analyze their 

contents. The researchers used an aircraft 

to measure the total carbon emissions in the 

Athabasca oil sands. A total of thirty flights 

were conducted flying both upwind and 

downwind near five different facilities, some 

of which were for surface mining and others 

for in situ mining. Surface mining consists 

of the removal of overlying rock or soil to 

access the valuable minerals underneath 

and is ideal when the minerals are located 

close to the surface. In situ mining consists 

of extracting minerals directly from their 

location without the removal of overlying 

rock or soil. The five facilities were Syncrude 

Mildred Lake, Suncor, Canadian Natural 

Resources, Imperial Kearl Lake, and MJP 

Petroleum Corporation. 

“The aircrafts were equipped with 

instruments capable of analyzing gas-phase 

organic pollutants and were supplemented 

by samples taken in the field,” Gardner 

said. After the samples were analyzed, 

the researchers found that the total 

reported annual carbon emissions were 

underestimated by about 1,900 percent 

to over 6,300 percent, depending on the 

respective facility. The researchers focused 

on the three facilities that had the highest 

carbon emissions, which were Syncrude 

Mildred Lake, Suncor, and Canadian Natural 

Resources. Of the three facilities, Syncrude 

Mildred Lake was found to have the highest 

IMAGE COURTESY OF FLICKR 

Various stages of oil production contribute to global emissions. Offshore oil rigs, constructed for the extraction, 

storage, and processing of oil, release vast amounts of greenhouse gases into the atmosphere. 


FOCUS 

Environmental Engineering 


The Keystone Pipeline System transports crude oil from the Athabasca oil sands in Alberta, Canada, to various destinations 

in the United States. 

percentage difference between estimated 

carbon emissions and reported values (6,324 

percent), while Canadian Natural Resources 

had the lowest difference (1,922 percent). 

“The benefit of a total gas-phase organic 

carbon measurement is that you convert 

all of the complex mixture of organic 

carbon compounds to carbon dioxide with 

a catalyst and just measure the produced 

carbon dioxide,” Gentner said. This means 

that instead of individually quantifying 

each organic carbon compound present 

in the atmosphere, the researchers were 

able to directly measure carbon content, 

streamlining the measurement process. 

Consequently, IVOCs and SVOCs are just 

as much a part of the equation as VOCs 

normally are. However, this conversion 

makes it difficult to attribute respective 

measurements to the specific organic 

carbon compounds. Thus, additional 

measurements were necessary to conduct 

the experiments and distinguish between 

different organic compounds. In addition, 

based on observations from the aircraft, 

the researchers determined that non- 

combustion-related sources largely 

contribute to the emissions. “[This] is likely 

contributed to by a range of on-site sources 

across the lifecycle of oil sands extraction 

[and] processing,” He said. 

Supplementary experiments were 

conducted to determine whether mature 

fine tailings also contributed to the total 

organic carbon observed during the flights. 

Mature fine tailings are structures that 

are built into the earth and house mining 

waste from oil sands. This waste consists 

of a mixture of particles, such as sand, clay, 

and silt, which are difficult to separate 

from wastewater and serve as a persistent 

environmental pollutant. Over time, off- 

gassing emissions—emissions released 

under normal environmental conditions— 

were measured. The magnitude and chemical 

composition of emissions were determined, 

and the researchers demonstrated that 

mature fine tailings contribute to the total 

organic carbon observed. 

“The collection of aircraft and laboratory 

measurements in the study demonstrates 

the importance of considering life-cycle- 

wide emissions, spanning from mining 

through waste management and disposal,” 

Gentner said. 

Limitations of Aircraft-Based Emissions 

Monitoring 

These new aircraft-based measurements 

elucidated stark differences between the total 

reported annual carbon emissions compared 

to the total annual carbon emission estimates, 

calling for a need to better monitor the impact 

of oil production on our climate. However, 

there are a few limitations to this study. 

Methane is responsible for approximately 


sixteen percent of global emissions, making 

it the second-largest contributor to climate 

warming after carbon dioxide. Despite being 

one of the most abundant greenhouse gases, it 

was excluded from the study. “Other research 

by Environment and Climate Change 

Canada has specifically examined methane 

[and carbon dioxide] emissions,” He said. 

Thus, the researchers decided to specifically 

focus on VOCs, IVOCs, and SVOCs, which 

methane does not fall under. 

In addition, it may be difficult to use 

aircraft-based measurements in other cases 

beyond Canada’s oil sands due to sensitivity. 

“Generally speaking, aircraft-based 

measurements are challenging since you have 

an array of sensitive instrumentation on the 

aircraft that you are preparing for each flight,” 

Gentner said. The researchers were careful to 

adequately calibrate and monitor each flight 

to prevent any inaccurate measurements. 

Improving Reporting of Total Organic 

Carbon Emissions 

Ultimately, the findings from this 

study can help inform future policy. The 

researchers identified challenges with 

reporting and monitoring diverse gaseous 

organic compounds but also highlighted 

the necessity of obtaining comprehensive 

emissions data. With these new methods 

for quantifying total carbon emissions 

beyond VOCs, policymakers will be able 

to determine which programs must be 

implemented. As we seek to mitigate 

worsening climate change, it is imperative to 

have accurate measurements of total carbon 

emissions to create accurate, effective, 

and crucial environmental policies and 

regulations across the globe. ■ 

ABIGAIL JOLTEUS 

ABIGAIL JOLTEUS is a junior in Berkeley College from Toronto, Canada, and West Palm Beach, Florida. 

Outside of YSM, she conducts research in the Konnikova Lab. She enjoys poeticizing the mundane, the 

smell of books, and the sound of rain. She also loves canoeing, swimming, and gardening. 

THE AUTHOR WOULD LIKE TO THANK Megan He, Lexie Gardner, and Drew Gentner for their time, 

dedicaton, and expertise. 

FURTHER READING: 

Liggio, J., Li, S. M., Hayden, K., Taha, Y. M., Stroud, C., Darlington, A., Drollette, B. D., Gordon, M., Lee, P., 

Liu, P., Leithead, A., Moussa, S. G., Wang, D., O'Brien, J., Mittermeier, R. L., Brook, J. R., Lu, G., Staebler, R. 

M., Han, Y.,…Gentner, D. R. (2016). Oil sands operations as a large source of secondary organic aerosols. 

Nature, 534(7605), 91–94. https://doi.org/10.1038/nature17646 

Rios, B., Díaz-Esteban, Y., & Raga, G. B. (2023). Smoke emissions from biomass burning in Central Mexico 

and their impact on air quality in Mexico City: May 2019 case study. Science of the Total Environment, 904, 

166912. https://doi.org/10.1016/j.scitotenv.2023.16691 


Astrochemistry 

FOCUS 

Cosmic Time 

Capsules 

Carbonic Clues from Ancient 

Asteroid Molecules 


By Diya Naik and Max Watzky 

Art by Cara Chong 


FOCUS 


A 

little beyond Earth, an unassuming 

lump of rock quietly orbits around 

the Sun. This is the asteroid 

(162173) Ryugu, and although it may 

not seem impressive at first glance, it has 

borne witness to billions of years of cosmic 

history. Ryugu was forged in the furnace of 

the early Solar System when the Sun was 

still a young protostar and the planets were 

nothing more than knots of gas, dust, and 

rock in a churning disk. Devoid of active 

geological processes or atmosphere, Ryugu’s 

composition has remained unchanged since 

its birth, making it a perfect chemical 

time capsule. 

So, when the Japanese spacecraft 

Hayabusa2 returned with samples from 

Ryugu’s surface, it held the promise of 

unlocking new insights into the chemical 

history of our solar system, and, perhaps, 

shedding light on the origins of life 

on Earth. The international team that 

analyzed the Ryugu samples consisted 

of experts from various academic fields 

including astrophysicists, statisticians, 

biologists, geologists, chemists, and 

more. In just four years since Hayabusa2’s 

return, this team has already made 

remarkable discoveries about the 

samples’ composition, such as identifying 

the presence of nucleobases (the building 

blocks of genetic material) and amino 

acids (the building blocks of proteins). 

Two of the key scientists on the project 

were Sarah S. Zeichner, a postdoctoral 

researcher in geochemistry at the California 

Institute of Technology, and José C. Aponte, 

an astrochemist at NASA. 

In a recent study, their team used the 

Ryugu samples to uncover clues about 

the cosmic origins of a special class of 

organic molecules: polycyclic aromatic 

hydrocarbons (PAHs). 

Carbonic Clues 

Until recently, the study of the 

chemical history of the Solar System has 

been limited to studying meteorites— 

meteoroids that have fallen to Earth. 

But this can be problematic: only certain 

kinds of meteoroids can survive the 

perilous journey through the atmosphere, 

and their chemical composition might 

be altered once they hit the ground. It’s 

important to look at returned samples 

rather than meteorites because especially 

for organic molecules, it’s very easy for 

meteorites to become contaminated 

[once they fall onto the surface of 

Earth],” Zeichner said. “In addition, 

the atmosphere is very discriminating 

in terms of what meteorites can make 

it to Earth, which we think creates a 

preservation bias.” That’s why sending 

a spacecraft directly to Ryugu for 

samples—rather than waiting for it to 

come to us—was so appealing. 

Zeichner and her team focused their 

study on PAHs within the Ryugu samples. 

PAHs are rings of carbon and hydrogen 

that range from the humble six-carbon 

benzene to sixty-carbon behemoths. 

“PAHs are produced through many 

natural processes here on Earth,” said 

Allison Karp, a post-doctoral researcher 

at Yale and co-author of the study. “They 

are found in petroleum products and [are] 

considered EPA-regulated pollutants. They 

are also produced through biomass burning.” 

PAHs are interesting for several reasons. 

First, they are similar to refractory 

carbon, which is a type of long-lasting 

organic compound. Refractory carbon is 

the oldest kind of organic matter present 

in Earth’s rock record and is thus key to 

understanding the development of life. 

Second, PAHs are ubiquitous throughout 

the galaxy and represent a significant 

portion of the galactic carbon budget. 

Radio surveys have shown that PAHs 

make up around twenty percent of all 

carbon in the Milky Way, making them 

important tracers for carbon chemistry 

on the largest scales. Terrestrial and 

extraterrestrial carbon compounds can 

be distinguished by the ratios of carbon 

isotopes they have. Carbon isotopes are 

different versions of carbon atoms, where 

the number of neutrons in the nucleus 

varies. On Earth, the isotope carbon-12 

( 12 C), which contains six protons and six 

neutrons, is much more common than 

carbon-13 ( 13 C), which has an additional 

neutron. Both isotopes are stable and nonradioactive. 

Aponte explained that the 

prevalence of 12 C is due to biology favoring 

it. “Biological processes require [using] 

the least possible amount of energy,” 

Aponte said. This preference arises 

because breaking bonds between two 12 C 

atoms requires less energy than breaking 

bonds between two 13 C atoms. In the Solar 

System, however, the ratio of 12 C to 13 C is 

much lower. Checking the approximate 

ratio between the two isotopes helps verify 

whether the detected PAHs are actually 

from space. 

Examining the ratio of isotopes with 

more refinement can also help discern 

which pathways for PAH formation are 

most likely. Although the precise origins 

of PAHs remain unknown, several 

hypotheses have been proposed to explain 

their formation. The most widely accepted 

hypothesis is that PAHs were formed in 

a “hot” process, forged in the scorching, 

energetic environments around dying stars. 

However, there is a flaw in this hypothesis. 

“Once PAHs are expelled into interstellar 

space, they are quickly broken down by UV 

and shockwave radiation, about as fast as 

they can be created in stellar environments. 

But how can these timescales be similar if 

PAHs make up twenty percent of the carbon 

in the galaxy?” Zeichner said. In other 

words, if PAHs can be easily broken down 

with common processes, there shouldn’t be 

so many of them. 

A New Origin Story 

IMAGE COURTESY OF WIKIMEDIA COMMONS 

The asteroid Ryugu imaged by the Hayabusa2 lander. 

The fact that PAHs have accumulated 

to such an enormous extent indicates that 

another formation mechanism must be at 

play. Astrochemists have proposed that 

PAHs could also be formed in the interstellar 

medium, which exists in the space between 

stars within a galaxy. Specifically, they 

believe that PAHs could be formed in 

molecular clouds—dense regions of gas 

and dust that serve as nurseries for young 

stars—within the interstellar medium. But 

molecular clouds are cold—about ten 

Kelvin, or 260 degrees Celsius below 

the freezing point—meaning that only 



FOCUS 

very low-energy molecules could form 

there. In such environments, PAHs are 

more likely to be formed with highermass 

isotopes of carbon, such as 13 C, 

due to the lower energy required to form 

bonds. In the case where a PAH has two 

13 

C atoms, which is called a double- 13 C 

substitution, the energy is lowered even 

more. “At very cold temperatures, having 

this isotopic substitution really matters 

for the stability of the molecule. So by 

measuring the amount of double-13C 

substitutions in the molecules within 

extraterrestrial samples, we can see 

if they carry the fingerprint of cold, 

interstellar chemistry,” Zeichner said. 

Zeichner and her team set out to do 

just that, using the 13 C concentrations in 

Ryugu’s PAHs to probe how they might 

have formed. But the team faced a problem: 

they had almost no PAHs to analyze. The 

team had only been allocated a few drops of 

dissolved rock samples to work with. “The 

PAHs in the sample [...] were three orders 

of magnitude lower than the concentration 

you would need to do traditional isotope 

measurements,” Zeichner said. In the end, 

Zeichner found a way around this problem 

using new techniques to eliminate the 

noise from her mass spectrometer, which 

measures the mass of molecules and can 

be used to measure the content of different 

isotopes. Using this tool, her team was able 

to make precise measurements of the 13 C 

isotopes in the rock samples, recording their 

abundance in five different types of PAHs. 

Zeichner also used a similar spectroscopic 

process on the carbon-based Murchison 

meteorite, which is approximately seven 

billion years old. Although it may have 

experienced some alteration in its chemical 

composition during its journey through the 

Earth’s atmosphere, the scientists believed 

that data gathered from its samples could 

help with gaining a better understanding 

of the results from Ryugu. After further 

spectroscopic measurements and rigorous 

statistical analysis, the results were in, and 

they were surprising. 

Cold Beginnings 

Both the Ryugu and Murchison samples had 

elevated values of 13 C. “Within three of the five 

PAHs we measured, we saw an enrichment 

in the double- 13 C content [within PAHs] 

relative to what we would expect if they were 

distributed randomly,” said Zeichner of the 

Ryugu sample. These low-energy molecules 

likely formed in an abnormally cold, energydepleted 

environment, providing some 

of the first solid evidence that PAHs are 

formed in molecular clouds. Additionally, the 

highest quantities of 13 C were recorded from 

Murchison for fluoranthene—a specific PAH. 

The exact value matched what the team had 

expected to observe if the PAHs were indeed 

synthesized in the cold interstellar medium. 

Thus, for Ryugu and Murchison, it 

appeared that both the carbon bond 

formation and the linking of aromatic 

carbon rings happened at low temperatures. 

Although “hot” processes would have 

partially contributed to PAH formation, the 

chemical analysis pointed to cold formation 

being the dominant process. 

This result has broad implications for the 

synthesis of all kinds of organic compounds, 

which are key for the development of life. 

“Knowing that a small bit of you could have 

originated from processes in interstellar 

clouds, far out in space, is a profound thing 

to think about,” Zeichner said. 

But Zeichner and her team are just 

getting started. “I think that the analytical 

advancements are really promising— 

we’re just scratching the surface of 

what this particular methodology can 

do,” Zeichner added. Recently the team 

has had their eye on OSIRIS REX, a 

NASA mission that returned samples 

of the asteroid Bennu in September 

2023. Asteroids are not homogenous, 

meaning the team’s findings from Ryugu 

will not necessarily apply to Bennu. 

When the catalog of data from Bennu 

is released, the team will be able to 

determine if their findings align with 

other asteroids. Over the next several 

years, subsequent missions are set to 

probe far-flung asteroids, planets, and 

moons looking for organic molecules. 

With more sample analysis, we will learn 

fascinating details about the formation 

of organic compounds from before the 

Solar System. Whether coalesced among 

the cold shrouds of molecular clouds or 

in the vast interstellar medium, what we 

find on these desolate time capsules will 

allow us to peer into the history of both 

the Solar System and life itself. ■ 

PHOTO COURTESY OF S.S. ZEICHNER COMMUNICATED BY LYNNA THAI 

Zeichner, the first author of the study, prepares vials 

of meteorite samples for analysis. 

ABOUT THE 

AUTHORS 

DIYA NAIK 

MAX WATZKY 

DIYA NAIK is a first-year physics major in Pierson. Apart from YSM, she is currently a member of the 

Yale Undergraduate Quantum Computing group and an avid enjoyer of bad science puns. 

MAX WATZKY is a first-year astrophysics major in Benjamin Franklin. Outside of YSM, he conducts 

research on the origins of stellar-mass black holes and plays trombone in the Yale Concert Band. 

THE AUTHOR WOULD LIKE TO THANK Dr. Sarah Zeichner, Dr. José C. Aponte, and Dr. Allison Karp 

for their time and enthusiasm in sharing their work. 

FURTHER READING 

Zeichner, S. S., Aponte, J. C., Bhattacharjee, S., Dong, G., Hofmann, A. E., Dworkin, J. P., Glavin, D. P., 

Elsila, J. E., Graham, H. V., Naraoka, H., Takano, Y., Tachibana, S., Karp, A. T., Grice, K., Holman, A. I., 

Freeman, K. H., Yurimoto, H., Nakamura, T., Noguchi, T., … Eiler, J. M. (2023). Polycyclic aromatic 

hydrocarbons in samples of Ryugu formed in the interstellar medium. Science, 382(6677), 1411-1416. 

http://doi.org/10.1126/science.adg6304 



FOCUS 

Biochemistry 

It's an RNA World 

Again 

The Surprising Role of RNA on a Cell's Surface 

By Kenny Cheng and Risha Chakraborty 

Art by Luna Aguilar 


Ribonucleic acids (RNA) are among 

the most important molecules in the 

human body. Early in the evolution of 

life, RNA controlled all molecular and cellular 

functions, including the catalysis of biochemical 

reactions. Today, RNA carries out myriad 

functions within cells, such as communicating 

genetic information from DNA to functional 

protein products, regulating gene expression, 

and defending cells against viral infections. 

Recently, however, it has been discovered that 

RNA is not only confined within the cell but 

also present on the cell’s surface. 

RNA…Outside of Cells? 

In 2011, RNA was first discovered binding 

to the cell membrane—which separates a cell’s 

interior from the outside—in bacteria in the 

lab of Ronald Breaker, a Sterling Professor 

of Molecular, Cellular, and Developmental 

Biology at Yale. It was not until 2020 that 

Liangfang Zhang and Sheng Zhong, professors 

of bioengineering at the University of 

California, San Diego, discovered what they 

coined “membrane-associated extracellular 

RNAs.” These “maxRNAs” were RNAs stably 

associated with the outer membrane surface 

of human cells, presenting a mysterious new 

role of RNAs. This discovery was quickly 

compounded upon by Nobel Laureate Carolyn 

Bertozzi in a 2021 paper announcing the 

discovery of “glycoRNAs,” small extracellular 

noncoding RNAs with special sugar molecules 

attached to them. These recent discoveries 

opened the door for further exploration into 

the functions of extracellular RNAs. 

When Jun Lu, an associate professor of 

genetics at the Yale School of Medicine (YSM), 

learned of these findings, he was surprised 

by the reported stability of the extracellular 

RNAs. “Outside of cells, we know that there 

are lots of RNases that act as Pac-Mans to 

chew up extracellular RNAs very efficiently,” 

Lu said. Indeed, the idea that RNAs could 

exist outside of cells for prolonged periods 

posed a confounding mystery. Interested 

in uncovering the functional roles of 

glycoRNAs, Lu approached his upstairs lab 

neighbor, frequent collaborator, and expert 

on neutrophil biology, Dianqing (Dan) 

Wu, the Gladys Phillips Crofoot Professor 

of Pharmacology at YSM. The result was a 

study affirming the presence of extracellular 

RNAs on neutrophils and their function 

in facilitating neutrophil recruitment to 

infection sites. 

Wenwen Tang (front row, left), Ningning Zhang (front row, right), Jun Lu (back row, left), and Dan 

Wu (back row, right) pose for a picture in their laboratory. 

The Firefighters of the Blood Stream 

Neutrophils are the most common white 

blood cell, or infection-fighting cell, in the 

human bloodstream. While extensive research 

has been done on their immune function at 

infection sites, less is known about how they 

navigate to these locations. Traditionally, 

neutrophil biologists have focused on the 

process of rolling adhesion as an important 

step for this movement. Neutrophils typically 

float in the bloodstream untethered to any 

scaffolding. But when injury or inflammation 

exposes the cell adhesion molecules on 

endothelial tissue lining blood vessels, 

neutrophils adhere to the walls of blood 

vessels and roll toward the site of injury to fight 

accumulating pathogens. 

Before this collaboration, Wu didn’t have 

much experience in RNA research. Being 

a neutrophil biologist, however, he did 

have the intuition that something in 

the neutrophil-endothelial interaction 

included sugar-binding. Neutrophil 

biologists had previously identified a 

class of proteins found on endothelial 

cells called selectins that appeared to 

bind proteins with attached sugars on the 

surface of neutrophils. These interactions were 

reversible, allowing neutrophils to swiftly 

engage with endothelial tissue repeatedly, 

which underlies the ability of these cells to roll 

along blood vessel walls. 

To investigate the presence of cell surface 

RNAs in this process, the authors utilized a 

sophisticated technique called click chemistry, 

which won Bertozzi her Nobel Prize in 

Chemistry in 2022. Click chemistry describes 

reactions that are simple, highly efficient, 

and selective, just like clicking a button. 

Ideally, these reactions should also avoid 

side reactions and provide high yields of the 

PHOTOGRAPHY BY EMILY POAG 

desired product at mild conditions. Click 

chemistry is often used to join molecular 

building blocks together with applications 

in bioconjugation, materials science, and 

drug discovery. In this study specifically, 

the authors employed a bioorthogonal 

reaction, which is a click reaction in a 

biochemical setting that selectively targets 

biological molecules without disturbing 

other cellular processes. 

First, the authors labeled the RNA of 

cells with a sialic acid sugar mimetic called 

Ac4ManNAz, which acts as a molecular 

tag, forming glycoRNAs. Then, using click 

chemistry, they attached a biotin molecule 

to the labeled sugars in the glycoRNAs. 

The attached biotin subsequently served as 

a beacon, allowing glycoRNAs to be easily 

detectable. The researchers found a strong 

biotin signal on the surface of neutrophils, 

suggesting the startling presence of 

glycoRNA. They then confirmed that 

glycoRNAs bind to a specific selectin 

called P-selectin on endothelial cells. 

By binding P-selectin, glycoRNAs help 

facilitate the neutrophil-endothelial 

interaction necessary for neutrophils to 

roll along blood vessels. 

The combination of discovering the 

glycosylated ligands on the neutrophil 

cell surface and elucidating at least one 

functional role of extracellular RNA 

involved a fair bit of serendipity. “I think 

both of us were a little skeptical initially 

[at the magnitude of the effects of removal 

of extracellular RNAs]. We wanted to 

make sure this wasn’t just a single-time 

interaction,” Wu said. Together, Wu and 

Lu’s labs were able to demonstrate the 

functional importance of neutrophil cell 

surface RNAs dozens of times, giving them 

the green light in terms of reproducibility. 



FOCUS 

Biochemistry 

How Firefighters Fight the Fire 

While much remains unknown about 

how neutrophils produce extracellular 

glycoRNA, biologists know that neutrophils 

aren’t recruited until they are needed. 

When tissue is injured or inflamed, it must 

somehow signal for neutrophils to come and 

bind to the tissue. Lu likens this process of 

neutrophil recruitment to firefighters rushing 

to a fire. Upon injury, damaged cells release 

proinflammatory proteins called cytokines 

that signal nearby endothelial cells to express 

selectins, like P-selectin, which are normally 

tightly controlled. This “fire” prompts the 

neutrophils, acting as firefighters, to attend 

to the site of injury. “Selectins are like glue 

that try to capture circulating white blood 

cells—mostly neutrophils because of their 

abundance—which starts the neutrophil 

infiltration process,” Wu said. P-selectin– 

neutrophil–glycoRNA binding is central to 

this glue-like interaction, but this is likely just 

part of the picture. 

Wu and Lu performed an experiment called 

RNA sequencing on glycoRNA isolated using 

click chemistry from three kinds of neutrophils 

in the mouse bloodstream and several human 

cell lines. Analyzing the mapping of these 

RNAs to the mouse or human genomes 

indicated specific rules that could govern 

RNA glycosylation. Lu describes these rules 

as a “licensing step.” Although the existence 

of these rules is not currently known, Lu 

speculates that they may involve special RNA 

sequences, structures, or modifications. Wu 

expressed that it may not be sufficient for an 

RNA to be glycosylated for recognition by the 

P-selectin; P-selectin’s specificity may include 

the RNA as well. These discoveries are only 

the first steps in characterizing the specificity 

of the P-selectin-neutrophil-glycoRNA 

interaction, but the methodology used in this 

study will likely inform future explorations of 

extracellular protein-glycoRNA interactions 

across the body. 

PHOTOGRAPHY BY EMILY POAG 

Ningning Zhang (left) and Wenwen Tang (right) discuss 

an image shown on the computer screen. 

How Did GlycoRNAs Get Outside of 

the Cell? 

The authors proposed two potential 

models to explain the mechanism by which 

glycoRNAs moved from the cytoplasm inside 

the cell to the outer surface of neutrophils. 

In the cell-to-cell model, cellular RNAs are 

released from one cell and are captured on an 

adjacent cell’s surface. On the other hand, in 

the cell-autonomous model, the production 

and transport of cellular RNAs to the cell 

surface occur in the same cell. To differentiate 

between these models, a co-culture experiment 

was conducted. One group of neutrophils was 

labeled with the Ac4ManNAz sugar and a 

fluorescent green dye, while another group was 

only labeled with a fluorescent red dye. These 

cells were then mixed and incubated together. 

Afterward, the researchers found only strong 

fluorescent signals in the green cells but not 

the red cells, confirming the second cellautonomous 

model of the production and 

transportation of glycoRNAs across the 

cell membrane. 

Once they had confirmed the cellular 

origin of glycoRNAs, Lu and Wu began to 

consider the pathways by which glycoRNAs 

could leave the cells. One such pathway 

was inspired by the C. elegans worm. In this 

model organism, the Sidt1 gene was found to 

encode RNA transporters that facilitated the 

uptake of digested RNA in the gut into the 

cells of the worm across cellular membranes. 

Therefore, the Yale scientists reasoned that the 

Sidt genes expressed in neutrophils could be 

facilitating the transport of RNAs across the 

cell membrane. To test this hypothesis, they 

ABOUT THE 

AUTHORS 

disrupted the expression of both Sidt1 and 

Sidt2 in cells in a knockdown experiment. As 

a result, the presence of Ac4ManNAz-labeled 

glycoRNAs was abolished, highlighting the 

crucial role of Sidt RNA transporters in the 

presence of glycoRNAs in cells. Importantly, 

the Sidt-knockdown cells also exhibited a 

significant reduction in in vivo recruitment 

to inflammatory sites, underscoring the 

essential role of Sidt genes in the functionality 

of neutrophils. 

The Future of the RNA World 

This novel collaboration between a 

neutrophil biologist and an RNA biologist is 

only the beginning of a growing field focused 

on glycoRNA interactions outside the cell. 

Lu and Wu are both eager to continue their 

collaboration and begin answering the many 

questions opened by this paper. As this field 

is still in its infancy, Lu suggests that it will 

take some work to even begin elucidating 

the initial mechanistic questions, such as 

exploring the molecular pathways involved 

in making extracellular glycosylated RNAs 

and figuring out the environments in which 

they are selectively produced or glycosylated. 

“We can’t work on all of these questions, 

so we have to be careful about picking the 

lower-hanging fruits first to work on. Then, 

I expect many people will start to work on 

it,” Lu said. After that, Wu and Lu hope other 

labs explore more disease-specific questions, 

like studying the disease conditions in which 

these RNAs are dysregulated and whether 

there are any therapeutic or diagnostic roles 

for extracellular RNAs. ■ 

KENNY CHENG 

RISHA CHAKRABORTY 

KENNY CHENG is a first-year student majoring in Molecular, Cellular, and Developmental Biology in 

Pauli Murray College. Outside of YSM, Kenny carries out research on ornate, large, extremophilic (OLE) 

RNAs in the Breaker lab and is an editorial associate for the Yale School of Medicine and the Yale 

Medicine Magazine. 

RISHA CHAKRABORTY is a third-year Neuroscience and Chemistry major in Saybrook College. In 

addition to writing for YSM, Risha plays trumpet for the Yale Precision Marching Band and La Orquesta 

Tertulia, volunteers at YNHH, and researches Parkinson’s Disease at the Chandra lab in the Yale School of 

Medicine. She enjoys cracking jokes, having “philosophical” discussions with her friends, and having boba 

with her PLees at the Asian American Cultural Center. 

THE AUTHORS WOULD LIKE TO THANK Dr. Jun Lu and Dr. Dan Wu for their time and enthusiasm 

for their research. 

FURTHER READING: 

Zhang, N., Tang, W., Torres, L., Wang, X., Ajaj, Y., Zhu, L., Luan, Y., Zhou, H., Wang, Y., Zhang, D., Kurbatov, 

V., Khan, S. A., Kumar, P., Hidalgo, A., Wu, D., & Lu, J. (2024). Cell surface RNAs control neutrophil 

recruitment. Cell, 187(4): 846-860. https://doi.org/10.1016/j.cell.2023.12.033 

24 Yale Scientific Magazine March 2024

WEATHERING 

Evolutionary Biology 

FEATURE 

THE STORM 

ART BY 

PATRICIA 

JOSEPH 

BY SAMANTHA LIU 

HOW TINY BUGS SURVIVE THE RAIN 

Over a still pond, a raindrop falls over a line of water striders. It 

engulfs one of the insects, launching it upward amid a water 

jet. Momentarily the water strider is airborne—then the 

jet collapses, whips back up. The bug is left submerged, twisting just 

beneath the glassy surface. 

The Gerridae insect family has long drawn scientists’ fascination with 

its unusual water-walking ability. But how these bugs fare on turbulent 

seas has just been uncovered in a new study by a team of physicists from 

Florida Polytechnic University. Led by assistant professor of mechanical 

engineering Daren Watson, researchers captured on stunning video how 

water striders survive simulated rain drops. After plunging subsurface 

with their water-repellent coat, they rise back upward atop a jetstream. 

When a second collision pulls the bugs underwater, they paddle along 

with swift strokes. 

As a result, these tiny striders can weather a violent rainstorm— 

an insight that surprisingly may extend into how microplastics 

persist in marine environments. 

“I think it’s my best work yet,” noted Watson. “We’ve answered a 

fundamental question, but there’s much to explore in studies to come.” 

Watson’s foray into aquatic insects began on his Florida campus, 

where he found himself curious about the bugs skimming across his 

local pools. He couldn’t understand how their millimeters-long bodies 

could survive a free-falling drop, much less a storm. “[As] opposed to us 

humans, these insects have nowhere to hide,” Watson noted. 

With a little guidance from the “Bug Closet” at University of Central 

Florida, and a lot of scouring from nearby ponds, Watson captured and 

reared a group of water striders in a mini aquarium. He placed twenty 

of these insects in a chamber with an elevated nozzle and a syringe 

A water strider balances atop a pool with its delicate legs. 

IMAGE COURTESY OF WIKIMEDIA COMMONS 

pump. To simulate rainfall, he directed water from the nozzle through 

a long, narrow channel, landing droplets one at a time onto the bugs. 

After some tinkering and tailoring, the results—rendered in crystalclear, 

3200 frames-per-second video resolution—reveal a valiant battle 

by the Gerridae. While some scatter and leap away at an impending 

raindrop, a bug caught in the splash zone must bear its full brunt. 

“The force of the raindrop striking the water strider is significantly 

higher than the weight of the water strider,” Watson said (up to forty 

times higher, to be precise—imagine a small delivery truck crashing 

atop you). “But it does not cause the strider to die.” 

Hydrophobic, densely-packed hairs along the bug’s exoskeleton repel 

the water, forming a bubble, called the first crater, around its body. This 

crater generates a buoyant force that pulls the water strider back to 

surface, then shoots upward as a water jet—which a well-positioned bug 

can surf like a gentle tidal wave. 

But when this jet collapses back downward and forms a second crater, 

the collision this time comes faster and harsher. “You can think of it like 

you’re stretching a rubber band… [it’s] going to rapidly go back to its 

original position,” Watson said. 

As the bug sinks down again, the crater retracts so quickly that 

the swimming creatures struggle to follow. According to Watson’s 

calculations, if this crater’s acceleration exceeds a threshold value—5.7 

times the acceleration due to gravity—it tears away from the insect body, 

leaving the water strider submerged beneath the cavity. 

Though some footage shows intrepid water striders pedaling their legs 

to come up for air, they do not always succeed. “They must be able to 

swim and survive below the waterline for a period of time,” Watson said. 

“And that also adds to their survival during rainfall.” 

He wonders if this is an evolutionary predisposition for creatures 

exposed to rain—why resurface if another drop will come plummeting 

down seconds later? But as a physicist, Watson is more proud of cracking 

the mathematics of the second crater’s growth and collapse, something 

never before reported. Noting water striders’ similarities in size and 

buoyancy to ocean microplastics, he looks forward to translating his 

findings toward studying these waterway pollutants. 

When [microplastics] get into our water bodies, how do they become 

submerged?” he said. “How are they going to be exposed to the fishes, 

the marine life within those water bodies? How does rainfall precipitate 

that exposure?” 

For now, Watson has moved on from sea critters and back toward his 

realm of inanimate objects, though his study has opened new doors for 

biologists and engineers alike. In the meantime, across the swamps of 

Florida, water striders continue to twist and swirl beneath our marine 

surfaces, braving the onslaught of rain. ■ 



FEATURE 

Climate Engineering 

ART BY MOLLY HILL 

GROWING 

SMARTER 

SIMPLE SENSORS HELP CROPS 

GROW WITH LESS WATER 

BY BRANDON NGO 

Consider a scenario where you’re at a doctor’s office 

battling the flu. Your doctor diligently measures your 

blood pressure, listens to your lungs with a stethoscope, 

checks your reflexes, and examines your body temperature. 

These thorough examinations directly listen to your body and 

are essential for your doctor to evaluate your health condition. 

Now, imagine a similar approach to monitoring the health of 

plants using devices that directly track their health. How could 

this be possible? 

Currently, the most common technology in smart agriculture 

involves sensors that track environmental conditions to 

determine the health of the plants grown nearby. Researcher 

Uberto Garlando and professor Danilo Demarchi, both affiliated 

with the Italian university Politecnico di Torino, and members 

of the Institute of Electrical and Electronics Engineers Council 

are taking a more advanced approach to understanding the 

plants’ needs. “To understand the plant status and be able to 

detect stresses such as pest infections, we developed devices 

and electronic systems that are ‘plant-wearable’ that focused on 

proper status detection [by] simply ‘asking’ the plant [what it 

needs],” Garlando said. 

These sensors work by tracking electrical signals within the 

plant that vary when subjected to different environmental 

conditions like leaf temperature and water content stress. When 

the plants “wear” these sensors, the farmers can monitor the 

health of their plants based on the variance of these electrical 

signals. “The sensors extract a signaling frequency proportional 

to the electrical signals of the plants that can give us information 

about the plants’ health,” Demarchi said. 

To monitor plants at a lower cost, these sensors extract 

a signaling frequency that is less accurate than previous 

renditions of similar sensors. Despite the trade-off between 

cost and accuracy, the researchers concluded that the 

frequency they used was still meaningful enough for the 

farmers to understand the needs of their plants. “The best 

trade-off is when you can get information out of the minimum 

cost possible,” Garlando said. “Our final goal is to reduce the 

cost to a few cents for each device.” 

Empowered by information about the plants’ health from these 

cheaper sensors, farmers can avoid the overuse of resources 

necessary for growing plants. “With this technology, it’s possible 

to reduce, for example, the use of pesticides or chemicals in 

agriculture because instead of spreading the pesticide on all the 

crops, I know where specifically I need to use the pesticide,” 

Demarchi said. Reducing the use of chemicals in agriculture 

limits waste, protecting local ecosystems and bodies of water 

from chemical pollutants. 

These “plant-wearable” sensors also come at a time of accelerating 

climate change, with the amount of arable farmland drastically 

decreasing. Electrical engineers like Garlando and Demarchi have 

been working on developing low-cost, smart agri-food systems in 

the past decade to benefit farmers with higher agricultural yields 

under harsh conditions. 

Overall, Garlando and Demarchi believe that these “plantwearable” 

devices will fundamentally change the agricultural 

industry, making it more environmentally sustainable and efficient 

in the hopes of increasing global food security. The sensors also pave 

the way for the popularization of agricultural technology (AgriTech) 

engineering in universities. The Politecnico di Torino University 

recently released a new master’s degree program in AgriTech 

engineering. “The engineering AgriTech culture still has to grow,” 

Demarchi said. By working with agricultural companies, Demarchi 

hopes that engineers can bring their ideas to real-world use. He also 

aspires to motivate more researchers to work on problems faced by 

the agricultural industry in Italy and beyond. 

Looking at the future of the AgriTech industry, Garlando, 

Demarchi, and other engineers are hoping to improve their 

technology by further decreasing the costs of the sensors while 

maintaining enough accuracy to determine the needs of the plants. 

“Of course, we are proud of these sensors so far,” Demarchi said. 

“However, we are always going to continue to improve our devices 

and our sensors. We are working toward reducing the device size 

and power consumption in the future.” For now, we can only wonder 

whether the fruits and vegetables we have been eating have worn 

these “plant-wearable” sensors, developed to fight against climate 

change and enhance food security. ■ 


Biology FEATURE 

DITCHING OPIOIDS 

NEW COMPOUND MAY PROVIDE NON-OPIOID PAIN 

BY MEGAN KERNIS 

ART BY JIYA MODY 


According to the CDC, overdoses 

involving opioids claimed the 

lives of 80,411 Americans in 2021. 

Amid this crisis, healthcare professionals 

increasingly rely on treatment strategies 

that limit the use of opioids for patients 

in need of pain relief. The CDC’s current 

recommendations on opioid use suggest 

alternative first-line therapies, low-dose 

prescriptions, and goal-oriented treatments. 

But to bring an end to opioid abuse without 

compromising on quality of care, it might 

be necessary to remove opioids from 

clinical use altogether. To provide a safe 

alternative, researchers are scrambling to 

create non-opioid pain relief medications. 

A team based out of the University of Texas 

at Dallas recently published research on a 

new compound that alleviates nerve pain 

by changing the way cells send signals to 

each other. 

The new compound works by targeting 

the sigma-2 receptor transmembrane 

protein 97 (σ 2 

R), an endoplasmic reticulumresident 

protein. σ 2 

R is widely expressed 

in cells in the central nervous system 

and is known to regulate cholesterol 

transportation. Additional properties of this 

protein have remained relatively unknown 

for a long time. Stephen Martin and Jim 

Sahn, chemistry professors at UT Dallas, 

came across ligands that bind to σ 2 

R while 

synthesizing compounds for a study of 

the receptor conducted by the National 

Institutes of Health. Further experiments 

revealed that these ligands reduced pain 

hypersensitivity in a mouse model. 

“In the beginning, it was really curiositydriven,” 

Sahn said. “So [reducing 

hypersensitivity] was motivating in the early 

days.” With the prospect of pain relief on the 

table, Martin and Sahn sought to translate 

their discovery of these complex ligands 

(FEM-1689 and DKR) into a simpler form 

that resulted in the same outcome but was 

easier to produce. Interestingly, Martin said 

that the ligands were named after friends 

and family, including Martin’s wife (FEM- 

1689) and a decorated UT Dallas football 

coach, Daryll K. Royal (DKR). 

Originally, Martin and Sahn had a fuzzy 

understanding of how the ligands worked. 

They knew that the ligands inhibited 

nerve pain, but they weren’t sure how. 

To investigate this phenomenon, Martin 

started talking to his colleagues, seeking 

out someone who could help them work 

out an answer. “Through networking […] 

we traversed the path from Alzheimer’s 

to traumatic brain injury,” Martin said. “I 

wanted a risk-taking biologist who would 

be willing to look at this.” 

The biologist he found was Theodore 

Price. Price and his colleague, Saad Yousuf, 

elucidated the mechanism behind the 

ligands’ action. Yousuf demonstrated 

that the receptor σ 2 

R is responsible for 

regulating other proteins that have much 

broader implications down a long chain—a 

signaling pathway—leading to the cause 

of nerve pain. Price, eager to make use of 

Yousuf ’s discovery, coupled this signaling 

mechanism with his own tests in mouse 

models to develop a potential drug. 

One novelty of their research is that 

the scientists began experimenting 

with animals directly. Typically, drug 

developers work with cellular models 

before moving to animal models and 

eventually clinical trials. However, since 

Price and his colleagues already knew 

that the compound was bound to a specific 

receptor, σ 2 

R, they were able to jump straight 

into animal testing. Beyond that, the drug’s 

efficacy and long-lasting properties were 

surprising to the researchers. “The thing 

that has impressed me from the start is 

how efficacious this is after a long period 

of time,” Price said. “It’s something that is 

unheard of,” Yousuf added. 

The team was quick to credit Martin for 

bringing them together and providing a 

strong foundation for the entire project. 

“[Martin] is really good at making friends,” 

Sahn said. Martin, meanwhile, emphasized 

the role of collaboration among scientists 

across disciplines. “What I learned is you 

get a name, you call them up, and you ask 

them if they’re interested,” Martin said. “If 

the answer is no, you ask them if they know 

somebody who might be, and you call them 

up until you find the right person.” 

The team received a grant through the 

initiative “Helping End Addiction Long- 

Term” (HEAL), which will help develop 

a drug using their foundational research. 

“In four years, hopefully, we’ll be close 

to submitting an IND [Investigational 

New Drug] to the FDA and being able 

to start the clinical trials soon after that,” 

Price said. With an established group and 

promising experimental findings, the 

possibility of a non-opioid pain relief 

drug is on the horizon. ■ 


FEATURE 

Computational Biology 

AI VS. SUPERBUGS 

CAN DEEP LEARNING BEAT 

ANTIBIOTIC RESISTANCE? 

BY MADELEINE POPOFSKY | ART BY MADELEINE POPOFSKY 

The great irony of recent advances 

in artificial intelligence (AI) 

is that even as programs have 

gained capabilities that ten years 

ago we could only dream of, most of 

the time, we have no idea how they 

do it. This lack of explainability has 

particularly frustrating consequences 

for the use of AI in drug discovery. 

Lacking the understanding of how AI 

generates predictions of successful drug 

candidates, scientists struggle to design 

drugs similar to those predicted. Felix 

Wong, a postdoctoral fellow at MIT, 

worked in collaboration with other 

researchers to solve this explainability 

problem in a recent Nature paper. The 

team applied newly explainable AI 

results to one of the most 

pressing medical crises 

of our age: antibiotic 

resistance. Currently, 

bacteria are 

developing resistance to antibiotics at 

a rate that outpaces researchers’ ability 

to design new ones. “Antimicrobial 

resistance is a public health crisis that 

is projected to kill ten million people 

worldwide per year by 2050,” Wong 

said. An especially deadly enigma is 

methicillin-resistant Staphylococcus 

aureus (MRSA), which already kills 

over ten thousand per year in the 

United States. For researchers, MRSA 

has proved to be an elusive target. As 

a Gram-positive bacterium, S. aureus 

lacks an outer membrane that helps 

many bacteria defend themselves from 

antibiotics, but it has nevertheless 

independently evolved resistance to 

many antibiotics. Thus, to find an 

antibiotic for a bacterium as unique 

as MRSA, researchers would need to 

identify a whole new structural class 

of drugs—a tall order, given that gaps 

between such kinds of discoveries have 

previously exceeded thirty-five years. 

This is where AI steps in. Over the 

years, researchers have trained deep 

learning models, a type of AI, to 

identify certain desirable molecules 

that are linked to antimicrobial activity. 

Such models have limited success when 

researchers cannot identify the models’ 

reasoning—without it, researchers can’t 

point to specific chemical features that 

give the molecules their desired effects. 

These models are typically referred to 

as “black box” models. 

Equipped with these standard “black 

box” models and determined to shed 

light on their inner workings, Wong and 

his colleagues took on the challenge of 

creating an antibiotic for MRSA. Their 

crucial insight was to focus on specific 

chemical substructures as units for the 

deep learning models. If a model focuses 

on specific substructures, Wong and his 

colleagues thought, then maybe they 

could get the model to explain which 

substructures in its chosen molecules 

account for its antimicrobial activity. 

During preliminary testing, this idea 

was confirmed. “We noticed that 

compounds with similar structures have 

consistently similar model prediction 


Computational Biology 

FEATURE 

We can now [...] provide a justification for why 

some molecules work better than others in a way 

that directly aims to produce the next generation 

of antibiotic candidates. 

scores,” Wong said. The next step was 

to get the models to explain why these 

substructures matter. 

To accomplish this, Wong and his 

colleagues started by manually screening 

nearly forty thousand compounds for 

their ability to inhibit MRSA growth and 

their toxicity to human cells. They then 

trained deep learning models on this 

data, testing the models with additional 

data afterward to ensure accuracy. 

Next, they fed over twelve million new 

compounds with unknown effects into 

these models. The models returned the 

compounds expected to have the best 

ability to inhibit MRSA growth with 

low toxicity to humans. Finally, the 

researchers applied a technique known 

as a Monte Carlo tree search, which 

performed the all-important task of 

identifying substructures responsible 

for the outputs of the models. 

“We set out to see if we could ‘open 

the box,’” Wong said. In the end, the 

model used an algorithm similar to the 

one used in the game-playing AI called 

AlphaGo. While playing AlphaGo and 

identifying a new antibiotic class may 

seem like two very different processes, 

they have a key similarity: a need to 

search through an extremely large space 

of possibilities efficiently. 

Armed with potential structural 

classes, Wong and his colleagues 

sorted through the data. They found 

explanations from the algorithm that 

matched the logic behind already 

identified antibiotic classes. However, 

the model also identified five different 

justifications for 

substructures that 

could potentially 

identify new classes. After narrowing 

down activity, they found that over 

forty percent of molecules within these 

newly identified classes showed activity 

that inhibited MRSA growth. All of these 

molecules were new to antibiotic researchers. 

Further testing in the lab isolated the 

two best candidates, forming an entirely 

new class of antibiotics likely able to 

combat MRSA effectively in a clinical 

setting. These two compounds share 

a common substructure which was 

identified by the model as the source 

of their antimicrobial ability. Testing 

of their abilities in living organisms 

showed that they worked specifically 

against Gram-positive bacteria such as 

MRSA while avoiding injury of healthy 

cells. They kill bacteria by dissipating 

the pH gradient within them, causing 

them to burst open. The compounds 

succeeded in the tough task of killing 

MRSA in afflicted mice, showing 

promising clinical potential. 

In identifying this new class, Wong 

and his colleagues opened the proverbial 

“black box,” finding a way to make 

deep learning algorithms explain their 

results using chemical substructures. 

While successful in explaining the 

properties that give a potential drug 

antimicrobial abilities, the model 

falls short in other areas. There are 

other important properties necessary 

for a potential antibiotic, including 

avoiding side effects such as hemolysis, 

the destruction of red blood cells, or 

genotoxicity, the damaging of DNA. 

Wong and his colleagues were forced 

to consider these possible side effects 

only after they had identified their new 

structural class. “Better predicting of 

all of these properties remains a critical 

challenge,” Wong said. 

This process took two years, but 

since a large part of that time was spent 

developing the methodology, future 

research could take place considerably 

faster. Therefore, this new technique 

is a crucial new way to fight antibiotic 

resistance. “This discovery directly 

contributes to our arsenal of antibiotic 

candidates,” Wong said. “Our work also 

promises to accelerate antibiotic drug 

discovery by making deep learning 

models more explainable and providing 

publicly available large datasets and 

models that accurately predict selective 

antibiotic activity.” 

Wong and his colleagues are currently 

working on using the substructurebased 

explanations given by AI to 

design new antibiotics from scratch. But 

impacts extend beyond just antibiotics. 

“We have also been continuing to 

develop and apply approaches like the 

one published here to discover other 

types of drugs—for instance, those 

that modulate aging and age-related 

pathways,” Wong said. 

With the black box open, the future 

of antibiotic resistance is looking less 

bleak. “This is a very different approach 

from the one-target, one-disease 

approach prevalent in drug discovery, 

which typically aims to just optimize 

the fit of the small molecule against 

the target,” Wong said. “We can now 

[...] provide a justification for why some 

molecules work better than others in a 

way that directly aims to produce the 

next generation of antibiotic candidates.” 

In the end, when describing the 

process of reaching this crucial 

finding, Wong had only one word to 

use: “Exhilarating.” ■ 



FEATURE 

Astronomy 

MASSIVE, 

MYSTERIOUS 

CIRCLES IN SPACE 

HOW DYING STARS EXPLAIN RADIO ODDITY 

BY DAVID GAETANO ART BY ALONDRA MORENO SANTANA 

Scientists believe they may have found 

a possible explanation for a puzzling, 

recently discovered cosmological 

phenomenon. First observed in 2019, odd 

radio circles (ORCs) are haloes of radio 

waves centered around certain galaxies. 

At first, these haloes were especially 

perplexing because they didn’t match 

the known signatures of any large-scale 

astronomical events. There was something 

more unique about this phenomenon, 

hence its namesake. 

Professor Alison Coil of the University of 

California San Diego and her team believe 

they discovered something particularly 

new and exciting about these ORCs. 

Unlike others before them, Coil’s team 

looked at the optical light signatures from 

one of the ORC galaxies instead of merely 

inspecting the glowing halo of signals in 

radio wavelengths. This turned out to be 

the right call, as their observations gave 

way to a deeper understanding of the 

haloes’ mysterious origins in an article 

recently published in Nature. 

The insight arose from their previous 

work. Before ORCs, Coil and her team had 

been studying the evolution of galaxies 

by assessing supermassive black holes 

and outflowing galactic winds, which are 

streams of high-speed gas particles expelled 

due to colossal events like supernovae— 

large star explosions that expel gaseous 

matter into the surroundings. They used 

observational data collected from some 

of the most advanced telescopes in the 

world to create a timeline of how certain 

galaxies evolved. In particular, their work 

was concerned with the formation of 

“starburst” galaxies, which experience 

rapid star formation over a relatively 

short timescale, resulting in a rapid series 

of supernovae. 

Coil and her team stumbled upon ORCs 

somewhat unexpectedly. During one of 

their scheduled research trips to the Keck 

Telescope in Hawaii, they capitalized 

on their time with the equipment and 

pointed the telescope at one of the special 

ORC galaxies. Other research had shown 

evidence that these ORCs behaved like 

three-dimensional expanding shells, 

which made Coil and her team wonder 

whether this phenomenon could be a latestage 

effect of the galactic winds they had 

been studying. They postulated that these 

radio signals could be made up of gas 

from galactic winds being rapidly pushed 

outward, originally stemming from 

starburst explosions. Based on their 

hypothesis, the team captured 

optical wavelength images of 

the galaxy, which allowed 

them to make some new 

and exciting discoveries. 

The most jarring 

observation that arose 

from these optical 

images was the presence 

of an abnormally large 

amount of shocked gas 

sitting within the galaxy 

at the heart of each ORC. This shocked 

gas is essentially an abundance of singly 

ionized oxygen gas, which is highly 

unusual in these types of galaxies. 

“Galaxies that are like that—ones that 

aren’t forming stars anymore—[usually] 

don’t have a ton of gas in them still,” Coil 

said. Typically, galaxies that have had 

many stars form and die have lost much 

of their gas because these colossal events 

push most of it out. 

Coil and her team hypothesized that 

this shocked gas could be the long-term 

result of the galactic winds decoupling, 

or separating, and collapsing back into 

the galaxy after 

the rapid 


Astronomy 

FEATURE 

succession of supernovae ceases. Put 

differently, once the supernovae “shut 

off,” these galactic winds may fall in on 

themselves, causing them to turn back into 

the turbulent, shocked pools of gas seen in 

the radio telescope images. The key is the 

wind that continues to propagate through 

space after this decoupling stage. Coil and 

her team believe that these outflowing 

galactic winds may be what’s causing the 

ORCs. “You need an extreme starburst and 

extreme winds,” Coil said. “You need to be 

pushing a lot of mass out for a long period 

of time, and then it has to shut off.” A galaxy 

like this is uncharted territory in the field 

because of the unique set of conditions that 

must be present. 

To confirm their findings, the team reached 

out to Cassandra Lochhaas, an astronomer 

at the Space Telescope Science Institute, who 

was able to create a computer simulation that 

confirmed the physics of the hypothesis and 

modeled what such an event would look like. 

This simulation showed that the result of 

decoupling is twofold. Much of the gas 

collapses back into the galaxy, 

where there are large areas 

of evacuated space after 

the burst, yet some of 

the gas continues 

to flow 

outwards into the space surrounding the 

galaxy. This, they believe, is a highly plausible 

explanation for the radio signals observed 

around the special galaxies. 

Though this information is a 

breakthrough in our understanding of 

ORCs, it is only just the beginning. Coil 

and her team were the first to observe an 

ORC galaxy with optical wavelengths—but 

even still, their team only observed in blue 

optical wavelengths, meaning additional 

wavelengths may paint a more detailed 

picture of how these ORCs came to be. 

The researchers currently plan to collect 

more data on the original ORC galaxy 

they were concerned with, but their longterm 

goals extend further. This summer, 

they will record data on other ORC 

galaxies using the aptly named Very Large 

Telescope (VLT) in Chile in the hopes of 

expanding upon their current research. 

Looking back on the entire process, 

Coil emphasized the pivotal role of 

collaboration in scientific discovery. “It’s 

a good example of [how] one person 

doesn’t figure everything out,” Coil said. 

“You need to have collaborators—people 

with the data need to talk to the people 

with the theory.” The work she conducted 

alongside her team and collaborators 

exemplifies the essential nature of datasharing 

and scientific cooperation. Such 

collaborative efforts not only enhance the 

reliability of scientific findings but also 

make way for new questions and scientific 

avenues to explore. 

Coil and her team underscore 

the importance of collaboration 

in understanding ORCs. Their 

work creatively combines concrete 

observational data with theoretical 

modeling to better understand this 

puzzling cosmic phenomenon. Their 

discovery of charged gas in one of these 

special ORC galaxies paves the way for 

further observation and modeling to solidify 

their hypotheses and uncover the 

mysteries behind these odd 

galactic formations. ■ 



FEATURE 

Paleontology 

BY HANWEN ZHANG 

ART BY PATRICIA JOSEPH 

Tracking an Ancient Woolly Mammoth’s Journey of a Lifetime 

For all our Ice Age movies, artistic 

renderings, and sci-fi murmurings 

of de-extinction, mammoths have 

never quite lost their mythic proportions. 

The thirteen-foot darlings of every natural 

history museum continue to loom with about 

as much mystery as majesty. We know that 

they roamed the tundra steppes for roughly 

290,000 years, during which they grazed on 

arctic plants, briefly brushed shoulders with 

prehistoric humans, and had their likenesses 

transferred onto cave paintings. Then, around 

the time humans were building pyramids, 

they disappeared. The causes for their 

extinction—human hunting, climate change, 

or some mix of both—have been hotly debated 

as they remain tantalizingly unclear. 

Enter Elma, an ancient woolly mammoth, 

and one of only two specimens with complete 

tusks in all of Alaska. In a study published last 

month in Science, Elma is the star as a team 

of anthropologists and biologists provides an 

intricate reconstruction of her entire lifetime 

with the help of isotopic dating technologies. 

As just the second mammoth reconstruction 

of its kind, it offers an intimate glimpse into 

the creature’s habits—and an enticing glance 

at what mammoth interactions with early 

humans may have looked like. 

“We can’t [...] say for sure that humans killed 

this mammoth, but we’ve got means and 

motive at this point,” said Audrey Rowe, 

a PhD candidate at the University of 

Alaska and the lead researcher on 

the study. Elma 

was uncovered at Swan Point, the oldest 

archaeological site in Alaska, by researchers 

during the early 2000s. 

The study’s genetic and isotopic analysis 

chronicles an impressive yet punishing 

journey through the Alaskan hinterlands that 

ends in a cryptic fashion. According to the 

study, Elma trekked roughly one thousand 

kilometers from southeast Beringia, in 

present-day Canada, deep into interior 

Alaska in the span of two and a half years. 

Then, still at the peak of her life and roughly 

twenty years old, she died—right next to an 

area of known human settlement. 

This cold case has the set-up of a prehistoric 

Agatha Christie plot, but there’s no smoking 

gun. Elma’s remains were uncovered 

alongside another closely related juvenile and 

a newborn and were dated from around the 

same time humans had started populating 

the region. She died in healthy condition, and 

her body lacked physical evidence of having 

been hunted, unlike mammoth samples in 

Siberia or Poland, which feature spear points 

lodged in spinal vertebrae or microblades 

buried in ribs. 

Image Courtesy of Flickr 

All signs nonetheless point to death by 

humans. “These early people in Alaska also 

certainly seem to have the technology [...] to 

bring down a mammoth,” said Matthew 

Wooller, a University of Alaska professor 

of chemical oceanography and an author 

of the study. Elma was found in the same 

time layer as the remains of the two younger 

mammoths, and her path overlaps neatly 

with human settlement at a time when 

they were capable of developing lethal 

stone projectiles—there are simply too 

many coincidences. 

Researchers were just as lucky to come 

across a tusk as uncompromised as hers. 

The equivalent of rings on a tree trunk, 

mammoth tusks offer telling records of life. 

Rowe explained that their tusks—similar to 

those of elephants—stack new layers atop 

each other as they grow, almost like ice 

cream cones. Elma’s tusk unraveled her story 

from the tip to her trunk. 

Using recently developed isotope analysis 

techniques, the researchers were able to chart 

Elma’s footsteps across prehistoric Alaska. 

They sliced open her tusk, drilled into the 

ivory at millimeter-length increments, and 

measured the isotopic ratios of strontium, 

sulfur, and oxygen—all of whose stable halflives 

can be deeply informative. Levels of 

strontium-87, an isotope formed in rocks by 

decaying rubidium, vary across the world; 

what follows is a telltale geographic 

signature, since 


Paleontology 

FEATURE 

strontium can vary across mountain ranges or 

even just a few valleys. The broad outlines of 

Elma’s journey took shape when researchers 

paired their isotope measurements with maps 

that captured the geographic distribution 

of strontium-87 ratios. Once coupled with 

oxygen-18 and sulfur-34—which can track 

water sources and mean annual temperature, 

respectively—the 14,000-year-old picture 

became even clearer. What the data sketched 

was a trek inland, across highlands and the 

more arid swaths of the tundra. 

Peripatetic, or nomadic, mammoths 

are no strangers to long-distance, crosscontinental 

hauls. Wooller explained that 

the previous study of this kind—featuring 

an 18,000-year-old male—had unearthed 

even longer treks that had taken the 

mammoth to similar regions in interior 

Alaska. Sexual differences were probably at 

play: like elephants, male mammoths may 

have left their herds at a younger age and 

traveled more during their lifetimes. 

Roaming some three thousand years 

after her male counterpart, this study’s 

mammoth offers a more dramatic portrait 

of her kind’s sunset, and of an arctic 

habitat hardly recognizable from the one 

we might imagine today. “A lot of Alaska 

was not covered by ice at all,” Wooller said. 

The mammoth population would have 

peaked some six thousand years before 

Elma. The Last Glacial Maximum—the 

last moment when glaciers covered nearly 

eight percent of the world’s total surface— 

had ended, ushering in scrubby forests 

that crept onto riverbanks and cropped 

up along the steppes. 

For a species so used to their barrenly 

flat haunts, the dramatic ecological 

changes would have fractured habitats 

and made them increasingly vulnerable 

to predation. The mammoths gravitated 

towards the same regions as human 

settlements and increasingly crossed 

paths with our earliest ancestors. Some 

combination of human-driven extinction 

and the forces of climate change likely 

led to the mammoth’s demise. “I think, 

at least in interior Alaska, the answer is 

more nuanced than that black or white,” 

Rowe said. 

Like the mammoth’s shaggy, fiftycentimeter 

coat, the details remain 

understandably hairy; piecing together 

the entire arc of a species calls for a 

sample size greater than just two. Wooller 

and Rowe both pointed out the need to 

analyze more sequences of this kind. In 

the interim, research could also take new 

directions—Wooller noted that recent 

excavations in Canada and Siberia have 

detected mammoth DNA in permafrost 

layers less than ten thousand years 

old, indicating the possibility of latesurviving 

groups. 

“Now that we’ve got something 

more about the mobility 

of the animals in this 

region, it 

would be 

great to get at the people as well,” said 

Ellery Frahm, a Yale anthropology 

professor not involved in the study. Frahm, 

whose research focuses on early human 

group interactions in Eurasia, explained 

that tracking mammoth movements is crucial 

to discovering the ways our ancestors engaged 

with their food sources. 

For the researchers, simply coming face 

to face with our mammoth ancestors is 

as fulfilling as playing detective. “It’s 

more exciting to just be learning about 

mammoth behavior because we have so 

little knowledge about that right now,” 

Rowe said. “Studies like this one are 

starting to actually pin down some actual 

truths instead of forcing us to make 

these assumptions.” Amid the decadeslong 

buzz of mammoth DNA extraction 

and de-extinction projects, tracing their 

stories may well be the truest gesture of 

bringing them back to life. 

Elma would have been about 13,600 

years old by the time “mammoth” entered 

the dictionary. It came with Russian 

roots, surfacing in the English vocabulary 

during the eighteenth century and 

coming to signify largeness. 

Big. Colossal. Huge. Gigantic, 

still fitting today for animals 

about which there can never be 

too much space for wonder 

or questions. ■ 

Studies like this one are starting 

to actually pin down some 

actual truths instead of forcing 

us to make these assumptions. 



SHORT Profile 

MADHAV LAVAKARE 

YC ’25 

BY PROUD UA-ARAK 

Madhav Lavakare’s (YC ’25) dive into the world of assistive 

technology traces back to his junior year of high school, 

when he witnessed a close friend grapple with hearing 

loss. After his friend, unable to understand what was being said 

in class, had to drop out of school, Lavakare embarked on a quest 

to explore existing solutions, only to encounter extravagant costs 

and imperfect outcomes. Traditional aids, such as hearing aids 

and cochlear implants, often cost tens of thousands of dollars and 

merely amplify sounds without clarifying them, so users may still 

easily miss out on what’s being said. Closed captioning on a device 

offers a solution to this issue of auditory comprehension but at 

the cost of missing visual communication cues. Hard-of-hearing 

individuals often have to play a “tennis match” of looking at subtitles 

on a mobile device and then back up at the person speaking. Since 

a simple phrase such as “Hey” may vary in meaning based on the 

expressed emotion and facial cues, closed captioning remains an 

imperfect solution for those who rely on it. 

Madhav’s invention, TranscribeGlass, emerges as a solution to 

these two issues faced by the hard-of-hearing community. 

Hoping to bridge the gap between auditory comprehension and 

visual cues, Lavakare designed TranscribeGlass to be affordable 

real-time captioning glasses. After interviewing and testing 

prototypes with members of the deaf community every weekend 

while working on this project full-time in India, Lavakare 

envisioned a device that seamlessly integrated real-time captions 

into the user’s field of view. 

Using Bluetooth technology, TranscribeGlass transmits caption 

data to a hardware device attached to a pair of glasses, mirroring 

the functionality of a movie projector. Imagine a transparent screen 

that acts as a see-through projector, enabling users to effortlessly 

follow along with captions in real-time, whether in a cinema hall, 

a classroom, or in day-to-day conversations. TranscribeGlass has 

evolved through a user-centric approach, driven by continuous 

feedback and iterative refinement. 

Lavakare refers to American 

entrepreneur Eric Ries’s mantra 

of the “build-measurelearn” 

cycle in describing 

how TranscribeGlass’s first 

prototype, albeit bulky and 

rudimentary, served as a 

starting point that was later 

refined by feedback. From 

India to Gallaudet 

University for the 

deaf and hardof-hearing 

in 

W a s h i n g t o n , 

D.C., over 350 

individuals have 

PHOTOGRAPHY BY FAREED SALMON 

IMAGE COURTESY OF TRANSCRIBEGLASS 

TranscribeGlass’s beta model allows real-time speech to be converted into captions 

and shown in the user’s field of vision. 

been part of the prototype testing process, paving the way for 

subsequent iterations with greater compactness, longer battery 

life, and user-friendliness. 

The culmination of Lavakare’s efforts is a sleek device weighing 

less than eighteen grams—allowing users to not feel the burden of 

the device on their glasses—and boasting an impressive eight-hour 

battery life. Unlike conventional alternatives entailing exorbitant costs 

and invasive surgical procedures, TranscribeGlass offers a plug-andplay 

solution at $95, democratizing access to assistive technology. Its 

light design and prolonged battery life ensure uninterrupted usage, 

transcending the constraints imposed by traditional aids. 

Furthermore, Lavakare’s device offers a unique feature—captionsource 

independence. Unlike its counterparts, which often rely 

on a single provider and demand constant internet connectivity, 

TranscribeGlass utilizes a diverse array of methods to generate accurate 

captions, even in offline mode. By integrating with speech recognition 

software from companies such as Google, Apple, and Microsoft, as 

well as connecting to movie subtitle files and human transcription 

providers, it ensures accuracy and reliability across various contexts. 

The impact of this technology resonates with users worldwide. 

After a video of TranscribeGlass’s product showcase went viral 

with over twenty-six million views, demand for the product’s final 

release has skyrocketed with over fourteen thousand sign-ups for 

preorders. “I had a woman write to me saying, ‘Hey, I have two deaf 

twin daughters who are starting their freshman year of college, 

and this device would change their lives,’ and another shared 

how her father’s recent hearing loss has isolated him, believing 

TranscribeGlass would bring a newfound sense of inclusion and 

confidence for him. So, the feedback we’ve gotten has been very 

positive,” Lavakare said. 

Looking ahead, the future is ripe with possibilities for TranscribeGlass. 

Lavakare hopes to incorporate real-time translation into his model 

and cater to disabilities such as autism and ADHD by including visual 

cues and reminding users of past conversations. Lavakare’s journey 

with TranscribeGlass continues, fueled by his ability to innovate and 

driven by his commitment to ensure accessibility for all. ■ 


Profile 

SHORT 

EMILY BORING 

YC ’18 BY KENNA MORGAN 

Although religion and science are frequently portrayed 

as conflicting forces, Emily Boring (YC ’18, DIV ’23) 

has proven herself to be a refreshing departure from this 

paradigm, embodying the intersection between science and faith. 

Growing up along the Oregon coast, Emily developed a sense 

of wonder for the ocean that ultimately inspired her studies in 

Ecology and Evolutionary Biology (E&EB) as an undergraduate 

at Yale. In line with her childhood dream of working along the 

boundary of what we do know and what we haven’t proven 

yet, Boring conducted research in the lab of Thomas Near, a 

Yale professor and the chair of the E&EB Department. As an 

undergraduate, she used genomic sequencing to discover a new 

species of freshwater fish called Percina freemanorum, found 

in Georgia’s Etowah River System. She also took classes at the 

nearby Yale Divinity School, where she developed an interest in 

religious literature and poetry. She now describes these courses 

as the first time she recognized the ability of language to hold 

the same sense of wonder, transcendence, and interconnection 

that she had always experienced in her scientific pursuits. 

“To me, science and faith were never separate; they were two 

different vocabularies to express the interconnection of our 

world,” Boring said. 

Upon graduating from Yale in 2018, Boring returned to her 

home state for further studies in integrative biology. At Oregon 

State University, she explored the ecology of Leptasterias sp. 

(a six-rayed sea star) and was inspired by Jane Lubchenco, a 

professor of marine biology, to think critically about how to 

communicate scientific information to wider audiences of 

non-scientists. Although she completed her Master of Science 

in marine ecology and genetics, she quickly felt called back to 

religious studies at the Yale 

Divinity School. “[At YDS], I 

studied at the Institute of 

Sacred Music, [...] exploring 

what it means to find a 

new language of faith 

that speaks to people, 

even in this time of a 

lot of skepticism 

and distrust of 

religion,” Boring 

said. Outside of her 

coursework, she also 

worked as a hospital 

chaplain—a moving 

experience that, for 

Boring, epitomized 

the intersection 

between science 

IMAGE COURTESY OF EMILY BORING 


and spirituality. While 

working with patients 

in the emergency room 

and the burn intensive 

care unit, Boring 

witnessed firsthand 

how the breakdown 

of the body—through 

disease or injury— 

often pushes people to 

ask big questions that 

can be answered by 

IMAGE COURTESY OF EMILY BORING 

Emily Boring holding an octopus while snorkeling. 

medicine and psychology to a certain extent, but are inherently 

informed by aspects of spirituality. Since earning her Master of 

Arts in Religion in 2023, Boring has been ordained as a priest 

and now serves as an Associate Rector at All Souls Episcopal 

Parish in Berkeley, California. 

Though returning to formal work in the sciences is not 

beyond the realm of possibility for Boring, for now she keeps 

busy by preaching and interacting with those in her parish 

community, while dedicating time to her long-held passion 

for creative writing. As an undergraduate, writing for the 

Yale Scientific Magazine’s Scope blog allowed Boring to push 

the boundaries of traditionally “scientific” publications by 

incorporating creativity, art, and storytelling. Additionally, 

she credits Verlyn Klinkenborg, a lecturer at the Yale English 

Department and School of the Environment, for mentoring her 

during her journey to become a writer who is curious, attentive 

to systems in place around her, and confident in her point of 

view. “That stance of open perception and curiosity, for me, has 

tied together a lot of what I try to do in my scientific research 

and also as a person of faith as I’m listening to people and 

trying to be present to their life moments,” Boring said. Boring 

is well-versed in the genre of creative nonfiction essays, and 

has recently discovered that the magazine Christian Century 

aligns closely with her work. For this particular publication, 

Boring enjoys pulling from the vocabulary and observations 

of science to shed light on patterns within our world that 

produce awe and contribute to spiritual experiences. Currently, 

she is working on a book project that will include a series 

of nonfiction essays. By drawing from her experiences as a 

chaplain, evolutionary biologist, and priest, Boring hopes to 

elucidate the answers to profound questions surrounding what 

it means to be a self, what it means to heal, and how we can 

bear witness to one another in life’s critical moments. Given 

Boring’s interdisciplinary expertise and personal experiences 

with illness and recovery, it is sure to be a compelling piece 

that—just as Boring herself does—lies at the crossroads of 

science, medicine, and spirituality. ■ 


BRIDGING BIOLOGY AND FEMINISM 

A REVIEW OF PERFORMANCE ALL THE WAY DOWN 

BY RICHARD PRUM 

BY GENEVIEVE KIM 

SCIENCE 

IN 


In his book Performance All the Way Down, Yale curator and ornithologist Richard 

Prum champions intersectionality to explore evolutionary and developmental 

biology through the lens of queer feminist theory. “What can I—pale, male, and 

Yale—bring to the discussion of the profound questions of sex and gender?” Prum 

asks in the prologue. His book is a response to his own question: a thoughtful blend 

of biological evidence, the history of feminist theory, and an appeal for conversations 

about sex and gender to involve both. 

Over the last seventy years, most traditional biological research involving sex has 

reinforced the binary concept of ‘gender/sex’, a term Prum uses to encompass the 

biological and cultural aspects of human sex and social behavior. In recent years, 

however, the field of material feminism has worked to engage genetics and biology in 

the understanding of gender. Feminist philosophers have suggested the idea of gender 

as a performance, with every individual collecting and presenting their interpretation 

of cultural norms and personal desires. Each person’s performance is constrained by 

the boundaries drawn by their community around their understanding and acceptance 

of gender. Using this feminist theory as a foundation, Prum proposes that the 

phenotype—the observable features of an organism, as opposed to the genotype, which 

is the organism’s heritable genetic material—is the biological and cultural performance 

of a constantly developing self. That is to say, someone's sex/gender is not biologically 

predetermined but is instead a collection of traits presented to society. 

Prum details the continuous sequence of molecular pathways that lead to sexual 

development as evidence for his case that the performance goes ‘all the way down’ to 

the most microscopic aspects of self. He presents the phenomenon of evolution as being 

generatively queering, as its randomness, which has led to changes in species, ends 

up destabilizing sexual phenotypes. By using feminist queer theory’s vernacular and 

incorporating empirically supported evidence, Prum not only challenges the idea 

that science supports a gender binary but also the binary between sciences and 

the humanities. 

Prum’s work disrupts academic conventions because it unpacks the intersectionality 

of knowledge, showing how scientific facts about the sexual body may be impossible to 

dissociate from cultural norms and biases. He questions the strict delineation between 

developmental and evolutionary biology and argues against gene-level selection, 

where natural selection applies at the level of specific genes instead of at the level of 

organisms, both long-standing scientific conventions. Instead, he uses a perspective 

of the phenotype as a performance to incorporate developmental biology at the core 

of evolution, cementing how much more interdisciplinary each field is than common 

academia suggests. With feminist queer theory by his side and biological evidence 

behind his claims, Prum explores the fundamental question of how one becomes 

oneself. He turns common queer-phobic arguments on their head, showing how 

science regards gender as a performance instead of an innate trait, revolutionizing the 

way we think about gender. ■ 


WORD WIZARDS IN 'SCIENCE DICTION' 

ETYMOLOGY AS A BRIDGE BETWEEN 

BARBIE LAND AND THE GENOME 

BY ANDREA ORTEGA 

How did Ken and Barbie make their way into the genome? In the 

podcast Science Friday, “Science Diction” host and producer 

Johanna Mayer constructs a bridge between worlds as diverse 

as Barbie Land and a fruit fly’s body. Scientific disciplines, infamously 

convoluted with jargon, can become inaccessible to the general public 

despite their societal relevance. Mayer even produces an episode about 

jargon: in “Jargon: We Love to Hate It,” she invites “plain language” 

advocates to discuss the widespread confusion caused by technical 

language. By explaining the etymology behind words like “meme” and 

“rocky road” in fifteen-minute episodes, Mayer highlights how social 

science, science, and pop culture intersect. This podcast is an accessible 

introduction to science for podcast enthusiasts across a wide range of 

tastes and curiosities. 

So, how does Barbie converge with the study of science? The association 

comes from a gene appropriately named “Ken and Barbie” due to the 

ability of its mutated form to interrupt the mechanism responsible for 

genital formation. Interestingly, fruit flies with the mutation completely 

lack external genitals. Equally silly are gene names such as “Sonic 

Hedgehog” and “Van Gogh.” As Mayer conveys in her podcast, each gene 

name usually relates to the symptoms of the gene’s related disorders, such 

as a fruit fly’s hedgehog-like, spiny appearance or swirly hair patterns 

that resemble Van Gogh’s Starry Night. Highlighting the amusing parts 

of science is key to defying perceptions of it as unimaginative to a 

broader audience. 

Another enticing aspect of Mayer’s podcasts is her use of vibrant 

analogies at the beginning of each podcast episode to playfully prime 

the listener’s curiosity. In her episode “Vaccines,” she begins with a 

description of a “cowpalooza” painted by nineteenth-century cartoonist 

James Gillray. Gillray’s satirical illustration depicts a room full of 

people who begin developing parts of a cow’s anatomy, alluding to the 

THE 

SPOTLIGHT 

historical backlash against the cowpox vaccine. This analogy becomes 

the foundation for her explanation of the Latin word “vacca,” translating 

to “cow,” and Edward Jenner’s development of the first vaccination 

for cowpox. By instilling images that are easy to imagine, Mayer 

makes science and its etymology easily accessible to a wide audience. 

Additionally, Mayer’s analogies delve into specific aspects of a broader 

field. One episode on the element cobalt allows for audience members 

to ask specific questions relating to their cobalt-blue sweater, a medieval 

goblin named “Kobold,” and of course, the ore. “Science Diction” probes 

the questions and curiosities of its listeners by introducing them to the 

rich, but unseen, histories of scientific words. ■ 




COUNTERPOINT 

Elon Musk has blown up Twitter—sorry, X—again! 

On January 29, 2024, the multibillionaire investor 

and innovator announced that human trials for 

the long-anticipated Neuralink brain implant project 

have finally begun. The tweet specifically read, “The first 

human received an implant from @Neuralink yesterday 

and is recovering well. Initial results show promising 

neural spike detection.” Now, some of you may already 

recognize the impact of such an announcement. But for 

those just entering the complex world of neurotechnology, 

here’s a small crash course. 

Neuralink, an ambitious tech company, was quietly 

started in 2016 by Musk as his first foray into the incredible 

sector of neurotechnology. Three years later in 2019, the 

company made its first major splash in the news when 

it unveiled its main project: the development of a small 

brain implant called N1. N1 is about the size of a coin, 

with wires thinner than human hair running through the 

brain. Ideas, theories, and hopes for Neuralink’s future 

were matched by a healthy dash of skepticism about 

cyborgs and the artificial intelligence (AI) singularity. 

Of the various features unique to the N1 brain chip, 

the most interesting is the novel electrode density on 

the sixty-four threads at 1,024 electrodes, which pick up 

signals from neurons. With this, the device will be able 

to collect much more brain data which would allow for 

more precise control from the user. Such precision could 

manifest itself in more accessible computer interfaces, 

prosthetic devices with fine motor controls, and 

treatment for neurological disorders such as Parkinson’s. 

It could bring us one step closer to allowing people who 

lost their arms to play the guitar again. 

Despite its great potential, common worries about 

Neuralink stem from Musk’s turbulent track record 

in business management. This huge development 

was announced in a tweet and was not registered on 

ClinicalTrials.gov, a database most research institutions 

use to monitor research protocols. All we have is the 

brochure Neuralink used to find volunteers for the 

Mind Over Matter: 

Neurolink’s Groundbreaking 

BRAIN-COMPUTER 

Interface Implantation 

By Lee Ngatia Muita 

research. The brochure claimed the study would take 

about six years with ‘regular follow-ups’. 

While not strictly illegal, it is troubling that the public 

does not know what protocols the company is taking to 

conduct these human experiments. What makes it more 

disturbing is that the animal rights group Physicians 

Committee for Responsible Medicine previously 

accused Neuralink of mistreating the monkeys used for 

experiments with the brain chip. Claims such as these 

are deeply worrying when it comes to experimentation 

on the human brain. Novel brain chips are touted to be 

built for long-term use, yet the only way to verify this 

longevity is to wait and see if things go wrong with time. 

This could mean a stroke or death. Yet Musk is not 

known to be a patient man. 

This technology would be wonderful if successfully 

developed, but first, we need Neuralink to improve in a 

variety of ways. We need more transparency regarding 

Neuralink’s research procedures, a demonstration of 

their dedication to maximizing the safety of the implant 

chip, and an indication of their accountability for the 

various allegations they are facing. While many remain 

cautiously optimistic about the future of this technology, 

we cannot forget that the man who is feeding us these 

Neuralink updates once tweeted, “Next, I’m buying 

Coca-Cola to put the cocaine back in.” 

Humanity stands to benefit greatly from the 

development of such incredible technologies, but with 

great power comes great responsibility. One only needs 

to look at the success of OpenAI’s generative models 

to see how much the public appreciates transparency 

from companies when presenting epic and somewhat 

scary technology. Building trust with the target 

market for developing technology is important in 

establishing a loyal customer base that will understand 

the complications that arise from experimentation. 

This is a lesson Neuralink must learn quickly before 

something devastating happens to an innocent 

human brain. ■ 


BY YUSUF RASHEED 

What do you think of when you hear the phrase ‘climate 

change’? Perhaps it’s magnificent glaciers melting away into 

nothingness, or tall pine trees toppling like dominoes as they 

go up in flames. Maybe it’s the greenhouse gas emissions from poorly 

regulated factories or the Atlantic Ocean slowly rising over Florida to 

swallow it up. For Yale professor Karla Neugebauer, the first image that 

pops into her mind is one of biochemistry. 

Neugebauer, a professor of molecular biophysics and biochemistry 

and director of the Yale Center for RNA Science and Medicine, teaches 

the spring semester class “Biochemistry and Our Changing Climate.” 

The course focuses on understanding and finding solutions to climate 

change through the lens of biochemistry. When asked about the focus, 

Neugebauer used one of her lecture topics to illustrate her point. “In 

2016, the Great Barrier Reef spiked a fever. It was literally forty-five 

degrees Celsius [113 degrees Fahrenheit], resulting in coral bleaching, 

which happens when the water temperature goes up too high. But a 

biochemist would ask, ‘Why? What’s the molecular mechanism? And 

what happened in between?’” she said. Using our understanding of 

biochemistry, we now know that elevated temperatures can promote the 

overproduction of reactive oxygen species, unstable molecules that react 

readily in the cell, damaging DNA, RNA, and proteins and even causing 

cell death. According to Neugebauer, understanding the molecular 

mechanisms that underlie this would allow us to look into evolving coral 

symbiotes that are capable of tolerating higher temperatures—or in other 

words, to innovate in the face of climate change. This is just one example 

of the many lecture topics Neugebauer covers in the class, including 

extremophiles, soil health, and forest fires. 

Neugebauer’s motivation for creating the class, which began in the 

fall of 2021, was to show students that different fields of study must 

come together to solve the world’s most pressing issues. “Everyone has 

something to offer. I was concerned that college students didn’t really 

see the point of digging into a discipline when the world is falling apart,” 

CROSS 

BIOCHEMISTRY AND 

OUR CHANGING CLIMATE 

Neugebauer said. “So I think that it’s very important for people 

to understand that it’s still very important to learn a discipline, 

whether it’s acting or music or biochemistry—all of those 

things are going to be applicable to helping humanity face the 

challenges ahead.” 

The class is divided into one lecture and one discussion 

section every week. The lecture introduces the week’s topic 

and places its biology in the context of climate change, while 

the discussion section offers the opportunity to explore this 

further through the week’s assigned original research paper. In 

the spring 2024 semester, which is Neugebauer’s third iteration 

of the course, there are thirty-eight students, the majority of 

which are MB&B majors, including seven BS/MS students. 

Other majors include EVST, MCDB, and non-STEM fields 

such as English and Philosophy. 

The class also features several other unique programs and 

assignments. Neugebauer takes the students on a field trip to 

East Rock Park, where they go birding and catch tardigrades, 

which they bring back to her house to observe over pizza. 

“There are a lot of people in biochemistry who don’t interact 

with living things, which is crazy. Your interest is in biology, 

so you should go out in nature and have a look,” she said. 

Each student is also required to complete a mini-review, 

in which Professor Neugebauer asks them to write a short 

paper on a biochemical issue pertinent to climate change. 

This is then presented as a five-minute flash talk at the class’s 

Climate Biochemistry Summit, the culmination of students’ 

research. “We get to hear all forty projects, and everybody is 

working on something completely different. Some are more 

chemistry-oriented, […] and others are more environmentoriented,” 

she said. 

As Neugebauer looks ahead at the ways that biochemistry 

may inform climate change, there is one topic she is particularly 

interested in: carbon drawdown, the process by which carbon 

is sequestered, or stored, in the long-lived products that we 

need on the planet, such as cement. “Manmade stuff is already 

over half the mass of the planet. We need to build more 

buildings because there’s gonna be a ton more human beings 

on the planet by 2050,” she said. “If we build them out of the 

current building materials, that’s going to take up the entire 

carbon budget.” This means that buildings can no longer be 

made out of concrete and steel. “The answer is to build things 

out of massive wood because it has carbon dioxide in it and 

thus can’t go back into the air,” she said. 

“Biochemistry and our Changing Climate” is offered in 

the spring semester and is an MB&B elective. Neugebauer 

welcomes all students to register. ■ 

ROADS 

ART BY LUNA AGUILAR 



Interested in getting involved with 

Yale Scientific 

for writing, production, web, 

business or outreach? 

Learn more at 

yalescientific.org/get-involved 

AD_Yale_Congrats_half_Winter_2_22_draft_1..qxp_8 2/6/18 10:02 AM Page 1 

Congratulations Class of 2024! 

The Yale Science and Engineering 

Association is here for you. 

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

organizations in the world with a focus on STEM. 

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

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

engineering community. 

Our goal is to support your Yale journey far beyond graduation. 

Join us at: ysea.org

YSM Issue 97.1

You also want an ePaper? Increase the reach of your titles

Delete template?

Save as template?